Search results for: sudden cardiac arrest/death
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2025

Search results for: sudden cardiac arrest/death

195 Assessing the Blood-Brain Barrier (BBB) Permeability in PEA-15 Mutant Cat Brain using Magnetization Transfer (MT) Effect at 7T

Authors: Sultan Z. Mahmud, Emily C. Graff, Adil Bashir

Abstract:

Phosphoprotein enriched in astrocytes 15 kDa (PEA-15) is a multifunctional adapter protein which is associated with the regulation of apoptotic cell death. Recently it has been discovered that PEA-15 is crucial in normal neurodevelopment of domestic cats, a gyrencephalic animal model, although the exact function of PEA-15 in neurodevelopment is unknown. This study investigates how PEA-15 affects the blood-brain barrier (BBB) permeability in cat brain, which can cause abnormalities in tissue metabolite and energy supplies. Severe polymicrogyria and microcephaly have been observed in cats with a loss of function PEA-15 mutation, affecting the normal neurodevelopment of the cat. This suggests that the vital role of PEA-15 in neurodevelopment is associated with gyrification. Neurodevelopment is a highly energy demanding process. The mammalian brain depends on glucose as its main energy source. PEA-15 plays a very important role in glucose uptake and utilization by interacting with phospholipase D1 (PLD1). Mitochondria also plays a critical role in bioenergetics and essential to supply adequate energy needed for neurodevelopment. Cerebral blood flow regulates adequate metabolite supply and recent findings also showed that blood plasma contains mitochondria as well. So the BBB can play a very important role in regulating metabolite and energy supply in the brain. In this study the blood-brain permeability in cat brain was measured using MRI magnetization transfer (MT) effect on the perfusion signal. Perfusion is the tissue mass normalized supply of blood to the capillary bed. Perfusion also accommodates the supply of oxygen and other metabolites to the tissue. A fraction of the arterial blood can diffuse to the tissue, which depends on the BBB permeability. This fraction is known as water extraction fraction (EF). MT is a process of saturating the macromolecules, which has an effect on the blood that has been diffused into the tissue while having minimal effect on intravascular blood water that has not been exchanged with the tissue. Measurement of perfusion signal with and without MT enables to estimate the microvascular blood flow, EF and permeability surface area product (PS) in the brain. All the experiments were performed with Siemens 7T Magnetom with 32 channel head coil. Three control cats and three PEA-15 mutant cats were used for the study. Average EF in white and gray matter was 0.9±0.1 and 0.86±0.15 respectively, perfusion in white and gray matter was 85±15 mL/100g/min and 97±20 mL/100g/min respectively, PS in white and gray matter was 201±25 mL/100g/min and 225±35 mL/100g/min respectively for control cats. For PEA-15 mutant cats, average EF in white and gray matter was 0.81±0.15 and 0.77±0.2 respectively, perfusion in white and gray matter was 140±25 mL/100g/min and 165±18 mL/100g/min respectively, PS in white and gray matter was 240±30 mL/100g/min and 259±21 mL/100g/min respectively. This results show that BBB is compromised in PEA-15 mutant cat brain, where EF is decreased and perfusion as well as PS are increased in the mutant cats compared to the control cats. This findings might further explain the function of PEA-15 in neurodevelopment.

Keywords: BBB, cat brain, magnetization transfer, PEA-15

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194 A Study on the Effects of Urban Density, Sociodemographic Vulnerability, and Medical Service on the Impact of COVID-19

Authors: Jang-hyun Oh, Kyoung-ho Choi, Jea-sun Lee

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The outbreak of the COVID-19 pandemic brought reconsiderations and doubts about urban density as compact cities became epidemic hot spots. Density, though, provides an upside in that medical services required to protect citizens against the spread of disease are concentrated within compact cities, which helps reduce the mortality rate. Sociodemographic characteristics are also a crucial factor in determining the vulnerability of the population, and the purpose of this study is to empirically discover how these three urban factors affect the severity of the epidemic impacts. The study aimed to investigate the influential relationships between urban factors and epidemic impacts and provide answers to whether superb medical service in compact cities can scale down the impacts of COVID-19. SEM (Structural Equation Modeling) was applied as a suitable research method for verifying interrelationships between factors based on theoretical grounds. The study accounted for 144 municipalities in South Korea during periods from the first emergence of COVID-19 to December 31st, 2022. The study collected data related to infection and mortality cases from each municipality, and it holds significance as primary research that enlightens the aspects of epidemic impact concerning urban settings and investigates for the first time the mediated effects of medical service. The result of the evaluation shows that compact cities are most likely to have lower sociodemographic vulnerability and better quality of medical service, while cities with low density contain a higher portion of vulnerable populations and poorer medical services. However, the quality of medical service had no significant influence in reducing neither the infection rate nor the mortality rate. Instead, density acted as the major influencing factor in the infection rate, while sociodemographic vulnerability was the major determinant of the mortality rate. Thus, the findings strongly paraphrase that compact cities, although with high infection rates, tend to have lower mortality rates due to less vulnerability in sociodemographics, Whereas death was more frequent in less dense cities due to higher portions of vulnerable populations such as the elderly and low-income classes. Findings suggest an important lesson for post-pandemic urban planning-intrinsic characteristics of urban settings, such as density and population, must be taken into account to effectively counteract future epidemics and minimize the severity of their impacts. Moreover, the study is expected to contribute as a primary reference material for follow-up studies that further investigate related subjects, including urban medical services during the pandemic.

Keywords: urban planning, sociodemographic vulnerability, medical service, COVID-19, pandemic

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193 Intensive Care Unit Patient Self-Determination When Facing Cardiovascular Surgery for the First Time

Authors: Hsiao-Lin Fang

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The Patient Self-Determination Act is based on the belief that each life is unique. The act regards each patient as an autonomous entity and explicitly protects the patient’s rights to know and make decisions and choices while ensuring that the patient’s wish for a peaceful end is granted. Even when the patient is unconscious and unable to express himself/herself, the patient’s self-determination and its exercise are still protected under the law. The act also ensures that healthcare professionals (HCPs) have a specific set of rules to follow and complete legal protection when their patients are unable to express themselves clearly. This report is about a 55-year-old female patient who weighed 110 kg and was diagnosed with acute type A aortic dissection. The case was that the patient suddenly felt backache and nausea during sleep before daybreak and was therefore transferred to this hospital from the original one. After the doctor explained the patient’s conditions, it was concluded that surgery was necessary. However, the patient’s family was immediately against the surgery after having heard its possible complications. Nevertheless, the patient was still willing to receive the surgery. Being at odds with her family, the patient decided to sign the surgery agreement herself and agreed to receive the two surgical procedures: (1) ascending aorta replacement and (2) innominate artery debranching. After the surgery, the patient did not regain consciousness and therefore received computed tomography scanning of the brain, which revealed false lumen involving proximal left common carotid artery, left subclavian artery and innominate artery, and severe compression of the true lumen with total/subtotal occlusion in the left common carotid artery. On the following day, the doctor discussed two further surgical procedures: (1) endografting for descending aorta and (2) endografting for left common carotid artery and subclavian artery with the family. However, as the patient’s postoperative recovery of consciousness only reached the level of stupor and her family had no intention of subsequent healthcare for the patient, the family made the joint decision three days later to have the endotracheal tube removed from the patient and let her die a natural death. Suggestion: An advance directive (AD) can be created beforehand. Once the patient is in a special clinical state (e.g., terminal illness, permanent vegetative state, etc.), the AD can determine whether to sustain the patient’s life through ‘medical intervention’ or to respect the patient’s rights to choose a peaceful end and receive palliative care. Through the expression of self-determination, it is possible to respect the patient’s medical practice autonomy and protect the patient’s dignity and right to a peaceful end, thereby respecting and supporting the patient’s decision. This also allows the three sides: the patient, the family and the medical team to understand the patient’s true wish in the process of advance care planning (ACP) and thereby promote harmony in the HCP-patient relationship.

Keywords: intensive care unit patient, cardiovascular surgery, self-determination, advance directive

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192 Reintegrating Forensic Mental Health Service Users into Communities in the Western Cape, South Africa

Authors: Zolani Metu

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The death of more than 140 psychiatric patients who were unethically deinstitutionalized from the Life Esidimeni hospital Johannesburg, in 2016, shined a light on South Africa’s failing public mental healthcare system. Compounded by insufficient research evidence on African deinstitutionalization, this necessitates inquiries into deinstitutionalized mental healthcare, reintegration and community-based mental healthcare within the South African context. This study employed a quantitative research approach which utilized a cross-sectional research design, to investigate experiences with the reintegration of institutionalized forensic mental health service users into communities in the Western Cape, South Africa. A convenience sample of 100 mental health care workers from different occupational and organizational backgrounds in the Western Cape was purposively selected using the Western Cape Health Directorate as a sampling frame. A self-administered questionnaire (SAQ) was used as the data collection instrument. The results of the study indicate that criminogenic factors such as substance use, history of violent behaviour, criminal history and disruptive social behaviour complicate the reintegration of forensic mental health service users into communities. The current extent of reintegration of forensic mental health service users was found to be 'poor' (46%; n= 46); and financial difficulties, criminogenic factors and limited Community-Based Care (CBC) facilities were identified as key barriers to the reintegration process. 56% of all job applications for forensic mental health service users were unsuccessful, and 53% of all applications for their admission into CBC facilities were declined. Although social support (informal) was found to be essential for successful reintegration, institutional support (formal) through assertive community treatment (35%; n= 35) and CBC facilities (21%) and the disability grant (DG=50%) was found to be more important for family coping and reintegration. Moreover, 72% of respondents had positive perceptions about the process of reintegration; no statistically significant relationship was found between years of experience and perceptions about reintegration (P-value = 0.062); and perceptions were not found to be a barrier to reintegration. No statistically significant relationship was found between years of working experience and understanding the legislative framework of deinstitutionalization (P-Value =.0.061). However, using a Chi-square test, a significant relationship (P-value = 0.021) was found between sex and understanding the legal framework involved in the process of reintegration. The study recommends a post-2020 deinstitutionalization agenda that factors-in criminogenic realities associated with forensic mental health service users, and affirms the strengthening of PHC and community based care systems as precedents of successful deinstitutionalization and reintegration of mental health service users.

Keywords: forensic mental health, deinstitutionalization, reintegration, mental health service users

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191 Skin-to-Skin Contact Simulation: Improving Health Outcomes for Medically Fragile Newborns in the Neonatal Intensive Care Unit

Authors: Gabriella Zarlenga, Martha L. Hall

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Introduction: Premature infants are at risk for neurodevelopmental deficits and hospital readmissions, which can increase the financial burden on the health care system and families. Kangaroo care (skin-to-skin contact) is a practice that can improve preterm infant health outcomes. Preterm infants can acquire adequate body temperature, heartbeat, and breathing regulation through lying directly on the mother’s abdomen and in between her breasts. Due to some infant’s condition, kangaroo care is not a feasible intervention. The purpose of this proof-of-concept research project is to create a device which simulates skin-to-skin contact for pre-term infants not eligible for kangaroo care, with the aim of promoting baby’s health outcomes, reducing the incidence of serious neonatal and early childhood illnesses, and/or improving cognitive, social and emotional aspects of development. Methods: The study design is a proof-of-concept based on a three-phase approach; (1) observational study and data analysis of the standard of care for 2 groups of pre-term infants, (2) design and concept development of a novel device for pre-term infants not currently eligible for standard kangaroo care, and (3) prototyping, laboratory testing, and evaluation of the novel device in comparison to current assessment parameters of kangaroo care. A single center study will be conducted in an area hospital offering Level III neonatal intensive care. Eligible participants include newborns born premature (28-30 weeks of age) admitted to the NICU. The study design includes 2 groups: a control group receiving standard kangaroo care and an experimental group not eligible for kangaroo care. Based on behavioral analysis of observational video data collected in the NICU, the device will be created to simulate mother’s body using electrical components in a thermoplastic polymer housing covered in silicone. It will be designed with a microprocessor that controls simulated respiration, heartbeat, and body temperature of the 'simulated caregiver' by using a pneumatic lung, vibration sensors (heartbeat), pressure sensors (weight/position), and resistive film to measure temperature. A slight contour of the simulator surface may be integrated to help position the infant correctly. Control and monitoring of the skin-to-skin contact simulator would be performed locally by an integrated touchscreen. The unit would have built-in Wi-Fi connectivity as well as an optional Bluetooth connection in which the respiration and heart rate could be synced with a parent or caregiver. A camera would be integrated, allowing a video stream of the infant in the simulator to be streamed to a monitoring location. Findings: Expected outcomes are stabilization of respiratory and cardiac rates, thermoregulation of those infants not eligible for skin to skin contact with their mothers, and real time mother Bluetooth to the device to mimic the experience in the womb. Results of this study will benefit clinical practice by creating a new standard of care for premature neonates in the NICU that are deprived of skin to skin contact due to various health restrictions.

Keywords: kangaroo care, wearable technology, pre-term infants, medical design

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190 Depressive-Like Behavior in a Murine Model of Colorectal Cancer Associated with Altered Cytokine Levels in Stress-Related Brain Regions

Authors: D. O. Miranda, L. R. Azevedo, J. F. C. Cordeiro, A. H. Dos Santos, S. F. Lisboa, F. S. Guimarães, G. S. Bisson

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Background: The Colorectal cancer (CRC) is one of the most common cancers and the fourth leading cause of cancer death in the world. The prevalence of psychiatric-disorders among CRC patients, mainly depression, is high, resulting in impaired quality of life and side effects of primary treatment. High levels of proinflammatory cytokines at tumor microenvironment is a feature of CRC and the literature suggests that those mediators could contribute to the development of psychiatric disorders. Nevertheless, the ability of tumor-associated biological processes to affect the central nervous system (CNS) has only recently been explored in the context of symptoms of depression and is still not well understood. Therefore, the aim of the present study was to test the hypothesis that depressive-like behavior in an experimental model of CCR induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was correlated to proinflammatory profile in the periphery and in the brain. Methods: Colorectal carcinogenesis was induced in adult C57BL/6 mice (n=12) by administration of MNNG (5mg/kg, 0.1ml/intrarectal instillation) 2 times a week, for 2 week. Control group (n=12) received saline (0.1ml/intrarectal instillation). Eight weeks after beginning of MNNG administration animals were submitted to the forced swim test (FST) and the sucrose preference test for evaluation, respectively, of depressive- and anhedonia-like behaviors. After behavioral evaluation, the colon was collected and brain regions dissected (cortex-C, striatum-ST and hippocampus-HIP) for posterior evaluation of cytokine levels (IL-1β, IL-10, IL-17, and CX3CL1) by ELISA. Results: MNNG induced depressive-like behavior, represented by increased immobility time in the FST (Student t test, p < 0.05) and lower sucrose preference (Student t test, p < 0.05). Moreover, there were increased levels of IL-1β, IL-17 and CX3CL1 in the colonic tissue (Student t test, p < 0.05) and in the brain (IL-1 β in the ST and HIP, Student t test, p < 0.05; IL-17 and CX3CL1 in the C and HIP, p < 0.05). IL-10 levels, in contrast, were decreased in both the colon (p < 0.05) and the brain (C and HIP, p < 0.05). Conclusions: The results obtained in the present work support the notion that tumor growth induces neuroinflammation in stress-related brain regions and depressive-like behavior, which could be related to the high incidence of depression in colorectal carcinogenesis. This work have important clinical and research implications, taken into account that cytokine levels may be a marker promissory for the developing depression in CRC patients. New therapeutic strategies to assist in alleviating mental suffering in cancer patients might result from a better understanding of the role of cytokines in the pathophysiology of depression in these subjects.

Keywords: cytokines, brain, depression, colorectal cancer

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189 Ultra-Sensitive Point-Of-Care Detection of PSA Using an Enzyme- and Equipment-Free Microfluidic Platform

Authors: Ying Li, Rui Hu, Shizhen Chen, Xin Zhou, Yunhuang Yang

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Prostate cancer is one of the leading causes of cancer-related death among men. Prostate-specific antigen (PSA), a specific product of prostatic epithelial cells, is an important indicator of prostate cancer. Though PSA is not a specific serum biomarker for the screening of prostate cancer, it is recognized as an indicator for prostate cancer recurrence and response to therapy for patient’s post-prostatectomy. Since radical prostatectomy eliminates the source of PSA production, serum PSA levels fall below 50 pg/mL, and may be below the detection limit of clinical immunoassays (current clinical immunoassay lower limit of detection is around 10 pg/mL). Many clinical studies have shown that intervention at low PSA levels was able to improve patient outcomes significantly. Therefore, ultra-sensitive and precise assays that can accurately quantify extremely low levels of PSA (below 1-10 pg/mL) will facilitate the assessment of patients for the possibility of early adjuvant or salvage treatment. Currently, the commercially available ultra-sensitive ELISA kit (not used clinically) can only reach a detection limit of 3-10 pg/mL. Other platforms developed by different research groups could achieve a detection limit as low as 0.33 pg/mL, but they relied on sophisticated instruments to get the final readout. Herein we report a microfluidic platform for point-of-care (POC) detection of PSA with a detection limit of 0.5 pg/mL and without the assistance of any equipment. This platform is based on a previously reported volumetric-bar-chart chip (V-Chip), which applies platinum nanoparticles (PtNPs) as the ELISA probe to convert the biomarker concentration to the volume of oxygen gas that further pushes the red ink to form a visualized bar-chart. The length of each bar is used to quantify the biomarker concentration of each sample. We devised a long reading channel V-Chip (LV-Chip) in this work to achieve a wide detection window. In addition, LV-Chip employed a unique enzyme-free ELISA probe that enriched PtNPs significantly and owned 500-fold enhanced catalytic ability over that of previous V-Chip, resulting in a significantly improved detection limit. LV-Chip is able to complete a PSA assay for five samples in 20 min. The device was applied to detect PSA in 50 patient serum samples, and the on-chip results demonstrated good correlation with conventional immunoassay. In addition, the PSA levels in finger-prick whole blood samples from healthy volunteers were successfully measured on the device. This completely stand-alone LV-Chip platform enables convenient POC testing for patient follow-up in the physician’s office and is also useful in resource-constrained settings.

Keywords: point-of-care detection, microfluidics, PSA, ultra-sensitive

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188 Implementation of a Web-Based Clinical Outcomes Monitoring and Reporting Platform across the Fortis Network

Authors: Narottam Puri, Bishnu Panigrahi, Narayan Pendse

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Background: Clinical Outcomes are the globally agreed upon, evidence-based measurable changes in health or quality of life resulting from the patient care. Reporting of outcomes and its continuous monitoring provides an opportunity for both assessing and improving the quality of patient care. In 2012, International Consortium Of HealthCare Outcome Measurement (ICHOM) was founded which has defined global Standard Sets for measuring the outcome of various treatments. Method: Monitoring of Clinical Outcomes was identified as a pillar of Fortis’ core value of Patient Centricity. The project was started as an in-house developed Clinical Outcomes Reporting Portal by the Fortis Medical IT team. Standard sets of Outcome measurement developed by ICHOM were used. A pilot was run at Fortis Escorts Heart Institute from Aug’13 – Dec’13.Starting Jan’14, it was implemented across 11 hospitals of the group. The scope was hospital-wide and major clinical specialties: Cardiac Sciences, Orthopedics & Joint Replacement were covered. The internally developed portal had its limitations of report generation and also capturing of Patient related outcomes was restricted. A year later, the company provisioned for an ICHOM Certified Software product which could provide a platform for data capturing and reporting to ensure compliance with all ICHOM requirements. Post a year of the launch of the software; Fortis Healthcare has become the 1st Healthcare Provider in Asia to publish Clinical Outcomes data for the Coronary Artery Disease Standard Set comprising of Coronary Artery Bypass Graft and Percutaneous Coronary Interventions) in the public domain. (Jan 2016). Results: This project has helped in firmly establishing a culture of monitoring and reporting Clinical Outcomes across Fortis Hospitals. Given the diverse nature of the healthcare delivery model at Fortis Network, which comprises of hospitals of varying size and specialty-mix and practically covering the entire span of the country, standardization of data collection and reporting methodology is a huge achievement in itself. 95% case reporting was achieved with more than 90% data completion at the end of Phase 1 (March 2016). Post implementation the group now has one year of data from its own hospitals. This has helped identify the gaps and plan towards ways to bridge them and also establish internal benchmarks for continual improvement. Besides the value created for the group includes: 1. Entire Fortis community has been sensitized on the importance of Clinical Outcomes monitoring for patient centric care. Initial skepticism and cynicism has been countered by effective stakeholder engagement and automation of processes. 2. Measuring quality is the first step in improving quality. Data analysis has helped compare clinical results with best-in-class hospitals and identify improvement opportunities. 3. Clinical fraternity is extremely pleased to be part of this initiative and has taken ownership of the project. Conclusion: Fortis Healthcare is the pioneer in the monitoring of Clinical Outcomes. Implementation of ICHOM standards has helped Fortis Clinical Excellence Program in improving patient engagement and strengthening its commitment to its core value of Patient Centricity. Validation and certification of the Clinical Outcomes data by an ICHOM Certified Supplier adds confidence to its claim of being leaders in this space.

Keywords: clinical outcomes, healthcare delivery, patient centricity, ICHOM

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187 Knowledge of Nature through the Ultimate Methodology of Buddhism and Philosophy of Karmic Consequence to Uproot through the Buddha’s Perspective

Authors: Pushpa Debnath

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Buddhism implies the ultimate methodology to obtain the acknowledgment to get out from cycling existence applied by the sutras. The Buddha’s natural methodology is the highest way of cessation from suffering existence. To be out of it, one must know the suffering before having tentativeness. According to the Buddha’s methodology, one can observe every being suffer from chronologically grasping craving. It is because lack of knowledge that the Buddha finds the four noble truths which are the basic states. These are suffering, the origin of suffering, cessation of suffering, and the path leading to the cessation of suffering. The Buddha describes that birth is suffering, aging is suffering, sickness is suffering, death is suffering, association with the unexpected is suffering, separation from the pleasant is suffering, and not receiving what one desires is suffering, In brief, the five aggregates of clinging are suffering. As the five aggregates are form, feeling, perception, mental formation, and consciousness. These are known as the matter that we identify with “You, Me” or “He.” The second truth cause of suffering is craving which has three types: craving for sense pleasures, craving for existence, and craving for non-existence. The third truth is the obliteration of craving, suffering can be eliminated to attain the Nibbana. The fourth truth is the path of liberation is the noble eight-fold path consisting of the right view, right intention, right speech, right action, right livelihood, right effort, right mindfulness, and right concentration. The six senses are the media of the eye, ear, nose, tongue, body, and mind sense faculties relating with the five aggregates and the six senses objects visual objects, sounds, smells, tastes, touch, and mind-objects that are contained by every visible being. The first five internal sense bases are material while the mind is a non-material phenomenon. Contact with the external world maintains by receiving through the six senses; visual objects through the eye, sounds through the ear, smells through the nose, tastes through the tongue, touch through the body, and mind-objects through sense faculties. These are the six senses a living being experiences by craving. Everything is conglomerated with all senses faculties through the natural phenomenon which are earth, water, fire, and air element. In this analysis, it is believed that beings are well adapted to the natural phenomenon. Everybody has fear of life because we have hatred, delusion, and anger which are the primary resources of falling into (Samsara) continuously that is the continuity of the natural way. These are the reasons for the suffering that chronically self-diluting through the threefold way. These are the roots of the entire beings suffering so the Buddha finds the enlightenment to uproot from cycling existence and the understanding of the natural consequence. When one could uproot ignorance, one could able to realize the ultimate happiness of Nirvana. From the craving of ignorance, everything starts to be present to the future which gives us mental agonies in existence.

Keywords: purification, morality, natural phenomenon, analysis, development of mind, observatory, Nirvana

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186 Principles and Guidance for the Last Days of Life: Te Ara Whakapiri

Authors: Tania Chalton

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In June 2013, an independent review of the Liverpool Care Pathway (LCP) identified a number of problems with the implementation of the LCP in the UK and recommended that it be replaced by individual care plans for each patient. As a result of the UK findings, in November 2013 the Ministry of Health (MOH) commissioned the Palliative Care Council to initiate a programme of work to investigate an appropriate approach for the care of people in their last days of life in New Zealand (NZ). The Last Days of Life Working Group commenced a process to develop national consensus on the care of people in their last days of life in April 2014. In order to develop its advice for the future provision of care to people in their last days of life, the Working Group (WG) established a comprehensive work programme and as a result has developed a series of working papers. Specific areas of focus included: An analysis of the UK Independent Review findings and an assessment of these findings to the NZ context. A stocktake of services providing care to people in their last days of life, including aged residential care (ARC); hospices; hospitals; and primary care. International and NZ literature reviews of evidence and best practice. Survey of family to understand the consumer perspective on the care of people in their last days of life. Key aspects of care that required further considerations for NZ were: Terminology: clarify terminology used in the last days of life and in relation to death and dying. Evidenced based: including specific review of evidence regarding, spiritual, culturally appropriate care as well as dementia care. Diagnosis of dying: need for both guidance around the diagnosis of dying and communication with family. Workforce issues: access to an appropriate workforce after hours. Nutrition and hydration: guidance around appropriate approaches to nutrition and hydration. Symptom and pain management: guidance around symptom management. Documentation: documentation of the person’s care which is robust enough for data collection and auditing requirements, not ‘tick box’ approach to care. Education and training: improved consistency and access to appropriate education and training. Leadership: A dedicated team or person to support and coordinate the introduction and implementation of any last days of life model of care. Quality indicators and data collection: model of care to enable auditing and regular reviews to ensure on-going quality improvement. Cultural and spiritual: address and incorporate any cultural and spiritual aspects. A final document was developed incorporating all the evidence which provides guidance to the health sector on best practice for people at end of life: “Principles and guidance for the last days of life: Te Ara Whakapiri”.

Keywords: end of life, guidelines, New Zealand, palliative care

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185 Mitigating the Negative Health Effects from Stress - A Social Network Analysis

Authors: Jennifer A. Kowalkowski

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Production agriculture (farming) is a physically, emotionally, and cognitively stressful occupation, where workers have little control over the stressors that impact both their work and their lives. In an occupation already rife with hazards, these occupational-related stressors have been shown to increase farm workers’ risks for illness, injury, disability, and death associated with their work. Despite efforts to mitigate the negative health effects from occupational-related stress (ORS) and to promote health and well-being (HWB) among farmers in the US, marked improvements have not been attained. Social support accessed through social networks has been shown to buffer against the negative health effects from stress, yet no studies have directly examined these relationships among farmers. The purpose of this study was to use social network analysis to explore the social networks of farm owner-operators and the social supports available to them for mitigating the negative health effects of ORS. A convenience sample of 71 farm owner-operators from a Midwestern County in the US completed and returned a mailed survey (55.5% response rate) that solicited information about their social networks related to ORS. Farmers reported an average of 2.4 individuals in their personal networks and higher levels of comfort discussing ORS with female network members. Farmers also identified few connections (3.4% density) and indicated low comfort with members of affiliation networks specific to ORS. Findings from this study highlighted that farmers accessed different social networks and resources for their personal HWB than for issues related to occupational(farm-related) health and safety. In addition, farmers’ social networks for personal HWB were smaller, with different relational characteristics than reported in studies of farmers’ social networks related to occupational health and safety. Collectively, these findings suggest that farmers conceptualize personal HWB differently than farm health and safety. Therefore, the same research approaches and targets that guide occupational health and safety research may not be appropriate for personal HWB for farmers. Interventions and programming targeting ORS and HWB have largely been offered through the same platforms or mechanisms as occupational health and safety programs. This may be attributed to the significant overlap between the farm as a family business and place of residence, or that ORS stems from farm-related issues. However, these assumptions translated to health research of farmers and farm families from the occupational health and safety literature have not been directly studied or challenged. Thismay explain why past interventions have not been effective at improving health outcomes for farmers and farm families. A close examination of findings from this study raises important questions for researchers who study agricultural health. Findings from this study have significant implications for future research agendas focused on addressing ORS, HWB, and health disparities for farmersand farm families.

Keywords: agricultural health, occupational-related stress, social networks, well-being

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184 Prediction of Coronary Artery Stenosis Severity Based on Machine Learning Algorithms

Authors: Yu-Jia Jian, Emily Chia-Yu Su, Hui-Ling Hsu, Jian-Jhih Chen

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Coronary artery is the major supplier of myocardial blood flow. When fat and cholesterol are deposit in the coronary arterial wall, narrowing and stenosis of the artery occurs, which may lead to myocardial ischemia and eventually infarction. According to the World Health Organization (WHO), estimated 740 million people have died of coronary heart disease in 2015. According to Statistics from Ministry of Health and Welfare in Taiwan, heart disease (except for hypertensive diseases) ranked the second among the top 10 causes of death from 2013 to 2016, and it still shows a growing trend. According to American Heart Association (AHA), the risk factors for coronary heart disease including: age (> 65 years), sex (men to women with 2:1 ratio), obesity, diabetes, hypertension, hyperlipidemia, smoking, family history, lack of exercise and more. We have collected a dataset of 421 patients from a hospital located in northern Taiwan who received coronary computed tomography (CT) angiography. There were 300 males (71.26%) and 121 females (28.74%), with age ranging from 24 to 92 years, and a mean age of 56.3 years. Prior to coronary CT angiography, basic data of the patients, including age, gender, obesity index (BMI), diastolic blood pressure, systolic blood pressure, diabetes, hypertension, hyperlipidemia, smoking, family history of coronary heart disease and exercise habits, were collected and used as input variables. The output variable of the prediction module is the degree of coronary artery stenosis. The output variable of the prediction module is the narrow constriction of the coronary artery. In this study, the dataset was randomly divided into 80% as training set and 20% as test set. Four machine learning algorithms, including logistic regression, stepwise regression, neural network and decision tree, were incorporated to generate prediction results. We used area under curve (AUC) / accuracy (Acc.) to compare the four models, the best model is neural network, followed by stepwise logistic regression, decision tree, and logistic regression, with 0.68 / 79 %, 0.68 / 74%, 0.65 / 78%, and 0.65 / 74%, respectively. Sensitivity of neural network was 27.3%, specificity was 90.8%, stepwise Logistic regression sensitivity was 18.2%, specificity was 92.3%, decision tree sensitivity was 13.6%, specificity was 100%, logistic regression sensitivity was 27.3%, specificity 89.2%. From the result of this study, we hope to improve the accuracy by improving the module parameters or other methods in the future and we hope to solve the problem of low sensitivity by adjusting the imbalanced proportion of positive and negative data.

Keywords: decision support, computed tomography, coronary artery, machine learning

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183 Road Accidents to School Children’s in Dar Es Salaam, Tanzania

Authors: Kabuga Daniel

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Road accidents resulting to deaths and injuries have become a new public health challenge especially in developing countries including Tanzania. Reports from Tanzania Traffic Police Force shows that last year 2016 accidents increased compare to previous year 2015, accident happened from 3710 up to 5219, accidents and safety data indicate that children are the most vulnerable to road crashes where 78 pupils died and 182 others were seriously injured in separate roads accident last year. A survey done by Amend indicates that Pupil mode of transport in Dar es salaam schools are by walk 87%, bus 9.21%, car 1.32%, motorcycle 0.88%, 3-wheeler 0.24%, train 0.14%, bicycle 0.10%, ferry 0.07%, and combined mode 0.44%. According to this study, majority of school children’s uses walking mode, most of school children’s agreed to continue using walking mode and request to have signs for traffic control during crossing road like STOP sign and CHILD CROSSING sign for safe crossing. Because children not only sit inside this buses (Daladala) but also they walk in a group to/from school, and few (33.2%) parents or adults are willing to supervise their children’s during working to school while 50% of parents agree to let their children walking alone to school if the public transport started from nearby street. The study used both qualitative and quantitative methods of research by conducting physical surveying on sample districts. The main objectives of this research are to carries out all factors affecting school children’s when they use public road, to promote and encourage the safe use of public road by all classes especially pupil or student through the circulation of advice, information and knowledge gain from research and to recommends future direction for the developments for road design or plan to vulnerable users. The research also critically analyze the problems causing death and injuries to school children’s in Dar es Salaam Region. This study determines the relationship between road traffic accidents and factors, such as socio-economic, status, and distance from school, number of sibling, behavioral problems, knowledge and attitudes of public and their parents towards road safety and parent educational study traffic. The study comes up with some of recommendations including Infrastructure Improvements like, safe footpaths, Safe crossings, Speed humps, Speed limits, Road signs. However, Planners and policymakers wishing to increase walking and cycling among children need to consider options that address distance constraints, the land use planners and transport professionals use better understanding of the various factors that affect children’s choices of school travel mode, results suggest that all school travel attributes should be considered during school location.

Keywords: accidents, childrens, school, Tanzania

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182 Uses of Fibrinogen Concentrate in the Management of Trauma-Induced Coagulopathy in the Prehospital Environment: A Scoping Review

Authors: Nura Khattab, Fayad Al-Haimus, Teruko Kishibe, Netanel Krugliak, Melissa McGowan, Brodie Nolan

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Trauma-induced coagulopathy remains a significant contributor to mortality in severely injured patients. Fibrinogen is essential for early hemostasis and is recognized as the first coagulation factor to fall below critical levels, compromising the coagulation cascade. Early administration of fibrinogen concentrate may be feasible and effective to prevent coagulopathy. We conducted this scoping review to characterize the existing quantity of literature, and to explore the usage of prehospital fibrinogen concentrate products in improving clinical outcomes in trauma patients. Methods: A search strategy was developed in consultation with an information specialist. We searched MEDLINE, Embase, Cochrane, and Scopus from inception to May 6th 2024. English studies evaluating prehospital/military usage of fibrinogen concentrate in trauma patients were included. Studies were assessed by three independent reviewers for meeting inclusion and exclusion criteria. Reference lists of included articles were reviewed to identify additional studies meeting inclusion criteria. Clinical endpoints regarding fibrinogen concentrate were extracted and synthesized. Results: The literature search returned 1301 articles with seven studies meeting the inclusion criteria. Five studies (71%) were conducted in civilian settings and two studies (29%) were conducted in military settings. Of the included studies, three (43%) utilized a randomized control trial. We identified seven outcomes that compared varying concentrations of fibrinogen or fibrinogen concentrate to a placebo group. The outcomes included overall mortality, death from hemorrhage, thromboembolic events, clotting time, maximum clot firmness, clot stability at ER admission, and fibrinogen concentration at ER admission. Apart from thromboembolic events, all other reported outcomes showed statistically significant differences in group comparisons, determined using p values. The four (57%) non-clinical studies underscored the robustness, practicality, and degree of fibrinogen concentrate utilization in military environments and retrieval services. Conclusion: Preliminary research suggests that prehospital fibrinogen concentrate administration in traumatic bleeding patients is both feasible and effective, improving mortality and clotting parameters. While implementing a time-saving and proactive approach with fibrinogen holds potential for enhancing trauma care, the current evidence is limited. Further studies in this novel field are warranted.

Keywords: fibrinogen concentrate, prehospital, military, trauma, trauma-induced coagulopathy

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181 Predictors for Success in Methadone Maintenance Treatment Clinic: 24 Years of Experience

Authors: Einat E. Peles, Shaul Schreiber, Miriam Adelson

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Background: Since established more than 50 years ago, methadone maintenance treatment (MMT) is the most effective treatment for opioid addiction, a chronic relapsing brain disorder that became an epidemic in western societies. Treatment includes daily individual optimal medication methadone dose (a long acting mu opioid receptor full agonist), accompanied with psychosocial therapy. It is well established that the longer retention in treatment the better outcome and survival occur. It reduces the likelihood to infectious diseases and overdose death that associated with drug injecting, enhanced social rehabilitation and eliminate criminal activity, and lead to healthy productive life. Aim: To evaluate predictors for long term retention in treatment we analyzed our prospective follow up of a major MMT clinic affiliated to a big tertiary medical center. Population Methods: Between June 25, 1993, and June 24, 2016, all 889 patients ( ≥ 18y) who ever admitted to the clinic were prospectively followed-up until May 2017. Duration in treatment from the first admission until the patient quit treatment or until the end of follow-up (24 years) was taken for calculating cumulative retention in treatment using survival analyses (Kaplan Meier) with log-rank and Cox regression for multivariate analyses. Results: Of the 889 patients, 25.2% were females who admitted to treatment at younger age (35.0 ± 7.9 vs. 40.6 ± 9.8, p < .0005), but started opioid usage at same age (22.3 ± 6.9). In addition to opioid use, on admission to MMT 58.5% had positive urine for benzodiazepines, 25% to cocaine, 12.4% to cannabis and 6.9% to amphetamines. Hepatitis C antibody tested positive in 55%, and HIV in 7.8% of the patients and 40%. Of all patients, 75.7% stayed at least one year in treatment, and of them, 67.7% stopped opioid usage (based on urine tests), and a net reduction observed in all other substance abuse (proportion of those who stopped minus proportion of those who have started). Long term retention up to 24 years was 8.0 years (95% Confidence Interval (CI) 7.4-8.6). Predictors for longer retention in treatment (Cox regression) were being older on admission ( ≥ 30y) Odds Ratio (OR) =1.4 (CI 1.1-1.8), not abusing opioids after one year OR=1.8 (CI 1.5-2.1), not abusing benzodiazepine after one year OR=1.7 (CI 1.4-2.1) and treating with methadone dose ≥ 100mg/day OR =1.8 (CI 1.5-2.3). Conclusions: Treating and following patients over 24 years indicate success of two main outcomes, high rate of retention after one year (75.7%) and high proportion of opiate abuse cessation (67.7%). As expected, longer cumulative retention was associated with patients treated with high adequate methadone dose that successfully result in opioid cessation. Based on these findings, in order to reduce morbidity and mortality, we find the establishment of more MMT clinics within a general hospital, a most urgent necessity.

Keywords: methadone maintenance treatment, epidemic, opioids, retention

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180 Immunomodulatory Role of Heat Killed Mycobacterium indicus pranii against Cervical Cancer

Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay

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Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.

Keywords: cancer, mycobacterium, immunity, immunotherapy.

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179 The Antimicrobial Activity of Marjoram Essential Oil Against Some Antibiotic Resistant Microbes Isolated from Hospitals

Authors: R. A. Abdel Rahman, A. E. Abdel Wahab, E. A. Goghneimy, H. F. Mohamed, E. M. Salama

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Infectious diseases are a major cause of death worldwide. The treatment of infections continues to be problematic in modern time because of the severe side effects of some drugs and the growing resistance to antimicrobial agents. Hence, the search for newer, safer and more potent antimicrobials is a pressing need. Herbal medicines have received much attention as a source of new antibacterial drugs since they are considered time-tested and comparatively safe both for human use and the environment. In the present study, the antimicrobial activity of marjoram (Origanum majorana L.) essential oil on some gram positive and gram negative reference bacteria, as well as some hospital resistant microbes, was tested. Marjoram oil was extracted and the oil chemical constituents were identified using GC/MS analysis. Staphylococcus aureas ATCC 6923, Pseudomonus auregonosa ATCC 9027, Bacillus subtilis ATCC 6633, E. coli ATCC 8736 and two hospital resistant microbes isolates 16 and 21 were used. The two isolates were identified by biochemical tests and 16s rRNA as proteus spp. and Enterococcus facielus. The effect of different concentrations of essential oils on bacterial growth was tested using agar disk diffusion assay method to determine the minimum inhibitory concentrations and using micro dilution method to determine the minimum bactericidal concentrations. Marjoram oil was found to be effective against both reference and hospital resistance strains. Hospital strains were more resistant to marjoram oil than reference strains. P. auregonosa growth was completely inhibited at a low concentration of oil (4µl/ml). The other reference strains showed sensitivity to marjoram oil at concentrations ranged from 5 to 7µl/ml. The two hospital strains showed sensitivity at media containing 10 and 15µl/ml oil. The major components of oil were terpineol, cis-beta (23.5%), 1,6 – octadien –3-ol,3,7-dimethyl, 2 aminobenzoate (10.9%), alpha terpieol (8.6%) and linalool (6.3%). Scanning electron microscope (SEM) and transmission electron microscope (TEM) analysis were used to determine the difference between treated and untreated hospital strains. SEM results showed that treated cells were smaller in size than control cells. TEM data showed that cell lysis has occurred to treated cells. Treated cells have ruptured cell wall and appeared empty of cytoplasm compared to control cells which shown to be intact with normal volume of cytoplasm. The results indicated that marjoram oil has a positive antimicrobial effect on hospital resistance microbes. Natural crude extracts can be perfect resources for new antimicrobial drugs.

Keywords: antimicrobial activity, essential oil, hospital resistance microbes, marjoram

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178 Exploring the Challenges of Post-conflict Peacebuilding in the Border Districts of Eastern Zone of Tigray Region

Authors: Gebreselassie Sebhatleab

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According to the Global Peace Index report (GPI, 2023), global peacefulness has deteriorated by more than 0.42%. Old and new conflicts, COVID-19, and political and cultural polarization are the main drivers of conflicts in the world. The 2022 was the deadliest year for armed conflict in the history of the GPI. In Ethiopia, over half a million people died in the Tigray war, which was the largest conflict death event since the 1994 Rwandan genocide. In total, 84 countries recorded an improvement, while 79 countries recorded a deterioration in peacefulness across the globe. The Russia-Ukraine war and its consequences were the main drivers of the deterioration in peacefulness globally. Both Russia and Ukraine are now ranked amongst the ten least peaceful countries, and Ukraine had the largest deterioration of any country in the 2023 GPI. In the same year, the global impact of violence on the economy was 17 percent, which was equivalent to 10.9% of global GDP. Besides, the brutal conflict in Tigray started in November. 2020 claimed more than half a million lives lost and displaced nearly 3 million people, along with widespread human rights violations and sexual violence has left deep damage on the population. The displaced people are still unable to return home because the western, southern and Eastern parts of Tigray are occupied by Eritrean and Amhara forces, despite the Pretoria Agreement. Currently, armed conflicts in Amhara in the Oromya regions are intensified, and human rights violations are being reported in both regions. Meanwhile, protests have been held by war-injured TDF members, IDPs and teachers in the Tigray region. Hence, the general objective of this project is to explore the challenges of peace-building processes in the border woredas of the Eastern Zone of the Tigray Region. Methodologically, the project will employ exploratory qualitative research designs to gather and analyze qualitative data. A purposive sampling technique will be applied to gather pertinent information from the key stakeholders. Open-ended interview questions will be prepared to gather relevant information about the challenges and perceptions of peacebuilding in the study area. Data will be analyzed using qualitative methods such as content analysis, narrative analysis and phenomenological analysis to deeply investigate the challenges of peace-building in the study woredas. Findings of this research project will be employed for program intervention to promote sustainable peace in the study area.

Keywords: peace building, conflcit and violence, political instability, insecurity

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177 Development a Home-Hotel-Hospital-School Community-Based Palliative Care Model for Patients with Cancer in Suratthani, Thailand

Authors: Patcharaporn Sakulpong, Wiriya Phokhwang

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Background: Banpunrug (Love Sharing House) established in 2013 provides a community-based palliative care for patients with cancer from 7 provinces in southern Thailand. These patients come to receive outpatient chemotherapy and radiotherapy at Suratthani Cancer Hospital. They are poor and uneducated; they need an accommodation during their 30-45 day course of therapy. Methods: A community-participatory action research (PAR) was employed to establish a model of palliative care for patients with cancer. The participants included health care providers, community, and patients and families. The PAR process includes problem identification and need assessment, community and team establishment, field survey, organization founding, model of care planning, action and inquiry (PDCA), outcome evaluation, and model distribution. Results: The model of care at Banpunrug involves the concepts of HHHS model, in that Banpunrug is a Home for patients; patients live in a house comfortable like in a Hotel resource; the patients are given care and living facilities similarly to those in a Hospital; the house is a School for patients to learn how to take care themselves, how to live well with cancer, and most importantly how to prepare themselves for a good death. The house is also a humanized care school for health care providers. Banpunrug’s philosophy of care is based on friendship therapy, social and spiritual support, community partnership, patient-family centeredness, Live & Love sharing house, and holistic and humanized care. With this philosophy, the house is managed as a home of the patients and everyone involved; everything is costless for all eligible patients and their family members; all facilities and living expense are donated from benevolent people, friends, and community. Everyone, including patients and family, has a sense of belonging to the house and there is no authority between health care providers and the patients in the house. The house is situated in a temple and a community and supported by many local nonprofit organizations and healthcare facilities such as a health promotion hospital at sub-disctrict level and Suratthani Cancer Hospital. Village health volunteers and multi-professional health care volunteers have contributed not only appropriate care, but also knowledge and experience to develop a distinguishing HHHS community-based palliative care model for patients with cancer. Since its opening the house has been a home for more than 400 patients and 300 family members. It is also a model for many national and international healthcare organizations and providers, who come to visit and learn about palliative care in and by community. Conclusions: The success of this palliative care model comes from community involvement, multi-professional volunteers and distributions, and concepts of HHHS model. Banpunrug promotes a consistent care across the cancer trajectory independent of prognosis in order to strengthen a full integration of palliative

Keywords: community-based palliative care, model, participatory action research, patients with cancer

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176 A 20 Year Comparison of Australian Childhood Bicycle Injuries – Have We Made a Difference?

Authors: Bronwyn Griffin, Caroline Acton, Tona Gillen, Roy Kimble

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Background: Bicycle riding is a common recreational activity enjoyed by many children throughout Australia that has been associated with the usual caveat of benefits related to exercise and recreation. Given Australia was the first country in the world to introduce cyclist helmet laws in 1991, very few publications have reviewed paediatric cycling injuries (fatal or non-fatal) since. Objectives: To identify trends in children (0-16 years) who required admission for greater than 24 hours following a bicycle-related injury (fatal and non-fatal) in Queensland. Further, to discuss changes that have occurred in paediatric cycling injury trends in Queensland since a prominent local study/publication in 1995. This paper aims to establish evidence to inform interventions promoting safer riding to parents, children and communities. Methods: Data on paediatric (0-16 years) cycling injuries in Queensland resulting in hospital admission more than 24 hours across three tertiary paediatric hospitals in Brisbane between November 2008-June 2015 was compiled by the Paediatric Trauma Data Registry for non-fatal injuries. The Child Death Review Team at the Queensland Families and Childhood Commission provided data on fatalities in children <17years from (June 2004 –June 2015). Comparing trends to a local study published in 1995 Results: Between 2008-2015 there were 197 patients admitted for greater than 24 hours following a cycling injury. The median age was 11 years, with males more frequently involved (n=139, 87%) compared to females. Mean length of stay was three days, with 47 (28%) children admitted to PICU, location of injury was most often the street (n=63, 37%). Between 2004 –2015 there were 15 fatalities (Incidence rate 0.25/100,000); all were male, 14/15 occurred on the street, with eight stated to have not been wearing a helmet, 11/15 children came from the least advantaged socio-economic group (SEIFA) compared to a local publication in 1995, finding of 94 fatalities between (1981-1992). Conclusions: There has been a notable decrease in incidence of fatalities between the two time periods with incidence rates dropping from 1.75-0.25/100,000. More statistics need to be run to ascertain if this is a true reduction or perhaps a decrease in children riding bicycles. Injuries that occur on the street that come in contact with a car remain of serious concern. The purpose of this paper is not to discourage bicycle riding among child and adolescent populations, rather, inform parents and the wider community about the risks associated with cycling in order to reduce injuries associated with this sport, whilst promoting safe cycling.

Keywords: paediatric, cycling, trauma, prevention, emergency

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175 Reconceptualising the Voice of Children in Child Protection

Authors: Sharon Jackson, Lynn Kelly

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This paper proposes a conceptual review of the interdisciplinary literature which has theorised the concept of ‘children’s voices’. The primary aim is to identify and consider the theoretical relevance of conceptual thought on ‘children’s voices’ for research and practice in child protection contexts. Attending to the ‘voice of the child’ has become a core principle of social work practice in contemporary child protection contexts. Discourses of voice permeate the legislative, policy and practice frameworks of child protection practices within the UK and internationally. Voice is positioned within a ‘child-centred’ moral imperative to ‘hear the voices’ of children and take their preferences and perspectives into account. This practice is now considered to be central to working in a child-centered way. The genesis of this call to voice is revealed through sociological analysis of twentieth-century child welfare reform as rooted inter alia in intersecting political, social and cultural discourses which have situated children and childhood as cites of state intervention as enshrined in the 1989 United Nations Convention on the Rights of the Child ratified by the UK government in 1991 and more specifically Article 12 of the convention. From a policy and practice perspective, the professional ‘capturing’ of children’s voices has come to saturate child protection practice. This has incited a stream of directives, resources, advisory publications and ‘how-to’ guides which attempt to articulate practice methods to ‘listen’, ‘hear’ and above all – ‘capture’ the ‘voice of the child’. The idiom ‘capturing the voice of the child’ is frequently invoked within the literature to express the requirements of the child-centered practice task to be accomplished. Despite the centrality of voice, and an obsession with ‘capturing’ voices, evidence from research, inspection processes, serious case reviews, child abuse and death inquires has consistently highlighted professional neglect of ‘the voice of the child’. Notable research studies have highlighted the relative absence of the child’s voice in social work assessment practices, a troubling lack of meaningful engagement with children and the need to more thoroughly examine communicative practices in child protection contexts. As a consequence, the project of capturing ‘the voice of the child’ has intensified, and there has been an increasing focus on developing methods and professional skills to attend to voice. This has been guided by a recognition that professionals often lack the skills and training to engage with children in age-appropriate ways. We argue however that the problem with ‘capturing’ and [re]representing ‘voice’ in child protection contexts is, more fundamentally, a failure to adequately theorise the concept of ‘voice’ in the ‘voice of the child’. For the most part, ‘The voice of the child’ incorporates psychological conceptions of child development. While these concepts are useful in the context of direct work with children, they fail to consider other strands of sociological thought, which position ‘the voice of the child’ within an agentic paradigm to emphasise the active agency of the child.

Keywords: child-centered, child protection, views of the child, voice of the child

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174 Design, Construction, Validation And Use Of A Novel Portable Fire Effluent Sampling Analyser

Authors: Gabrielle Peck, Ryan Hayes

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Current large scale fire tests focus on flammability and heat release measurements. Smoke toxicity isn’t considered despite it being a leading cause of death and injury in unwanted fires. A key reason could be that the practical difficulties associated with quantifying individual toxic components present in a fire effluent often require specialist equipment and expertise. Fire effluent contains a mixture of unreactive and reactive gases, water, organic vapours and particulate matter, which interact with each other. This interferes with the operation of the analytical instrumentation and must be removed without changing the concentration of the target analyte. To mitigate the need for expensive equipment and time-consuming analysis, a portable gas analysis system was designed, constructed and tested for use in large-scale fire tests as a simpler and more robust alternative to online FTIR measurements. The novel equipment aimed to be easily portable and able to run on battery or mains electricity; be able to be calibrated at the test site; be capable of quantifying CO, CO2, O2, HCN, HBr, HCl, NOx and SO2 accurately and reliably; be capable of independent data logging; be capable of automated switchover of 7 bubblers; be able to withstand fire effluents; be simple to operate; allow individual bubbler times to be pre-set; be capable of being controlled remotely. To test the analysers functionality, it was used alongside the ISO/TS 19700 Steady State Tube Furnace (SSTF). A series of tests were conducted to assess the validity of the box analyser measurements and the data logging abilities of the apparatus. PMMA and PA 6.6 were used to assess the validity of the box analyser measurements. The data obtained from the bench-scale assessments showed excellent agreement. Following this, the portable analyser was used to monitor gas concentrations during large-scale testing using the ISO 9705 room corner test. The analyser was set up, calibrated and set to record smoke toxicity measurements in the doorway of the test room. The analyser was successful in operating without manual interference and successfully recorded data for 12 of the 12 tests conducted in the ISO room tests. At the end of each test, the analyser created a data file (formatted as .csv) containing the measured gas concentrations throughout the test, which do not require specialist knowledge to interpret. This validated the portable analyser’s ability to monitor fire effluent without operator intervention on both a bench and large-scale. The portable analyser is a validated and significantly more practical alternative to FTIR, proven to work for large-scale fire testing for quantification of smoke toxicity. The analyser is a cheaper, more accessible option to assess smoke toxicity, mitigating the need for expensive equipment and specialist operators.

Keywords: smoke toxicity, large-scale tests, iso 9705, analyser, novel equipment

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173 The Effects of Grape Waste Bioactive Compounds on the Immune Response and Oxidative Stress in Pig Kidney

Authors: Mihai Palade, Gina Cecilia Pistol, Mariana Stancu, Veronica Chedea, Ionelia Taranu

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Nutrition is an important determinant of general health status, with especially focus on prevention and/or attenuation of the inflammatory-associated pathologies. People with chronic kidney disease can experience chronic inflammation that can lead to cardiovascular disease and even an increased rate of death. There are important links between chronic kidney diseases, inflammation and nutritional strategies that may prevent or protect against undesirable inflammation and oxidative stress. The grape by-products either seeds or pomace are rich in polyphenols which may be beneficial in prevention of inflammatory, antioxidant and antimicrobial processes. As a model for studying the impact of grape seeds on renal inflammation and oxidative stress, we used in this study weaned piglets. After a feeding trial of 30 days with a control diet and an experimental diet containing 5% grape seed (GS), kidney samples were collected. In renal tissues were determined the expression and activity of important markers of immune respose and oxidative stress: pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6, IL-8, IFN-gamma), anti-inflammatory cytokines (IL-4, IL-10), anti-oxidant enzymes (catalase CAT, superoxide dismutase SOD, glutathione peroxidise GPx) and important mediators belonging to nuclear receptors (NF-kB1, Nrf-2 and PPAR-gamma). Gene expression was evaluated by qPCR, whereas protein concentration was determined using proteomic techniques (ELISA). The activity of anti-oxidant enzymes was determined using specific kits. Our results showed that GS enriched in polyphenols does not have effect on TNF-alpha, IL-6 and IL-1 beta gene expression and protein concentration in kidney. By contrast, the gene expression and protein level of IL-8 and IFN-gamma were decreased in GS kidney. Anti-inflammatory cytokines IL-4 and IL-10 gene levels were increased in kidneys collected from GS piglets in comparison with controls, with no modification of protein levels between the two groups. The activities of anti-oxidant enzymes CAT and GPx were increased in kidney by GS, whereas SOD activity was unmodified in comparison with control samples. Also, the GS diet was associated with no modulation of mRNAs for nuclear receptors NF-kB1, Nrf-2 and PPAR-gamma gene expressions in kidneys. In conclusion, our results demonstrated that GS enriched in bioactive compounds such polyphenols could modulate inflammation and oxidative stress markers in kidney tissues. Further studies are necessary to elucidate the mechanism of action of GS compounds in case kidney inflammation associated with oxidative stress, and signalling molecules involved in these mechanisms.

Keywords: animal model, kidney inflammation, oxidative stress, grape seed

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172 Incidence and Risk Factors of Traumatic Lumbar Puncture in Newborns in a Tertiary Care Hospital

Authors: Heena Dabas, Anju Paul, Suman Chaurasia, Ramesh Agarwal, M. Jeeva Sankar, Anurag Bajpai, Manju Saksena

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Background: Traumatic lumbar puncture (LP) is a common occurrence and causes substantial diagnostic ambiguity. There is paucity of data regarding its epidemiology. Objective: To assess the incidence and risk factors of traumatic LP in newborns. Design/Methods: In a prospective cohort study, all inborn neonates admitted in NICU and planned to undergo LP for a clinical indication of sepsis were included. Neonates with diagnosed intraventricular hemorrhage (IVH) of grade III and IV were excluded. The LP was done by operator - often a fellow or resident assisted by bedside nurse. The unit has policy of not routinely using any sedation/analgesia during the procedure. LP is done by 26 G and 0.5-inch-long hypodermic needle inserted in third or fourth lumbar space while the infant is in lateral position. The infants were monitored clinically and by continuous measurement of vital parameters using multipara monitor during the procedure. The occurrence of traumatic tap along with CSF parameters and other operator and assistant characteristics were recorded at the time of procedure. Traumatic tap was defined as presence of visible blood or more than 500 red blood cells on microscopic examination. Microscopic trauma was defined when CSF is not having visible blood but numerous RBCs. The institutional ethics committee approved the study protocol. A written informed consent from the parents and the health care providers involved was obtained. Neonates were followed up till discharge/death and final diagnosis was assigned along with treating team. Results: A total of 362 (21%) neonates out of 1726 born at the hospital were admitted during the study period (July 2016 to January, 2017). Among these neonates, 97 (26.7%) were suspected of sepsis. A total of 54 neonates were enrolled who met the eligibility criteria and parents consented to participate in the study. The mean (SD) birthweight was 1536 (732) grams and gestational age 32.0 (4.0) weeks. All LPs were indicated for late onset sepsis at the median (IQR) age of 12 (5-39) days. The traumatic LP occurred in 19 neonates (35.1%; 95% C.I 22.6% to 49.3%). Frank blood was observed in 7 (36.8%) and in the remaining, 12(63.1%) CSF was detected to have microscopic trauma. The preliminary risk factor analysis including birth weight, gestational age and operator/assistant and other characteristics did not demonstrate clinically relevant predictors. Conclusion: A significant number of neonates requiring lumbar puncture in our study had high incidence of traumatic tap. We were not able to identify modifiable risk factors. There is a need to understand the reasons and further reduce this issue for improving management in NICUs.

Keywords: incidence, newborn, traumatic, lumbar puncture

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171 Atypical Retinoid ST1926 Nanoparticle Formulation Development and Therapeutic Potential in Colorectal Cancer

Authors: Sara Assi, Berthe Hayar, Claudio Pisano, Nadine Darwiche, Walid Saad

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Nanomedicine, the application of nanotechnology to medicine, is an emerging discipline that has gained significant attention in recent years. Current breakthroughs in nanomedicine have paved the way to develop effective drug delivery systems that can be used to target cancer. The use of nanotechnology provides effective drug delivery, enhanced stability, bioavailability, and permeability, thereby minimizing drug dosage and toxicity. As such, the use of nanoparticle (NP) formulations in drug delivery has been applied in various cancer models and have shown to improve the ability of drugs to reach specific targeted sites in a controlled manner. Cancer is one of the major causes of death worldwide; in particular, colorectal cancer (CRC) is the third most common type of cancer diagnosed amongst men and women and the second leading cause of cancer related deaths, highlighting the need for novel therapies. Retinoids, consisting of natural and synthetic derivatives, are a class of chemical compounds that have shown promise in preclinical and clinical cancer settings. However, retinoids are limited by their toxicity and resistance to treatment. To overcome this resistance, various synthetic retinoids have been developed, including the adamantyl retinoid ST1926, which is a potent anti-cancer agent. However, due to its limited bioavailability, the development of ST1926 has been restricted in phase I clinical trials. We have previously investigated the preclinical efficacy of ST1926 in CRC models. ST1926 displayed potent inhibitory and apoptotic effects in CRC cell lines by inducing early DNA damage and apoptosis. ST1926 significantly reduced the tumor doubling time and tumor burden in a xenograft CRC model. Therefore, we developed ST1926-NPs and assessed their efficacy in CRC models. ST1926-NPs were produced using Flash NanoPrecipitation with the amphiphilic diblock copolymer polystyrene-b-ethylene oxide and cholesterol as a co-stabilizer. ST1926 was formulated into NPs with a drug to polymer mass ratio of 1:2, providing a stable formulation for one week. The contin ST1926-NP diameter was 100 nm, with a polydispersity index of 0.245. Using the MTT cell viability assay, ST1926-NP exhibited potent anti-growth activities as naked ST1926 in HCT116 cells, at pharmacologically achievable concentrations. Future studies will be performed to study the anti-tumor activities and mechanism of action of ST1926-NPs in a xenograft mouse model and to detect the compound and its glucuroconjugated form in the plasma of mice. Ultimately, our studies will support the use of ST1926-NP formulations in enhancing the stability and bioavailability of ST1926 in CRC.

Keywords: nanoparticles, drug delivery, colorectal cancer, retinoids

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170 Insights into Child Malnutrition Dynamics with the Lens of Women’s Empowerment in India

Authors: Bharti Singh, Shri K. Singh

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Child malnutrition is a multifaceted issue that transcends geographical boundaries. Malnutrition not only stunts physical growth but also leads to a spectrum of morbidities and child mortality. It is one of the leading causes of death (~50 %) among children under age five. Despite economic progress and advancements in healthcare, child malnutrition remains a formidable challenge for India. The objective is to investigate the impact of women's empowerment on child nutrition outcomes in India from 2006 to 2021. A composite index of women's empowerment was constructed using Confirmatory Factor Analysis (CFA), a rigorous technique that validates the measurement model by assessing how well-observed variables represent latent constructs. This approach ensures the reliability and validity of the empowerment index. Secondly, kernel density plots were utilised to visualise the distribution of key nutritional indicators, such as stunting, wasting, and overweight. These plots offer insights into the shape and spread of data distributions, aiding in understanding the prevalence and severity of malnutrition. Thirdly, linear polynomial graphs were employed to analyse how nutritional parameters evolved with the child's age. This technique enables the visualisation of trends and patterns over time, allowing for a deeper understanding of nutritional dynamics during different stages of childhood. Lastly, multilevel analysis was conducted to identify vulnerable levels, including State-level, PSU-level, and household-level factors impacting undernutrition. This approach accounts for hierarchical data structures and allows for the examination of factors at multiple levels, providing a comprehensive understanding of the determinants of child malnutrition. Overall, the utilisation of these statistical methodologies enhances the transparency and replicability of the study by providing clear and robust analytical frameworks for data analysis and interpretation. Our study reveals that NFHS-4 and NFHS-5 exhibit an equal density of severely stunted cases. NFHS-5 indicates a limited decline in wasting among children aged five, while the density of severely wasted children remains consistent across NFHS-3, 4, and 5. In 2019-21, women with higher empowerment had a lower risk of their children being undernourished (Regression coefficient= -0.10***; Confidence Interval [-0.18, -0.04]). Gender dynamics also play a significant role, with male children exhibiting a higher susceptibility to undernourishment. Multilevel analysis suggests household-level vulnerability (intra-class correlation=0.21), highlighting the need to address child undernutrition at the household level.

Keywords: child nutrition, India, NFHS, women’s empowerment

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169 Kidnapping of Migrants by Drug Cartels in Mexico as a New Trend in Contemporary Slavery

Authors: Itze Coronel Salomon

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The rise of organized crime and violence related to drug cartels in Mexico has created serious challenges for the authorities to provide security to those who live within its borders. However, to achieve a significant improvement in security is absolute respect for fundamental human rights by the authorities. Irregular migrants in Mexico are at serious risk of abuse. Research by Amnesty International as well as reports of the NHRC (National Human Rights) in Mexico, have indicated the major humanitarian crisis faced by thousands of migrants traveling in the shadows. However, the true extent of the problem remains invisible to the general population. The fact that federal and state governments leave no proper record of abuse and do not publish reliable data contributes to ignorance and misinformation, often spread by the media that portray migrants as the source of crime rather than their victims. Discrimination and intolerance against irregular migrants can generate greater hostility and exclusion. According to the modus operandi that has been recorded criminal organizations and criminal groups linked to drug trafficking structures deprive migrants of their liberty for forced labor and illegal activities related to drug trafficking, even some have been kidnapped for be trained as murderers . If the victim or their family cannot pay the ransom, the kidnapped person may suffer torture, mutilation and amputation of limbs or death. Migrant women are victims of sexual abuse during her abduction as well. In 2011, at least 177 bodies were identified in the largest mass grave found in Mexico, located in the town of San Fernando, in the border state of Tamaulipas, most of the victims were killed by blunt instruments, and most seemed to be immigrants and travelers passing through the country. With dozens of small graves discovered in northern Mexico, this may suggest a change in tactics between organized crime groups to the different means of obtaining revenue and reduce murder profile methods. Competition and conflict over territorial control drug trafficking can provide strong incentives for organized crime groups send signals of violence to the authorities and rival groups. However, as some Mexican organized crime groups are increasingly looking to take advantage of income and vulnerable groups, such as Central American migrants seem less interested in advertising his work to authorities and others, and more interested in evading detection and confrontation. This paper pretends to analyze the introduction of this new trend of kidnapping migrants for forced labors by drug cartels in Mexico into the forms of contemporary slavery and its implications.

Keywords: international law, migration, transnational organized crime

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168 Post COVID-19 Multi-System Inflammatory Syndrome Masquerading as an Acute Abdomen

Authors: Ali Baker, Russel Krawitz

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This paper describes a rare occurrence where a potentially fatal complication of COVID-19 infection (MIS-A) was misdiagnosed as an acute abdomen. As most patients with this syndrome present with fever and gastrointestinal symptoms, they may inadvertently fall under the care of the surgical unit. However, unusual imaging findings and a poor response to anti-microbial therapy should prompt clinicians to suspect a non-surgical etiology. More than half of MIS-A patients require ICU admission and vasopressor support. Prompt referral to a physician is key, as the cornerstone of treatment is IVIG and corticosteroid therapy. A 32 year old woman presented with right sided abdominal pain and fevers. She had also contracted COVID-19 two months earlier. Abdominal examination revealed generalised right sided tenderness. The patient had raised inflammatory markers, but other blood tests were unremarkable. CT scan revealed extensive lymphadenopathy along the ileocolic chain. The patient proved to be a diagnostic dilemma. She was reviewed by several surgical consultants and discussed with several inpatient teams. Although IV antibiotics were commenced, the right sided abdominal pain, and fevers persisted. Pan-culture returned negative. A mild cholestatic derangement developed. On day 5, the patient underwent preparation for colonoscopy to assess for a potential intraluminal etiology. The following day, the patient developed sinus tachycardia and hypotension that was refractory to fluid resuscitation. That patient was transferred to ICU and required vasopressor support. Repeat CT showed peri-portal edema and a thickened gallbladder wall. On re-examination, the patient was Murphy’s sign positive. Biliary ultrasound was equivocal for cholecystitis. The patient was planned for diagnostic laparoscopy. The following morning, a marked rise in cardiac troponin was discovered, and a follow-up echocardiogram revealed moderate to severe global systolic dysfunction. The impression was post-COVID MIS with myocardial involvement. IVIG and Methylprednisolone infusions were commenced. The patient had a great response. Vasopressor support was weaned, and the patient was discharged from ICU. The patient continued to improve clinically with oral prednisolone, and was discharged on day 17. Although MIS following COVID-19 infection is well-described syndrome in children, only recently has it come to light that it can occur in adults. The exact incidence is unknown, but it is thought to be rare. A recent systematic review found only 221 cases of MIS-A, which could be included for analysis. Symptoms vary, but the most frequent include fever, gastrointestinal, and mucocutaneous. Many patients progress to multi-organ failure and require vasopressor support. 7% succumb to the illness. The pathophysiology of MIS is only partly understood. It shares similarities with Kawasaki disease, macrophage activation syndrome, and cytokine release syndrome. Importantly, by definition, the patient must have an absence of severe respiratory symptoms. It is thought to be due to a dysregulated immune response to the virus. Potential mechanisms include reduced levels of neutralising antibodies and autoreactive antibodies that promote inflammation. Further research into MIS-A is needed. Although rare, this potentially fatal syndrome should be considered in the unwell surgical patient who has recently contracted COVID-19 and poses a diagnostic dilemma.

Keywords: acute-abdomen, MIS, COVID-19, ICU

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167 Determinants of Unmet Need for Contraception among Currently Married Women in Rural and Urban Communities of Osun State, South-West Nigeria

Authors: Abiola O. Temitayo-Oboh, Olugbenga L. Abodunrin, Wasiu O. Adebimpe, Micheal C. Asuzu

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Introduction: Many women who are sexually active would prefer to avoid becoming pregnant but are not using any method of contraception. These women are considered to have an unmet need for contraception. In an ideal situation, all women who want to space or limit their births and are exposed to the risk of conception would use some kind of conception; in practice, however, some women fail to use contraception which put them at risk of having mistimed or unwanted births, induced abortion, or maternal death. This study, therefore, aimed to assess the determinants of unmet need for contraception among currently married women in rural and urban communities of Osun State, South-West Nigeria. Methods: This was an analytical cross-sectional comparative study, which was carried out among currently married women. Three hundred and twenty respondents each were selected for the rural and urban groups from four Local Government Areas using multi-stage sampling technique. Data were collected using a pre-tested semi-structured interviewer-administered questionnaire and focus group discussion (FGD) guide; data analysis was done with Statistical Package for Social Sciences (SPSS) version 17.0 and detailed content analysis method respectively. Statistical analysis of the difference between proportions was done by the use of the Chi-square test and T-test was used to compare the means of the continuous variables. The study also utilized descriptive, bivariate and multivariate analytical techniques to examine the effect of some variables on unmet need. Level of statistical significance was set at p-value < 0.05 for all values. Results: Two hundred and ninety-six (92.5%) of the rural and 306 (95.6%) of the urban study population had heard of contraception, 365 (57.0 %) of the total respondents had good knowledge [162 (50.6 %) for rural respondents and 203 (63.4 %) for urban respondents]. This difference was statistically significant (p < 0.001). Five hundred and twenty-one (81.4%) respondents had a positive attitude towards contraception [243 (75.9%) in the rural and 278 (86.9%) in the urban area], and the difference was also statistically significant (p < 0.001). Only 47 (14.7%) and 59 (18.4%) of rural and urban women were current contraceptive users respectively. The total unmet need for contraception among rural women was 138 (43.1%) of which 82 (25.6%) was for spacing and 56 (17.5%), for limiting. While the total unmet need for contraception among urban women was 145 (45.3%) of which 96 (30.0%) was for spacing and 49 (15.3%) for limiting. Number of living children, knowledge of contraceptive methods, discussion with health workers about family planning, couples discussion about family planning and availability of family planning services were found to be predictors of women’s unmet need for contraception (p < 0.05). Conclusion: It is, therefore, recommended that there is need to intensify reproductive health education in bridging the knowledge gap, improving attitude and modifying practices regarding use of contraception in Nigeria. Hence, this will help to enhance the utilization of family planning services among Nigerian women.

Keywords: contraception, married women, Nigeria, rural, urban, unmet need

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166 Combined Treatment of Estrogen-Receptor Positive Breast Microtumors with 4-Hydroxytamoxifen and Novel Non-Steroidal Diethyl Stilbestrol-Like Analog Produces Enhanced Preclinical Treatment Response and Decreased Drug Resistance

Authors: Sarah Crawford, Gerry Lesley

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This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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