Search results for: clinical care
Commenced in January 2007
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Paper Count: 6551

Search results for: clinical care

41 Spectroscopic Study of the Anti-Inflammatory Action of Propofol and Its Oxidant Derivatives: Inhibition of the Myeloperoxidase Activity and of the Superoxide Anions Production by Neutrophils

Authors: Pauline Nyssen, Ange Mouithys-Mickalad, Maryse Hoebeke

Abstract:

Inflammation is a complex physiological phenomenon involving chemical and enzymatic mechanisms. Polymorphonuclear neutrophil leukocytes (PMNs) play an important role by producing reactive oxygen species (ROS) and releasing myeloperoxidase (MPO), a pro-oxidant enzyme. Released both in the phagolysosome and the extracellular medium, MPO produces during its peroxidase and halogenation cycles oxidant species, including hypochlorous acid, involved in the destruction of pathogen agents, like bacteria or viruses. Inflammatory pathologies, like rheumatoid arthritis, atherosclerosis induce an excessive stimulation of the PMNs and, therefore, an uncontrolled release of ROS and MPO in the extracellular medium, causing severe damages to the surrounding tissues and biomolecules such as proteins, lipids, and DNA. The treatment of chronic inflammatory pathologies remains a challenge. For many years, MPO has been used as a target for the development of effective treatments. Numerous studies have been focused on the design of new drugs presenting more efficient MPO inhibitory properties. However, some designed inhibitors can be toxic. An alternative consists of assessing the potential inhibitory action of clinically-known molecules, having antioxidant activity. Propofol, 2,6-diisopropyl phenol, which is used as an intravenous anesthetic agent, meets these requirements. Besides its anesthetic action employed to induce a sedative state during surgery or in intensive care units, propofol and its injectable form Diprivan indeed present antioxidant properties and act as ROS and free radical scavengers. A study has also evidenced the ability of propofol to inhibit the formation of the neutrophil extracellular traps fibers, which are important to trap pathogen microorganisms during the inflammation process. The aim of this study was to investigate the potential inhibitory action mechanism of propofol and Diprivan on MPO activity. To go into the anti-inflammatory action of propofol in-depth, two of its oxidative derivatives, 2,6-diisopropyl-1,4-p-benzoquinone (PPFQ) and 3,5,3’,5’-tetra isopropyl-(4,4’)-diphenoquinone (PPFDQ), were studied regarding their inhibitory action. Specific immunological extraction followed by enzyme detection (SIEFED) and molecular modeling have evidenced the low anti-catalytic action of propofol. Stopped-flow absorption spectroscopy and direct MPO activity analysis have proved that propofol acts as a reversible MPO inhibitor by interacting as a reductive substrate in the peroxidase cycle and promoting the accumulation of redox compound II. Overall, Diprivan exhibited a weaker inhibitory action than the active molecule propofol. In contrast, PPFQ seemed to bind and obstruct the enzyme active site, preventing the trigger of the MPO oxidant cycles. PPFQ induced a better chlorination cycle inhibition at basic and neutral pH in comparison to propofol. PPFDQ did not show any MPO inhibition activity. The three interest molecules have also demonstrated their inhibition ability on an important step of the inflammation pathway, the PMNs superoxide anions production, thanks to EPR spectroscopy and chemiluminescence. In conclusion, propofol presents an interesting immunomodulatory activity by acting as a reductive substrate in the peroxidase cycle of MPO, slowing down its activity, whereas PPFQ acts more as an anti-catalytic substrate. Although PPFDQ has no impact on MPO, it can act on the inflammation process by inhibiting the superoxide anions production by PMNs.

Keywords: Diprivan, inhibitor, myeloperoxidase, propofol, spectroscopy

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40 Using Health Literacy and Medico-Legal Guidance to Improve Restorative Dentistry Patient Information Leaflets

Authors: Hasneet K. Kalsi, Julie K. Kilgariff

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Introduction: Within dentistry, the process for gaining informed consent has become more complex. To consent for treatment, patients must understand all reasonable treatment options and associated risks and benefits. Consenting is therefore deeply embedded in health literacy. Patients attending for dental consultation are often presented with an array of information and choices, yet studies show patients recall less than half of the information provided immediately after. Appropriate and comprehensible patient information leaflets (PILs) may be useful aid memories. In 2016 the World Health Organisation set improving health literacy as a global priority. Soon after, Scotland’s 2017-2025 Making it Easier: A Health Literacy Action Plan followed. This project involved the review of Restorative PILs used within Dundee Dental Hospital to assess the Content and Readability. Method: The current PIL on Root Canal Treatment (RCT) was created in 2011. This predates the Montgomery vs. NHS Lanarkshire case, a ruling which significantly impacted dental consenting processes, as well as General Dental Council’s (GDC’s) Standards for the Dental Team and Faculty of General Dental Practice’s Good Practice Guidance on Clinical Examination and Record-Keeping. Current evidence-based guidance, including that stipulated by the GDC, was reviewed. A 20-point Essential Content Checklist was designed to conform to best practice guidance for valid consenting processes. The RCT leaflet was scored against this to ascertain if the content was satisfactory. Having ensured the content satisfied medicolegal requirements, health literacy considerations were reviewed regarding readability. This was assessed using McLaughlin’s Simple Measure of Gobbledygook (SMOG) formula, which identifies school stages that would have to be achieved to comprehend the PIL. The sensitivity of the results to alternative readability methods were assessed. Results: The PIL was not sufficient for modern consenting processes and reflected a suboptimal level of health literacy. Evaluation of the leaflet revealed key content was missing, including information pertaining to risks and benefits. Only five points out of the 20-point checklist were present. The readability score was 16, equivalent to a level 2 in National Adult Literacy Standards/Scottish Credit and Qualification Framework Level 5; 62% of Scottish adults are able to read to this standard. Discussion: Assessment of the leaflet showed it was no longer fit for purpose. Reasons include a lack of pertinent information, a text-heavy leaflet lacking flow, and content errors. The SMOG score indicates a high level of comprehension is required to understand this PIL, which many patients may not possess. A new PIL, compliant with medicolegal and health literacy guidance, was designed with patient-driven checklists, notes spaces for annotations/ questions and areas for clinicians to highlight important case-specific information. It has been tested using the SMOG formula. Conclusion: PILs can be extremely useful. Studies show that interactive use can enhance their effectiveness. PILs should reflect best practice guidance and be understood by patients. The 2020 leaflet designed and implemented aims to fulfill the needs of a modern healthcare system and its service users. It embraces and embeds Scotland’s Health Literacy Action Plan within the consenting process. A review of further leaflets using this model is ongoing.

Keywords: consent, health literacy, patient information leaflet, restorative dentistry

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39 Deep Learning Based on Image Decomposition for Restoration of Intrinsic Representation

Authors: Hyohun Kim, Dongwha Shin, Yeonseok Kim, Ji-Su Ahn, Kensuke Nakamura, Dongeun Choi, Byung-Woo Hong

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Artefacts are commonly encountered in the imaging process of clinical computed tomography (CT) where the artefact refers to any systematic discrepancy between the reconstructed observation and the true attenuation coefficient of the object. It is known that CT images are inherently more prone to artefacts due to its image formation process where a large number of independent detectors are involved, and they are assumed to yield consistent measurements. There are a number of different artefact types including noise, beam hardening, scatter, pseudo-enhancement, motion, helical, ring, and metal artefacts, which cause serious difficulties in reading images. Thus, it is desired to remove nuisance factors from the degraded image leaving the fundamental intrinsic information that can provide better interpretation of the anatomical and pathological characteristics. However, it is considered as a difficult task due to the high dimensionality and variability of data to be recovered, which naturally motivates the use of machine learning techniques. We propose an image restoration algorithm based on the deep neural network framework where the denoising auto-encoders are stacked building multiple layers. The denoising auto-encoder is a variant of a classical auto-encoder that takes an input data and maps it to a hidden representation through a deterministic mapping using a non-linear activation function. The latent representation is then mapped back into a reconstruction the size of which is the same as the size of the input data. The reconstruction error can be measured by the traditional squared error assuming the residual follows a normal distribution. In addition to the designed loss function, an effective regularization scheme using residual-driven dropout determined based on the gradient at each layer. The optimal weights are computed by the classical stochastic gradient descent algorithm combined with the back-propagation algorithm. In our algorithm, we initially decompose an input image into its intrinsic representation and the nuisance factors including artefacts based on the classical Total Variation problem that can be efficiently optimized by the convex optimization algorithm such as primal-dual method. The intrinsic forms of the input images are provided to the deep denosing auto-encoders with their original forms in the training phase. In the testing phase, a given image is first decomposed into the intrinsic form and then provided to the trained network to obtain its reconstruction. We apply our algorithm to the restoration of the corrupted CT images by the artefacts. It is shown that our algorithm improves the readability and enhances the anatomical and pathological properties of the object. The quantitative evaluation is performed in terms of the PSNR, and the qualitative evaluation provides significant improvement in reading images despite degrading artefacts. The experimental results indicate the potential of our algorithm as a prior solution to the image interpretation tasks in a variety of medical imaging applications. This work was supported by the MISP(Ministry of Science and ICT), Korea, under the National Program for Excellence in SW (20170001000011001) supervised by the IITP(Institute for Information and Communications Technology Promotion).

Keywords: auto-encoder neural network, CT image artefact, deep learning, intrinsic image representation, noise reduction, total variation

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38 Image Segmentation with Deep Learning of Prostate Cancer Bone Metastases on Computed Tomography

Authors: Joseph M. Rich, Vinay A. Duddalwar, Assad A. Oberai

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Prostate adenocarcinoma is the most common cancer in males, with osseous metastases as the commonest site of metastatic prostate carcinoma (mPC). Treatment monitoring is based on the evaluation and characterization of lesions on multiple imaging studies, including Computed Tomography (CT). Monitoring of the osseous disease burden, including follow-up of lesions and identification and characterization of new lesions, is a laborious task for radiologists. Deep learning algorithms are increasingly used to perform tasks such as identification and segmentation for osseous metastatic disease and provide accurate information regarding metastatic burden. Here, nnUNet was used to produce a model which can segment CT scan images of prostate adenocarcinoma vertebral bone metastatic lesions. nnUNet is an open-source Python package that adds optimizations to deep learning-based UNet architecture but has not been extensively combined with transfer learning techniques due to the absence of a readily available functionality of this method. The IRB-approved study data set includes imaging studies from patients with mPC who were enrolled in clinical trials at the University of Southern California (USC) Health Science Campus and Los Angeles County (LAC)/USC medical center. Manual segmentation of metastatic lesions was completed by an expert radiologist Dr. Vinay Duddalwar (20+ years in radiology and oncologic imaging), to serve as ground truths for the automated segmentation. Despite nnUNet’s success on some medical segmentation tasks, it only produced an average Dice Similarity Coefficient (DSC) of 0.31 on the USC dataset. DSC results fell in a bimodal distribution, with most scores falling either over 0.66 (reasonably accurate) or at 0 (no lesion detected). Applying more aggressive data augmentation techniques dropped the DSC to 0.15, and reducing the number of epochs reduced the DSC to below 0.1. Datasets have been identified for transfer learning, which involve balancing between size and similarity of the dataset. Identified datasets include the Pancreas data from the Medical Segmentation Decathlon, Pelvic Reference Data, and CT volumes with multiple organ segmentations (CT-ORG). Some of the challenges of producing an accurate model from the USC dataset include small dataset size (115 images), 2D data (as nnUNet generally performs better on 3D data), and the limited amount of public data capturing annotated CT images of bone lesions. Optimizations and improvements will be made by applying transfer learning and generative methods, including incorporating generative adversarial networks and diffusion models in order to augment the dataset. Performance with different libraries, including MONAI and custom architectures with Pytorch, will be compared. In the future, molecular correlations will be tracked with radiologic features for the purpose of multimodal composite biomarker identification. Once validated, these models will be incorporated into evaluation workflows to optimize radiologist evaluation. Our work demonstrates the challenges of applying automated image segmentation to small medical datasets and lays a foundation for techniques to improve performance. As machine learning models become increasingly incorporated into the workflow of radiologists, these findings will help improve the speed and accuracy of vertebral metastatic lesions detection.

Keywords: deep learning, image segmentation, medicine, nnUNet, prostate carcinoma, radiomics

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37 Effects of Applying Low-Dye Taping in Performing Double-Leg Squat on Electromyographic Activity of Lower Extremity Muscles for Collegiate Basketball Players with Excessive Foot Pronation

Authors: I. M. K. Ho, S. K. Y. Chan, K. H. P. Lam, G. M. W. Tong, N. C. Y. Yeung, J. T. C. Luk

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Low-dye taping (LDT) is commonly used for treating foot problems, such as plantar fasciitis, and supporting foot arch for runners and non-athletes patients with pes planus. The potential negative impact of pronated feet leading to tibial and femoral internal rotation via the entire kinetic chain reaction was postulated and identified. The changed lower limb biomechanics potentially leading to poor activation of hip and knee stabilizers, such as gluteus maximus and medius, may associate with higher risk of knee injuries including patellofemoral pain syndrome and ligamentous sprain in many team sports players. It is therefore speculated that foot arch correction with LDT might enhance the use of gluteal muscles. The purpose of this study was to investigate the effect of applying LDT on surface electromyographic (sEMG) activity of superior gluteus maximus (SGMax), inferior gluteus maximus (IGMax), gluteus medius (GMed) and tibialis anterior (TA) during double-leg squat. 12 male collegiate basketball players (age: 21.72.5 years; body fat: 12.43.6%; navicular drop: 13.72.7mm) with at least three years regular basketball training experience participated in this study. Participants were excluded if they had recent history of lower limb injuries, over 16.6% body fat and lesser than 10mm drop in navicular drop (ND) test. Recruited subjects visited the laboratory once for the within-subject crossover study. Maximum voluntary isometric contraction (MVIC) tests on all selected muscles were performed in randomized order followed by sEMG test on double-leg squat during LDT and non-LDT conditions in counterbalanced order. SGMax, IGMax, GMed and TA activities during the entire 2-second concentric and 2-second eccentric phases were normalized and interpreted as %MVIC. The magnitude of the difference between taped and non-taped conditions of each muscle was further assessed via standardized effect90% confidence intervals (CI) with non-clinical magnitude-based inference. Paired samples T-test showed a significant decrease (4.71.4mm) in ND (95% CI: 3.8, 5.6; p < 0.05) while no significant difference was observed between taped and non-taped conditions in sEMG tests for all muscles and contractions (p > 0.05). On top of traditional significant testing, magnitude-based inference showed possibly increase in IGMax activity (small standardized effect: 0.270.44), likely increase in GMed activity (small standardized effect: 0.340.34) and possibly increase in TA activity (small standardized effect: 0.220.29) during eccentric phase. It is speculated that the decrease of navicular drop supported by LDT application could potentially enhance the use of inferior gluteus maximus and gluteus medius especially during eccentric phase in this study. As the eccentric phase of double-leg squat is an important component of landing activities in basketball, further studies on the onset and amount of gluteal activation during jumping and landing activities with LDT are recommended. Since both hip and knee kinematics were not measured in this study, the underlying cause of the observed increase in gluteal activation during squat after LDT is inconclusive. In this regard, the investigation of relationships between LDT application, ND, hip and knee kinematics, and gluteal muscle activity during sports specific jumping and landing tasks should be focused in the future.

Keywords: flat foot, gluteus maximus, gluteus medius, injury prevention

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36 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

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35 Provision of Afterschool Programs: Understanding the Educational Needs and Outcomes of Newcomer and Refugee Students in Canada

Authors: Edward Shizha, Edward Makwarimba

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Newcomer and refugee youth feel excluded in the education system in Canada, and the formal education environment does not fully cater for their learning needs. The objective of this study was to build knowledge and understanding of the educational needs and experiences of these youth in Canada and how available afterschool programs can most effectively support their learning needs and academic outcomes. The Employment and Social Development Canada (ESDC), which funded this research, enables and empowers students to advance their educational experience through targeted investments in services that are delivered by youth-serving organizations outside the formal education system through afterschool initiatives. A literature review and a provincial/territorial internet scan were conducted to determine the availability of services and programs that serve the educational needs and academic outcomes of newcomer youth in 10 provinces and 3 territories in Canada. The goal was to identify intersectional factors (e.g., gender, sexuality, culture, social class, race, etc.) that influence educational outcomes of newcomer/refugee students and to recommend ways the ESDC could complement settlement services to enhance students’ educational success. First, data was collected through a literature search of various databases, including PubMed, Web of Science, Scopus, Google docs, ACADEMIA, and grey literature, including government documents, to inform our analysis. Second, a provincial/territorial internet scan was conducted using a template that was created by ESDC staff with the input of the researchers. The objective of the web-search scan was to identify afterschool programs, projects, and initiatives offered to newcomer/refugee youth by service provider organizations. The method for the scan included both qualitative and quantitative data gathering. Both the literature review and the provincial/territorial scan revealed that there are gender disparities in educational outcomes of newcomer and refugee youth. High school completion rates by gender show that boys are at higher risk of not graduating than girls and that girls are more likely than boys to have at least a high school diploma and more likely to proceed to postsecondary education. Findings from literature reveal that afterschool programs are required for refugee youth who experience mental health challenges and miss out on significant periods of schooling, which affect attendance, participation, and graduation from high school. However, some refugee youth use their resilience and ambition to succeed in their educational outcomes. Another finding showed that some immigrant/refugee students, through ethnic organizations and familial affiliation, maintain aspects of their cultural values, parental expectations and ambitious expectations for their own careers to succeed in both high school and postsecondary education. The study found a significant combination of afterschool programs that include academic support, scholarships, bursaries, homework support, career readiness, internships, mentorship, tutoring, non-clinical counselling, mental health and social well-being support, language skills, volunteering opportunities, community connections, peer networking, culturally relevant services etc. These programs assist newcomer youth to develop self-confidence and prepare for academic success and future career development. The study concluded that advantages of afterschool programs are greatest for youth at risk for poor educational outcomes, such as Latino and Black youth, including 2SLGBTQI+ immigrant youth.

Keywords: afterschool programs, educational outcomes, newcomer youth, refugee youth, youth-serving organizations

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34 Working at the Interface of Health and Criminal Justice: An Interpretative Phenomenological Analysis Exploration of the Experiences of Liaison and Diversion Nurses – Emerging Findings

Authors: Sithandazile Masuku

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Introduction: Public health approaches to offender mental health are driven by international policies and frameworks in response to the disproportionately large representation of people with mental health problems within the offender pathway compared to the general population. Public health service innovations include mental health courts in the US, restorative models in Singapore and, liaison and diversion services in Australia, the UK, and some other European countries. Mental health nurses are at the forefront of offender health service innovations. In the U.K. context, police custody has been identified as an early point within the offender pathway where nurses can improve outcomes by offering assessments and share information with criminal justice partners. This scope of nursing practice has introduced challenges related to skills and support required for nurses working at the interface of health and the criminal justice system. Parallel literature exploring experiences of nurses working in forensic settings suggests the presence of compassion fatigue, burnout and vicarious trauma that may impede risk harm to the nurses in these settings. Published research explores mainly service-level outcomes including monitoring of figures indicative of a reduction in offending behavior. There is minimal research exploring the experiences of liaison and diversion nurses who are situated away from a supportive clinical environment and engaged in complex autonomous decision-making. Aim: This paper will share qualitative findings (in progress) from a PhD study that aims to explore the experiences of liaison and diversion nurses in one service in the U.K. Methodology: This is a qualitative interview study conducted using an Interpretative Phenomenological Analysis to gain an in-depth analysis of lived experiences. Methods: A purposive sampling technique was used to recruit n=8 mental health nurses registered with the UK professional body, Nursing and Midwifery Council, from one UK Liaison and Diversion service. All participants were interviewed online via video call using semi-structured interview topic guide. Data were recorded and transcribed verbatim. Data were analysed using the seven steps of the Interpretative Phenomenological Analysis data analysis method. Emerging Findings Analysis to date has identified pertinent themes: • Difficulties of meaning-making for nurses because of the complexity of their boundary spanning role. • Emotional burden experienced in a highly emotive and fast-changing environment. • Stress and difficulties with role identity impacting on individual nurses’ ability to be resilient. • Challenges to wellbeing related to a sense of isolation when making complex decisions. Conclusion Emerging findings have highlighted the lived experiences of nurses working in liaison and diversion as challenging. The nature of the custody environment has an impact on role identity and decision making. Nurses left feeling isolated and unsupported are less resilient and may go on to experience compassion fatigue. The findings from this study thus far point to a need to connect nurses working in these boundary spanning roles with a supportive infrastructure where the complexity of their role is acknowledged, and they can be connected with a health agenda. In doing this, the nurses would be protected from harm and the likelihood of sustained positive outcomes for service users is optimised.

Keywords: liaison and diversion, nurse experiences, offender health, staff wellbeing

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33 Urban Ecosystem Health and Urban Agriculture

Authors: Mahbuba Kaneez Hasna

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Introductory Statement outlining the background: Little has been written about political ecology of urban gardening, such as a network of knowledge generation, technologies of food production and distribution, food consumption practices, and the regulation of ‘agricultural activities. For urban food gardens to sustain as a long-term food security enterprise, we will need to better understand the anthropological, ecological, political, and institutional factors influencing their development, management, and ongoing viability. Significance of the study: Dhaka as one of the fastest growing city. There are currently no studies regards to Bangladesh on how urban slum dwellerscope with the changing urban environment in the city, where they overcome challenges, and how they cope with the urban ecological cycle of food and vegetable production. It is also essential to understand the importance of their access to confined spaces in the slums they apply their indigenous knowledge. These relationships in nature are important factors in community and conservation ecology. Until now, there has been no significant published academic work on relationships between urban and environmental anthropology, urban planning, geography, ecology, and social anthropology with a focus on urban agriculture and how this contributes to the moral economies, indigenous knowledge, and government policies in order to improve the lives and livelihoods of slum dwellers surrounding parks and open spaces in Dhaka, Bangladesh. Methodology: it have applied participant observation, semi-structured questionnaire-based interviews, and focus group discussions to collect social data. Interviews were conducted with the urban agriculture practitioners who are slum dwellers who carry out their urban agriculture activities. Some of the interviews were conducted with non-government organisations (NGOs) and local and state government officials, using semi-structured interviews. Using these methods developed a clearer understanding of how green space cultivation, local economic self-reliance, and urban gardening are producing distinctive urban ecologies in Dhaka and their policy-implications on urban sustainability. Major findings of the study: The research provided an in-depth knowledge on the challenges that slum dwellers encounter in establishing and maintaining urban gardens, such as the economic development of the city, conflicting political agendas, and environmental constraints in areas within which gardening activities take place. The research investigated (i) How do slum dwellers perform gardening practices from rural areas to open spaces in the city? (ii) How do men and women’s ethno-botanical knowledge contribute to urban biodiversity; (iii) And how do slum dwellers navigate complex constellations of land use policy, competing political agendas, and conflicting land and water tenures to meet livelihood functions provided by their gardens. Concluding statement: Lack of infrastructure facilities such as water supply and sanitation, micro-drains and waste disposal areas, and poor access to basic health care services increase the misery of people in the slum areas. Lack of environmental health awareness information for farmers, such as the risks from the use of chemical pesticides in gardens and from grazing animals in contaminated fields or cropping and planting trees or vegetable in contaminated dumping grounds, can all cause high health risk to humans and their environment.

Keywords: gender, urban agriculture, ecosystem health, urban slum systems

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32 A Parallel Cellular Automaton Model of Tumor Growth for Multicore and GPU Programming

Authors: Manuel I. Capel, Antonio Tomeu, Alberto Salguero

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Tumor growth from a transformed cancer-cell up to a clinically apparent mass spans through a range of spatial and temporal magnitudes. Through computer simulations, Cellular Automata (CA) can accurately describe the complexity of the development of tumors. Tumor development prognosis can now be made -without making patients undergo through annoying medical examinations or painful invasive procedures- if we develop appropriate CA-based software tools. In silico testing mainly refers to Computational Biology research studies of application to clinical actions in Medicine. To establish sound computer-based models of cellular behavior, certainly reduces costs and saves precious time with respect to carrying out experiments in vitro at labs or in vivo with living cells and organisms. These aim to produce scientifically relevant results compared to traditional in vitro testing, which is slow, expensive, and does not generally have acceptable reproducibility under the same conditions. For speeding up computer simulations of cellular models, specific literature shows recent proposals based on the CA approach that include advanced techniques, such the clever use of supporting efficient data structures when modeling with deterministic stochastic cellular automata. Multiparadigm and multiscale simulation of tumor dynamics is just beginning to be developed by the concerned research community. The use of stochastic cellular automata (SCA), whose parallel programming implementations are open to yield a high computational performance, are of much interest to be explored up to their computational limits. There have been some approaches based on optimizations to advance in multiparadigm models of tumor growth, which mainly pursuit to improve performance of these models through efficient memory accesses guarantee, or considering the dynamic evolution of the memory space (grids, trees,…) that holds crucial data in simulations. In our opinion, the different optimizations mentioned above are not decisive enough to achieve the high performance computing power that cell-behavior simulation programs actually need. The possibility of using multicore and GPU parallelism as a promising multiplatform and framework to develop new programming techniques to speed-up the computation time of simulations is just starting to be explored in the few last years. This paper presents a model that incorporates parallel processing, identifying the synchronization necessary for speeding up tumor growth simulations implemented in Java and C++ programming environments. The speed up improvement that specific parallel syntactic constructs, such as executors (thread pools) in Java, are studied. The new tumor growth parallel model is proved using implementations with Java and C++ languages on two different platforms: chipset Intel core i-X and a HPC cluster of processors at our university. The parallelization of Polesczuk and Enderling model (normally used by researchers in mathematical oncology) proposed here is analyzed with respect to performance gain. We intend to apply the model and overall parallelization technique presented here to solid tumors of specific affiliation such as prostate, breast, or colon. Our final objective is to set up a multiparadigm model capable of modelling angiogenesis, or the growth inhibition induced by chemotaxis, as well as the effect of therapies based on the presence of cytotoxic/cytostatic drugs.

Keywords: cellular automaton, tumor growth model, simulation, multicore and manycore programming, parallel programming, high performance computing, speed up

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31 Rationally Designed Dual PARP-HDAC Inhibitor Elicits Striking Anti-leukemic Effects

Authors: Amandeep Thakur, Yi-Hsuan Chu, Chun-Hsu Pan, Kunal Nepali

Abstract:

The transfer of ADP-ribose residues onto target substrates from nicotinamide adenine dinucleotide (NAD) (PARylation) is catalyzed by Poly (ADP-ribose) polymerases (PARPs). Amongst the PARP family members, the DNA damage response in cancer is majorly regulated by PARP1 and PARP2. The blockade of DNA repair by PARP inhibitors leads to the progression of DNA single-strand breaks (induced by some triggering factors) to double-strand breaks. Notably, PARP inhibitors are remarkably effective in cancers with defective homologous recombination repair (HRR). In particular, cancer cells with BRCA mutations are responsive to therapy with PARP inhibitors. The aforementioned requirement for PARP inhibitors to be effective confers a narrow activity spectrum to PARP inhibitors, which hinders their clinical applicability. Thus, the quest to expand the application horizons of PARP inhibitors beyond BRCA mutations is the need of the hour. Literature precedents reveal that HDAC inhibition induces BRCAness in cancer cells and can broaden the therapeutic scope of PARP inhibitors. Driven by such disclosures, dual inhibitors targeting both PARP and HDAC enzymes were designed by our research group to extend the efficacy of PARP inhibitors beyond BRCA-mutated cancers to cancers with induced BRCAness. The design strategy involved the installation of Veliparib, an investigational PARP inhibitor, as a surface recognition part in the HDAC inhibitor pharmacophore model. The chemical architecture of veliparib was deemed appropriate as a starting point for the generation of dual inhibitors by virtue of its size and structural flexibility. A validatory docking study was conducted at the outset to predict the binding mode of the designed dual modulatory chemical architectures. Subsequently, the designed chemical architectures were synthesized via a multistep synthetic route and evaluated for antitumor efficacy. Delightfully, one compound manifested impressive anti-leukemic effects (HL-60 cell lines) mediated via dual inhibition of PARP and class I HDACs. The outcome of the western blot analysis revealed that the compound could downregulate the expression levels of PARP1 and PARP2 and the HDAC isoforms (HDAC1, 2, and 3). Also, the dual PARP-HDAC inhibitor upregulated the protein expression of the acetyl histone H3, confirming its abrogation potential for class I HDACs. In addition, the dual modulator could arrest the cell cycle at the G0/G1 phase and induce autophagy. Further, polymer-based nanoformulation of the dual inhibitor was furnished to afford targeted delivery of the dual inhibitor at the cancer site. Transmission electron microscopy (TEM) results indicate that the nanoparticles were monodispersed and spherical. Moreover, the polymeric nanoformulation exhibited an appropriate particle size. Delightfully, pH-sensitive behavior was manifested by the polymeric nanoformulation that led to selective antitumor effects towards the HL-60 cell lines. In light of the magnificent anti-leukemic profile of the identified dual PARP-HDAC inhibitor, in-vivo studies (pharmacokinetics and pharmacodynamics) are currently being conducted. Notably, the optimistic findings of the aforementioned study have spurred our research group to initiate several medicinal chemistry campaigns to create bifunctional small molecule inhibitors addressing PARP as the primary target.

Keywords: PARP inhibitors, HDAC inhibitors, BRCA mutations, leukemia

Procedia PDF Downloads 17
30 A Lightning Strike Mimic: The Abusive Use of Dog Shock Collar Presents as Encephalopathy, Respiratory Arrest, Cardiogenic Shock, Severe Hypernatremia, Rhabdomyolysis, and Multiorgan Injury

Authors: Merrick Lopez, Aashish Abraham, Melissa Egge, Marissa Hood, Jui Shah

Abstract:

A 3 year old male with unknown medical history presented initially with encephalopathy, intubated for respiratory failure, and admitted to the pediatric intensive care unit (PICU) with refractory shock. During resuscitation in the emergency department, he was found to be in severe metabolic acidosis with a pH of 7.03 and escalated on vasopressor drips for hypotension. His initial sodium was 174. He was noted to have burn injuries to his scalp, forehead, right axilla, bilateral arm creases and lower legs. He had rhabdomyolysis (initial creatinine kinase 5,430 U/L with peak levels of 62,340 normal <335 U/L), cardiac injury (initial troponin 88 ng/L with peak at 145 ng/L, normal <15ng/L), hypernatremia (peak 174, normal 140), hypocalcemia, liver injury, acute kidney injury, and neuronal loss on magnetic resonance imaging (MRI). Soft restraints and a shock collar were found in the home. He was critically ill for 8 days, but was gradually weaned off drips, extubated, and started on feeds. Discussion Electrical injury, specifically lightning injury is an uncommon but devastating cause of injury in pediatric patients. This patient with suspected abusive use of a dog shock collar presented similar to a lightning strike. Common entrance points include the hands and head, similar to our patient with linear wounds on his forehead. When current enters, it passes through tissues with the least resistance. Nerves, blood vessels, and muscles, have high fluid and electrolyte content and are commonly affected. Exit points are extremities: our child who had circumferential burns around his arm creases and ankles. Linear burns preferentially follow areas of high sweat concentration, and are thought to be due to vaporization of water on the skin’s surface. The most common cause of death from a lightning strike is due to cardiopulmonary arrest. The massive depolarization of the myocardium can result in arrhythmias and myocardial necrosis. The patient presented in cardiogenic shock with evident cardiac damage. Electricity going through vessels can lead to vaporization of intravascular water. This can explain his severe hypernatremia. He also sustained other internal organ injuries (adrenal glands, pancreas, liver, and kidney). Electrical discharge also leads to direct skeletal muscle injury in addition to prolonged muscular spasm. Rhabdomyolysis, the acute damage of muscle, leads to release of potentially toxic components into the circulation which could lead to acute renal failure. The patient had severe rhabdomyolysis and renal injury. Early hypocalcemia has been consistently demonstrated in patients with rhabdomyolysis. This was present in the patient and led to increased vasopressor needs. Central nervous system injuries are also common which can include encephalopathy, hypoxic injury, and cerebral infarction. The patient had evidence of brain injury as seen on MRI. Conclusion Electrical injuries due to lightning strikes and abusive use of a dog shock collar are rare, but can both present in similar ways with respiratory failure, shock, hypernatremia, rhabdomyolysis, brain injury, and multiorgan damage. Although rare, it is essential for early identification and prompt management for acute and chronic complications in these children.

Keywords: cardiogenic shock, dog shock collar, lightning strike, rhabdomyolysis

Procedia PDF Downloads 84
29 Speciation of Bacteria Isolated from Clinical Canine and Feline Urine Samples by Using ChromID CPS Elite Agar: A Preliminary Study

Authors: Delsy Salinas, Andreia Garcês, Augusto Silva, Paula Brilhante Simões

Abstract:

Urinary tract infection (UTI) is a common disease affecting dogs and cats in both community and hospital environment. Bacteria is the most frequent agent isolated, fewer than 1% of infections are due to parasitic, fungal, or viral agents. Common symptoms and laboratory abnormalities includeabdominal pain, pyrexia, renomegaly, and neutrophilia with left shift. A rapid and precise identification of the bacterial agent is still a challenge in veterinarian laboratories. Therefore, this cross-sectional study aims to describe bacterial colony patterns of urine samples by using chromID™ CPS® EliteAgar (BioMérieux, France) from canine and feline specimens submitted to a veterinary laboratory in Portugal (INNO Veterinary Laboratory, Braga)from January to March2022. All urine samples were cultivated in CPS Elite Agar with calibrated 1 µL inoculating loop and incubated at 37ºC for 18-24h. Color,size, and shape (regular or irregular outline)were recorded for all samples. All colonies were classified as Gram-negative or Gram-positive bacteriausing Gram stain (PREVI® Color BioMérieux, France) and determined if they were pure colonies. Identification of bacteria species was performed using GP and GN cards inVitek 2® Compact(BioMérieux, France). A total of 256/1003 submitted urine samples presented bacterial growth, from which 172 isolates were included in this study. The sample’s population included 111 dogs (n=45 males and n=66 females) and 61 cats (n=35 males and n=26 females). The most frequent isolated bacteria wasEscherichia coli (44,7%), followed by Proteus mirabilis (13,4%). All Escherichia coli isolates presented red to burgundy colonies, a colony diameter between 2 to 6 mm, and regular or irregular outlines. Similarly, 100% of Proteus mirabilis isolates were dark yellow colonies with a diffuse pigment and the same size and shape as Escherichia coli. White and pink pale colonies where Staphylococcus species exclusively and S. pseudintermedius was the most frequent (8,2 %). Cian to blue colonies were mostly Enterococcusspp. (8,2%) and Streptococcus spp. (4,6%). Beige to brown colonies were Pseudomonas aeruginosa (2,9%) and Citrobacter spp. (1,2%).Klebsiella spp.,Serratia spp. and Enterobacter spp were green colonies. All Gram-positive isolates were 1 to 2 mm diameter long and had a regular outline, meanwhile, Gram-negative rods presented variable patterns. This results showed that theprevalence of E coli and P. mirabilis as uropathogenic agents follows the same trends in Europe as previously described in other studies. Both agents presented a particular color pattern in CPS Elite Agar to identify them without needing complementary tests. No other bacteria genus could be correlated strongly to a specific color pattern, and similar results have been observed instudies using human’s samples. Chromogenic media shows a great advantage for common urine bacteria isolation than traditional COS, McConkey, and CLEDAgar mediums in a routine context, especially when mixed fermentative Gram-negative agents grow simultaneously. In addition, CPS Elite Agar is versatile for Artificial Intelligent Reading Plates Systems. Routine veterinarian laboratories could use CPS Elite Agar for a rapid screening for bacteria identification,mainlyE coli and P.mirabilis, saving 6h to 10h of automatized identification.

Keywords: cats, CPS elite agar, dogs, urine pathogens

Procedia PDF Downloads 100
28 Uterine Leiomyomas and Urological Complications

Authors: Dharshini Selvarajah, Nicula Lui, Karen Kong

Abstract:

Background: Uterine fibroids are a common benign gynaecologic neoplasm in reproductive-aged women. Fibroids may become symptomatic in a vast majority of nulliparous women. Their diagnosis and management is often coordinated between gyneacologists, radiologists and urologists depending on the anatomical location, growth, size and the fibroids sarcomatous evolvement. Some patients may develop obstructive uropathy symptoms, either uni or bilateral secondary urethral obstruction causing hydronephrosis. Uterine artery emoblisation (UAE) has previously shown to effectively resolve symptoms as well as relieve urethral obstruction and resolve the hydronephrosis. UAE has now established itself as an organ preserving and minimally invasive procedure in the management of symptomatic uterine fibroids. It is a safe and effective alternative to hysterectomy for resolving fibroid related pressure symptoms. The case presented examines the clinical manifestations and impact of uterine fibroids on the urinary tract system. The therapeutic options to relieve the urological symptoms as well as preserve fertility are explored and presented. Case: The case is a 29-year-old Nepalese female admitted to hospital with recurrent urosepsis with multiresistant organisms. This was on a background of an enlarged uterus (measuring 17cm x11cm) with multiple subserosal, intramural and exophytic fibroids- causing external ureteric compression. She had bilateral ureteric stents insitu and required bilateral right and left nephrostomies during repeated episodes of urosepsis and bilateral ureteric obstruction. The left nephrostomy was removed a month prior to admission and her most recent CT KUB demonstrated hypofunctioning ureteric stents with bilateral hydronephrosis. Options of hysterectomy versus uterine artery emoblisation (UAE) were extensively explored. The patient was keen to preserve fertility. Risks associated with UAE such as expulsion of the submucosal component of the fibroids and the possibilities of sepsis in the setting of ongoing ureteric colonisation were particularly high. The patient opted to trial UAE even though the risks of recurrent hospital admissions with urosepsis were going to be particularly high. In the event, the uterus fails to shrink adequately enough to relieve the obstructed ureters a hysterectomy would inevitably be required in future. Day 3 post UAE the patient developed fevers, was hypotensive and tachycardic post-receiving prophylactic meropenem and fluconazole pre emoblisation. She was noted to have a CRP of 293 with the most recent urine culture during this time growing Candida albicans. The patient was recommenced on oral fluconazole and IV meropenem, with good effect. Her repeat renal tract ultrasound post-UAE showed ongoing marked left hydronephrosis relatively unchanged from the scan one month prior to the procedure, however the right-sided hydronephrosis had resolved. The patient was discharged on a 2-week course of antibiotics. The patient will have a repeat renal tract ultrasound and MRI of the ureters to re-evaluate the degree of hydronephrosis and progress- this was unavailable at the time of abstract submission and will be presented at the conference. Conclusion: Fibroids are a common benign tumour of the uterus and can frequently impact the lower urinary system resulting in significant uropathy. They often enlarge and compress the urinary bladder, urethra and lower end of the ureters. The effectiveness of UAE as a fertility preserving option is described.

Keywords: Uterine leiomyomas and urological complications, uterine artery embolisation for fibroids, Uterine fibroids and complications, Management of uterine fibroids

Procedia PDF Downloads 218
27 Burkholderia Cepacia ST 767 Causing a Three Years Nosocomial Outbreak in a Hemodialysis Unit

Authors: Gousilin Leandra Rocha Da Silva, Stéfani T. A. Dantas, Bruna F. Rossi, Erika R. Bonsaglia, Ivana G. Castilho, Terue Sadatsune, Ary Fernandes Júnior, Vera l. M. Rall

Abstract:

Kidney failure causes decreased diuresis and accumulation of nitrogenous substances in the body. To increase patient survival, hemodialysis is used as a partial substitute for renal function. However, contamination of the water used in this treatment, causing bacteremia in patients, is a worldwide concern. The Burkholderia cepacia complex (Bcc), a group of bacteria with more than 20 species, is frequently isolated from hemodialysis water samples and comprises opportunistic bacteria, affecting immunosuppressed patients, due to its wide variety of virulence factors, in addition to innate resistance to several antimicrobial agents, contributing to the permanence in the hospital environment and to the pathogenesis in the host. The objective of the present work was to characterize molecularly and phenotypically Bcc isolates collected from the water and dialysate of the Hemodialysis Unit and from the blood of patients at a Public Hospital in Botucatu, São Paulo, Brazil, between 2019 and 2021. We used 33 Bcc isolates, previously obtained from blood cultures from patients with bacteremia undergoing hemodialysis treatment (2019-2021) and 24 isolates obtained from water and dialysate samples in a Hemodialysis Unit (same period). The recA gene was sequenced to identify the specific species among the Bcc group. All isolates were tested for the presence of some genes that encode virulence factors such as cblA, esmR, zmpA and zmpB. Considering the epidemiology of the outbreak, the Bcc isolates were molecularly characterized by Multi Locus Sequence Type (MLST) and by pulsed-field gel electrophoresis (PFGE). The verification and quantification of biofilm in a polystyrene microplate were performed by submitting the isolates to different incubation temperatures (20°C, average water temperature and 35°C, optimal temperature for group growth). The antibiogram was performed with disc diffusion tests on agar, using discs impregnated with cefepime (30µg), ceftazidime (30µg), ciprofloxacin (5µg), gentamicin (10µg), imipenem (10µg), amikacin 30µg), sulfametazol/trimethoprim (23.75/1.25µg) and ampicillin/sulbactam (10/10µg). The presence of ZmpB was identified in all isolates, while ZmpA was observed in 96.5% of the isolates, while none of them presented the cblA and esmR genes. The antibiogram of the 33 human isolates indicated that all were resistant to gentamicin, colistin, ampicillin/sulbactam and imipenem. 16 (48.5%) isolates were resistant to amikacin and lower rates of resistance were observed for meropenem, ceftazidime, cefepime, ciprofloxacin and piperacycline/tazobactam (6.1%). All isolates were sensitive to sulfametazol/trimethoprim, levofloxacin and tigecycline. As for the water isolates, resistance was observed only to gentamicin (34.8%) and imipenem (17.4%). According to PFGE results, all isolates obtained from humans and water belonged to the same pulsotype (1), which was identified by recA sequencing as B. cepacia¸, belonging to sequence type ST-767. By observing a single pulse type over three years, one can observe the persistence of this isolate in the pipeline, contaminating patients undergoing hemodialysis, despite the routine disinfection of water with peracetic acid. This persistence is probably due to the production of biofilm, which protects bacteria from disinfectants and, making this scenario more critical, several isolates proved to be multidrug-resistant (resistance to at least three groups of antimicrobials), turning the patient care even more difficult.

Keywords: hemodialysis, burkholderia cepacia, PFGE, MLST, multi drug resistance

Procedia PDF Downloads 97
26 Management of Urological Complications Secondary to Uterine Fibroids

Authors: Dharshini Selvarajah, Karen Kong

Abstract:

Background: Uterine fibroids are a common benign gynaecologic neoplasm in reproductive-aged women. Fibroids may become symptomatic in a vast majority of nulliparous women. Their diagnosis and management are often coordinated between gyneacologists, radiologists and urologists depending on the anatomical location, growth, size and the fibroids' sarcomatous evolvement. Some patients may develop obstructive uropathy symptoms, either uni or bilateral secondary urethral obstruction causing hydronephrosis. Uterine artery embolization (UAE) has previously been shown to effectively resolve symptoms as well as relieve urethral obstruction and resolve hydronephrosis. UAE has now established itself as an organ-preserving and minimally invasive procedure in the management of symptomatic uterine fibroids. It is a safe and effective alternative to hysterectomy for resolving fibroid-related pressure symptoms. The case presented examines the clinical manifestations and impact of uterine fibroids on the urinary tract system. The therapeutic options to relieve the urological symptoms as well as preserve fertility are explored and presented. Case: The case is a 29-year-old Nepalese female admitted to the hospital with recurrent urosepsis with multiresistant organisms. This was on a background of an enlarged uterus (measuring 17cm x11cm) with multiple subserosal, intramural and exophytic fibroids- causing external ureteric compression. She had bilateral ureteric stents in situ and required bilateral right and left nephrostomies during repeated episodes of urosepsis and bilateral ureteric obstruction. The left nephrostomy was removed a month prior to admission, and her most recent CT KUB demonstrated hypofunctioning ureteric stents with bilateral hydronephrosis. Options of hysterectomy versus uterine artery embolization (UAE) were extensively explored. The patient was keen to preserve fertility. Risks associated with UAE, such as the expulsion of the submucosal component of the fibroids and the possibilities of sepsis in the setting of ongoing ureteric colonisation were particularly high. The patient opted to trial UAE even though the risks of recurrent hospital admissions with urosepsis were going to be particularly high. In the event, the uterus fails to shrink adequately enough to relieve the obstructed ureters, a hysterectomy would inevitably be required in the future. Day 3 post-UAE the patient developed fevers, was hypotensive and tachycardic post-receiving prophylactic meropenem and fluconazole pre emoblisation. She was noted to have a CRP of 293 with the most recent urine culture during this time growing Candida albicans. The patient was recommenced on oral fluconazole and IV meropenum, with good effect. Her repeat renal tract ultrasound post-UAE showed ongoing marked left hydronephrosis relatively unchanged from the scan one month prior to the procedure; however, the right-sided hydronephrosis had resolved. The patient was discharged on a 2-week course of antibiotics. The patient will have a repeat renal tract ultrasound and MRI of the ureters to re-evaluate the degree of hydronephrosis and progress- this was unavailable at the time of abstract submission and will be presented at the conference. Conclusion: Fibroids are a common benign tumor of the uterus and can frequently impact the lower urinary system resulting in significant uropathy. They often enlarge and compress the urinary bladder, urethra and lower end of the ureters. The effectiveness of the UAE as a fertility-preserving option is described.

Keywords: uterine artery embolisation for fibroids, urological complications from fibroids, uropathy of fibroids, obstructive fibroid management

Procedia PDF Downloads 205
25 Cardiolipin-Incorporated Liposomes Carrying Curcumin and Nerve Growth Factor to Rescue Neurons from Apoptosis for Alzheimer’s Disease Treatment

Authors: Yung-Chih Kuo, Che-Yu Lin, Jay-Shake Li, Yung-I Lou

Abstract:

Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with cardiolipin (CL) to downregulate the phosphorylation of mitogen-activated protein kinases for Alzheimer’s disease (AD) management. AD belongs to neurodegenerative disorder with a gradual loss of memory, yielding irreversible dementia. CL-conjugated LIP loaded with CRM (CRM-CL/LIP) and that with NGF (NGF-CL/LIP) were applied to AD models of SK-N-MC cells and Wistar rats with an insult of β-amyloid peptide (Aβ). Lipids comprising 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (Avanti Polar Lipids, Alabaster, AL), 1',3'-bis[1,2- dimyristoyl-sn-glycero-3-phospho]-sn-glycerol (CL; Avanti Polar Lipids), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (Avanti Polar Lipids), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (Avanti Polar Lipids) and CRM (Sigma–Aldrich, St. Louis, MO) were dissolved in chloroform (J. T. Baker, Phillipsburg, NJ) and condensed using a rotary evaporator (Panchum, Kaohsiung, Taiwan). Human β-NGF (Alomone Lab, Jerusalem, Israel) was added in the aqueous phase. Wheat germ agglutinin (WGA; Medicago AB, Uppsala, Sweden) was grafted on LIP loaded with CRM for (WGA-CRM-LIP) and CL-conjugated LIP loaded with CRM (WGA-CRM-CL/LIP) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (Sigma–Aldrich) and N-hydroxysuccinimide (Alfa Aesar, Ward Hill, MA). The protein samples of SK-N-MC cells (American Type Tissue Collection, Rockville, MD) were used for sodium dodecyl sulfate (Sigma–Aldrich) polyacrylamide gel (Sigma–Aldrich) electrophoresis. In animal study, the LIP formulations were administered by intravenous injection via a tail vein of male Wistar rats (250–280 g, 8 weeks, BioLasco, Taipei, Taiwan), which were housed in the Animal Laboratory of National Chung Cheng University in accordance with the institutional guidelines and the guidelines of Animal Protection Committee under the Council of Agriculture of the Republic of China. We found that CRM-CL/LIP could inhibit the expressions of phosphorylated p38 (p-p38), p-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 (p-Ser202) to retard the neuronal apoptosis. Free CRM and released CRM from CRM-LIP and CRM-CL/LIP were not in a straightforward manner to effectively inhibit the expression of p-p38 and p-JNK in the cytoplasm. In addition, NGF-CL/LIP enhanced the quantities of p-neurotrophic tyrosine kinase receptor type 1 (p-TrkA) and p-extracellular-signal-regulated kinase 5 (p-ERK5), preventing the Aβ-induced degeneration of neurons. The membrane fusion of NGF-LIP activated the ERK5 pathway and the targeting capacity of NGF-CL/LIP enhanced the possibility of released NGF to affect the TrkA level. Moreover, WGA-CRM-LIP improved the permeation of CRM across the blood–brain barrier (BBB) and significantly reduced the Aβ plaque deposition and malondialdehyde level and increased the percentage of normal neurons and cholinergic function in the hippocampus of AD rats. This was mainly because the encapsulated CRM was protected by LIP against a rapid degradation in the blood. Furthermore, WGA on LIP could target N-acetylglucosamine on endothelia and increased the quantity of CRM transported across the BBB. In addition, WGA-CRM-CL/LIP could be effective in suppressing the synthesis of acetylcholinesterase and reduced the decomposition of acetylcholine for better neurotransmission. Based on the in vitro and in vivo evidences, WGA-CRM-CL/LIP can rescue neurons from apoptosis in the brain and can be a promising drug delivery system for clinical AD therapy.

Keywords: Alzheimer’s disease, β-amyloid, liposome, mitogen-activated protein kinase

Procedia PDF Downloads 329
24 Improving Data Completeness and Timely Reporting: A Joint Collaborative Effort between Partners in Health and Ministry of Health in Remote Areas, Neno District, Malawi

Authors: Wiseman Emmanuel Nkhomah, Chiyembekezo Kachimanga, Moses Banda Aron, Julia Higgins, Manuel Mulwafu, Kondwani Mpinga, Mwayi Chunga, Grace Momba, Enock Ndarama, Dickson Sumphi, Atupere Phiri, Fabien Munyaneza

Abstract:

Background: Data is key to supporting health service delivery as stakeholders, including NGOs rely on it for effective service delivery, decision-making, and system strengthening. Several studies generated debate on data quality from national health management information systems (HMIS) in sub-Saharan Africa. This limits the utilization of data in resource-limited settings, which already struggle to meet standards set by the World Health Organization (WHO). We aimed to evaluate data quality improvement of Neno district HMIS over a 4-year period (2018 – 2021) following quarterly data reviews introduced in January 2020 by the district health management team and Partners In Health. Methods: Exploratory Mixed Research was used to examine report rates, followed by in-depth interviews using Key Informant Interviews (KIIs) and Focus Group Discussions (FGDs). We used the WHO module desk review to assess the quality of HMIS data in the Neno district captured from 2018 to 2021. The metrics assessed included the completeness and timeliness of 34 reports. Completeness was measured as a percentage of non-missing reports. Timeliness was measured as the span between data inputs and expected outputs meeting needs. We computed T-Test and recorded P-values, summaries, and percentage changes using R and Excel 2016. We analyzed demographics for key informant interviews in Power BI. We developed themes from 7 FGDs and 11 KIIs using Dedoose software, from which we picked perceptions of healthcare workers, interventions implemented, and improvement suggestions. The study was reviewed and approved by Malawi National Health Science Research Committee (IRB: 22/02/2866). Results: Overall, the average reporting completeness rate was 83.4% (before) and 98.1% (after), while timeliness was 68.1% and 76.4 respectively. Completeness of reports increased over time: 2018, 78.8%; 2019, 88%; 2020, 96.3% and 2021, 99.9% (p< 0.004). The trend for timeliness has been declining except in 2021, where it improved: 2018, 68.4%; 2019, 68.3%; 2020, 67.1% and 2021, 81% (p< 0.279). Comparing 2021 reporting rates to the mean of three preceding years, both completeness increased from 88% to 99% (in 2021), while timeliness increased from 68% to 81%. Sixty-five percent of reports have maintained meeting a national standard of 90%+ in completeness while only 24% in timeliness. Thirty-two percent of reports met the national standard. Only 9% improved on both completeness and timeliness, and these are; cervical cancer, nutrition care support and treatment, and youth-friendly health services reports. 50% of reports did not improve to standard in timeliness, and only one did not in completeness. On the other hand, factors associated with improvement included improved communications and reminders using internal communication, data quality assessments, checks, and reviews. Decentralizing data entry at the facility level was suggested to improve timeliness. Conclusion: Findings suggest that data quality in HMIS for the district has improved following collaborative efforts. We recommend maintaining such initiatives to identify remaining quality gaps and that results be shared publicly to support increased use of data. These results can inform Ministry of Health and its partners on some interventions and advise initiatives for improving its quality.

Keywords: data quality, data utilization, HMIS, collaboration, completeness, timeliness, decision-making

Procedia PDF Downloads 80
23 The Systematic Impact of Climatic Disasters on the Maternal Health in Pakistan

Authors: Yiqi Zhu, Jean Francois Trani, Rameez Ulhassan

Abstract:

Extreme weather phenomena increased by 46% between 2007 and 2017 and have become more intense with the rise in global average temperatures. This increased intensity of climate variations often induces humanitarian crises and particularly affects vulnerable populations in low- and middle-income countries (LMICs). Expectant and lactating mothers are among the most vulnerable groups. Pakistan ranks 10th among the most affected countries by climate disasters. In 2022, monsoon floods submerged a third of the country, causing the loss of 1,500 lives. Approximately 650,000 expectant and lactating mothers faced systematic stress from climatic disasters. Our study used participatory methods to investigate the systematic impact of climatic disasters on maternal health. In March 2023, we conducted six Group Model Building (GMB) workshops with healthcare workers, fathers, and mothers separately in two of the most affected areas in Pakistan. This study was approved by the Islamic Relief Research Review Board. GMB workshops consist of three sessions. In the first session, participants discussed the factors that impact maternal health. After identifying the factors, they discussed the connections among them and explored the system structures that collectively impact maternal health. Based on the discussion, a causal loop diagram (CLD) was created. Finally, participants discussed action ideas that could improve the system to enhance maternal health. Based on our discussions and the causal loop diagram, we identified interconnected factors at the family, community, and policy levels. Mothers and children are directly impacted by three interrelated factors: food insecurity, unstable housing, and lack of income. These factors create a reinforcing cycle that negatively affects both mothers and newborns. After the flood, many mothers were unable to produce sufficient breastmilk due to their health status. Without breastmilk and sufficient food for complementary feeding, babies tend to get sick in damp and unhygienic environments resulting from temporary or unstable housing. When parents take care of sick children, they miss out on income-generating opportunities. At the community level, the lack of access to clean water and sanitation (WASH) and maternal healthcare further worsens the situation. Structural failures such as a lack of safety nets and programs associated with flood preparedness make families increasingly vulnerable with each disaster. Several families reported that they had not fully recovered from a flood that occurred ten years ago, and this latest disaster destroyed their lives again. Although over twenty non-profit organizations are working in these villages, few of them provide sustainable support. Therefore, participants called for systemic changes in response to the increasing frequency of climate disasters. The study reveals the systematic vulnerabilities of mothers and children after climatic disasters. The most vulnerable populations are often affected the most by climate change. Collaborative efforts are required to improve water and forest management, strengthen public infrastructure, increase access to WASH, and gradually build climate-resilient communities. Governments, non-governmental organizations, and the community should work together to develop and implement effective strategies to prevent, mitigate, and adapt to climate change and its impacts.

Keywords: climatic disasters, maternal health, Pakistan, systematic impact, flood, disaster relief.

Procedia PDF Downloads 74
22 A Chemical Perspective to Nineteenth-Century Female Medical Pioneers: Utilizing Mass Spectrometry in the Museum Space

Authors: Elizabeth R. LaFave, Grayson Sink, Anna Vassallo, Samantha Mills, Eli G. Hvastkovs

Abstract:

Throughout history and into modern times, the continuation of male influence over female healthcare has created inadequacies in availability and access to treatments, often further limited in rural communities. The historical plight of women in healthcare can be understood by studying the advancements made by women in the field, both through their career arcs and by delving into the treatments they offer. An early example is the case of Martha Ballard (1735-1812), a midwife in New York who practiced when female practitioners were dismissed in favor of less educated male physicians, which was a well-accepted practice into the twentieth century. In order to overcome these setbacks, a strategy used by some female practitioners was to develop and market their own remedies in an attempt to better serve female patients. By highlighting the compromises and social manipulation of female entrepreneurs, in comparison with the medicines they developed and used, we can map their ability to carve a specific niche for themselves and their targeted customers. The application of modern chemical approaches in a historical context serves to enhance a variety of perspectives within the museum sphere necessary for the comprehension and understanding of the female plight in both medical care and service. In order to further examine the overall bias and scrutiny for women in the medical field, specifically those undertaking entrepreneurial roles, examples of alternative remedies from female founders will be analyzed utilizing these approaches. Modern analytical chemistry techniques, specifically mass spectrometry (MS), have been successful in offering compositional analyses for both labeled and unlabeled ingredients in old medicines. Previously, we have analyzed two forms of alternative treatment options created by male medical professionals to address lingering historical questions of purity and validity. Although primarily sugar based, both Humphreys’ Specifics and Boericke & Tafel remedies also contained unique ingredients, albeit in small quantities, with medicinal properties. Here, we applied the same methodology to study another highly politicized 19th-century debate surrounding the contribution and role of women in the medical profession through analyzing three remedies, each from a different female-led manufacturing company; Mrs. Joe Persons, Lydia Pinkham, and Winslow’s Syrups. Following MS analyses for both labeled and unlabeled ingredients, both Winslow’s and Pinkham’s remedies were similar to their male counterparts in advertisement strategy, targeted customer base, and overall composition of remedy (primarily sugar-based with small amounts of unique ingredients). In effect, these unbiased chemical assessments are used to dissect the rationality of both market and physician criticism for each individual manufacturer through assessment of authenticity, benefaction, and comparison among female entrepreneurs and their aims to enter the medical community (i.e., geographic location, market size). Our work aims to increase collaboration between STEM (Science, Technology, Engineering, Mathematics)-based fields and historical museum studies on a larger scale while also answering questions of potential bias towards females in the medical community as means of comparison to their male counterparts and in-depth historical analyses to unravel individual strategies to overcome the setback.

Keywords: nineteenth-century medicine, alternative remedies, female healthcare, chemical analyses, mass spectrometry

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21 Case Report: Ocular Helminth - In Unusual Site (Lens)

Authors: Chandra Shekhar Majumder, Md. Shamsul Haque, Khondaker Anower Hossain, Md. Rafiqul Islam

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Introduction: Ocular helminths are parasites that infect the eye or its adnexa. They can be either motile worms or sessile worms that form cysts. These parasites require two hosts for their life cycle, a definite host (usually a human) and an intermediate host (usually an insect). While there have been reports of ocular helminths infecting various structures of the eye, including the anterior chamber and subconjunctival space, there is no previous record of such a case involving the lens. Research Aim: The aim of this case report is to present a rare case of ocular helminth infection in the lens and to contribute to the understanding of this unusual site of infection. Methodology: This study is a case report, presenting the details and findings of an 80-year-old retired policeman who presented with severe pain, redness, and vision loss in the left eye. The patient had a history of diabetes mellitus and hypertension. The examination revealed the presence of a thread-like helminth in the lens. The patient underwent treatment and follow-up, and the helminth specimen was sent for identification to the department of Parasitology. Case report: An 80-year-old retired policeman attended the OPD, Faridpur Medical College Hospital with the complaints of severe pain, redness and gross dimness of vision of the left eye for 5 days. He had a history of diabetes mellitus and hypertension for 3 years. On examination, L/E visual acuity was PL only, moderate ciliary congestion, KP 2+, cells 2+ and posterior synechia from 5 to 7 O’clock position was found. Lens was opaque. A thread like helminth was found under the anterior of the lens. The worm was moving and changing its position during examination. On examination of R/E, visual acuity was 6/36 unaided, 6/18 with pinhole. There was lental opacity. Slit-lamp and fundus examination were within normal limit. Patient was admitted in Faridpur Medical College Hospital. Diabetes mellitus was controlled with insulin. ICCE with PI was done on the same day of admission under depomedrol coverage. The helminth was recovered from the lens. It was thread like, about 5 to 6 mm in length, 1 mm in width and pinkish in colour. The patient followed up after 7 days, VA was HM, mild ciliary congestion, few KPs and cells were present. Media was hazy due to vitreous opacity. The worm was sent to the department of Parasitology, NIPSOM, Dhaka for identification. Findings: The findings of this case report highlight the presence of a helminth in the lens, which has not been previously reported. The helminth was successfully removed from the lens, but the patient experienced complications such as anterior uveitis and vitreous opacity. The exact mechanism by which the helminth enters the lens remains unclear. Theoretical Importance: This case report contributes to the existing literature on ocular helminth infections by reporting a unique case involving the lens. It highlights the need for further research to understand the pathogenesis and mechanism of entry of helminths in the lens. Data Collection and Analysis Procedures: The data for this case report were collected through clinical examination and medical records of the patient. The findings were described and presented in a descriptive manner. No statistical analysis was conducted. Question Addressed: This case report addresses the question of whether ocular helminth infections can occur in the lens, which has not been previously reported. Conclusion: To the best of our knowledge, this is the first reported case of ocular helminth infection in the lens. The presence of the helminth in the lens raises interesting questions regarding its pathogenesis and entry mechanism. Further study and research are needed to explore these aspects. Ophthalmologists and parasitologists should be aware of the possibility of ocular helminth infections in unusual sites like the lens.

Keywords: ocular, helminth, unsual site, lens

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20 Radioprotective Effects of Super-Paramagnetic Iron Oxide Nanoparticles Used as Magnetic Resonance Imaging Contrast Agent for Magnetic Resonance Imaging-Guided Radiotherapy

Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

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Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

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19 Optical Coherence Tomography in Differentiation of Acute and Non-Healing Wounds

Authors: Ananya Barui, Provas Banerjee, Jyotirmoy Chatterjee

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Application of optical technology in medicine and biology has a long track-record. In this endeavor, OCT is able to attract both engineers and biologists to work together in the field of photonics for establishing a striking non-invasive imaging technology. In contrast to other in vivo imaging modalities like Raman imaging, confocal imaging, two-photon microscopy etc. which can perform in vivo imaging upto 100-200 micron depth due to limitation in numerical aperture or scattering, however, OCT can achieve high-resolution imaging upto few millimeters of tissue structures depending on their refractive index in different anatomical location. This tomographic system depends on interference of two light waves in an interferometer to produce a depth profile of specimen. In wound healing, frequent collection of biopsies for follow-up of repair process could be avoided by such imaging technique. Real time skin OCT (the optical biopsy) has efficacy in deeper and faster illumination of cutaneou tissue to acquire high resolution cross sectional images of their internal micro-structure. Swept Source-OCT (SS-OCT), a novel imaging technique, can generate high-speed depth profile (~ 2 mm) of wound at a sweeping rate of laser with micron level resolution and optimum coherent length of 5-6 mm. Normally multi-layered skin tissue depicts different optical properties along with variation in thickness, refractive index and composition (i.e. keratine layer, water, fat etc.) according to their anatomical location. For instance, stratum corneum, the upper-most and relatively dehydrated layer of epidermis reflects more light and produces more lucid and a sharp demarcation line with rest of the hydrated epidermal region. During wound healing or regeneration, optical properties of cutaneous tissue continuously altered with maturation of wound bed. More mature and less hydrated tissue component reflects more light and becomes visible as a brighter area in comparison to immature region which content higher amount water or fat that depicts as a darker area in OCT image. Non-healing wound possess prolonged inflammation and inhibits nascent proliferative stage. Accumulation of necrotic tissues also prevents the repair of non-healing wounds. Due to high resolution and potentiality to reflect the compositional aspects of tissues in terms of their optical properties, this tomographic method may facilitate in differentiating non-healing and acute wounds in addition to clinical observations. Non-invasive OCT offers better insight regarding specific biological status of tissue in health and pathological conditions, OCT images could be associated with histo-pathological ‘gold standard’. This correlated SS-OCT and microscopic evaluation of the wound edges can provide information regarding progressive healing and maturation of the epithelial components. In the context of searching analogy between two different imaging modalities, their relative performances in imaging of healing bed were estimated for probing an alternative approach. Present study validated utility of SS-OCT in revealing micro-anatomic structure in the healing bed with newer information. Exploring precise correspondence of OCT images features with histo-chemical findings related to epithelial integrity of the regenerated tissue could have great implication. It could establish the ‘optical biopsy’ as a potent non-invasive diagnostic tool for cutaneous pathology.

Keywords: histo-pathology, non invasive imaging, OCT, wound healing

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

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

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

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

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17 Transitioning towards a Circular Economy in the Textile Industry: Approaches to Address Environmental Challenges

Authors: Mozhdeh Khalili Kordabadi

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Textiles play a vital role in human life, particularly in the form of clothing. However, the alarming rate at which textiles end up in landfills presents a significant environmental risk. With approximately one garbage truck per second being filled with discarded textiles, urgent measures are required to mitigate this trend. Governments and responsible organizations are calling upon various stakeholders to shift from a linear economy to a circular economy model in the textile industry. This article highlights several key approaches that can be undertaken to address this pressing issue. These approaches include the creation of renewable raw material sources, rethinking production processes, maximizing the use and reuse of textile products, implementing reproduction and recycling strategies, exploring redistribution to new markets, and finding innovative means to extend the lifespan of textiles. By adopting these strategies, the textile industry can contribute to a more sustainable and environmentally friendly future. Introduction: Textiles, particularly clothing, are essential to human existence. However, the rapid accumulation of textiles in landfills poses a significant threat to the environment. This article explores the urgent need for the textile industry to transition from a linear economy model to a circular economy model. The linear model, characterized by the creation, use, and disposal of textiles, is unsustainable in the long term. By adopting a circular economy approach, the industry can minimize waste, reduce environmental impact, and promote sustainable practices. This article outlines key approaches that can be undertaken to drive this transition. Approaches to Address Environmental Challenges: Creation of Renewable Raw Materials Sources: Exploring and promoting the use of renewable and sustainable raw materials, such as organic cotton, hemp, and recycled fibers, can significantly reduce the environmental footprint of textile production. Rethinking Production Processes: Implementing cleaner production techniques, optimizing resource utilization, and minimizing waste generation are crucial steps in reducing the environmental impact of textile manufacturing. Maximizing Use and Reuse of Textile Products: Encouraging consumers to prolong the lifespan of textile products through proper care, maintenance, and repair services can reduce the frequency of disposal and promote a culture of sustainability. Reproduction and Recycling Strategies: Investing in innovative technologies and infrastructure to enable efficient reproduction and recycling of textiles can close the loop and minimize waste generation. Redistribution of Textiles to New Markets: Exploring opportunities to redistribute textiles to new and parallel markets, such as resale platforms, can extend their lifecycle and prevent premature disposal. Improvising Means to Extend Textile Lifespan: Encouraging design practices that prioritize durability, versatility, and timeless aesthetics can contribute to prolonging the lifespan of textiles. Conclusion: The textile industry must urgently transition from a linear economy to a circular economy model to mitigate the adverse environmental impact caused by textile waste. By implementing the outlined approaches, such as sourcing renewable raw materials, rethinking production processes, promoting reuse and recycling, exploring new markets, and extending the lifespan of textiles, stakeholders can work together to create a more sustainable and environmentally friendly textile industry. These measures require collective action and collaboration between governments, organizations, manufacturers, and consumers to drive positive change and safeguard the planet for future generations.

Keywords: textiles, circular economy, environmental challenges, renewable raw materials, production processes, reuse, recycling, redistribution, textile lifespan extension.

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16 Preparedness and Control of Mosquito-Borne Diseases: Experiences from Northwestern Italy

Authors: Federica Verna, Alessandra Pautasso, Maria Caramelli, Cristiana Maurella, Walter Mignone, Cristina Casalone

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Mosquito-Borne Diseases (MBDs) are dangerously increasing in prevalence, geographical distribution and severity, representing an emerging threat for both humans and animals. Interaction between multiple disciplines is needed for an effective early warning, surveillance and control of MBDs, according to the One Health concept. This work reports the integrated surveillance system enforced by IZSPLV in Piedmont, Liguria and Valle d’Aosta regions (Northwestern Italy) in order to control MDBs spread. Veterinary services and local human health authority are involved in an information network, to connect the surveillance of human clinical cases with entomological surveillance and veterinary monitoring in order to implement control measures in case of outbreak. A systematic entomological surveillance is carried out during the vector season using mosquitoes traps located in sites selected according to risk factors. Collected mosquitoes are counted, identified to species level by morphological standard classification keys and pooled by collection site, date and species with a maximum of 100 individuals. Pools are analyzed, after RNA extraction, by Real Time RT-PCR distinctive for West Nile Virus (WNV) Lineage 1 and Lineage 2, Real Time RT-PCR USUTU virus (USUV) and a traditional flavivirus End-point RT-PCR. Positive pools are sequenced and the related sequences employed to perform a basic local alignment search tool (BLAST) in the GenBank library. Positive samples are sent to the National Reference Centre for Animal Exotic Diseases (CESME, Teramo) for confirmation. With particular reference to WNV, after the confirmation, as provided by national legislation, control measures involving both local veterinary and human health services are activated: equine sera are randomly sampled within a 4 km radius from the positive collection sites and tested with ELISA kit and WNV NAT screening of blood donors is introduced. This surveillance network allowed to detect since 2011 USUV circulation in this area of Italy. WNV was detected in Piedmont and Liguria for the first time in 2014 in mosquitoes. During the 2015 vector season, we observed the expansion of its activity in Piedmont. The virus was detected in almost all Provinces both in mosquitoes (6 pools) and animals (19 equine sera, 4 birds). No blood bag tested resulted infected. The first neuroinvasive human case occurred too. Competent authorities should be aware of a potentially increased risk of MBDs activity during the 2016 vector season. This work shows that this surveillance network allowed to early detect the presence of MBDs in humans and animals, and provided useful information to public authorities, in order to apply control measures. Finally, an additional value of our diagnostic protocol is the ability to detect all viruses belonging to the Flaviviridae family, considering the emergence caused by other Flaviviruses in humans such as the recent Zika virus infection in South America. Italy has climatic and environmental features conducive to Zika virus transmission, the competent vector and many travellers from Brazil reported every year.

Keywords: integrated surveillance, mosquito borne disease, West Nile virus, Zika virus

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15 A Case Report on the Course and Outcome of a Patient Diagnosed with Trichotillomania and Major Depressive Disorder

Authors: Ziara Carmelli G. Tan, Irene Carmelle S. Tan

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Background: Trichotillomania (TTM) and Major Depressive Disorder (MDD) are two psychiatric conditions that frequently co-occur, presenting a significant challenge for treatment due to their complex interplay. TTM involves repetitive hair-pulling, leading to noticeable hair loss and distress, while MDD is characterized by persistent low mood and loss of interest or pleasure, leading to dysfunctionality. This case report examines the intricate relationship between TTM and MDD in a young adult female, emphasizing the need for a comprehensive, multifaceted therapeutic approach to address both disorders effectively. Case Presentation: The patient is a 21-year-old female college student and youth church leader who presented with chronic hair-pulling and depressive symptoms. Her premorbid personality was marked by low self-esteem and a strong need for external validation. Despite her academic and social responsibilities and achievements, she struggled with managing her emotional distress, which was exacerbated by her family dynamics and her role within her church community. Her hair-pulling and mood symptoms were particularly triggered by self-esteem threats and feelings of inadequacy. She was diagnosed with Trichotillomania, Scalp and Major Depressive Disorder. Intervention/Management: The patient’s treatment plan was comprehensive, incorporating both pharmacological and non-pharmacological interventions. Initial pharmacologic management was Fluoxetine 20mg/day up, titrated to 40mg/day with no improvement; hence, shifted to Escitalopram 20mg/day and started with N-acetylcysteine 600mg/day with noted significant improvement in symptoms. Psychotherapeutic strategies played a crucial role in her treatment. These included supportive-expressive psychodynamic psychotherapy, which helped her explore and understand underlying emotional conflicts. Cognitive-behavioral techniques were employed to modify her maladaptive thoughts and behaviors. Grief processing was integrated to help her cope with significant losses. Family therapy was done to address conflicts and collaborate with the treatment process. Psychoeducation was provided to enhance her understanding of her condition and to empower her in her treatment journey. A suicide safety plan was developed to ensure her safety during critical periods. An interprofessional approach, which involved coordination with the Dermatology service for co-management, was also a key component of her treatment. Outcome: Over the course of 15 therapy sessions, the patient demonstrated significant improvement in both her depressive symptoms and hair-pulling behavior. Her active engagement in therapy, combined with pharmacological support, facilitated better emotional regulation and a more cohesive sense of self. Her adherence to the treatment plan, along with the collaborative efforts of the interprofessional team, contributed to her positive outcomes. Discussion: This case underscores the significance of addressing both TTM and its comorbid conditions to achieve effective treatment outcomes. The intricate interplay between TTM and MDD in the patient’s case highlights the importance of a comprehensive treatment plan that includes both pharmacological and psychotherapeutic approaches. Supportive-expressive psychodynamic psychotherapy, Cognitive-behavioral techniques, and Family therapy were particularly beneficial in addressing the complex emotional and behavioral aspects of her condition. The involvement of an interprofessional team, including dermatology co-management, was crucial in providing holistic care. Future practice should consider the benefits of such a multidisciplinary approach to managing complex cases like this, ensuring that both the psychological and physiological aspects of the disorders are adequately addressed.

Keywords: cognitive-behavioral therapy, interprofessional approach, major depressive disorder, psychodynamic psychotherapy, trichotillomania

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14 Prospects of Acellular Organ Scaffolds for Drug Discovery

Authors: Inna Kornienko, Svetlana Guryeva, Natalia Danilova, Elena Petersen

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Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines.

Keywords: 3D models, decellularization, drug discovery, drug toxicity, scaffolds, spheroids, tissue engineering

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13 Unidentified Remains with Extensive Bone Disease without a Clear Diagnosis

Authors: Patricia Shirley Almeida Prado, Selma Paixão Argollo, Maria De Fátima Teixeira Guimarães, Leticia Matos Sobrinho

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Skeletal differential diagnosis is essential in forensic anthropology in order to differentiate skeletal trauma from normal osseous variation and pathological processes. Thus, part of forensic anthropological field is differentiate skeletal criminal injuries from the normal skeletal variation (bone fusion or nonunion, transitional vertebrae and other non-metric traits), non-traumatic skeletal pathology (myositis ossificans, arthritis, bone metastasis, osteomyelitis) from traumatic skeletal pathology (myositis ossificans traumatic) avoiding misdiagnosis. This case shows the importance of effective pathological diagnosis in order to accelerate the identification process of skeletonized human remains. THE CASE: An unidentified skeletal remains at the medico legal institute Nina Rodrigues-Salvador, of a male young adult (29 to 40 years estimated) showing a massive heterotopic ossification on its right tibia at upper epiphysis and adjacent articular femur surface; an extensive ossification on the right clavicle (at the sternal extremity) also presenting an heterotopic ossification at right scapulae (upper third of scapulae lateral margin and infraglenoid tubercule) and at the head of right humerus at the shoulder joint area. Curiously, this case also shows an unusual porosity in certain vertebrae´s body and in some tarsal and carpal bones. Likewise, his left fifth metacarpal bones (right and left) showed a healed fracture which led both bones distorted. Based on identification, of pathological conditions in human skeletal remains literature and protocols these alterations can be misdiagnosed and this skeleton may present more than one pathological process. The anthropological forensic lab at Medico-legal Institute Nina Rodrigues in Salvador (Brazil) adopts international protocols to ancestry, sex, age and stature estimations, also implemented well-established conventions to identify pathological disease and skeletal alterations. The most compatible diagnosis for this case is hematogenous osteomyelitis due to following findings: 1: the healed fracture pattern at the clavicle showing a cloaca which is a pathognomonic for osteomyelitis; 2: the metacarpals healed fracture does not present cloaca although they developed a periosteal formation. 3: the superior articular surface of the right tibia shows an extensive inflammatory healing process that extends to adjacent femur articular surface showing some cloaca at tibia bone disease. 4: the uncommon porosities may result from hematogenous infectious process. The fractures probably have occurred in a different moments based on the healing process; the tibia injury is more extensive and has not been reorganized, while metacarpals and clavicle fracture is properly healed. We suggest that the clavicle and tibia´s fractures were infected by an existing infectious disease (syphilis, tuberculosis, brucellosis) or an existing syndrome (Gorham’s disease), which led to the development of osteomyelitis. This hypothesis is supported by the fact that different bones are affected in diverse levels. Like the metacarpals that do not show the cloaca, but then a periosteal new bone formation; then the unusual porosities do not show a classical osteoarthritic processes findings as the marginal osteophyte, pitting and new bone formation, they just show an erosive process without bone formation or osteophyte. To confirm and prove our hypothesis we are working on different clinical approaches like DNA, histopathology and other image exams to find the correct diagnostic.

Keywords: bone disease, forensic anthropology, hematogenous osteomyelitis, human identification, human remains

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12 Exploratory Characterization of Antibacterial Efficacy of Synthesized Nanoparticles on Staphylococcus Isolates from Hospital Specimens in Saudi Arabia

Authors: Reham K. Sebaih, Afaf I. Shehata , Awatif A. Hindi, Tarek Gheith, Amal A. Hazzani Anas Al-Orjan

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Staphylococci spp are ubiquitous gram-positive bacteria is often associated with infections, especially nosocomial infections, and antibiotic resistanceStudy pathogenic bacteria and its use as a tool in the technology of Nano biology and molecular genetics research of the latest research trends of modern characterization and definition of different multiresistant of bacteria including Staphylococci. The Staphylococci are widespread all over the world and particularly in Saudi Arabia The present work study was conducted to evaluate the effect of five different types of nanoparticles (biosynthesized zinc oxide, Spherical and rod of each silver and gold nanoparticles) and their antibacterial impact on the Staphylococcus species. Ninety-six isolates of Staphylococcus species. Staphylococcus aureus, Staphylococcus epidermidis, MRSA were collected from different sources during the period between March 2011G to June 2011G. All isolates were isolated from inpatients and outpatients departments at Royal Commission Hospital in Yanbu Industrial, Saudi Arabia. High percentage isolation from males(55%) than females (45%). Staphylococcus epidermidis from males was (47%), (28%), and(25%). For Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MRSA. Isolates from females were Staphylococcus aureus with higher percent of (47%), (30%), and (23%) for MRSA, Staphylococcus epidermidis. Staphylococcus aureus from wound swab were the highest percent (51.42%) followed by vaginal swab (25.71%). Staphylococcus epidermidis were founded with higher percentage in blood (37.14%) and wound swab (34.21%) respectively related to other. The highest percentage of methicillin-resistant Staphylococcus aureus (MRSA)(80.77%) were isolated from wound swab, while those from nostrils were (19.23%). Staphylococcus species were isolates in highest percentage from hospital Emergency department with Staphylococcus aureus (59.37%), Methicillin-resistant Staphylococcus aureus (MRSA) (28.13%)and Staphylococcus epidermidis (12.5%) respectively. Evaluate the antibacterial property of Zinc oxide, Silver, and Gold nanoparticles as an alternative to conventional antibacterial agents Staphylococci isolates from hospital sources we screened them. Gold and Silver rods Nanoparticles to be sensitive to all isolates of Staphylococcus species. Zinc oxide Nanoparticles gave sensitivity impact range(52%) and (48%). The Gold and Silver spherical nanoparticles did not showed any effect on Staphylococci species. Zinc Oxide Nanoparticles gave bactericidal impact (25%) and bacteriostatic impact (75%) for of Staphylococci species. Detecting the association of nanoparticles with Staphylococci isolates imaging by scanning electron microscope (SEM) of some bacteriostatic isolates for Zinc Oxide nanoparticles on Staphylococcus aureus, Staphylococcus epidermidis and Methicillin resistant Staphylococcus aureus(MRSA), showed some Overlapping Bacterial cells with lower their number and appearing some appendages with deformities in external shape. Molecular analysis was applied by Multiplex polymerase chain reaction (PCR) used for the identification of genes within Staphylococcal pathogens. A multiplex polymerase chain reaction (PCR) method has been developed using six primer pairs to detect different genes using 50bp and 100bp DNA ladder marker. The range of Molecular gene typing ranging between 93 bp to 326 bp for Staphylococcus aureus and Methicillin resistant Staphylococcus aureus by TSST-1,mecA,femA and eta, while the bands border were from 546 bp to 682 bp for Staphylococcus epidermidis using icaAB and atlE. Sixteen isolation of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for the femA gene at 132bp,this allowed the using of this gene as an internal positive control, fifteen isolates of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for mecA gene at163bp.This gene was responsible for antibiotic resistant Methicillin, Two isolates of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for the TSST-1 gene at326bp which is responsible for toxic shock syndrome in some Staphylococcus species, None were positive for eta gene at 102bpto that was responsible for Exfoliative toxins. Six isolates of Staphylococcus epidermidis were positive for atlE gene at 682 bp which is responsible for the initial adherence, three isolates of Staphylococcus epidermidis were positive for icaAB gene at 546bp that are responsible for mediates the formation of the biofilm. In conclusion, this study demonstrates the ability of the detection of the genes to discriminate between infecting Staphylococcus strains and considered biological tests, they may potentiate the clinical criteria used for the diagnosis of septicemia or catheter-related infections.

Keywords: multiplex polymerase chain reaction, toxic shock syndrome, Staphylococcus aureus, nosocomial infections

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