Search results for: clinical residents
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4257

Search results for: clinical residents

2787 Exaptive Urbanism: Evolutionary Biology and the Regeneration of Mumbai’s Dhobighat

Authors: Piyush Bajpai, Sneha Pandey

Abstract:

Mumbai’s Dhobighat, 150 year old largest open laundry in the world, is the true live-work place and only source of income for some of Mumbai’s highest density ‘urban poor’ residents. The regeneration of Dhobighat, due to its ultra prime location and complex socio-political culture has been a complex issue. This once flourishing urban industrial core has been degrading for the past several decades mainly due to the decline of the open laundry business, the site’s over burdened infrastructure and conflicting socio-political and economic forces. The phenomena of ‘exaptation’ or ‘co-option’ has been observed by evolutionary biologists as a process responsible for producing highly tenacious and resilient offsprings within a species. The reddish egret uses its wings to cast shadow in shallow waters to attract small fish and hunt them. An unrelated feature used opportunistically to produce a very favorable result. How can this idea of co-option be applied to resolve the complex issue of Dhobighat’s regeneration? Our paper proposes a new methodology/approach for the regeneration of Dhobighat through the lens of evolutionary biology. Forces and systems (social, political, economic, cultural and ecological) that seem conflicting or unrelated by nature are opportunistically transformed into symbiotic and complimentary relationships that produce an inclusive, resilient and holistic solution for the regeneration of Dhobighat.

Keywords: urban regeneration, exaptation, resilience, Dhobighat, Mumbai

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2786 Ultrasensitive Detection and Discrimination of Cancer-Related Single Nucleotide Polymorphisms Using Poly-Enzyme Polymer Bead Amplification

Authors: Lorico D. S. Lapitan Jr., Yihan Xu, Yuan Guo, Dejian Zhou

Abstract:

The ability of ultrasensitive detection of specific genes and discrimination of single nucleotide polymorphisms is important for clinical diagnosis and biomedical research. Herein, we report the development of a new ultrasensitive approach for label-free DNA detection using magnetic nanoparticle (MNP) assisted rapid target capture/separation in combination with signal amplification using poly-enzyme tagged polymer nanobead. The sensor uses an MNP linked capture DNA and a biotin modified signal DNA to sandwich bind the target followed by ligation to provide high single-nucleotide polymorphism discrimination. Only the presence of a perfect match target DNA yields a covalent linkage between the capture and signal DNAs for subsequent conjugation of a neutravidin-modified horseradish peroxidase (HRP) enzyme through the strong biotin-nuetravidin interaction. This converts each captured DNA target into an HRP which can convert millions of copies of a non-fluorescent substrate (amplex red) to a highly fluorescent product (resorufin), for great signal amplification. The use of polymer nanobead each tagged with thousands of copies of HRPs as the signal amplifier greatly improves the signal amplification power, leading to greatly improved sensitivity. We show our biosensing approach can specifically detect an unlabeled DNA target down to 10 aM with a wide dynamic range of 5 orders of magnitude (from 0.001 fM to 100.0 fM). Furthermore, our approach has a high discrimination between a perfectly matched gene and its cancer-related single-base mismatch targets (SNPs): It can positively detect the perfect match DNA target even in the presence of 100 fold excess of co-existing SNPs. This sensing approach also works robustly in clinical relevant media (e.g. 10% human serum) and gives almost the same SNP discrimination ratio as that in clean buffers. Therefore, this ultrasensitive SNP biosensor appears to be well-suited for potential diagnostic applications of genetic diseases.

Keywords: DNA detection, polymer beads, signal amplification, single nucleotide polymorphisms

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2785 Pharmacokinetics and Safety of Pacritinib in Patients with Hepatic Impairment and Healthy Volunteers

Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

Abstract:

Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

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2784 A Next Generation Multi-Scale Modeling Theatre for in silico Oncology

Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

Abstract:

Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

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2783 Innovation in Sustainable Development: Sustainable Place-Making Strategies in Hong Kong

Authors: Tris Kee

Abstract:

As the urban design discipline develops renewed interests in participatory design and collaborative place-making, it becomes critical to review the potential and limitations in current processes to ensure a sustainable method for future development.This paper explores how collaborative design can be a key to future sustainable urban development through two case studies from Asia.The process involves a multi-disciplinary collaboration and an innovative learning process by sharing ideas as well as careful consideration on social, economic and political circumstances among government and district stakeholders.This intrinsic proposition of innovative participatory planning implies interdisciplinary collaboration between professionals and local residents to integrate knowledge into new urban place-making thinking.Design innovation in contemporary society can manifest itself in the discourse sustainable urban development by bottom-up planning and community driven design. This paper examines the emerging design pedagogy which promotes interdisciplinary coalition of professionals and local stakeholders in community development as an innovative design rubric to create a sustainable urban approach.Through two case studies in Hong Kong, this paper reviews and critically evaluates the process of how the notion of sustainable development in contemporary urban planning theory is underpinned by the collaborative design practice.

Keywords: collaborative design, design innovation, sustainable development, urban development

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2782 Clinical Profile of Oral Sensory Abilities in Developmental Dysarthria

Authors: Swapna N., Deepthy Ann Joy

Abstract:

One of the major causes of communication disorders in pediatric population is Motor speech disorders. These disorders which affect the motor aspects of speech articulators can have an adverse effect on the communication abilities of children in their developmental period. The motor aspects are dependent on the sensory abilities of children with motor speech disorders. Hence, oral sensorimotor evaluation is an important component in the assessment of children with motor speech disorders. To our knowledge, the importance of oral motor examination has been well established, yet the sensory assessment of the oral structures has received less focus. One of the most common motor speech disorders seen in children is developmental dysarthria. The present study aimed to assess the orosensory aspects in children with developmental dysarthria (CDD). The control group consisted of 240 children in the age range of four and eight years which was divided into four subgroups (4-4.11, 5-5.11, 6-6.11 and 7-7.11 years). The experimental group consisted of 15 children who were diagnosed with developmental dysarthria secondary to cerebral palsy who belonged in the age range of four and eight years. The oro-sensory aspects such as response to touch, temperature, taste, texture, and orofacial sensitivity were evaluated and profiled. For this purpose, the authors used the ‘Oral Sensorimotor Evaluation Protocol- Children’ which was developed by the authors. The oro-sensory section of the protocol was administered and the clinical profile of oro-sensory abilities of typically developing children and CDD was obtained for each of the sensory abilities. The oro-sensory abilities of speech articulators such as lips, tongue, palate, jaw, and cheeks were assessed in detail and scored. The results indicated that experimental group had poorer scores on oro-sensory aspects such as light static touch, kinetic touch, deep pressure, vibration and double simultaneous touch. However, it was also found that the experimental group performed similar to control group on few aspects like temperature, taste, texture and orofacial sensitivity. Apart from the oro-motor abilities which has received utmost interest, the variation in the oro-sensory abilities of experimental and control group is highlighted and discussed in the present study. This emphasizes the need for assessing the oro-sensory abilities in children with developmental dysarthria in addition to oro-motor abilities.

Keywords: cerebral palsy, developmental dysarthria, orosensory assessment, touch

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2781 One Building at a Time for Tambak Lorok

Authors: Etika Sukma Adiyanti, H. N. Nurul Huda Putu Ekapraja, Gugun Gunawan

Abstract:

Global warming causes climate change and sea level rise. This is a threat for coastal regions, especially for coastal settlements with activities that are influenced by this natural phenomenon. Consequences are damage of houses, humid house environment, sustainability of the houses, obstructed economic activities and domestic works, disruption of sanitation facilities, lack of electricity, failure of transport system, psychological issues and other. Icons Tambak Lorok as 'Fisherman Village' is not something familiar to residents of the city of Semarang. Especially for the housewife who every day have to buy the ingredients high in protein and omega fish auction which is adjacent to the main street market in the village of Tambak Lorok. However, there are major problems that are being experienced by this small neighborhood. In fact, this issue includes seven infrastructure that should spoil the fishermen in activity with marine life. With this research, we will investigate water urbanism and climate change resiliency in Semarang, specifically the traditional fisher community of Tambak Lorok. We intend to find out how the local people in the fisher settlement Tambak Lorok deal with water urbanism, proverty and living with floods. So, we have a good solution for this problem, Floating Stage. We think that Tambak Lorok needs a new design for the common future. With this, One Building at A Time for Tambak Lorok, will be a good solution.

Keywords: fisher community, environment, climate change, settlement

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2780 Caregiver Training Results in Accurate Reporting of Stool Frequency

Authors: Matthew Heidman, Susan Dallabrida, Analice Costa

Abstract:

Background:Accuracy of caregiver reported outcomes is essential for infant growth and tolerability study success. Crying/fussiness, stool consistencies, and other gastrointestinal characteristics are important parameters regarding tolerability, and inter-caregiver reporting can see a significant amount of subjectivity and vary greatly within a study, compromising data. This study sought to elucidate how caregiver reported questions related to stool frequency are answered before and after a short amount of training and how training impacts caregivers’ understanding, and how they would answer the question. Methods:A digital survey was issued for 90 daysin the US (n=121) and 30 days in Mexico (n=88), targeting respondents with children ≤4 years of age. Respondents were asked a question in two formats, first without a line of training text and second with a line of training text. The question set was as follows, “If your baby had stool in his/her diaper and you changed the diaper and 10 min later there was more stool in the diaper, how many stools would you report this as?” followed by the same question beginning with “If you were given the instruction that IF there are at least 5 minutes in between stools, then it counts as two (2) stools…”.Four response items were provided for both questions, 1) 2 stools, 2) 1stool, 3) it depends on how much stool was in the first versus the second diaper, 4) There is not enough information to be able to answer the question. Response frequencies between questions were compared. Results: Responses to the question without training saw some variability in the US, with 69% selecting “2 stools”,11% selecting “1 stool”, 14% selecting “it depends on how much stool was in the first versus the second diaper”, and 7% selecting “There is not enough information to be able to answer the question” and in Mexico respondents selected 9%, 78%, 13%, and 0% respectively. However, responses to the question after training saw more consolidation in the US, with 85% of respondents selecting“2 stools,” representing an increase in those selecting the correct answer. Additionally in Mexico, with 84% of respondents selecting “1 episode” representing an increase in the those selecting the correct response. Conclusions: Caregiver reported outcomes are critical for infant growth and tolerability studies, however, they can be highly subjective and see a high variability of responses without guidance. Training is critical to standardize all caregivers’ perspective regarding how to answer questions accurately in order to provide an accurate dataset.

Keywords: infant nutrition, clinical trial optimization, stool reporting, decentralized clinical trials

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2779 Factors Associated to Down Syndrome Causes in Patients of Cytogenetics Laboratory, Faculty of Medicine, Universitas Padjadjaran in 2014─2015

Authors: Bremmy Laksono, Nurul Qomarilla, Riksa Parikrama, Dyan K. Nugrahaeni, Willyanti Soewondo, Dadang S. H. Effendi, Eriska Rianti, Arlette S. Setiawan, Ine Sasmita, Risti S. Primanti, Erna Kurnikasari, Yunia Sribudiani

Abstract:

Down syndrome is a chromosomal abnormality of chromosome 21 which can appear in man or woman. Maternal age and paternal age, history of radiation are the common risk factors. This study was conducted to observe risk factors which related as causes of Down syndrome. In this case control study using purposive sampling technique, 84 respondents were chosen from Cell Culture and Cytogenetics Laboratory patients in Faculty of Medicine, Universitas Padjadjaran, Indonesia. They were used as study samples and divided into 42 Down syndrome cases and 42 control respondents. This study used univariate and bivariate analysis (chi-square). Samples population were West Java residents, the biggest province in Indonesia in number of population. The results showed maternal age, paternal age, history of radiation exposure and family history were not significantly related to Down syndrome baby. Moreover, all of those factors also did not contribute to the risk of having a child with Down syndrome in patients at Cell Culture and Cytogenetics Laboratory, Faculty of Medicine, Universitas Padjadjaran. Therefore, we should investigate other risk factors of Down syndrome in West Java population.

Keywords: down syndrome, family history, maternal age, paternal age, risk factor

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2778 Difficulty and Complexity in Dealing with Visual Pollution in the Historical Cities: The Historical City of Ibb-Yemen as a Case Study

Authors: Abdulfattah A. Q .Alwah, Wen Li, Mohammed A. Q. Alwah, Duc Thien Tran, Bing Xi Liu

Abstract:

The historical cities in the third world suffer from many environmental problems; one of them is the spread of visual pollution manifestations. These phenomena increase with low levels of public awareness and low per capita income. The historical city of Ibb is suffering from a variety of visual pollution of the urban environment, so it has been chosen as a case study. This study aims to identify the difficulty and complexity of dealing with visual pollutions manifestations in the historical city of Ibb, and to provide appropriate solutions, which suit with the complex and contradictory circumstances. The study relies on an inductive approach to achieve its aims through two methods; the first is a visual survey of the visual pollution phenomenon based on images and researcher notes. The Second method is the analyses of the opinions and impressions of the city's residents and visitors through interviews, in addition to interviews with the officials in the competent authorities, and some specialists in the field of urban environment. Through the results of the field study and discussion of the interview results, this study presents an analysis of the phenomenon of visual distortion of the historical city of Ibb regarding the appearances and the reasons. Furthermore, this study provides appropriate solutions, which suitable with the complex and contradictory circumstances. These solutions take two paths: the first one is to stop the spread of visual distortions, and the second path is to address the current visual pollutions.

Keywords: visual pollution, visual image, urban environment, difficulty, complexity, historical cities, the historical city of Ibb

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2777 Role of Tourism in Increasing of Price of Land and Housing in Iran: Case Study of Shahmirzad City

Authors: Hamidreza Joodaki, Sara Farzaneh, Jaleh Afshar Qhazvin

Abstract:

Tourism industry is considered as the greatest and most various industry in the world. Most of these countries know this dynamic industry as main source of income, occupation, growth of private sector and development of infrastructure. One of the old methods of investment in countries such as Iran have transitional economy, is buying land and house, sometimes is resulted to high profit and of course for this reason hustler's are very interested in this background. Nowadays buying and selling land in the areas with pleasant climate in our country is considered. Since, Shahmirzad is a city with fair and desired environmental attractions is located in the border of deserted cities, mainly has special climatic position and these conditions are resulted to attraction of passenger, tourist for passing their leisure hours from Semnan and other cities of the area and from other provinces in hot seasons and with regard to these suitable conditions in the city buying land and housing also have been considered by most of residents of Semnan and cities around Shahmirzad by now. The aim of present research is investigation the role of tourism in increasing price of land and housing in Shahmirzad city. By studying on price of land and housing especially in central area, that gardens of the city are located in this area, we have concluded that role of tourism have caused in price of land and housing specially these prices in central and old areas are more expensive than towns around the city.

Keywords: tourism, climate conditions, price of land and housing, Shahmirzad

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2776 Enhancing Urban Sustainability through Integrated Green Spaces: A Focus on Tehran

Authors: Azadeh Mohajer Milani

Abstract:

Urbanization constitutes an irreversible global trend, presenting myriad challenges such as heightened energy consumption, pollution, congestion, and the depletion of natural resources. Today's urban landscapes have emerged as focal points for economic, social, and environmental challenges, underscoring the pressing need for sustainable development. This article delves into the realm of sustainable urban development, concentrating on the pivotal role played by integrated green spaces as an optimal solution to address environmental concerns within cities. The study utilizes Tehran as a case study. Our findings underscore the imperative of preserving and expanding green spaces in urban areas, coupled with the establishment of well-designed ecological networks, to enhance environmental quality and elevate the sustainability of cities. Notably, Tehran's urban green spaces exhibit a disjointed design, lacking a cohesive network to connect various patches and corridors, resulting in significant environmental impacts. The results emphasize the necessity of a balanced and proportional distribution of urban green spaces and the creation of a cohesive patch-corridor-matrix network tailored to the ecological and social needs of residents. This approach is crucial for fostering a more sustainable and livable urban environment for all species, with a specific focus on humans.

Keywords: ecology, sustainable urban development, sustainable landscape, urban green space network

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2775 Research Inspiration for Urban Renewal in Regions with Historical Value in Developed Areas of China: A Case Study of the Hubei Ancient Village

Authors: Qingxiang Zeng

Abstract:

Since the beginning of the 21st century, China's urbanization process has rapidly progressed. Since 2005, China's developed regions have gradually entered the stage of urban conservation and updating. The over-pursuit of economic market benefits in urban construction in China has led to issues such as disrespect for residents' rights, neglect of historical context protection, and gentlemanization, which hinder urban social development in some developed urban areas. This article takes the Hubei Ancient Village renewal project in Shenzhen, China, as an example. The project took eight years to obtain government approval and implementation since its renewal proposal was launched, which has attracted attention from society and urban planning circles. Through an introduction to the project's general situation and renewal process, this article reflects on the issues of planning systems, historical context protection, conflicts between multiple values, and neglect of vulnerable groups in the Hubei Ancient Village renewal and protection project. Based on this reflection, this article summarizes the corresponding experience and provides theoretical help for urban renewal in developed regions in China, providing case references for urban renewal and construction in other developing countries and offering critical thinking and valuable experience for urban planning practitioners and policymakers.

Keywords: urban renewal, Hubei Ancient Village, historical context, public participation

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2774 Decentralization and Participatory Approach in the Cultural Heritage Management in Local Thailand

Authors: Amorn Kritsanaphan

Abstract:

This paper illustrates the decentralization of cultural heritage management in local Thailand, a place similar to other middle- income developing countries characterized by rapid tourism-industrialization, weakness formal state institutions and procedures, and intensity use of the cultural heritage resources. The author conducted field research in local Thailand, principally using qualitative primary data gathering. These were combined with records reviews and content analysis of documents. The author also attended local public meetings, and social activities, and interacted casually with local residents and governments. Cultural heritage management has been supposed to improve through multi-stakeholder participation and decentralization. However, processes and outcomes are far from being straightforward and depend on a variety of contingencies and contexts involved. Multi-stakeholder and participatory approach in decentralization of the cultural heritage management in Thailand have pushed to the forefront and sharpened a number of existing problems. However, under the decentralization, the most significant contribution has been in creating real political space where various local stakeholders have become active, respond and address their concerns in various ways vis-à-vis cultural heritage problems. Improving cultural heritage sustainability and viability of local livelihoods through decentralization and participatory approach is by no means certain. However, the shift instead creates spaces potent with possibilities for a meaningful and constructive engagement between and among local state and non-state actors that can lead to synergies and positive outcomes.

Keywords: decentralization, participatory approach, cultural heritage management, multi-stakeholder approach

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2773 Enhanced Cytotoxic Effect of Expanded NK Cells with IL12 and IL15 from Leukoreduction Filter on K562 Cell Line Exhibits Comparable Cytotoxicity to Whole Blood

Authors: Abdulbaset Mazarzaei

Abstract:

Natural killer (NK) cells are innate immune effectors that play a pivotal role in combating tumors and infected cells. In recent years, the therapeutic potential of NK cells has gained significant attention due to their remarkable cytotoxic ability. This study focuses on investigating the cytotoxic effect of expanded NK cells enriched with interleukin 12 (IL12) and interleukin 15 (IL15), derived from the leukoreduction filter, on the K562 cell line. Firstly, NK cells were isolated from whole blood samples obtained from healthy volunteers. These cells were subsequently expanded ex vivo using a combination of feeder cells, IL12, and IL15. The expanded NK cells were then harvested and assessed for their cytotoxicity against K562, a well-established human chronic myelogenous leukemia cell line. The cytotoxicity was evaluated using flow cytometry assay. Results demonstrate that the expanded NK cells significantly exhibited enhanced cytotoxicity against K562 cells compared to non-expanded NK cells. Interestingly, the expanded NK cells derived specifically from IL12 and IL15-enriched leukoreduction filters showed a robust cytotoxic effect similar to the whole blood-derived NK cells. These findings suggest that IL12 and IL15 in the leukoreduction filter are crucial in promoting NK cell cytotoxicity. Furthermore, the expanded NK cells displayed relatively similar cytotoxicity profiles to whole blood-derived NK cells, indicating their comparable capability in targeting and eliminating tumor cells. This observation is of significant relevance as expanded NK cells from the leukoreduction filter could potentially serve as a readily accessible and efficient source for adoptive immunotherapy. In conclusion, this study highlights the significant cytotoxic effect of expanded NK cells enriched with IL12 and IL15 obtained from the leukoreduction filter on the K562 cell line. Moreover, it emphasizes that these expanded NK cells exhibit comparable cytotoxicity to whole blood-derived NK cells. These findings reinforce the potential clinical utility of using expanded NK cells from the leukoreduction filter as an effective strategy in adoptive immunotherapy for the treatment of cancer. Further studies are warranted to explore the broader implications of this approach in clinical settings.

Keywords: natural killer (NK) cells, Cytotoxicity, Leukoreduction filter, IL-12 and IL-15 Cytokines

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2772 Correlation of Residential Community Layout and Neighborhood Relationship: A Morphological Analysis of Tainan Using Space Syntax

Authors: Ping-Hung Chen, Han-Liang Lin

Abstract:

Taiwan has formed diverse settlement patterns in different time and space backgrounds. Various socio-network links are created between individuals, families, communities, and societies, and different living cultures are also derived. But rapid urbanization and social structural change have caused the creation of densely-packed assembly housing complexes and made neighborhood community upward developed. This, among others, seemed to have affected neighborhood relationship and also created social problems. To understand the complex relations and socio-spatial structure of the community, it is important to use mixed methods. This research employs the theory of space syntax to analyze the layout and structural indicators of the selected communities in Tainan city. On the other hand, this research does the survey about residents' interactions and the sense of community by questionnaire of the selected communities. Then the mean values of the syntax measures from each community were correlated with the results of the questionnaire using a Pearson correlation to examine how elements in physical design affect the sense of community and neighborhood relationship. In Taiwan, most urban morphology research methods are qualitative study. This paper tries to use space syntax to find out the correlation between the community layout and the neighborhood relationship. The result of this study could be used in future studies or improve the quality of residential communities in Taiwan.

Keywords: community layout, neighborhood relationship, space syntax, mixed-method

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2771 Assessment of Groundwater Quality around a Cement Factory in Ewekoro, Ogun State, Southwest Nigeria

Authors: A. O. David, A. A. Akaho, M. A. Abah, J. O. Ogunjimi

Abstract:

This study focuses on the growing concerns about the quality of groundwater found around cement factories, which have caused several health issues for residents located within two (2) kilometer radius. The qualities of groundwater were determined by an investigative study that involved the determination of some heavy metals and physicochemical properties in drinking water samples. Eight (8) samples of groundwater were collected from the eight sampling sites. The samples were analysed for the following parameters; iron, copper, manganese, zinc, lead, color, dissolved solids, electrical conductivity, pH, dissolved oxygen (DO), biological oxygen demand (BOD), chemical oxygen demand (COD), temperature, turbidity and total hardness using standard methods. The test results showed the variation of the investigated parameters in the samples as follows: temperature 26-31oC, pH 5.9-7.2, electrical conductivity (EC) 0.37 – 0.78 µS/cm, total hardness 181.8 – 333.0 mg/l, turbidity 0.00-0.05 FTU, colour 5-10 TCU, dissolved oxygen 4.31-5.01 mg/l, BOD 0.2-1.0 mg/l, COD 2.0 -4.0 mg/l, Cu 0.04 – 0.09 mg/l, Fe 0.006-0.122 mg/l, Zn 0.016-0.306 mg/l, Mn 0.01-0.05 mg/l and Pb < 0.001 mg/l. The World Health Organization's standard for drinking water quality guidelines was exceeded in several of the analyzed parameters' amounts in the drinking water samples from the study area. The dissolved oxygen was found to exceed 5.0 mg/l, which is the WHO permissible limit; also, Limestone was found to exceed the WHO maximum limit of 170 mg/l. All the above results confirmed the high pollution of the groundwater sources, and hence, they are not suitable for consumption without any prior treatment.

Keywords: groundwater, quality, heavy metals, parameters

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2770 Recreating Home: Restoration and Reflections on the Traditional Houses of Kucapungane

Authors: Sasala Taiban

Abstract:

This paper explores the process and reflections on the restoration of traditional slate houses in the Rukai tribe's old settlement of Kucapungane. Designated as a "Class II Historical Site" by the Ministry of the Interior in 1991 and listed by UNESCO's World Monuments Fund in 2016, Kucapungane holds significant historical and cultural value. However, due to government neglect, tribal migration, and the passing of elders, the traditional knowledge and techniques for constructing slate houses face severe discontinuity. Over the past decades, residents have strived to preserve and transmit these traditional skills through the restoration and reconstruction of their homes. This study employs a qualitative methodology, combining ethnographic fieldwork, historical analysis, and participatory observation. The research includes in-depth interviews, focus group discussions, and hands-on participation in restoration activities to gather comprehensive data. The paper reviews the historical evolution of Kucapungane, the restoration process, and the challenges encountered, such as insufficient resources, technical preservation issues, material acquisition problems, and lack of community recognition. Furthermore, it highlights the importance of house restoration in indigenous consciousness and cultural revival, proposing strategies to address current issues and promote preservation. Through these efforts, the cultural heritage of the Rukai tribe can be sustained and carried forward into the future.

Keywords: rukai, kucapungane, slate house restoration, cultural heritage

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2769 Endometrial Ablation and Resection Versus Hysterectomy for Heavy Menstrual Bleeding: A Systematic Review and Meta-Analysis of Effectiveness and Complications

Authors: Iliana Georganta, Clare Deehan, Marysia Thomson, Miriam McDonald, Kerrie McNulty, Anna Strachan, Elizabeth Anderson, Alyaa Mostafa

Abstract:

Context: A meta-analysis of randomized controlled trials (RCTs) comparing hysterectomy versus endometrial ablation and resection in the management of heavy menstrual bleeding. Objective: To evaluate the clinical efficacy, satisfaction rates and adverse events of hysterectomy compared to more minimally invasive techniques in the treatment of HMB. Evidence Acquisition: A literature search was performed for all RCTs and quasi-RCTs comparing hysterectomy with either endometrial ablation endometrial resection of both. The search had no language restrictions and was last updated in June 2020 using MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials, PubMed, Google Scholar, PsycINFO, Clinicaltrials.gov and Clinical trials. EU. In addition, a manual search of the abstract databases of the European Haemophilia Conference on women's health was performed and further studies were identified from references of acquired papers. The primary outcomes were patient-reported and objective reduction in heavy menstrual bleeding up to 2 years and after 2 years. Secondary outcomes included satisfaction rates, pain, adverse events short and long term, quality of life and sexual function, further surgery, duration of surgery and hospital stay and time to return to work and normal activities. Data were analysed using RevMan software. Evidence synthesis: 12 studies and a total of 2028 women were included (hysterectomy: n = 977 women vs endometrial ablation or resection: n = 1051 women). Hysterectomy was compared with endometrial ablation only in five studies (Lin, Dickersin, Sesti, Jain, Cooper) and endometrial resection only in five studies (Gannon, Schulpher, O’Connor, Crosignani, Zupi) and a mixture of the Ablation and Resection in two studies (Elmantwe, Pinion). Of the 1² studies, 10 reported women’s perception of bleeding symptoms as improved. Meta-analysis showed that women in the hysterectomy group were more likely to show improvement in bleeding symptoms when compared with endometrial ablation or resection up to 2-year follow-up (RR 0.75, 95% CI 0.71 to 0.79, I² = 95%). Objective outcomes of improvement in bleeding also favored hysterectomy. Patient satisfaction was higher after hysterectomy within the 2 years follow-up (RR: 0.90, 95%CI: 0.86 to 0.94, I²:58%), however, there was no significant difference between the two groups at more than 2 years follow up. Sepsis (RR: 0.03, 95% CI 0.002 to 0.56; 1 study), wound infection (RR: 0.05, 95% CI: 0.01 to 0.28, I²: 0%, 3 studies) and Urinary tract infection (UTI) (RR: 0.20, 95% CI: 0.10 to 0.42, I²: 0%, 4 studies) all favoured hysteroscopic techniques. Fluid overload (RR: 7.80, 95% CI: 2.16 to 28.16, I² :0%, 4 studies) and perforation (RR: 5.42, 95% CI: 1.25 to 23.45, I²: 0%, 4 studies) however favoured hysterectomy in the short term. Conclusions: This meta-analysis has demonstrated that endometrial ablation and endometrial resection are both viable options when compared with hysterectomy for the treatment of heavy menstrual bleeding. Hysteroscopic procedures had better outcomes in the short term with fewer adverse events including wound infection, UTI and sepsis. The hysterectomy performed better when measuring more long-term impacts such as recurrence of symptoms, overall satisfaction at two years and the need for further treatment or surgery.

Keywords: menorrhagia, hysterectomy, ablation, resection

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2768 Risk Factors for Severe Typhoid Fever in Children: A French Retrospective Study about 78 Cases from 2000-2017 in Six Parisian Hospitals

Authors: Jonathan Soliman, Thomas Cavasino, Virginie Pommelet, Lahouari Amor, Pierre Mornand, Simon Escoda, Nina Droz, Soraya Matczak, Julie Toubiana, François Angoulvant, Etienne Carbonnelle, Albert Faye, Loic de Pontual, Luu-Ly Pham

Abstract:

Background: Typhoid and paratyphoid fever are systemic infections caused by Salmonella enterica serovar Typhi or paratyphi (A, B, C). Children traveling to tropical areas are at risk to contract these diseases which can be complicated. Methods: Clinical, biological and bacteriological data were collected from 78 pediatric cases reported between 2000 and 2017 in six Parisian hospitals. Children aged 0 to 18 years old, with a diagnosis of typhoid or paratyphoid fever confirmed by bacteriological exams, were included. Epidemiologic, clinical, biological features and presence of multidrug-resistant (MDR) bacteria or intermediate susceptibility to ciprofloxacin (nalidixic acid resistant) were examined by univariate analysis and by logistic regression analysis to identify risk factors of severe typhoid in children. Results: 84,6% of the children were imported cases of typhoid fever (n=66/78) and 15,4% were autochthonous cases (n=12/78). 89,7% were caused by S.typhi (n=70/78) and 12,8% by S.paratyphi (n=10/78) including 2 co-infections. 19,2% were intrafamilial cases (n=15/78). Median age at diagnosis was 6,4 years-old [6 months-17,9 years]. 28,2% of the cases were complicated forms (n=22/78): digestive (n=8; 10,3%), neurological (n=7; 9%), pulmonary complications (n=4; 5,1%) and hemophagocytic syndrome (n=4; 5,1%). Only 5% of the children had prior immunization with typhoid non-conjugated vaccine (n=4/78). 28% of the cases (n=22/78) were caused by resistant bacteria. Thrombocytopenia and diagnosis delay was significantly associated with severe infection (p= 0.029 and p=0,01). Complicated forms were more common with MDR (p=0,1) and not statistically associated with a young age or sex in this study. Conclusions: Typhoid and paratyphoid fever are not rare in children back from tropical areas. This multicentric pediatric study seems to show that thrombocytopenia, diagnosis delay, and multidrug resistant bacteria are associated with severe typhoid fever and complicated forms in children.

Keywords: antimicrobial resistance, children, Salmonella enterica typhi and paratyphi, severe typhoid

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2767 Retrospective Study for Elective Medical Patients Evacuation of Different Diagnoses Requiring Different Approach in Oxygen Usage

Authors: Branimir Skoric

Abstract:

Over the past two decades, number of international travels rose significantly in the United Kingdom and Worldwide in the shape of business travels and holiday travels as well. The fact that elderly people travel a lot, more than ever before increased the needs for medical evacuations (repatriations) back home if they fell ill abroad or had any kind of accident. This paper concerns medical evacuations of patients on the way back home to the United Kingdom (United Kingdom Residents) and their specific medical needs during short-haul or long-haul commercial scheduled flight and ground transportation to the final destination regardless whether it was hospital or usual place of residence. Particular medical need during medical evacuations is oxygen supply and it can be supplied via portable oxygen concentrator, pulse flow oxygenator or continuous free flow oxygenator depending on the main diagnosis and patient’s comorbidities. In this retrospective study, patients were divided into two groups. One group was consisted of patients suffering from cardio-respiratory diagnoses as primary illness. Another Group consisted of patients suffering from noncardiac illnesses who have other problems including any kind of physical injury. Needs for oxygen and type of supply were carefully considered in regards of duration of the flight, standard airline cabin pressure and results described in this retrospective study.

Keywords: commercial flight, elderly travellers, medical evacuations, oxygen

Procedia PDF Downloads 133
2766 Present an Active Solar Energy System to Supply Heating Demands of the Teaching Staff Dormitory of Islamic Azad University of Ramhormoz

Authors: M. Talebzadegan, S. Bina , I. Riazi

Abstract:

The purpose of this paper is to present an active solar energy system to supply heating demands of the teaching staff dormitory of Islamic Azad University of Ramhormoz. The design takes into account the solar radiations and climate data of Ramhormoz town and is based on the daily warm water consumption for health demands of 450 residents of the dormitory, which is equal to 27000 lit of 50 C° water, and building heating requirements with an area of 3500 m² well-protected by heatproof materials. First, heating demands of the building were calculated, then a hybrid system made up of solar and fossil energies was developed and finally, the design was economically evaluated. Since there is only roof space for using 110 flat solar water heaters, the calculations were made to hybridize solar water heating system with heat pumping system in which solar energy contributes 67% of the heat generated. According to calculations, the Net Present Value “N.P.V.” of revenue stream exceeds “N.P.V.” of cash paid off in this project over three years, which makes economically quite promising. The return of investment and payback period of the project is 4 years. Also, the Internal Rate of Return (IRR) of the project was 25%, which exceeds bank rate of interest in Iran and emphasizes the desirability of the project.

Keywords: solar energy, heat demand, renewable, pollution

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2765 Activation of NLRP3 Inflammasomes by Helicobacter pylori Infection in Innate Cellular Model and Its Correlation to IL-1β Production

Authors: Islam Nowisser, Noha Farag, Mohamed El Azizi

Abstract:

Helicobacter pylori is a highly important human pathogen which inhabits about 50% of the population worldwide. Infection with this bacteria is very hard to treat, with high probability of recurrence. H. pylori causes severe gastric diseases, including peptic ulcer, gastritis, and gastric cancer, which has been linked to chronic inflammation. The infection has been reported to be associated with high levels of pro-inflammatory cytokines, especially IL-1β and TNF-α. The aim of the current study is to investigate the molecular mechanisms by which H. pylori activates NLRP3 inflammasome and its contribution to Il-1 β production in an innate cellular model. H. pylori PMSS1 and G27 standard strains, as well as the PMSS1 isogenic mutant strain PMSS1ΔVacA and G27ΔVacA, G27ΔCagA in addition to clinical isolates obtained from biopsy samples from the antrum and corpus mucosa of chronic gastritis patients, were used to establish infection in RAW-264.7 macrophages. The production levels of TNF-α and IL-1β was assessed using ELISA. Since expression of these cytokines is often regulated by the transcription factor complex, nuclear factor-kB (NF-kB), the activation of NF-κB in H. pylori infected cells was also evaluated by luciferase assay. Genomic DNA was extracted from bacterial cultures of H. pylori clinical isolates as well as the standard strains and their corresponding mutants, where they were evaluated for the cagA pathogenicity island and vacA expression. The correlation between these findings and expression of the cagA Pathogenicity Island and vacA in the bacteria was also investigated. The results showed IL-1β, and TNF-α production significantly increased in raw macrophages following H. pylori infection. The cagA+ and vacA+ H. pylori strains induced significant production of IL-1β compared to cagA- and vacA- strains. The activation pattern of NF-κB was correlated in the isolates to their cagA and vacA expression profiles. A similar finding could not be confirmed for TNF-α production. Our study shows the ability of H. pylori to activate NF-kB and induce significant IL-1β production as a possible mechanism for the augmented inflammatory response seen in subjects infected with cagA+ and vacA+ H. pylori strains that would lead to the progression to more severe form of the disease.

Keywords: Helicobacter pylori, IL-1β, inflammatory cytokines, nuclear factor KB, TNF-α

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2764 Informal Carers in Telemonitoring of Users with Pacemakers: Characteristics, Time of Services Provided and Costs

Authors: Antonio Lopez-Villegas, Rafael Bautista-Mesa, Emilio Robles-Musso, Daniel Catalan-Matamoros, Cesar Leal-Costa

Abstract:

Objectives: The purpose of this trial was to evaluate the burden borne by and the costs to informal caregivers of users with telemonitoring of pacemakers. Methods: This is a controlled, non-randomised clinical trial, with data collected from informal caregivers, five years after implantation of pacemakers. The Spanish version of the Survey on Disabilities, Personal Autonomy, and Dependency Situations was used to get information on clinical and social characteristics, levels of professionalism, duration and types of care, difficulties in providing care, health status, economic and job aspects, impact on the family or leisure due to informal caregiving for patients with pacemakers. Results: After five years of follow-up, 55 users with pacemakers finished the study. Of which, 50 were helped by a caregiver, 18 were included in the telemonitoring group (TM) and 32 in the conventional follow-up group (HM). Overall, females represented 96.0% of the informal caregivers (88.89% in TM and 100.0% in HM group). The mean ages were 63.17 ± 15.92 and 63.13 ± 14.56 years, respectively (p = 0.83) in the groups. The majority (88.0%) of the caregivers declared that they had to provide their services between 6 and 7 days per week (83.33% in TM group versus 90.63% in HM group), without significant differences between both groups. The costs related to care provided by the informal caregivers were 47.04% higher in the conventional follow-up group than in the TM group. Conclusions: The results of this trial confirm that there were no significant differences between the informal caregivers regarding to baseline characteristics, workload and time worked in both groups of follow-up. The costs incurred by the informal caregivers providing care for users with pacemakers included in telemonitoring group are significantly lower than those in the conventional follow-up group. Trial registration: ClinicalTrials.gov NCT02234245. Funding: The PONIENTE study, has been funded by the General Secretariat for Research, Development and Innovation, Regional Government of Andalusia (Spain), project reference number PI/0256/2017, under the research call 'Development and Innovation Projects in the Field of Biomedicine and Health Sciences', 2017.

Keywords: costs, disease burden, informal caregiving, pacemaker follow-up, remote monitoring, telemedicine

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2763 Autosomal Dominant Polycystic Kidney Patients May Be Predisposed to Various Cardiomyopathies

Authors: Fouad Chebib, Marie Hogan, Ziad El-Zoghby, Maria Irazabal, Sarah Senum, Christina Heyer, Charles Madsen, Emilie Cornec-Le Gall, Atta Behfar, Barbara Ehrlich, Peter Harris, Vicente Torres

Abstract:

Background: Mutations in PKD1 and PKD2, the genes encoding the proteins polycystin-1 (PC1) and polycystin-2 (PC2) cause autosomal dominant polycystic kidney disease (ADPKD). ADPKD is a systemic disease associated with several extrarenal manifestations. Animal models have suggested an important role for the polycystins in cardiovascular function. The aim of the current study is to evaluate the association of various cardiomyopathies in a large cohort of patients with ADPKD. Methods: Clinical data was retrieved from medical records for all patients with ADPKD and cardiomyopathies (n=159). Genetic analysis was performed on available DNA by direct sequencing. Results: Among the 58 patients included in this case series, 39 patients had idiopathic dilated cardiomyopathy (IDCM), 17 had hypertrophic obstructive cardiomyopathy (HOCM), and 2 had left ventricular noncompaction (LVNC). The mean age at cardiomyopathy diagnosis was 53.3, 59.9 and 53.5 years in IDCM, HOCM and LVNC patients respectively. The median left ventricular ejection fraction at initial diagnosis of IDCM was 25%. Average basal septal thickness was 19.9 mm in patients with HOCM. Genetic data was available in 19, 8 and 2 cases of IDCM, HOCM, and LVNC respectively. PKD1 mutations were detected in 47.4%, 62.5% and 100% of IDCM, HOCM and LVNC cases. PKD2 mutations were detected only in IDCM cases and were overrepresented (36.8%) relative to the expected frequency in ADPKD (~15%). The prevalence of IDCM, HOCM, and LVNC in our ADPKD clinical cohort was 1:17, 1:39 and 1:333 respectively. When compared to the general population, IDCM and HOCM was approximately 10-fold more prevalent in patients with ADPKD. Conclusions: In summary, we suggest that PKD1 or PKD2 mutations may predispose to idiopathic dilated or hypertrophic cardiomyopathy. There is a trend for patients with PKD2 mutations to develop the former and for patients with PKD1 mutations to develop the latter. Predisposition to various cardiomyopathies may be another extrarenal manifestation of ADPKD.

Keywords: autosomal dominant polycystic kidney (ADPKD), polycystic kidney disease, cardiovascular, cardiomyopathy, idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy, left ventricular noncompaction

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2762 Malaria Menace in Pregnancy; Hard to Ignore

Authors: Nautiyal Ruchira, Nautiyal Hemant, Chaudhury Devnanda, Bhargava Surbhi, Chauhan Nidhi

Abstract:

Introduction: South East Asian region contributes 2.5 million cases of malaria each year to the global burden of 300 to 500 million of which 76% is reported from India. Government of India launched a national program almost half a century ago, still malaria remains a major public health challenge. Pregnant women are more susceptible to severe malaria and its fetomaternal complications. Inadequate surveillance and under-reporting underestimates the problem. Aim: Present study aimed to analyze the clinical course and pattern of malaria during pregnancy and to study the feto-maternal outcome. Methodology: This is a prospective observational study carried out at Himalayan Institute of Medical Sciences – a tertiary care center in the sub-Himalayan state of Uttarakhand, Northern India. All the pregnant women with malaria and its complications were recruited in the study during 2009 to 2014 which included referred cases from the state of western Uttar Pradesh. A thorough history and clinical examination were carried out to assess maternal and fetal condition. Relevant investigations including haemogram, platelet count, LFT, RFT, and USG was done. Blood slides and rapid diagnostic tests were done to diagnose the type of malaria.The primary outcomes measured were the type of malaria infection, maternal complications associated with malaria, outcome of pregnancy and effect on the fetus. Results: 67 antenatal cases with malaria infection were studied. 71% patients were diagnosed with plasmodium vivax infection, 25% cases were plasmodium falciparum positive and in 3% cases mixed infection was found. 38(56%) patients were primigravida and 29(43%) were multiparous. Most of the patients had already received some treatment from their local doctors and presented with severe malaria with the complications. Thrombocytopenia was the commonest manifestation seen in 35(52%) patients, jaundice in 28%, severe anemia in 18%, and severe oligohydramnios in 10% and renal failure in 6% cases. Regarding pregnancy outcome there were 44 % preterm deliveries, 22% had IUFD and abortions in 6% cases.20% of newborn were low birth weight and 6% were IUGR. There was only one maternal death which occurred due to ARDS in falciparum malaria. Although Plasmodium vivax was the main parasite considering the severity of clinical presentation, all the patients received intensive care. As most of the patients had received chloroquine therapy hence they were treated with IV artesunate followed by oral artemesinin combination therapy. Other therapies in the form of packed RBC’s and platelet transfusions, dialysis and ventilator support were provided when required. Conclusion: Even in areas with annual parasite index (API) less than 2 like ours, malaria in pregnancy could be an alarming problem. Vivax malaria cannot be considered benign in pregnancy because of high incidence of morbidity. Prompt diagnosis and aggressive treatment can reduce morbidity and mortality significantly. Increased community level research, integrating ANC checkups with the distribution of insecticide-treated nets in areas of high endemicity, imparting education and awareness will strengthen the existing control strategies.

Keywords: severe malaria, pregnancy, plasmodium vivax, plasmodium falciparum

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2761 The Issue of Affordability in Housing and Implications for the Regional Planning of Drainage Infrastructure: A Case of Affordability as Part of Inclusive Decision Making

Authors: Kwadwo Afari Gyan

Abstract:

Cities are growing at unprecedented levels. Meanwhile, governments in the Global South are already overwhelmed by this growth and are unable to provide infrastructure proactively as expected. As a result, urban residents resort to providing their own infrastructure, such as drainage systems, as part of self-built housing development. Their small-scale, incremental housing practices, which often represent the formation of dense and diverse housing types, styles, and ages, have been identified to affect the planning of drainage systems at the regional scale. Such developments reflect the varied, affordable responses as part of a collective effort to curb regional problems, specifically flooding in this case. However, while some are included in this collective action, others are excluded as they are unable to afford to be included. This phenomenon, in addition to the formation of new autonomous localities, has led to challenges in mitigating flooding and has affected resilience to climate change. Using a qualitative approach, this paper explores how the mismatch between housing development, which occurs at an individual scale, and drainage infrastructure, which is provided at a regional scale, affects a regional effort to mitigate flooding in Tema, Ghana. It seeks to explore and reveal a relationship between affordability and inclusiveness. It also explores how density and diversity influence public infrastructure provision and their connection with affordability.

Keywords: climate change, affordability, inclusivity, equity, contextualization, regionalism

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2760 Implementation of Synthesis and Quality Control Procedures of ¹⁸F-Fluoromisonidazole Radiopharmaceutical

Authors: Natalia C. E. S. Nascimento, Mercia L. Oliveira, Fernando R. A. Lima, Leonardo T. C. do Nascimento, Marina B. Silveira, Brigida G. A. Schirmer, Andrea V. Ferreira, Carlos Malamut, Juliana B. da Silva

Abstract:

Tissue hypoxia is a common characteristic of solid tumors leading to decreased sensitivity to radiotherapy and chemotherapy. In the clinical context, tumor hypoxia assessment employing the positron emission tomography (PET) tracer ¹⁸F-fluoromisonidazole ([¹⁸F]FMISO) is helpful for physicians for planning and therapy adjusting. The aim of this work was to implement the synthesis of 18F-FMISO in a TRACERlab® MXFDG module and also to establish the quality control procedure. [¹⁸F]FMISO was synthesized at Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN/Brazil) using an automated synthesizer (TRACERlab® MXFDG, GE) adapted for the production of [¹⁸F]FMISO. The FMISO chemical standard was purchased from ABX. 18O- enriched water was acquired from Center of Molecular Research. Reagent kits containing eluent solution, acetonitrile, ethanol, 2.0 M HCl solution, buffer solution, water for injections and [¹⁸F]FMISO precursor (dissolved in 2 ml acetonitrile) were purchased from ABX. The [¹⁸F]FMISO samples were purified by Solid Phase Extraction method. The quality requirements of [¹⁸F]FMISO are established in the European Pharmacopeia. According to that reference, quality control of [¹⁸F]FMISO should include appearance, pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins, and sterility. The duration of the synthesis process was 53 min, with radiochemical yield of (37.00 ± 0.01) % and the specific activity was more than 70 GBq/µmol. The syntheses were reproducible and showed satisfactory results. In relation to the quality control analysis, the samples were clear and colorless at pH 6.0. The spectrum emission, measured by using a High-Purity Germanium Detector (HPGe), presented a single peak at 511 keV and the half-life, determined by the decay method in an activimeter, was (111.0 ± 0.5) min, indicating no presence of radioactive contaminants, besides the desirable radionuclide (¹⁸F). The samples showed concentration of tetrabutylammonium (TBA) < 50μg/mL, assessed by visual comparison to TBA standard applied in the same thin layer chromatographic plate. Radiochemical purity was determined by high performance liquid chromatography (HPLC) and the results were 100%. Regarding the residual solvents tested, ethanol and acetonitrile presented concentration lower than 10% and 0.04%, respectively. Healthy female mice were injected via lateral tail vein with [¹⁸F]FMISO, microPET imaging studies (15 min) were performed after 2 h post injection (p.i), and the biodistribution was analyzed in five-time points (30, 60, 90, 120 and 180 min) after injection. Subsequently, organs/tissues were assayed for radioactivity with a gamma counter. All parameters of quality control test were in agreement to quality criteria confirming that [¹⁸F]FMISO was suitable for use in non-clinical and clinical trials, following the legal requirements for the production of new radiopharmaceuticals in Brazil.

Keywords: automatic radiosynthesis, hypoxic tumors, pharmacopeia, positron emitters, quality requirements

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2759 Comparative Efficacy of Angiotensin Converting Enzymes Inhibitors and Angiotensin Receptor Blockers in Patients with Heart Failure in Tanzania: A Prospective Cohort Study

Authors: Mark P. Mayala, Henry Mayala, Khuzeima Khanbhai

Abstract:

Background: Heart failure has been a rising concern in Tanzania. New drugs have been introduced, including the group of drugs called Angiotensin receptor Neprilysin Inhibitor (ARNI), but due to their high cost, angiotensin-converting enzymes inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs) have been mostly used in Tanzania. However, according to our knowledge, the efficacy comparison of the two groups is yet to be studied in Tanzania. The aim of this study was to compare the efficacy of ACEIs and ARBs among patients with heart failure. Methodology: This was a hospital-based prospective cohort study done at Jakaya Kikwete Cardiac Institution (JKCI), Tanzania, from June to December 2020. Consecutive enrollment was done until fulfilling the inclusion criteria. Clinical details were measured at baseline. We assessed the relationship between ARBs and ACEIs users with N-terminal pro-brain natriuretic peptide (NT pro-BNP) levels at admission and at 1-month follow-up using a chi-square test. A Kaplan-Meier curve was used to estimate the survival time of the two groups. Results: 155 HF patients were enrolled, with a mean age of 48 years, whereby 52.3% were male, and their mean left ventricular ejection fraction (LVEF) was 37.3%. 52 (33.5%) heart failure patients were on ACEIs, 57 (36.8%) on ARBs, and 46 (29.7%) were neither using ACEIs nor ARBs. At least half of the patients did not receive a guideline-directed medical therapy (GDMT), with only 82 (52.9%) receiving a GDMT. A drop in NT pro-BNP levels was observed during admission and at 1-month follow-up on both groups, from 6389.2 pg/ml to 4000.1 pg/ml for ARB users and 5877.7 pg/ml to 1328.2 pg/ml for the ACEIs users. There was no statistical difference between the two groups when estimated by the Kaplan-Meier curve, though more deaths were observed in those who were neither on ACEIs nor ARBs, with a calculated P value of 0.01. Conclusion: This study demonstrates that ACEIs have more efficacy and overall better clinical outcome than ARBs, but this should be taken under the patient-based case, considering the side effects of ACEIs and patients’ adherence.

Keywords: angiotensin converting enzymes inhibitors, angiotensin receptor blockers, guideline direct medical therapy, N-terminal pro-brain natriuretic peptide

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2758 Proprotein Convertase Subtilisin/Kexin Type 9 Enhances Arterial Medial Calcification in a Uremic Rat Model of Chronic Kidney Disease

Authors: Maria Giovanna Lupo, Marina Camera, Marcello Rattazzi, Nicola Ferri

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A complex interplay among chronic kidney disease, lipid metabolism and aortic calcification has been recognized starting from results of many clinical and experimental studies. Here we investigated the influence of kidney function on PCSK9 levels, both in uremic rats and in clinical observation study, and its potential direct action on cultured smooth muscle cells (SMCs) calcification. In a cohort of 594 subjects enrolled in a single centre, observational, cross-sectional and longitudinal study, a negative association between GFR and plasma PCSK9 was found. Atherosclerotic cardiovascular disease (ASCVD), as co-morbidity, further increased PCSK9 plasma levels. Diet-induced uremic condition in rats, induced aortic calcification and increased total cholesterol and PCSK9 levels in plasma, livers and kidneys. Immunohistochemical analysis confirmed PCSK9 expression in aortic SMCs. SMCs overexpressing PCSK9 (SMCsPCSK9), cultured for 7-days in a pro-calcification environment (2.0mM or 2.4mM inorganic phosphate, Pi) showed a significantly higher extracellular calcium (Ca2+) deposition compared to mocked SMCs. Under the same experimental conditions, the addition of exogenous recombinant PCSK9 did not increase the extracellular calcification of SMCs. By flow cytometry analysis we showed that SMCsPCSK9, in response to 2.4mM Pi, released higher number of extracellular vesicles (EVs) positive for three tetraspanin molecules, such as CD63, CD9, and CD81. EVs derived from SMCsPCSK9 tended to be more enriched in calcium and alkaline phosphatase (ALPL), compared to EVs from mocks SMCs. In conclusion, our study reveals a direct role of PCSK9 on vascular calcification induced by higher inorganic phosphate levels associated to CKD condition. This effect appears to be mediated by a positive effect of endogenous PCSK9 on the release of EVs containing Ca2+ and ALP, which facilitate the deposition inorganic calcium phosphate crystals.

Keywords: PCSK9, calcification, extracellular vesicles, chronic kidney disease

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