Search results for: sibling’s death
1098 Significance of Molecular Autophagic Pathway in Gaucher Disease Pathology
Authors: Ozlem Oral, Emre Taskin, Aysel Yuce, Serap Dokmeci, Devrim Gozuacik
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Autophagy is an evolutionary conserved lysosome-dependent catabolic pathway, responsible for the degradation of long-lived proteins, abnormal aggregates and damaged organelles which cannot be degraded by the ubiquitin-proteasome system. Lysosomes degrade the substrates through the activity of lysosomal hydrolases and lysosomal membrane-bound proteins. Mutations in the coding region of these proteins cause malfunctional lysosomes, which contributes to the pathogenesis of lysosomal storage diseases. Gaucher disease is a lysosomal storage disease resulting from the mutation of a lysosomal membrane-associated glycoprotein called glucocerebrosidase and its cofactor saposin C. The disease leads to intracellular accumulation of glucosylceramide and other glycolipids. Because of the essential role of lysosomes in autophagic degradation, Gaucher disease may directly be linked to this pathway. In this study, we investigated the expression of autophagy and/or lysosome-related genes and proteins in fibroblast cells isolated from patients with different mutations. We carried out confocal microscopy analysis and examined autophagic flux by utilizing the differential pH sensitivities of RFP and GFP in mRFP-GFP-LC3 probe. We also evaluated lysosomal pH by active lysosome staining and lysosomal enzyme activity. Beside lysosomes, we also performed proteasomal activity and cell death analysis in patient samples. Our data showed significant attenuation in the expression of key autophagy-related genes and accumulation of their proteins in mutant cells. We found decreased the ability of autophagosomes to fuse with lysosomes, associated with elevated lysosomal pH and reduced lysosomal enzyme activity. Proteasomal degradation and cell death analysis showed reduced proteolytic activity of the proteasome, which consequently leads to increased susceptibility to cell death. Our data indicate that the major degradation pathways are affected by multifunctional lysosomes in mutant patient cells and may underlie in the mechanism of clinical severity of Gaucher patients. (This project is supported by TUBITAK-3501-National Young Researchers Career Development Program, Project No: 112T130).Keywords: autophagy, Gaucher's disease, glucocerebrosidase, mutant fibroblasts
Procedia PDF Downloads 3241097 In vitro Evaluation of the Synergistic Antiviral Activity of Amantadine Coupled with Magnesium Lithospermate B against Enterovirus 71 Infection
Authors: Wen-Yu Lin, Yi-Ching Chung, Jhao-Ren Lin, Tzyy-Rong Jinn
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It is well known that enterovirus 71(EV71) causes recurring outbreaks of hand, foot and mouth disease and encephalitis leading to complications or death in young children. And, several enterovirus 71 (EV71) of hand foot and mouth disease (HFMD) with high mortalities occurred in Asia country, such as Hong Kung (1985), Malaysia (1997), Taiwan (1998) and China (2008) that EV71 results in severe neurological complications and sudden death in infants and young children. However, there are still no effective drugs and vaccines to reduce and inhibit EV71 infection. Therefore, the development of specific and effective antiviral strategies against EV71 has become an urgent issue for the protection of children from the hazards of the HFMD. As reported, amantadine is effective in prophylaxis and treatment of the EV71 infections. Thus, the aim of this study was to further evaluate the synergistic antiviral activity of amantadine coupled with magnesium lithospermate B (MLB) against enterovirus 71 infection. In a preliminary test, it is shown that the infected RD cells were treated with amantadine after virus absorption, at concentrations of 3 and 5µM of amantadine suppressed EV71-induced CPE to 13% and 23%, respectively at MOI of 3. Alternatively, at concentrations of 5µg/ml of MLB combined with 3 and 5 µM of amantadine apparently suppressed EV71-induced CPE to 45% and 63%, respectively at MOI of 3. Thus, amantadine coupled with MLB may have the potential for further study to development as the chemopreventive reagents against EV71 infection.Keywords: amantadine, Enterovirus 71, magnesium lithospermate B, RD cells, synergistic effects
Procedia PDF Downloads 2421096 Liposomal Encapsulation of Silver Nanoparticle for Improved Delivery and Enhanced Anticancer Properties
Authors: Azeez Yusuf, Alan Casey
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Silver nanoparticles (AgNP) are one of the most widely investigated metallic nanoparticles due to their promising antibacterial activities. In recent years, AgNP research has shifted beyond antimicrobial use to potential applications in the medical arena. This shift coupled with the extensive commercial applications of AgNP will further increase human exposure, and the subsequent risk of adverse effects that may result from repeated exposures and inefficient delivery meaning research into improved AgNP delivery is of paramount importance. In this study, AgNP were encapsulated in a natural bio-surfactant, dipalmitoylphosphatyidyl choline (DPPC), in an attempt to enhance the intracellular delivery and simultaneously mediate the associated cytotoxicity of the AgNP. It was noted that as a result of the encapsulation, liposomal-AgNP (Lipo-AgNP) at 0.625 μg/ml induced significant cell death in THP1 cell lines a notably lower dose than that of the uncoated AgNP induced cytotoxicity. The induced cytotoxicity was shown to result in an increased level of DNA fragmentation resulting in a cell cycle interruption at the S phase of the cell cycle. It was shown that the predominate form of cell death upon exposure to both uncoated and Lipo-AgNP was apoptosis, however, a ROS-independent activation of the executioner caspases 3/7 occurred when exposed to the Lipo-AgNP. These findings showed that encapsulation of AgNP enhances AgNP cytotoxicity and mediates an ROS-independent induction of apoptosis.Keywords: silver nanoparticles, AgNP, cytotoxicity, encapsulation, liposome
Procedia PDF Downloads 1561095 Normal Hematopoietic Stem Cell and the Toxic Effect of Parthenolide
Authors: Alsulami H., Alghamdi N., Alasker A., Almohen N., Shome D.
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Most conventional chemotherapeutic agents which are used for the treatment of cancers not only eradicate cancer cells but also affect normal hematopoietic Stem cells (HSCs) that leads to severe pancytopenia during treatment. Therefore, a need exists for novel approaches to treat cancer without or with minimum effect on normal HSCs. Parthenolide (PTL), a herbal product occurring naturally in the plant Feverfew, is a potential new chemotherapeutic agent for the treatment of many cancers such as acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). In this study we investigated the effect of different PTL concentrations on the viability of normal HSCs and also on the ability of these cells to form colonies after they have been treated with PTL in vitro. Methods: In this study, 24 samples of bone marrow and cord blood were collected with consent, and mononuclear cells were separated using density gradient separation. These cells were then exposed to various concentrations of PTL for 24 hours. Cell viability after culture was determined using 7ADD in a flow cytometry test. Additionally, the impact of PTL on hematopoietic stem cells (HSCs) was evaluated using a colony forming unit assay (CFU). Furthermore, the levels of NFҝB expression were assessed by using a PE-labelled anti-pNFκBP65 antibody. Results: this study showed that there was no statistically significant difference in the percentage of cell death between untreated and PTL treated cells with 5 μM PTL (p = 0.7), 10 μM PTL (p = 0.4) and 25 μM (p = 0.09) respectively. However, at higher doses, PTL caused significant increase in the percentage of cell death. These results were significant when compared to untreated control (p < 0.001). The response of cord blood cells (n=4) on the other hand was slightly different from that for bone marrow cells in that the percentage of cell death was significant at 100 μM PTL. Therefore, cord blood cells seemed more resistant than bone marrow cells. Discussion &Conclusion: At concentrations ≤25 μM PTL has a minimum or no effect on HSCs in vitro. Cord blood HSCs are more resistant to PTL compared to bone marrow HSCs. This could be due to the higher percentage of T-lymphocytes, which are resistant to PTL, in CB samples (85% in CB vs. 56% in BM. Additionally, CB samples contained a higher proportion of CD34+ cells, with 14.5% of brightly CD34+ cells compared to only 1% in normal BM. These bright CD34+ cells in CB were mostly negative for early-stage stem cell maturation antigens, making them young and resilient to oxidative stress and high concentrations of PTL.Keywords: stem cell, parthenolide, NFKB, CLL
Procedia PDF Downloads 481094 Machine Learning for Classifying Risks of Death and Length of Stay of Patients in Intensive Unit Care Beds
Authors: Itamir de Morais Barroca Filho, Cephas A. S. Barreto, Ramon Malaquias, Cezar Miranda Paula de Souza, Arthur Costa Gorgônio, João C. Xavier-Júnior, Mateus Firmino, Fellipe Matheus Costa Barbosa
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Information and Communication Technologies (ICT) in healthcare are crucial for efficiently delivering medical healthcare services to patients. These ICTs are also known as e-health and comprise technologies such as electronic record systems, telemedicine systems, and personalized devices for diagnosis. The focus of e-health is to improve the quality of health information, strengthen national health systems, and ensure accessible, high-quality health care for all. All the data gathered by these technologies make it possible to help clinical staff with automated decisions using machine learning. In this context, we collected patient data, such as heart rate, oxygen saturation (SpO2), blood pressure, respiration, and others. With this data, we were able to develop machine learning models for patients’ risk of death and estimate the length of stay in ICU beds. Thus, this paper presents the methodology for applying machine learning techniques to develop these models. As a result, although we implemented these models on an IoT healthcare platform, helping clinical staff in healthcare in an ICU, it is essential to create a robust clinical validation process and monitoring of the proposed models.Keywords: ICT, e-health, machine learning, ICU, healthcare
Procedia PDF Downloads 1101093 The Impact of Breast Cancer Diagnosis on Omani Women
Authors: H. Al-Awaisi, M. H. Al-Azri, S. Al-Rasbi, M. Al-Moundhri
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Breast cancer is the most common cancer among females worldwide. It is also the most common cancer among females in Oman with 100 new breast cancer cases diagnosed every year. It has been found that breast cancer have a devastating effect on women’s life. Women diagnosed with breast cancer might develop negative attitudes towards the illness and their bodies. They might also suffer from psychological ailments such as depression. Despite the evidence on the impact of breast cancer diagnosis on women, there was no study found to explore the impact of breast cancer diagnosis among women in Oman. A phenomenological qualitative study was conducted to explore the impact of breast cancer diagnosis on Omani women. Data was collected through semi-structured individual interviews with 11 Omani women diagnosed with breast cancer. Interviews were transcribed verbatim and data were analyzed thematically. From the data, there are four main themes identified in relation to the impact of cancer diagnosis on Omani women. These are 'shock and disbelieve', 'a death sentence', “uncertain future” and “social stigma”. At the time of interviews, all participants had advanced breast cancer with some participants having metastatic disease. The impact of the word “cancer” had a profound and catastrophic effect on the women and their close relatives. In conclusion, breast cancer diagnosis was shocking and mainly perceived as a death sentence by Omani women with uncertain future and social stigma. Regardless of age, maternal status and education level, it is evident that Omani women participated in this study lacked awareness about breast cancer diagnosis, treatment and prognosis.Keywords: breast cancer, coping, diagnosis, Oman, women
Procedia PDF Downloads 5061092 The Effect of Aromatherapy Candle as Insecticide from Citrus Extract of Lemongrass (Cymbopogon) to Increase Ae. aegypti Mortality
Authors: Nurul Hidayah, Farida Rahmatika, Fathimah Azzahra, Nesty Herennadia
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Aromatherapy candles are one of the insecticide media that have not been much researched. The active ingredient that is proven to have the effect of insecticide is a citrus extract from lemongrass oil (Cymbopogon). Aromatherapy candles are added by citrus compounds to be insecticidal for Ae. aegypti mosquito that was related to the infectious disease such as dengue fever. This research aims to find out if aromatherapy candles of citrus compounds have an insecticidal effect on Ae. aegypti mosquito. We used true experimental design including posttest only with control group design. The samples are 20 male and female Ae. aegypti mosquitos with aged 1-7 days belong to the inclusion criteria. The subjects were divided into 6 groups, consisting of 1 negative control group and 5 treatment groups with variation concentration are 1%; 2%; 3%; 4%; 5%. Each group will be treated for 2 hours and observed death after 24 hours. Replication in each group is done 4 times. The results were then tested statistically using Kruskal-Wallis and probit test. Mean of death in negative control group, and treatment group 1%; 2%; 3%; 4%; 5% respectively 0; 1; 0.25; 0; 1 and 1 mosquito. The Kruskal-Wallis test in the study group found no significant difference (p = 0.178). The probit analysis showed that LC50 and LC90 were 20.069% and 31.557%. The aromatherapy candle of a citrus compound has an insecticidal effect on the Ae aegypti mosquito.Keywords: Ae. aegypti insecticide, aromatherapy candle, citrus compound, lemongrass oil (Cymbopogon)
Procedia PDF Downloads 1901091 The Toxic Effects of Kynurenine Metabolites on SH-SY5Y Neuroblastoma Cells
Authors: Susan Hall, Gary D. Grant, Catherine McDermott, Devinder Arora
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Introduction /Aim: The kynurenine pathway is thought to play an important role in the pathophysiology of numerous neurodegenerative diseases including depression, Alzheimer’s disease, and Parkinson’s disease. Numerous neuroactive compounds, including the neurotoxic 3-hydroxyanthranilic acid, 3-hydroxykynurenine and quinolinic acid and the neuroprotective kynurenic acid and picolinic acid, are produced through the metabolism of kynurenine and are thought to be the causative agents responsible for neurodegeneration. The toxicity of 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid has been widely evaluated and demonstrated in primary cell cultures but to date only 3-hydroxykynurenine and 3-hydroxyanthranilic acid have been shown to cause toxicity in immortal tumour cells. The aim of this study was to evaluate the toxicity of kynurenine metabolites, both individually and in combination, on SH-SY5Y neuroblastoma cells after 24 and 72 h exposure in order to explore a cost-effective model to study their neurotoxic effects and potential protective agents. Methods: SH-SY5Y neuroblastoma cells were exposed to various concentrations of the neuroactive kynurenine metabolites, both individually and in combination, for 24 and 72 h, and viability was subsequently evaluated using the Resazurin (Alamar blue) proliferation assay. Furthermore, the effects of these compounds, alone and in combination, on specific death pathways including apoptosis, necrosis and free radical production was evaluated using various assays. Results: Consistent with literature, toxicity was shown with short-term 24-hour treatments at 1000 μM concentrations for both 3-hydroxykynurenine and 3-hydroxyanthranilic acid. Combinations of kynurenine metabolites showed modest toxicity towards SH-SY5Y neuroblastoma cells in a concentration-dependent manner. Specific cell death pathways, including apoptosis, necrosis and free radical production were shown to be increased after both 24 and 72 h exposure of SH-SY5Y neuroblastoma cells to 3-hydroxykynurenine and 3-hydroxyanthranilic acid and various combinations of neurotoxic kynurenine metabolites. Conclusion: It is well documented that neurotoxic kynurenine metabolites show toxicity towards primary human neurons in the nanomolar to low micromolar concentration range. Results show that the concentrations required to show significant cell death are in the range of 1000 µM for 3-hydroxykynurenine and 3-hydroxyanthranilic acid and toxicity of quinolinic acid towards SH-SY5Y was unable to be shown. This differs significantly from toxicities observed in primary human neurons. Combinations of the neurotoxic metabolites were shown to have modest toxicity towards these cells with increased toxicity and activation of cell death pathways observed after 72 h exposure. This study suggests that the 24 h model is unsuitable for use in neurotoxicity studies, however, the 72 h model better represents the observations of the studies using primary human neurons and may provide some benefit in providing a cost-effective model to assess possible protective agents against kynurenine metabolite toxicities.Keywords: kynurenine metabolites, neurotoxicity, quinolinic acid, SH-SY5Y neuroblastoma
Procedia PDF Downloads 4171090 Comparing the Quality of Electronic and Paper Do-Not-Resucscitate Forms in Hosptail
Authors: Anmol Patel
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Cardiopulmonary resuscitation is medical intervention which should be considered for all inpatients; with a patient centred approach, open communication and accurate documentation of clinical decisions. National enquiries have shown that in a significant number of cases CPR was attempted when it was considered inappropriate. In these circumstances attempting to prevent a natural death and subjecting a patient to trauma at the end of life would deprive them of a dignified death. Anticipatory “do not attempt CPR (DNACPR)” decisions aim to prevent this for those considered appropriate. As a legal document, these forms are required to be completed accurately and thoroughly. The aim of this study was to evaluate the difference in quality of DNACPR forms completed using electronic versus paper formats. A retrospective review of DNACPR forms and related documentation was completed in two District General Hospitals in South-East England, one of which uses electronic forms, while the other uses paper red forms. 50 completed forms from each hospital were analysed to assess for legibility, and quality of completion of all subsections of the form, including communications with family, relatives and the Multidisciplinary team. The hospital using paper forms showed a 40-44% rate of completion of sections relating to communication with patients and family, compared to 70% with the hospital using electronic forms. Similar trends were observed with other sections of the form. Conclusion: This study suggests that the implementation of electronic DNACPR forms significantly improves clinical practice and promotes better open communication with patients, family and the MDT.Keywords: DNACPR, resuscitation, DNAR, patient communication
Procedia PDF Downloads 781089 “Congratulations, I Am Sorry for Your Loss”. A Qualitative Study to Help Healthcare Providers Search for Words When a Baby Dies
Authors: Liesbeth Van Kelst, Jozefiene Jansens
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Background: All care providers within mother and child care are confronted, at some point in their career, with the care for parents who (will) lose or have lost a baby. Obtaining the correct attitude and communicating well during these difficult moments are aspects that many healthcare provides continue to struggle with. Parents still encounter well-intentioned but inappropriate communication from healthcare providers. Aim: To study how communication, both verbal and non-verbal, around the death of a baby during pregnancy, birth, or in the first ten days postnatal was experienced by parents and healthcare providers. Methods: A qualitative study using grounded theory principles was conducted. Data were collected through 22 individual face-to-face in-depth interviews with parents who had lost a baby (n = 12) and intramural caregivers, such as midwives, nurses, gynecologists and neonatologists (n=10). In the first phase, data were analyzed within each group separately (parents and healthcare providers) and in the second phase, findings from both groups were compared and analyzed according to meta-synthesis principles. Results: The themes that emerged from the data demonstrated congruent experiences between the group of the parents and the health care providers. Both strengths and weaknesses in current care were named and suggestions for appropriate communication were formulated. Conclusion: Since most health care providers only occasionally care for parents with a deceased baby, a communication tool can optimize communication between healthcare professionals and parents who lose a baby. This is very important as the words which are said at this difficult period last a lifetime in the heads of parents.Keywords: communication, death, perinatal loss, stillbirth
Procedia PDF Downloads 2251088 Assessment of Incidence and Predictors of Mortality Among HIV Positive Children on Art in Public Hospitals of Harer Town Who Were Enrolled From 2011 to 2021
Authors: Getahun Nigusie Demise
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Background; antiretroviral treatment reduce HIV-related morbidity, and prolonged survival of patients however, there is lack of up-to-date information concerning the treatment long term effect on the survival of HIV positive children especially in the study area. Objective: The aim of this study is to assess the incidence and predictors of mortality among HIV positive children on antiretroviral therapy (ART) in public hospitals of Harer town who were enrolled from 2011 to 2021. Methodology: Institution based retrospective cohort study was conducted among 429 HIV positive children enrolled in ART clinic from January 1st 2011 to December30th 2021. Data were collected from medical cards by using a data extraction form, Descriptive analyses were used to Summarized the results, and life table was used to estimate survival probability at specific point of time after introduction of ART. Kaplan Meier survival curve together with log rank test was used to compare survival between different categories of covariates, and Multivariate Cox-proportional hazard regression model was used to estimate adjusted Hazard rate. Variables with p-values ≤0.25 in bivariable analysis were candidates to the multivariable analysis. Finally, variables with p-values < 0.05 were considered as significant variables. Results: The study participants had followed for a total of 2549.6 child-years (30596 child months) with an overall mortality rate of 1.5 (95% CI: 1.1, 2.04) per 100 child-years. Their median survival time was 112 months (95% CI: 101–117). There were 38 children with unknown outcome, 39 deaths, and 55 children transfer out to different facility. The overall survival at 6, 12, 24, 48 months were 98%, 96%, 95%, 94% respectively. being in WHO clinical Stage four (AHR=4.55, 95% CI:1.36, 15.24), having anemia(AHR=2.56, 95% CI:1.11, 5.93), baseline low absolute CD4 count (AHR=2.95, 95% CI: 1.22, 7.12), stunting (AHR=4.1, 95% CI: 1.11, 15.42), wasting (AHR=4.93, 95% CI: 1.31, 18.76), poor adherence to treatment (AHR=3.37, 95% CI: 1.25, 9.11), having TB infection at enrollment (AHR=3.26, 95% CI: 1.25, 8.49),and no history of change their regimen(AHR=7.1, 95% CI: 2.74, 18.24), were independent predictors of death. Conclusion: more than half of death occurs within 2 years. Prevalent tuberculosis, anemia, wasting, and stunting nutritional status, socioeconomic factors, and baseline opportunistic infection were independent predictors of death. Increasing early screening and managing those predictors are required.Keywords: human immunodeficiency virus-positive children, anti-retroviral therapy, survival, treatment, Ethiopia
Procedia PDF Downloads 491087 Profile of Programmed Death Ligand-1 (PD-L1) Expression and PD-L1 Gene Amplification in Indonesian Colorectal Cancer Patients
Authors: Akterono Budiyati, Gita Kusumo, Teguh Putra, Fritzie Rexana, Antonius Kurniawan, Aru Sudoyo, Ahmad Utomo, Andi Utama
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The presence of the programmed death ligand-1 (PD-L1) has been used in multiple clinical trials and approved as biomarker for selecting patients more likely to respond to immune checkpoint inhibitors. However, the expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence. Positive PD-L1 within tumors may result from two mechanisms, induced PD-L1 expression by T-cell presence or genetic mechanism that lead to constitutive PD-L1 expression. Amplification of PD-L1 genes was found as one of genetic mechanism which causes an increase in PD-L1 expression. In case of colorectal cancer (CRC), targeting immune checkpoint inhibitor has been recommended for patients with microsatellite instable (MSI). Although the correlation between PD-L1 expression and MSI status has been widely studied, so far the precise mechanism of PD-L1 gene activation in CRC patients, particularly in MSI population have yet to be clarified. In this present study we have profiled 61 archived formalin fixed paraffin embedded CRC specimens of patients from Medistra Hospital, Jakarta admitted in 2010 - 2016. Immunohistochemistry was performed to measure expression of PD-L1 in tumor cells as well as MSI status using antibodies against PD-L1 and MMR (MLH1, MSH2, PMS2 and MSH6), respectively. PD-L1 expression was measured on tumor cells with cut off of 1% whereas loss of nuclear MMR protein expressions in tumor cells but not in normal or stromal cells indicated presence of MSI. Subset of PD-L1 positive patients was then assessed for copy number variations (CNVs) using single Tube TaqMan Copy Number Assays Gene CD247PD-L1. We also observed KRAS mutation to profile possible genetic mechanism leading to the presence or absence of PD-L1 expression. Analysis of 61 CRC patients revealed 15 patients (24%) expressed PD-L1 on their tumor cell membranes. The prevalence of surface membrane PD-L1 was significantly higher in patients with MSI (87%; 7/8) compared to patients with microsatellite stable (MSS) (15%; 8/53) (P=0.001). Although amplification of PD-L1 gene was not found among PD-L1 positive patients, low-level amplification of PD-L1 gene was commonly observed in MSS patients (75%; 6/8) than in MSI patients (43%; 3/7). Additionally, we found 26% of CRC patients harbored KRAS mutations (16/61), so far the distribution of KRAS status did not correlate with PD-L1 expression. Our data suggest genetic mechanism through amplification of PD-L1 seems not to be the mechanism underlying upregulation of PD-L1 expression in CRC patients. However, further studies are warranted to confirm the results.Keywords: colorectal cancer, gene amplification, microsatellite instable, programmed death ligand-1
Procedia PDF Downloads 2221086 Morphological Transformations and Variations in Architectural Language from Tombs to Mausoleums: From Ottoman Empire to the Turkish Republic
Authors: Uğur Tuztaşi, Mehmet Uysal, Yavuz Arat
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The tomb (grave) structures that have influenced the architectural culture from the Seljuk times to the Ottoman throughout Anatolia are members of a continuing building tradition in terms of monumental expression and styles. This building typology which has religious and cultural permeability in view of spatial traces and structural formations follows the entire trajectory of the respect to death and the deceased from the Seljuks to the Ottomans and also the changing burial traditions epitomised in the form of mausoleums in the Turkish Republic. Although the cultural layers have the same contents with regards to the cult of monument this architectural tradition which evolved from tombs to mausoleums changed in both typological formation and structural size. In short, the tomb tradition with unique examples of architectural functions and typological formations has been encountered from 13th century onwards and continued during the Ottoman period with changes in form and has transformed to mausoleums during the 20th century. This study analyses the process of transformation from complex structures to simple structures and then to monumental graves in terms of architectural expression. Moreover, the study interrogates the architectural language of Anatolian Seljuk tombs to Ottoman tombs and monumental graves built during the republican period in terms of spatial and structural contexts.Keywords: death and space in Turks, monumental graves, language of architectural style, morphological transformations
Procedia PDF Downloads 3561085 Clinical Impact of Delirium and Antipsychotic Therapy: 10-Year Experience from a Referral Coronary Care Unit
Authors: Niyada Naksuk, Thoetchai Peeraphatdit, Vitaly Herasevich, Peter A. Brady, Suraj Kapa, Samuel J. Asirvatham
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Introduction: Little is known about the safety of antipsychotic therapy for delirium in the coronary care unit (CCU). Our aim was to examine the effect of delirium and antipsychotic therapy among CCU patients. Methods: Pre-study Confusion Assessment Method-Intensive Care Unit (CAM–ICU) criteria were implemented in screening consecutive patients admitted to Mayo Clinic, Rochester, the USA from 2004 through 2013. Death status was prospectively ascertained. Results: Of 11,079 study patients, the incidence of delirium was 8.3% (n=925). Delirium was associated with an increased risk of in-hospital mortality (adjusted OR 1.49; 95% CI, 1.08-2.08; P=.02) and one-year mortality among patients who survived from CCU admission (adjusted HR 1.46; 95% CI, 1.12-1.87; P=.005). A total of 792 doses of haloperidol (5 IQR [3-10] mg/day) or quetiapine (25 IQR [13-50] mg/day) were given to 244 patients with delirium. The clinical characteristics of patients with delirium who did and did not receive antipsychotic therapy were not different (baseline corrected QT [QTc] interval 460±61 ms vs. 457±58 ms, respectively; P = 0.57). In comparison to baseline, mean QTc intervals after the first and third doses of the antipsychotics were not significantly prolonged in haloperidol (448±56, 458±57, and 450±50 ms, respectively) or quetiapine groups (459±54, 467±68, and 462±46 ms, respectively) (P > 0.05 for all). Additionally, in-hospital mortality (adjusted OR 0.67; 95% CI, 0.42-1.04; P=.07), ventricular arrhythmia (adjusted OR 0.87; 95% CI, 0.17-3.62; P=.85) and one-year mortality among the hospital survivors (adjusted HR 0.86; 95% CI 0.62-1.17; P = 0.34) were not different in patients with delirium irrespective of whether or not they received antipsychotics. Conclusions: In patients admitted to the CCU, delirium was associated with an increase in both in-hospital and one-year mortality. Low doses of haloperidol and quetiapine appeared to be safe, without an increase in risk of sudden cardiac death, in-hospital mortality, or one-year mortality in carefully monitored patients.Keywords: arrhythmias, haloperidol, mortality, qtc interval, quetiapine
Procedia PDF Downloads 3721084 Temperature-Dependent Post-Mortem Changes in Human Cardiac Troponin-T (cTnT): An Approach in Determining Postmortem Interval
Authors: Sachil Kumar, Anoop Kumar Verma, Wahid Ali, Uma Shankar Singh
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Globally approximately 55.3 million people die each year. In the India there were 95 lakh annual deaths in 2013. The number of deaths resulted from homicides, suicides and unintentional injuries in the same period was about 5.7 lakh. The ever-increasing crime rate necessitated the development of methods for determining time since death. An erroneous time of death window can lead investigators down the wrong path or possibly focus a case on an innocent suspect. In this regard a research was carried out by analyzing the temperature dependent degradation of a Cardiac Troponin-T protein (cTnT) in the myocardium postmortem as a marker for time since death. Cardiac tissue samples were collected from (n=6) medico-legal autopsies, (in the Department of Forensic Medicine and Toxicology, King George’s Medical University, Lucknow India) after informed consent from the relatives and studied post-mortem degradation by incubation of the cardiac tissue at room temperature (20±2 OC), 12 0C, 25 0C and 37 0C for different time periods ((~5, 26, 50, 84, 132, 157, 180, 205, and 230 hours). The cases included were the subjects of road traffic accidents (RTA) without any prior history of disease who died in the hospital and their exact time of death was known. The analysis involved extraction of the protein, separation by denaturing gel electrophoresis (SDS-PAGE) and visualization by Western blot using cTnT specific monoclonal antibodies. The area of the bands within a lane was quantified by scanning and digitizing the image using Gel Doc. The data shows a distinct temporal profile corresponding to the degradation of cTnT by proteases found in cardiac muscle. The disappearance of intact cTnT and the appearance of lower molecular weight bands are easily observed. Western blot data clearly showed the intact protein at 42 kDa, two major (27 kDa, 10kDa) fragments, two additional minor fragments (32 kDa) and formation of low molecular weight fragments as time increases. At 12 0C the intensity of band (intact cTnT) decreased steadily as compared to RT, 25 0C and 37 0C. Overall, both PMI and temperature had a statistically significant effect where the greatest amount of protein breakdown was observed within the first 38 h and at the highest temperature, 37 0C. The combination of high temperature (37 0C) and long Postmortem interval (105.15 hrs) had the most drastic effect on the breakdown of cTnT. If the percent intact cTnT is calculated from the total area integrated within a Western blot lane, then the percent intact cTnT shows a pseudo-first order relationship when plotted against the log of the time postmortem. These plots show a good coefficient of correlation of r = 0.95 (p=0.003) for the regression of the human heart at different temperature conditions. The data presented demonstrates that this technique can provide an extended time range during which Postmortem interval can be more accurately estimated.Keywords: degradation, postmortem interval, proteolysis, temperature, troponin
Procedia PDF Downloads 3861083 Evaluation of Transfusion-Related Acute Lung Injury
Authors: Hossein Barri Ghazani
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Transfusion-related acute lung injury is the main reason of transfusion-related death, and it’s assigned to white blood cell reactive antibodies present in the blood product (anti-HLA class I and class II or anti granulocyte antibodies). TRALI may occur in the COVID-19 patients who are treated by convalescent plasma. The rate of TRALI’s reactions is the same in both males and females and can happen in all age groups. TRALI’s occurrence is higher for people who receive plasma from female donors because the parous female donors have multiple HLA antibodies in their plasma. Patients with chronic liver disease have an augmented risk of transfusion-related acute lung injuries from plasma containing blood products like FFP and PRP. The condition of TRALI suddenly starts with a non‐cardiogenic pulmonary Edema, often accompanied by marked systemic hypovolemic and hypotension. The conditions occur during or within a few hours of transfusion. Chest X-ray shows a nodular penetration or bats’ wing pattern of Edema which can be seen in acute respiratory distress syndrome as well. TRALI can occur with any type of blood products and can occur with as little as one unit. The blood donor center should be informed of the suspected TRALI reactions when the symptoms of TRALI are observed. After a review of the clinical data, the donors must be screened for granulocyte and HLA antibodies. The diagnosis and management of TRALI is not simple and is best done with a professional team and a specialty skilled nurse experienced with the upkeep of these patients.Keywords: TRALI, transfusion-related death, anti-granulocyte antibodies, anti-HLA antibodies, COVID-19
Procedia PDF Downloads 1631082 Long Non-Coding RNAs Mediated Regulation of Diabetes in Humanized Mouse
Authors: Md. M. Hossain, Regan Roat, Jenica Christopherson, Colette Free, Zhiguang Guo
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Long noncoding RNA (lncRNA) mediated post-transcriptional gene regulation, and their epigenetic landscapes have been shown to be involved in many human diseases. However, their regulation in diabetes through governing islet’s β-cell function and survival needs to be elucidated. Due to the technical and ethical constraints, it is difficult to study their role in β-cell function and survival in human under in vivo condition. In this study, humanized mice have been developed through transplanting human pancreatic islet under the kidney capsule of NOD.SCID mice and induced β-cell death leading to diabetes condition to study lncRNA mediated regulation. For this, human islets from 3 donors (3000 IEQ, purity > 80%) were transplanted under the kidney capsule of STZ induced diabetic NOD.scid mice. After at least 2 weeks of normoglycecemia, lymphocytes from diabetic NOD mice were adoptively transferred and islet grafts were collected once blood glucose reached > 200 mg/dl. RNA from human donor islets, islet grafts from humanized mice with either adoptive lymphocyte transfer (ALT) or PBS control (CTL) were ribodepleted; barcoded fragment libraries were constructed and sequenced on the Ion Proton sequencer. lncRNA expression in isolated human islets, islet grafts from humanized mice with and without induced β-cell death and their regulation in human islets function in vitro under glucose challenge, cytokine mediated inflammation and induced apoptotic condition were investigated. Out of 3155 detected lncRNAs, 299 that highly expressed in islets were found to be significantly downregulated and 224 upregulated in ALT compared to CTL. Most of these are found to be collocated within 5 kb upstream and 1 kb downstream of 788 up- and 624 down-regulated mRNAs. Genomic Regions Enrichment of Annotations Analysis revealed deregulated and collocated genes are related to pancreas endocrine development; insulin synthesis, processing, and secretion; pancreatitis and diabetes. Many of them, that found to be located within enhancer domains for islet specific gene activity, are associated to the deregulation of known islet/βcell specific transcription factors and genes that are important for β-cell differentiation, identity, and function. RNA sequencing analysis revealed aberrant lncRNA expression which is associated to the deregulated mRNAs in β-cell function as well as in molecular pathways related to diabetes. A distinct set of candidate lncRNA isoforms were identified as highly enriched and specific to human islets, which are deregulated in human islets from donors with different BMIs and with type 2 diabetes. These RNAs show an interesting regulation in cultured human islets under glucose stimulation and with induced β-cell death by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the media of islets cultured with cytokines. Results of this study suggest that the islet specific lncRNAs are deregulated in human islet with β-cell death, hence important in diabetes. These lncRNAs might be important for human β-cell function and survival thus could be used as biomarkers and novel therapeutic targets for diabetes.Keywords: β-cell, humanized mouse, pancreatic islet, LncRNAs
Procedia PDF Downloads 1641081 The Political Haunting of “Martyrdom” in the Palestinian Context
Authors: Mai Awad
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This paper aims to focus on the phenomenon of martyrdom—particularly its performative aspect—and how social and popular cultural representations address the multiple meanings of the loaded image of a Palestinian martyr. This focus will help us to explore the possible reasons that might push Palestinians to consider pursuing “martyrdom” or suicide operations. Tracing what happened in the past and what is currently happening (that is, haunting) will aid in theorizing how the act/practice of “martyrdom” is produced. It is believed that there are social and political forces, particularly in a colonial society like Palestine, that influence the subject and its experience. But what is unique about this paper is its attempt to disclose the invisible, hidden narratives and complexities of Palestinian life that we do not see. By giving “martyrs” a chance to speak and express their own narratives—since “martyrs” usually leave written letters for their families, which are published after their death—this study must broaden the whole picture and discuss what is missing. The analytic method to be used: For the methodology, the paper recruits discourse analysis as a method for tracing the emergence, circulation, and productivity of the martyrdom discourse across a range of social practices in Palestinians’ everyday life after the Nakba. The paper analyzes the letters that “martyrs” left to their families, relatives, and the Palestinian community after their death. By letting “martyrs” speak for themselves and hearing their unique discourses, the research would suggest that more explanation is needed to describe the “martyr” identity. Hence, it is not possible to study the “martyr” identity in Palestine without understanding the colonial context that governs it and shapes their subjective experience.Keywords: martyrdom, palestine, haunting, nakba 1948
Procedia PDF Downloads 681080 Injury Characteristics and Outcome of Road Traffic Accident among Victims at Adult Emergency Department of Tikur Anbesa Specialized Hospital, Addis Ababa, Ethiopia
Authors: Mohammed Seid, Aklilu Azazh, Fikre Enquselassie, Engida Yisma
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Background: Road traffic injuries are the eighth leading cause of death globally, and the leading cause of death for young people. More than a million people die each year on the world’s roads, and the risk of dying as a result of a road traffic injury is highest in the Africa. Methods: A prospective hospital-based study was undertaken to assess injury characteristics and outcome of road traffic accident among victims at Adult Emergency Department of Tikur Anbesa specialized hospital, Addis Ababa, Ethiopia. A structured pre-tested questionnaire was used to gather the required data. The collected data were analyzed using SPSS version 16.0. Results: A total of 230 road traffic accident victims were studied. The majority of the study subjects were men 165 (71.7%) and the male/female ratio was 2.6:1. The victims’ ages ranged from 14 to 80 years with the mean and standard deviations of 32.15 and ± 14.38 years respectively. Daily laborers (95 (41.3%)) and students (28 (12.2%)) were the majority of road traffic accident victims. Long-distance travelling Minibus (16.5%) was responsible for the majority of road traffic crash followed by followed by Taxi (14.8%) and pedestrians (62.6%) accounted for the majority of road traffic accident. Head (50.4%) and musculoskeletal (extremities) (47.0%) were the most common body region injured. Fractures (78.0%) and open wounds (56.5%) were the most common type of injuries sustained. Treatment of fracture was the most common procedure performed in 57.7 % of the victims. The overall length of hospital stay (LOS) ranged from 1 day to 61 days with mean (± standard deviation) of 7.12 ± 10.5 days and the mortality rate was 7.4 %. A significant higher proportion of victims aged 14-55 years were had less likelihood of death compared to those victims aged more than 55 years of age [Adjusted OR = 0.1 (95% CI: 0.01, 0.82)]. Conclusions: This study showed diverse injury characteristics and high morbidity and mortality among the victims attending Adult Emergency Department of Tikur Anbesa specialized hospital, Addis Ababa, Ethiopia. The findings reflect that road traffic accident is a major public health problem. Urgent road traffic accident preventive measures and prompt treatment of the victims are warranted in order to reduce morbidity and mortality among the victims.Keywords: road traffic accident, injury characteristics, outcome, Tikur Anbesa specialized hospital, Addis Ababa, Ethiopia
Procedia PDF Downloads 3841079 Medical Complications in Diabetic Recipients after Kidney Transplantation
Authors: Hakan Duger, Alparslan Ersoy, Canan Ersoy
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Diabetes mellitus is the most common etiology of end-stage renal disease (ESRD). Also, diabetic nephropathy is the etiology of ESRD in approximately 23% of kidney transplant recipients. A successful kidney transplant improves the quality of life and reduces the mortality risk for most patients. However, patients require close follow-up after transplantation due to medical complications. Diabetes mellitus can affect patient morbidity and mortality due to possible effects of immunosuppressive therapy on glucose metabolism. We compared the frequency of medical complications and the outcomes in diabetic and non-diabetic kidney transplant recipients. Materials and Methods: This retrospective study conducted in 498 patients who underwent kidney transplant surgery at our center in 10-year periods. The patients were divided into two groups: diabetics (46 ± 10 year, 26 males, 16 females) and non-diabetics (39 ± 12 year, 259 males, 197 females). The medical complications, graft functions, causes of graft loss and death were obtained from medical records. Results: There was no significant difference between recipient age, duration of dialysis, body mass index, gender, donor type, donor age, dialysis type, histories of HBV, HCV and coronary artery disease between two groups. The history of hypertension in diabetics was higher (69% vs. 36%, p < 0.001). The ratios of hypertension (50.1% vs. 57.1%), pneumonia (21.9% vs. 20%), urinary infection (16.9% vs. 20%), transaminase elevation (11.5% vs. 20%), hyperpotasemia (14.7% vs. 17.1%), hyponatremia (9.7% vs. 20%), hypotension (7.1% vs. 7.9%), hypocalcemia (1.4% vs. 0%), thrombocytopenia (8.6% vs. 8.6%), hypoglycemia (0.7% vs. 0%) and neutropenia (1.8% vs. 0%) were comparable in non-diabetic and diabetic groups, respectively. The frequency of hyperglycaemia in diabetics was higher (8.6% vs. 54.3%, p < 0.001). After transplantation, primary non-function (3.4% vs. 2.6%), delayed graft function (25.1% vs. 34.2%) and acute rejection (7.3% vs. 10.5%) ratios of in non-diabetic and diabetic groups were similar, respectively. Hospitalization durations in non-diabetics and diabetics were 22.5 ± 17.5 and 18.7 ± 13 day (p=0.094). Mean serum creatinine levels in non-diabetics and diabetics were 1.54 ± 0.74 and 1.52 ± 0.62 mg/dL at 6th month. Forty patients had graft loss. The ratios of graft loss and death in non-diabetic and diabetic groups were 8.2% vs. 7.1% and 7.1% vs. 2.6% (p > 0.05). There was no significant relationship between graft and patient survivals with the development of medical complication. Conclusion: As a result, medical complications are common in the early period. Hyperglycaemia was frequently seen following transplantation due to the effects of immunosuppressant regimens. However, the frequency of other medical complications in diabetic patients did not differ from non-diabetic one. The most important cause of death is still infections. The development of medical complications during the first 6 months did not significantly affect transplant outcomes.Keywords: kidney transplantation, diabetes mellitus, complication, graft function
Procedia PDF Downloads 3301078 Elderly Care for Bereaved Parents Following the Death of an Only Child in Mainland China
Authors: Chao Fang
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Due to the Confucian emphasis on filial piety and an undeveloped social welfare system in mainland China, adult children are both socially and legally obliged to care for their parents, including financial assistance and physical care as well as emotional and social support. Thus a family-centred care pattern for elderly people has been firmly established in China. However, because of the nationwide ‘One Child Policy’, over one million parents are excluded from such care because of the death of their only child and, therefore, their primary caregiver. Without their child’s support, these parents must manage the day to day challenges of growing old alone, with little support from society. By overturning established expectations of a ‘good’ elderly life, the loss of an only child may be accompanied by social and self-stigmatization, pushing these bereaved parents to the margin of society and threatening their economic, physical, emotional and social well-being. More importantly, since the One Child Policy was implemented from the late 1970s and early 1980s, the first generation of bereaved or ‘Shidu’ parents has reached an age at which those parents need elderly care. However, their predicament has been largely ignored. This paper reports on a qualitative interview study that found elderly care to be the main concern for Shidu parents’ everyday life. The paper identifies and discusses the concerns these bereaved parents raised about the prospect of having nowhere to turn at a time of increased need for financial, physical, social and emotional support in old age. The paper also identifies how Shidu parents have been coming together in grief and negotiate to make their predicament known to the government and wider society and to re-define their elderly life by rebuilding a sense of ‘family’.Keywords: culture, bereavement, China, elderly care
Procedia PDF Downloads 2731077 Determining of the Performance of Data Mining Algorithm Determining the Influential Factors and Prediction of Ischemic Stroke: A Comparative Study in the Southeast of Iran
Authors: Y. Mehdipour, S. Ebrahimi, A. Jahanpour, F. Seyedzaei, B. Sabayan, A. Karimi, H. Amirifard
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Ischemic stroke is one of the common reasons for disability and mortality. The fourth leading cause of death in the world and the third in some other sources. Only 1/3 of the patients with ischemic stroke fully recover, 1/3 of them end in permanent disability and 1/3 face death. Thus, the use of predictive models to predict stroke has a vital role in reducing the complications and costs related to this disease. Thus, the aim of this study was to specify the effective factors and predict ischemic stroke with the help of DM methods. The present study was a descriptive-analytic study. The population was 213 cases from among patients referring to Ali ibn Abi Talib (AS) Hospital in Zahedan. Data collection tool was a checklist with the validity and reliability confirmed. This study used DM algorithms of decision tree for modeling. Data analysis was performed using SPSS-19 and SPSS Modeler 14.2. The results of the comparison of algorithms showed that CHAID algorithm with 95.7% accuracy has the best performance. Moreover, based on the model created, factors such as anemia, diabetes mellitus, hyperlipidemia, transient ischemic attacks, coronary artery disease, and atherosclerosis are the most effective factors in stroke. Decision tree algorithms, especially CHAID algorithm, have acceptable precision and predictive ability to determine the factors affecting ischemic stroke. Thus, by creating predictive models through this algorithm, will play a significant role in decreasing the mortality and disability caused by ischemic stroke.Keywords: data mining, ischemic stroke, decision tree, Bayesian network
Procedia PDF Downloads 1741076 Prognosis of Interstitial Lung Disease (ILD) Based on Baseline Pulmonary Function Test (PFT) Results in Omani Adult Patients Diagnosed with ILD In Sultan Qaboos University Hospital
Authors: Manal Al Bahri, Saif Al Mubahisi, Shamsa Al Shahaimi, Asma Al Qasabi, Jamal Al Aghbari
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Introduction: ILD is a common disease worldwide and in Oman. No previous Omani study was published regarding ILD prognosis based on baseline PFT results and other factors. This study aims to determine the severity of ILD by the baseline PFT, correlate between baseline PFT and outcome, and study other factors that influence disease mortality. Method: It is a retrospective cohort study; data was collected from January 2011 to December 2021 from electronic patient records (EPR). Means, Standard Deviations, frequencies, and Chi-square tests were used to examine the different variables in the study. Results: The total population of the study was 146 patients; 87 (59.6%) were females, and 59 (40.4%) were males. The median age was 59 years. Age at diagnosis, CVA, rheumatological disease, and baseline FVC were found to be statistically significant predictors of mortality .59.6% of the patients are diagnosed with IPF. Most of our study patients had mild disease based on baseline FVC. Death was higher with the more severe disease based on FVC. In mild disease (FVC >70%), 26.9% of the patients died. In moderate disease (FVC 50-69%),55.7% of the patients died, and in the severe group (FVC <50 %), 55.1% died. This was statistically significant with a P value of 0. 001. There is no statistically significant difference in the overall survival distribution between the different groups of DLCO. Conclusion: In our study, we found that ILD is more common among females, but death is more common among males. Based on baseline PFT, we can predict mortality by FVC level, as moderate to severe limitation is associated with a lower survival rate. DLCO was not a statistically significant parameter associated with mortality.Keywords: PFT, ILD, FVC, DLCO, mortality
Procedia PDF Downloads 321075 Formulation and Test of a Model to explain the Complexity of Road Accident Events in South Africa
Authors: Dimakatso Machetele, Kowiyou Yessoufou
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Whilst several studies indicated that road accident events might be more complex than thought, we have a limited scientific understanding of this complexity in South Africa. The present project proposes and tests a more comprehensive metamodel that integrates multiple causality relationships among variables previously linked to road accidents. This was done by fitting a structural equation model (SEM) to the data collected from various sources. The study also fitted the GARCH Model (Generalized Auto-Regressive Conditional Heteroskedasticity) to predict the future of road accidents in the country. The analysis shows that the number of road accidents has been increasing since 1935. The road fatality rate follows a polynomial shape following the equation: y = -0.0114x²+1.2378x-2.2627 (R²=0.76) with y = death rate and x = year. This trend results in an average death rate of 23.14 deaths per 100,000 people. Furthermore, the analysis shows that the number of crashes could be significantly explained by the total number of vehicles (P < 0.001), number of registered vehicles (P < 0.001), number of unregistered vehicles (P = 0.003) and the population of the country (P < 0.001). As opposed to expectation, the number of driver licenses issued and total distance traveled by vehicles do not correlate significantly with the number of crashes (P > 0.05). Furthermore, the analysis reveals that the number of casualties could be linked significantly to the number of registered vehicles (P < 0.001) and total distance traveled by vehicles (P = 0.03). As for the number of fatal crashes, the analysis reveals that the total number of vehicles (P < 0.001), number of registered (P < 0.001) and unregistered vehicles (P < 0.001), the population of the country (P < 0.001) and the total distance traveled by vehicles (P < 0.001) correlate significantly with the number of fatal crashes. However, the number of casualties and again the number of driver licenses do not seem to determine the number of fatal crashes (P > 0.05). Finally, the number of crashes is predicted to be roughly constant overtime at 617,253 accidents for the next 10 years, with the worse scenario suggesting that this number may reach 1 896 667. The number of casualties was also predicted to be roughly constant at 93 531 overtime, although this number may reach 661 531 in the worst-case scenario. However, although the number of fatal crashes may decrease over time, it is forecasted to reach 11 241 fatal crashes within the next 10 years, with the worse scenario estimated at 19 034 within the same period. Finally, the number of fatalities is also predicted to be roughly constant at 14 739 but may also reach 172 784 in the worse scenario. Overall, the present study reveals the complexity of road accidents and allows us to propose several recommendations aimed to reduce the trend of road accidents, casualties, fatal crashes, and death in South Africa.Keywords: road accidents, South Africa, statistical modelling, trends
Procedia PDF Downloads 1611074 Inhibitory Effect of P2Y1R Agonist 1-Indolinoalkyl 2-Phenolic Derivative on Prostate Cancer Cell Proliferation via the MAPK Signalling
Authors: Hien Thi Thu Le, Nuno Rafael Candeias, Olli Yli-Harja, Meenakshisundaram Kandhavelu
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Purinergic receptor 1 (P2Y1R) is the potential therapeutic target for inducing prostate cancer (PCa) cell death. Recently, 1-indolinoalkyl 2-phenolic derivative, HIC, was identified as a P2Y1R agonist that increases apoptosis and inhibits cell proliferation of PCa. However, the biological effects of HIC have not been extensively studied at the molecular level. In the present study, we have investigated the anticancer effects of HIC and the molecular mechanisms underlying in PCa cells. Half maximal inhibitory concentration (IC₅₀) of HIC was measured as 15.98 μM and 15.64 μM for DU145 and PC3 cells, respectively. In addition, we found that HIC inhibited cell growth and metastasis of PC3 and DU145 cells colonies, spheroid areas, and migrated cells. RNA seq analysis revealed significant changes of over 3000 genes (p value < 0.05) upon HIC treatment in PC3 and DU145 cells. Genes involved in DNA damage, apoptosis, cell cycle arrest at G1/S phase were modulated by HIC treatment. MAPK and NF-κB protein array revealed the increased expression of ERK1/2, JNK1/2, p53 phosphorylation, and p53 protein. ERK1/2 and JNK1/2 activations are known to increase the stabilization of p53, a tumor suppressor protein, which is required to arrest the cell cycle at G1/S phase and cause cell death of PCa cells. Overall, our results suggest that HIC can serve as a multi-dimensional chemotherapeutic agent possessing strong cytotoxic, anti-cancer, and anti-metastasis against PCa growth.Keywords: prostate cancer, P2Y1 receptor, apoptosis, metastasis
Procedia PDF Downloads 1331073 Framing Mahsa Amini and Iran Protest: A Comparative Analysis of Tehran times and the Wall Street Journal
Authors: Nimmy Maria Joseph, Muhammed Hafiludheen
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On September 16, a 22-year-old Iranian woman, Mahsa Amini, died in Tehran after she was arrested by the ‘Morality police’ for an accusation of not wearing a hijab according to the standards laid down by the Iran Government. Suspicions aroused as the incident happened while Mahsa Amini was under the custody of Iran police. People of Iran accused that she was severely beaten up by the police, which led to her death. This initiated an array of women-led protests in Iran, leading to the ignition of massive uproars in the country. The Law Enforcement Command of Iran reported that she collapsed due to a heart attack and not due to police brutality. However, as a result, Iran faced a series of conflicts between the Government of Iran and the civilians, especially women. The research paper presents the framing analysis of online news stories on Mahsa Amini’s death and the resultant protest in Iran. The researcher analysed the online news stories of two popular newspapers, Tehran Times (Iran) and The Wall Street Journal (USA). The focus of the study is to have a comparative analysis of the frames of the news stories used and find out their agenda-setting pattern. It helps to comprehend how the news stories of popular news organisations try to channelise the perception of their audience on social issues. The researcher analysed the news stories considering their frames, valence, polysemy, rhetoric devices, and technical devices.Keywords: mahsa amini, iran protest, framing analysis, valence, rhetoric device, tehran times, the wall street journal
Procedia PDF Downloads 991072 Investigation of Ezetimibe Administration on Cell Survival Markers in Kidney Ischemia
Authors: Zahra Heydari
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Introduction: One of the major clinical issues is acute renal failure, which is caused by ischemia-reperfusion of the kidney and is associated with high mortality. Despite advances in this area, important issues such as tissue necrosis, cell apoptosis, and so on in damaged tissue are suggestive for more researches and study on this subject. Objective: Evaluation of the potential utility of Ezetimibe in reducing injuries and cell death induced by kidney ischemia/ reperfusion through inducing expression changes of different cellular pathways in adult Sprague-Dawley rats. Materials and methods: Forty rats weighing 180-200g were divided into 4 groups. For this purpose, the first right kidneys of the rats were removed during surgery. After 20 days, the left renal artery was closed with a soft clamp and reperfusion was performed. After 24 hours, blood samples were collected and sent to the laboratory with kidneys to measure bax and bcl-2 by Western blotting and histopathological tests. Results: Quantitative damage reviews of Kidney tissue indicates damage Acute and severe tubular lesions were observed in the ischemia group. Also, the amount of injury was significantly reduced in the treatment group. There was also a significant difference between the ischemia and sham groups. In general, the results show that a single dose of 1.2 mg/kg of ezetimibe can reduce the bax/ bcl-2 ratio compared to the ischemia group. In general, the results showed Ezetimibe is effective in reducing cell damage and death due to ischemia/ reperfusion after renal ischemia through changes in the expression of various cellular pathways in rats.Keywords: acute renal failure, renal ischemia-reperfusion injury, ezetimibe, apoptosis
Procedia PDF Downloads 1961071 hsa-miR-1204 and hsa-miR-639 Prominent Role in Tamoxifen's Molecular Mechanisms on the EMT Phenomenon in Breast Cancer Patients
Authors: Mahsa Taghavi
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In the treatment of breast cancer, tamoxifen is a regularly prescribed medication. The effect of tamoxifen on breast cancer patients' EMT pathways was studied. In this study to see if it had any effect on the cancer cells' resistance to tamoxifen and to look for specific miRNAs associated with EMT. In this work, we used continuous and integrated bioinformatics analysis to choose the optimal GEO datasets. Once we had sorted the gene expression profile, we looked at the mechanism of signaling, the ontology of genes, and the protein interaction of each gene. In the end, we used the GEPIA database to confirm the candidate genes. after that, I investigated critical miRNAs related to candidate genes. There were two gene expression profiles that were categorized into two distinct groups. Using the expression profile of genes that were lowered in the EMT pathway, the first group was examined. The second group represented the polar opposite of the first. A total of 253 genes from the first group and 302 genes from the second group were found to be common. Several genes in the first category were linked to cell death, focal adhesion, and cellular aging. Two genes in the second group were linked to cell death, focal adhesion, and cellular aging. distinct cell cycle stages were observed. Finally, proteins such as MYLK, SOCS3, and STAT5B from the first group and BIRC5, PLK1, and RAPGAP1 from the second group were selected as potential candidates linked to tamoxifen's influence on the EMT pathway. hsa-miR-1204 and hsa-miR-639 have a very close relationship with the candidates genes according to the node degrees and betweenness index. With this, the action of tamoxifen on the EMT pathway was better understood. It's important to learn more about how tamoxifen's target genes and proteins work so that we can better understand the drug.Keywords: tamoxifen, breast cancer, bioinformatics analysis, EMT, miRNAs
Procedia PDF Downloads 1291070 Death Due to Ulnar Artery Injury by Glassdoor: A Case Report
Authors: Ashok Kumar Rastogi
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Glass is a material commonly used for Glassdoor, glass bottles, cookware, and containers. It can be harmful, as it is a hard and blunt object. Glass has been associated with severe injury and is a common cause of injuries warranting hospital visits to the emergency department (ED). These injuries can be accidental or intentionally inflicted. Broken glass injuries can be severe, even deadly. If broken glass shards fall out on your arm, it may cause fatal injuries. Case history: A 20-year-old male dead body was found aside the road, police informed, and a video recording ceased during an investigation. In the video recording, the person was in a drunken state (unable to walk and disoriented), wandering in the residential area road. He saw a barber shop, the shop door made of Glass. Suddenly, he hit the Glassdoor with his right hand forcefully. The Glassdoor broke into multiple pieces, and multiple injuries were seen over the right hand. Observations: Multiple small and large lacerations were seen over the right anterior part of the elbow. The main injury looked like an incised wound caused by a hard and sharp object. The main injury was noted as a laceration of size 13 x 06 cm bone deep, placed obliquely over the anteromedial aspect of the right elbow joint, its medial end at medial end of elbow joint while its anterior end was 04 cm below the elbow joint with laceration of underline brachialis muscles and complete transaction of ulnar artery and vein, skin margins looking sharply cut with irregular margins with tiny cuts at the medial lower border of laceration. Injuries were antemortem and fresh in nature, caused by hard and blunt objects but looking like hard and sharp objects. All organs were found pale, and the cause of death was shock and hemorrhage because of ulnar vessel injury. Conclusion: The findings of this case report highlight the potentially lethal consequences of glass injuries, especially those involving Glassdoors. The study underscores the importance of accurate interpretation and identification of wounds caused by Glass, as they may resemble injuries caused by other objects. It emphasizes the challenges faced by autopsy surgeons when determining the cause and manner of death in cases where visual evidence of injury is absent or when the weapon is not recovered. Ultimately, this case report serves as a reminder of the potential dangers posed by Glass and the importance of comprehensive forensic examinations.Keywords: glassdoor, incised, wound, laceration, autopsy
Procedia PDF Downloads 761069 Empathy in the Work of Physiotherapists in Slovakia
Authors: Vladimir Littva, Peter Kutis
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Based on common practice, we know that an empathic approach to a patient is one of the characteristics of a physiotherapist. Although empathy is regarded as an essential condition of the psychotherapeutic relationship, it has taken quite a while for attention to be paid to it in clinical practice. Patients who are experiencing a sense of understanding from health care providers are more willing to cooperate, and treatment within the optimistic attunes a more comfortable framework of care. Age, experience, family, education and the working environment may have an impact on the degree of empathy for paramedics. Within the KEGA project no. 003KU-4-2021, we decided to investigate the level of empathy in the work of physiotherapists in Slovakia. Research sample and Methods: The sample comprised 194 respondents – physiotherapists working on the territory of Slovakia. 112 were men and 82 women. The age of respondents was between 21 and 64 years of age. 133 were married, 51 were single and ten were divorced. 98 were living in the countryside and 96 in towns. Twenty-two grew up without siblings, 95 with one sibling and 77 with two and more siblings. In the survey, we used the Empathy Assessment Questionnaire (EAQ) with 18 questions with four possible answers: strongly disagree, disagree, agree; and strongly agree, which we validated linguistically and psychometrically. All data were statistically processed by SPSS 25. Results: We evaluated the intrinsic reliability of the questionnaire EAQ using Cronbach's Alpha and the coefficient is 0.756 in the whole set. This means that the questionnaire is a quite strong and reliable measurement tool. The mean for individual questions ranged from 2.39 to 3.74 (maximum was 4). In Pearson's correlations, we confirmed the significant differences between the groups regarding sex in 8 questions out of 18, regarding age in 5 questions, regarding family status in 4 questions and regarding siblings in 4 questions out of 18 at the level 5% (p <0.05). Conclusion: The results obtained during the research show the importance of adequate communication with the patient due to his health and well-being. Empathy in the physiotherapists’ profession is very important. It would be worthwhile if the students of physiotherapy would receive a course during their study that would deal exclusively with empathy, empathic approach, burnout, or psycho-emotional hygiene.Keywords: empathy, approach, clinical practice, physiotherapists
Procedia PDF Downloads 186