Search results for: Death Trilogy

Authors: Edison Ramos, John Peter V. Dacanay, Milwida Josefa Villanueva

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Soil-Transmitted Helminth (STH) infections caused by helminths are the most prevalent neglected tropical diseases (NTDs). They are commonly found in warm, humid regions and developing countries, particularly in rural areas with poor hygiene. Occasionally, human hosts exposed to pig manure may harbor Ascaris suum parasites without experiencing any symptoms. To address the significant issue of helminth infections, an effective anthelmintic is necessary. However, the effectiveness of various medications as anthelmintics can be reduced due to mutations. In recent years, there has been a growing interest in using plants as a source of medicine due to their natural origin, accessibility, affordability, and potential lack of complications. Herbal medicine has been advocated as an alternative treatment for helminth infections, especially in underdeveloped countries, considering the numerous adverse effects and drug resistance associated with commercially available anthelmintics. Medicinal plants are considered suitable replacements for current anthelmintics due to their historical usage in treating helminth infections. The objective of this research was to investigate the effects of aqueous extraction of pomegranate peel (Punica granatum L.) as an anthelmintic on female Ascaris suum in vitro. The in vitro assay involved observing the motility of Ascaris suum in different concentrations (25%, 50%, 75%, and 100%) of pomegranate peel aqueous extraction, along with mebendazole as a positive control. The results indicated that as the concentration of the extract increased, the time required to paralyze the worms decreased. At 25% concentration, the average time for paralysis was 362.0 minutes, which decreased to 181.0 minutes at 50% concentration, 122.7 minutes at 75% concentration, and 90.0 minutes at 100% concentration. The time of death for the worms was directly proportional to the concentration of the pomegranate peel extract. Death was observed at an average time of 240.7 minutes at 75% concentration and 147.7 minutes at 100% concentration. The findings suggest that as the concentration of pomegranate peel extract increases, the time required for paralysis and death of Ascaris suum decreases. This indicates a concentration-dependent relationship, where higher concentrations of the extract exhibit greater effectiveness in inducing paralysis and causing the death of the worms. These results emphasize the potential anthelmintic properties of pomegranate peel extract and its ability to effectively combat Ascaris suum infestations. There was no significant difference in the anthelmintic effectiveness between the pomegranate peel extract and Mebendazole. These findings highlight the potential of pomegranate peel extract as an alternative anthelmintic treatment for Ascaris suum infections. The researchers recommend determining the optimal dose and administration route to maximize the effectiveness of pomegranate peel as an anthelmintic therapeutic against Ascaris suum.

Keywords: pomegranate peel, aqueous extract, anthelmintic, in vitro

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Authors: Prama Mukhopadhyay, Rishika Mukhopadhyay

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The twentieth century has seen the world getting divided into three distinct blocks, created by the proponents of the mainstream developmental discourse. India, which has now gained the label of being a ‘developing nation’, stands in between these three groups, as it constantly tries to ‘catch up’ and emulate the developmental standards of the ‘west’. In this endeavour, we find our country trying really hard to blindly replicate the health care infrastructures of the ‘first worlds’, without realizing the needs of evaluating the ground reality. In such a situation, the sudden outbreak of child death in the district of Malda, WB, poses an obvious questions towards the kind of development that our country has been engaging in, ever since its Post Colonial inception. Through this paper we thus try to understand the harsh veracity of the health care facility that exists in rural Bengal, and thereby challenge the conventional notion of ‘health-care’ as is normally discussed in the mainstream developmental discourse. Grounding our research work on detailed ethnography and through the help of questionnaire, interviews and focus group discussions with the local government officials(BDOs), health workers (ICDS, ASHA workers, ANHM and BMOHs) and members of families with experiences of child deaths, we have tried to find out the real and humane factors behind the sudden rise of reported infant deaths in the district, issues which are normally neglected and left out while discussing and evaluating IMR in the mainstream studies on health care and planning in our nation. Therefore the main aim of this paper is to try and look at child death from a ‘wider perspective’, where it is seen from an eye not bounded by the common registers of caste, class and religion. This paper, would thus be an eye opener in some sense, bringing in stories from the rural belt of the country; where the people are regularly torn between the binaries of the developing and shining modernity of ‘India’ which now gets ready to run the last lap and gain the status of becoming a ‘developed nation’ by 2020, and the staggering, dark traditional ‘ Bharat, which lags behind.

Keywords: child mortality, development discourse, health care, tradition and modernity

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Authors: Sopit Tubtimhin, Chaliya Wamaloon, Anchalee Supattagorn

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Background and Significance: Breast cancer is the most frequently diagnosed and leading cause of cancer death among women. This study aims to determine factors potentially predicting recurrence and long-term survival after the first recurrence in surgically treated patients between postmenopausal and younger women. Methods and Analysis: A retrospective cohort study was performed on 498 Thai women with invasive breast cancer, who had undergone mastectomy and been followed-up at Ubon Ratchathani Cancer Hospital, Thailand. We collected based on a systematic chart audit from medical records and pathology reports between January 1, 2002, and December 31, 2011. The last follow-up time point for surviving patients was December 31, 2016. A Cox regression model was used to calculate hazard ratios of recurrence and death. Findings: The median age was 49 (SD ± 9.66) at the time of diagnosis, 47% was post-menopausal women ( ≥ 51years and not experienced any menstrual flow for a minimum of 12 months), and 53 % was younger women ( ˂ 51 years and have menstrual period). Median time from the diagnosis to the last follow-up or death was 10.81 [95% CI = 9.53-12.07] years in younger cases and 8.20 [95% CI = 6.57-9.82] years in postmenopausal cases. The recurrence-free survival (RFS) for younger estimates at 1, 5 and 10 years of 95.0 %, 64.0% and 58.93% respectively, appeared slightly better than the 92.7%, 58.1% and 53.1% for postmenopausal women [HRadj = 1.25, 95% CI = 0.95-1.64]. Regarding overall survival (OS) for younger at 1, 5 and 10 years were 97.7%, 72.7 % and 52.7% respectively, for postmenopausal patients, OS at 1, 5 and 10 years were 95.7%, 70.0% and 44.5 respectively, there were no significant differences in survival [HRadj = 1.23, 95% CI = 0.94 -1.64]. Multivariate analysis identified five risk factors for negatively impacting on survival were triple negative [HR= 2.76, 95% CI = 1.47-5.19], Her2-enriched [HR = 2.59, 95% CI = 1.37-4.91], luminal B [HR = 2.29, 95 % CI=1.35-3.89], not free margin [HR = 1.98, 95%CI=1.00-3.96] and patients who received only adjuvant chemotherapy [HR= 3.75, 95% CI = 2.00-7.04]. Statistically significant risks of overall cancer recurrence were Her2-enriched [HR = 5.20, 95% CI = 2.75-9.80], triple negative [HR = 3.87, 95% CI = 1.98-7.59], luminal B [HR= 2.59, 95% CI = 1.48-4.54,] and patients who received only adjuvant chemotherapy [HR= 2.59, 95% CI = 1.48-5.66]. Discussion and Implications: Outcomes from this studies have shown that postmenopausal women have been associated with increased risk of recurrence and mortality. As the results, it provides useful information for planning the screening and treatment of early-stage breast cancer in the future.

Keywords: breast cancer, menopause status, recurrence-free survival, overall survival

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Authors: Seung Chul Lee, Jooyeong Kim, Ki Ok Ahn, Juok Park

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Background: Injuries caused by motorcycle crashes are one of the major public health burdens leading to high mortality, functional disability. The risk of death among motorcyclists is 30 times greater than that among car drivers, with head injuries the leading cause of death. The motorcycle helmet is crucial protective equipment for motorcyclists. Aims: This study aimed to measure the protective effect of motorcycle helmet use on intracranial injury and mortality and to compare the preventive effect in drivers and passengers. Methods: This is a cross-sessional study based on the Emergency Department (ED)–based Injury In-depth Surveillance (EDIIS) database from 23 EDs in Korea. All of the trauma patients injured in motorcycle crashes between January 1, 2013 and December 31, 2016 were eligible, excluding cases with unknown helmet use and outcomes. The primary and secondary outcomes were intracranial injury and in-hospital mortality. We calculated adjusted odds ratios (AORs) of helmet use for study outcomes after adjusting for potential confounders. Using interaction models, we compared the protective effect of helmet use on outcomes across driving status (driver and passenger). Results: Among 17,791 eligible patients, 10,668 (60.0%) patients were wearing helmets at the time of the crash, 2,128 (12.0%) patients had intracranial injuries and 331 (1.9%) patients had in-hospital death. 16,381 (92.1%) patients were drivers and 1410 (7.9%) patients were passengers. 62.6% of drivers and 29.1% of passengers were wearing helmets at the time of the crash. Compared to un-helmeted group, the helmeted group was less likely to have an intracranial injury(8.0% vs. 17.9%, AOR: 0.43 (0.39-0.48)) and in-hospital mortality (1.0% vs. 3.2%, AOR: 0.29 (0.22-0.37)).In the interaction model, AORs (95% CIs) of helmet use for intracranial injury were 0.42 (0.38-0.47) in drivers and 0.61(0.41-0.90) in passengers, respectively. There was a significant preventive effect of helmet use on in-hospital mortality in drivers (AOR: 0.26(0.21–0.34)). Discussion and conclusions: Wearing helmets in motorcycle crashes reduced intracranial injuries and in-hospital mortality. The preventive effect of motorcycle helmet use on intracranial injury was stronger in drivers than in passengers. There was a significant preventive effect of helmet use on in-hospital mortality in driver but not in passengers. Public health efforts to increase motorcycle helmet use are needed to reduce health burden from injuries caused by motorcycle crashes.

Keywords: intracranial injury, helmet, mortality, motorcycle crashes

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Authors: Mohammed Eltayeb Salih Elamin

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This study discusses the concept of the artificial heart using engineering concepts, of the fluid mechanics and the characteristics of the non-Newtonian fluid. For the purpose to serve heart patients and improve aspects of their lives and since the Statistics review according to world health organization (WHO) says that heart disease and blood vessels are the first cause of death in the world. Statistics shows that 30% of the death cases in the world by the heart disease, so simply we can consider it as the number one leading cause of death in the entire world is heart failure. And since the heart implantation become a very difficult and not always available, the idea of the artificial heart become very essential. So it’s important that we participate in the developing this idea by searching and finding the weakness point in the earlier designs and hoping for improving it for the best of humanity. In this study a pump was designed in order to pump blood to the human body and taking into account all the factors that allows it to replace the human heart, in order to work at the same characteristics and the efficiency of the human heart. The pump was designed on the idea of the diaphragm pump. Three models of blood obtained from the blood real characteristics and all of these models were simulated in order to study the effect of the pumping work on the fluid. After that, we study the properties of this pump by using Ansys15 software to simulate blood flow inside the pump and the amount of stress that it will go under. The 3D geometries modeling was done using SOLID WORKS and the geometries then imported to Ansys design modeler which is used during the pre-processing procedure. The solver used throughout the study is Ansys FLUENT. This is a tool used to analysis the fluid flow troubles and the general well-known term used for this branch of science is known as Computational Fluid Dynamics (CFD). Basically, Design Modeler used during the pre-processing procedure which is a crucial step before the start of the fluid flow problem. Some of the key operations are the geometry creations which specify the domain of the fluid flow problem. Next is mesh generation which means discretization of the domain to solve governing equations at each cell and later, specify the boundary zones to apply boundary conditions for the problem. Finally, the pre–processed work will be saved at the Ansys workbench for future work continuation.

Keywords: Artificial heart, computational fluid dynamic heart chamber, design, pump

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Authors: Ya-Ping Chang

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Starting from the early stages of pregnancy, parents begin to form hopes and dreams about the future of their child. They will think about the appearance and personality of their child and may even develop many expectations. The patient in this study experienced a successful pregnancy following multiple attempts at artificial insemination. However, due to arrested embryonic development, and based on the physician’s evaluation, a caesarean section was performed at week 25. However, the baby suffered from infections and subsequently died from multiple organ failures. This study collected and analyzed objective and subjective data through observation, interviews, recording, and interactions with the patient. The following nursing issues of the patient were identified: anxiety, anticipatory grief, and adjustment disorder. The psychology of caring as proposed in Watson’s theory was applied to address these nursing issues. Comprehensive and continuous care was provided to the patient on the basis of mutual trust and individual nursing guidelines in order to alleviate the patient’s anxiety, help her to cope with grief, and prepare her for the eventual death of her child. The author helped the patient to say goodbye to her child and accept the child’s death calmly, such that she had no regrets about the experience. This nursing experience may serve as a reference to nurses managing similar cases in the future.

Keywords: dying baby, mother, grief, Watson’s theory

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Authors: Haruna Modibbo Usman, Mustapha Muktar, Nasiru Inuwa

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This paper examined the long run relationship between health outcomes and economic growth in Nigeria from 1961 to 2012. Using annual time series data, Augmented Dickey-Fuller (ADF) test is conducted to check the stochastic properties of the variables. Also, the long run relationship among the variables is confirmed based on Johansen Multivariate Cointegration approach whereas the long run and short run dynamics are observed using Vector Error Correction Mechanism (VECM). In addition, VEC Granger causality test is employed to examine the direction of causality among the variables. On the whole, the results obtained revealed the existence of a long run relationship between health outcomes and economic growth in Nigeria and that both life expectancy and crude death rate as measures of health are found to have a long run negative and statistically significant impact on the economic growth over the study period. This is further buttressed by the results of Granger causality test which indicated the existence of unidirectional causality running from life expectancy and crude death rate to economic growth. The study therefore, calls for governments at various levels to create preconditions for health improvements in Nigeria in order to boost the level of health outcomes.

Keywords: cointegration, economic growth, Granger causality, health outcomes, VECM

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Authors: Hsiao-Lin Fang

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Every life is precious, and comprehensive care should be provided to individuals who are in the final stages of their lives. Hospice-shared care aims to provide optimal symptom control and palliative care to terminal (cancer) patients through the implementation of shared care, and to support patients and their families in making various physical and psychological adjustments in the face of death. This report examines a 10-year-boy diagnosed with Out-of-Hospital Cardiac Arrest (OHCA). The individual fainted when swimming at school and underwent 31 minutes of cardiopulmonary resuscitation (CPR). While receiving treatment at the hospital, the individual received extracorporeal membrane oxygenation(ECMO) due to unstable hemodynamics. Urgent cardiac catheterization found: Suspect acute fulminant myocarditis or underlying cardiomyopathy with acute decompensation, After the active rescue by the medical team, hemodynamics still showed only mean pressure value. With respect to the patient, interdepartmental hospice-shared care was implemented and a do-not-resuscitate (DNR) order was signed after family discussions were conducted. Assistance and instructions were provided as part of the comfort care process. A farewell gathering attended by the patient’s relatives, friends, teachers, and classmates was organized in an intensive care unit (ICU) in order to look back on the patient’s life and the beautiful memories that were created, as well as to alleviate the sorrow felt by family members, including the patient’s father and sister. For example, the patient was presented with drawings and accompanied to a garden to pick flowers. In this manner, the patient was able to say goodbye before death. Finally, the patient’s grandmother and father participated in the clinical hospice care and post-mortem care processes. A hospice-shared care clinician conducted regular follow-ups and provided care to the family of the deceased, supporting family members through the sorrowful period. Birth, old age, sickness, and death are the natural phases of human life. In recent years, growing attention has been paid to human-centered hospice care. Hospice care is individual holistic care provided by a professional team and it involves the provision of comprehensive care to a terminal patient. Hospice care aims to satisfy the physical, psychological, mental, and social needs of patients and their families. It does not involve the cessation of treatment but rather avoids the exacerbation or extension of the suffering endured by patients, thereby preserving the dignity and quality of life during the end-of-life period. Patients enjoy the company of others as they complete the last phase of their lives, and their families also receive guidance on how they can move on with their own lives after the patient’s death.

Keywords: hospice-shared care, extracorporeal membrane oxygenation (ECMO), hospice-shared care, child patient

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Authors: Cíntia Martins Sanches

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In the first part of Phoenissae of Seneca, Antigone is a guide to Oedipus, and they leave Thebes: he is blind searching for death (inflicting the punishment himself wished on the killer of Laius, ie exile and death); she is trying to convince him to give up such punishment and bring him back to Thebes. Concerning Oedipus lines, we observed a high frequency of Latin neuter in the treatment the protagonist gave to his daughter Antigone. We considered in this study that such frequency may be related to the sanctification of the daughter, who is seen by him as an enlightened being and without defects, free of the human condition (which takes on the existence of failures by essence). This study, thus, puts forward an analysis of the passages the said feature is present, relating them to the effect of meaning found in each occurrence. As part of a doctorate, this study investigates the stylistic idiom of Seneca in the Oedipus and Phoenissae tragedies, aiming at translating both tragedies expressively. The concept of stylistic idiom concerns the stylistic affinity required for a translation to be equivalent to the source text. In this wise, this study inquires into how the Latin text is organized poetically, pointing out the expressive features frequently appearing in both dramas. The method we used is based on the Semiotics theory — observing how connotation, ie a language use in which prevails the poetic function, naturally polysemous, acts to achieve each expressive effect.

Keywords: antigone, neuter, Oedipus, Phoenissae, Seneca

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Authors: Edilei Reis, Jose Carlos Felix

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This paper explores Waldir Dupont’s translations of William Faulkner’s novels to Brazilian Portuguese language in order to comprehend how his translation project regarding Faulkner’s works has addressed modernist traits of the novelist fiction, particularly the ambivalence of language, multiple and fragmented points of view and syntax. Wladir Dupont (1939-2014) was a prolific Brazilian journalist who benefitted from his experiences as an international correspondent living abroad (EUA and Mexico) to become an acclaimed translator later in life. He received a Jabuiti Award (Brazilian most prestigious literary award) for his translation of ‘La Otra Voz’ (1994), by Mexican poet, critic and translator Octavio Paz, a writer to whom he devoted the first years of his carrier as a translator. As Dupont pointed out in some interviews, the struggles in finding a way out to overcome linguistic and cultural obstacles in the process of translating texts from Spanish to Portuguese was paramount for ascertaining his engagement in the long-term project of translating to Brazilian Portuguese the fiction of William Faulkner. His first enterprise was the translation of Faulkner’s trilogy Snopes: The Hamlet (1940) and The Town (1957), the first two novels, were published in 1997 as O povoado and A cidade; in 1999 the last novel, The mansion (1959), was published as A mansão. In 2001, Dupont tackled what is considered one of the most challenging novels by the author due to his use of multiple points of view, As I lay dying (1930). In 2003, The Reivers (1962) was published under the title Os invictos. His enterprise finishes in 2012 with the publication of an anthology of Faulkner’s thriller short-stories Knight’s Gambit (1932) as Lance mortal. Hence, in this paper we will consider the Dupont’s trajectory as a translator, paying special attention to the way in which his identity as such is constituted through the process of translating Faulkner’s works.

Keywords: literary translation, translator’s identity, William Faulkner, Wladir DuPont

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Authors: Asma Rashid, Shazia Iram, Iftikhar Ahmad

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Mango sudden death is an emerging problem in Pakistan. As its prevalence is observed in almost all mango growing areas and severity varied from 2-5% in Punjab and 5-10% in Sindh. Symptoms on affected trees include bark splitting, discoloration of the vascular tissue, wilting, gummosis and at the end rapid death. Total of n= 45 isolates were isolated from different mango growing areas of Punjab and Sindh. Pathogenicity of these fungal isolates was tested through artificial inoculation method on different hosts (potato tubers, detached mango leaves, detached mango twigs and mango plants) under controlled conditions and all were proved pathogenic with varying degree of aggressiveness in reference to control. The findings of the present study proved that out of these four methods, potato tubers inoculation method was the most ideal as this fix the inoculums on the target site. Increased fungal growth and spore numbers may be due to soft tissues of potato tubers from which Ceratocystis isolates can easily pass. Lesion area on potato tubers was in the range of 7.09-0.14 cm2 followed by detached mango twigs which were ranged from 0.48-0.09 cm2). All pathological results were proved highly significant at P<0.05 through ANOVA but isolate to isolate showed non-significant behaviour but they have the positive effect on lesion area. Re-isolation of respective fungi was achieved with 100 percent success which results in the verification of Koch’s postulates. DNA of fungal pathogens was successfully extracted through phenol chloroform method. Amplification was done through ITS, b-tubulin gene, and Transcription Elongation Factor (EF1-a) gene primers and the amplified amplicons were sequenced and compared from NCBI which showed 99-100 % similarity with Ceratocystis manginecans. Fungus Ceratocystis manginecans formed one of strongly supported sub-clades through phylogenetic tree. Results obtained through this work would be supportive in establishment of relation of isolates with their region and will give information about pathogenicity level of isolates that would be useful to develop the management policies to reduce the afflictions in orchards caused by mango sudden death.

Keywords: artificial inoculation, mango, Ceratocystis manginecans, phylogenetic, screening

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Authors: Cansu Arslan Turan, Tuba Cimilli Ozturk, Ebru Unal Akoglu, Kemal Aygun, Ecem Deniz Kırkpantur, Ozge Ecmel Onur

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Although the mechanism of action is not well known, Intravenous Lipid Emulsion (ILE) has been shown to be effective in the treatment of lipophilic drug intoxications. It is thought that ILE probably separate the lipophilic drugs from target tissue by creating a lipid-rich compartment in the plasma. The second theory is that ILE provides energy to myocardium with high dose free fatty acids activating the voltage gated calcium channels in the myocytes. In this study, the effects of ILE treatment on digoxin overdose which are frequently observed in emergency departments was searched in an animal model in terms of cardiac side effects and survival. The study was carried out at Yeditepe University, Faculty of Medicine-Experimental Animals Research Center Labs in December 2015. 40 Sprague-Dawley rats weighing 300-400 g were divided into 5 groups randomly. As the pre-treatment, the first group received saline, the second group received lipid, the third group received DigiFab, and the fourth group received DigiFab and lipid. Following that, digoxin was infused to all groups until death except the control group. First arrhythmia and cardiac arrest occurrence times were recorded. As no medication causing arrhythmia was infused, Group 5 was excluded from the statistical analysis performed for the comparisons of first arrhythmia and death time. According to the results although there was no significant difference in the statistical analysis comparing the four groups, as the rats, only exposed to digoxin intoxication were compared with the rats pre-treated with ILE in terms of first arrhythmia time and cardiac arrest occurrence times, significant difference was observed between the groups. According to our results, using DigiFab treatment, intralipid treatment, intralipid and DigiFab treatment for the rats exposed to digoxin intoxication makes no significant difference in terms of the first arrhythmia and death occurrence time. However, it is not possible to say that at the doses we use in the study, ILE treatment might be successful at least as a known antidote. The fact that the statistical significance between the two groups is not observed in the inter-comparisons of all the groups, the study should be repeated in the larger groups.

Keywords: arrhytmia, cardiac arrest, DigiFab, digoxin intoxication

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Authors: Hanan Azzam1, Nashwa Abousamra1, Amany Mansour1, Yaser Abd El-dayem2, , Solafa Elsharawy1

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Background: Inherited thrombophilias are a heterogenous group of conditions which have been implicated in a variety of pregnancy complications. More recently, deficiency of protein Z (PZ) has been liked to pregnancy complications, including preterm delivery. Aim: We designed this study to evaluate the association of inherited thrombophilias including [Protein C (PC), Protein S (PS), Anti thrombin III (ATIII) deficiency and activated protein C (APC) resistance] and protein Z deficiency with a variety of pregnancy complications. Patients and Methods: 60 women with different pregnancy complications, including 20 patients with preeclampsia, 20 patients with intrauterine growth resistance (IUGR), and 20 patients with intrauterine fetal death (IUFD), in addition to 30 healthy pregnant women were recruited for the present study. PC and free PS antigen, ATIII activity, modified functional APC-resistance, and PZ levels were determined. Results: There was no significant association between inherited thrombophilias and complicated pregnancies as regards PC deficiency (p=1.0), AT III and PS deficiency (p=0.312), and APC-resistance (P=0.083). PZ was significantly associated with complicated pregnancies (p=0.012). Patients with protein Z levels below 1.5 µg/ml were considered deficient. Accordingly, we demonstrated protein Z deficiency in 30% of complicated pregnancies (RR 6.0, 95% CI 1.29-27.90;p=0.022), 20% of preeclampsia (RR 3.5, 95% CI 0.57 – 21.28; P = 0.174), 40% of IUGR (RR 9.3 95% CI 1.72-50.61; P = 0.010) and 30% of IUFD (RR 6, 95% CI 1.07 – 33.64; P = 0.042). Conclusions: These findings indicate the absence of association of inherited thrombophilias, including PC, PS, AT III deficiency, and APC resistance with pregnancy complications. However, PZ deficiency is associated with increased risk of pregnancy complications, especially intrauterine growth restriction and intrauterine fetal death.

Keywords: protein C, protein S, thrombophelia, pregnancy, protein Z

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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

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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

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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

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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

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Authors: H. Al-Awaisi, M. H. Al-Azri, S. Al-Rasbi, M. Al-Moundhri

Abstract:

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

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Authors: Nurul Hidayah, Farida Rahmatika, Fathimah Azzahra, Nesty Herennadia

Abstract:

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)

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Authors: Susan Hall, Gary D. Grant, Catherine McDermott, Devinder Arora

Abstract:

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

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Authors: Anmol Patel

Abstract:

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

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Authors: Liesbeth Van Kelst, Jozefiene Jansens

Abstract:

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

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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

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Authors: Akterono Budiyati, Gita Kusumo, Teguh Putra, Fritzie Rexana, Antonius Kurniawan, Aru Sudoyo, Ahmad Utomo, Andi Utama

Abstract:

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

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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

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Authors: Jaqueline Bohn Donada

Abstract:

The significance of Euripides’ Medea for contemporary literature is noticeable. Even if the bulk of Classical Reception studies does not tend to look carefully and consistently to the literature produced outside the Anglophone world, Brazilian literature offers abundant materials for such studies. Indeed, a certain Classical background can be observed in Brazilian literature at least since 1975 when Gota d’Água [The Final Straw, in English], a play that recreates the story of Medea and sets it in a favela in Rio de Janeiro. Also worthy of notice is Ivo Bender’s Trilogia Perversa [Perverse Trilogy, in English], a series of three historical plays set in Southern Brazil and based on Aeschylus’ Oresteia and on Euripides’ Iphigenia in Aulis published in the 1980s. Since then, a number of works directly inspired by the plays of Aeschylus, Sophocles and Euripides have been published, not to mention several adaptations of Homer’s two epic poems. This paper proposes a comparative analysis of two such works: Grace Passô’s 2017 play Mata teu Pai [Kill your father, in English] and Marcia Lima’s 2019 play Medeia Negra [Black Medea, in English] from the perspective of Classical Reception Studies in an intersection with feminist literary criticism. The paper intends to look at the endurance of Euripides’ character in contemporary Brazilian literature with a focus on how the character seems to have acquired special relevance to the treatment of pressing issues of the twenty-first century. Whereas Grace Passô’s play sets Medea at the center of a group of immigrant women, Marcia Limma has the character enact the dilemmas of incarcerated women in Brazil. The hypothesis that this research aims at testing is that both artists preserve the pathos of Euripides’s original character at the same time that they recreate his Medea in concrete circumstances of Brazilian contemporary social reality. At the end, the research aims at stating the significance of the Medea theme to contemporary Brazilian literature.

Keywords: Euripides, Medea, Grace Passô, Marcia Limma, Brazilian literature

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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

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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

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Authors: Hossein Barri Ghazani

Abstract:

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

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Authors: Md. M. Hossain, Regan Roat, Jenica Christopherson, Colette Free, Zhiguang Guo

Abstract:

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

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