Search results for: fetal death

Authors: Alex Eldo Simon, Abhishek Yadav

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This study aimed to evaluate the utility of postmortem computed tomography (CT) and heart weight measurements in the assessment of cardiomegaly in cases of sudden death due to cardiac origin by comparing the results of these two diagnostic methods. The study retrospectively analyzed postmortem computed tomography (PMCT) data from 54 cases of sudden natural death and compared the findings with those of the autopsy. The study involved measuring the cardiothoracic ratio (CTR) from coronal computed tomography (CT) images and determining the actual cardiac weight by weighing the heart during the autopsy. The inclusion criteria for the study were cases of sudden death suspected to be caused by cardiac pathology, while exclusion criteria included death due to unnatural causes such as trauma or poisoning, diagnosed natural causes of death related to organs other than the heart, and cases of decomposition. Sensitivity, specificity, and diagnostic accuracy were calculated, and to evaluate the accuracy of using the cardiothoracic ratio (CTR) to detect an enlarged heart, the study generated receiver operating characteristic (ROC) curves. The cardiothoracic ratio (CTR) is a radiological tool used to assess cardiomegaly by measuring the maximum cardiac diameter in relation to the maximum transverse diameter of the chest wall. The clinically used criteria for CTR have been modified from 0.50 to 0.57 for use in postmortem settings, where abnormalities can be detected by comparing CTR values to this threshold. A CTR value of 0.57 or higher is suggestive of hypertrophy but not conclusive. Similarly, heart weight is measured during the traditional autopsy, and a cardiac weight greater than 450 grams is defined as hypertrophy. Of the 54 cases evaluated, 22 (40.7%) had a cardiothoracic ratio (CTR) ranging from > 0.50 to equal 0.57, and 12 cases (22.2%) had a CTR greater than 0.57, which was defined as hypertrophy. The mean CTR was calculated as 0.52 ± 0.06. Among the 54 cases evaluated, the weight of the heart was measured, and the mean was calculated as 369.4 ± 99.9 grams. Out of the 54 cases evaluated, 12 were found to have hypertrophy as defined by PMCT, while only 9 cases were identified with hypertrophy in traditional autopsy. The sensitivity and specificity of the test were calculated as 55.56% and 84.44%, respectively. The sensitivity of the hypertrophy test was found to be 55.56% (95% CI: 26.66, 81.12¹), the specificity was 84.44% (95% CI: 71.22, 92.25¹), and the diagnostic accuracy was 79.63% (95% CI: 67.1, 88.23¹). The limitation of the study was a low sample size of only 54 cases, which may limit the generalizability of the findings. The comparison of the cardiothoracic ratio with heart weight in this study suggests that PMCT may serve as a screening tool for medico-legal autopsies when performed by forensic pathologists. However, it should be noted that the low sensitivity of the test (55.5%) may limit its diagnostic accuracy, and therefore, further studies with larger sample sizes and more diverse populations are needed to validate these findings.

Keywords: PMCT, virtopsy, CTR, cardiothoracic ratio

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Authors: Hasan Afarnegan, Ali Shahraki, Jafar Shahraki

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Paraquat is widely used as a strong nitrogen-based herbicide for controlling of weeds in agriculture. This poison is extremely toxic for humans which induces several – organ failure by accumulation in cells and many instances of death occurred due to its poisoning. Paraquat metabolized primarily in the liver. The purpose of this study was to assess the effects of aquatic extract of levisticum officinale on oxidative status and biochemical factors in hepatocytes exposed to paraquat. Our results determined that hepatocytes destruction induced by paraquat is mediated by reactive oxygen species (ROS) production, lipid peroxidation and decrease of mitochondrial membrane potential were significantly (P<0.05) prevented by aquatic extract of Levisicum officinale (100, 200 and 300 µg/ml). These effects of paraquat also prevented via antioxidants and ROS scavengers (α-tocopherol, DMSO, manitol), mitochondrial permeability transition (MPT) pore sealing compound (carnitine).MPT pore sealing compound inhibited the hepatotoxicity, indicating that paraquat induced cell death via mithochondrial pathway. Pretreatment of hepatocytes with aquatic extracts of Levisticum officinale, antioxidants and ROS scavengers also blocked hepatic cell death caused by paraquat, suggesting that oxidative stress may be directly induced decline of mithochondrial membrane potential. In conclusion, paraquat hepatotoxicity can be attributed to oxidative stress and continued by mithochondrial membrane potential disruption. Levisticum officinale aquatic extract, presumably due to its strong antoxidant properties, could protect the destructive effects of paraquat on rat hepatocytes.

Keywords: hepatocyte protection, levisticum officinale, oxidative stress, paraquat

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Authors: Huang Gui

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There can be little doubt that our world is inexorably moving towards being execution-free. However, China is still on the way until now, in other words, China is still a retentionist state in the term of capital punishment but it is developing domestic criminal law toward that goal (eventual abolition of the capital punishment). The alternative sanction to capital punishment, which would be imposed on a criminal who should have been sentenced to death by law, is a substitute for execution and it should be provided with the basis of the present criminal punishment structure and with the premise of abolishing capital punishment or limiting its use. The aim of this paper, therefore, is to explore a substitute for capital punishment in China. For the criminal sanction system in China, the death penalty with suspension, naturally, is an execution, so it wouldn’t be the substitute; life sentences without parole is out of the tune with punishment policy that promoting correction and rehabilitation; life-imprisonment, which is one of the most severe punishment measure in the sanction system, should be a suitable substitute for executing but it needs to be improved, including the term of imprisonment, the commutation and parole conditions.

Keywords: alternative sanctions, capital punishment, life imprisonment, life imprisonment without parole, China

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Authors: Byeongju Choi, Sanggil Lee, Kyung-Eun Lee

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Introduction: In the republic of Korea, the number of workers in the beauty industry has been increasing. Because the prevalence of hepatitis B carriers in Korea is higher than in other countries, the risk of blood-borne infection including viral hepatitis B and C, among the workers by using the sharp and contaminated instruments during procedure can be expected among beauty salon workers. However, the health care policies for the workers to prevent the blood-borne infection are not established due to the lack of evidences. Moreover, the workers in hair and nail salon were mostly employed at small businesses, where national mandatory systems or policies for workers’ health management are not applied. In this study, the risk of the viral hepatitis B and C from the job experiencing the hair and nail procedures in the mortality was assessed. Method: We conducted a retrospective review of the job histories and causes of death in the female deaths from 2006-2016. 132,744 of female deaths who had one more job experiences during their lifetime were included in this study. Job histories were assessed using the employment insurance database in Korea Employment Information Service (KEIS) and the causes of death were in death statistics produced by Statistics Korea. Case group (n= 666) who died from viral hepatitis was classified the death having record involved in ‘B15-B19’ as a cause of deaths based on Korean Standard Classification of Diseases(KCD) with the deaths from other causes, control group (n=132,078). The group of the workers in the beauty service industry were defined as the employees who had ever worked in the industry coded as ‘9611’ based on Korea Standard Industry Classification (KSIC) and others were others. Other than job histories, birth year, marital status, education level were investigated from the death statistics. Multiple logistic regression analysis were used to assess the risk of deaths from viral hepatitis in the case and control group. Result: The number of the deaths having ever job experiences at the hair and nail salon was 255. After adjusting confounders of age, marital status and education, the odds ratio(OR) for deaths from viral hepatitis was quite high in the group having experiences with working in the beauty service industry with 3.14(95% confidence interval(CI) 1.00-9.87). Other associated factors with increasing the risk of deaths from viral hepatitis were low education level(OR=1.34, 95% CI 1.04-1.73), married women (OR=1.42, 95% CI 1.02-1.97). Conclusion: The risk of deaths from viral hepatitis were high in the workers in the beauty service industry but not statistically significant, which might attributed from the small number of workers in beauty service industry. It was likely that the number of workers in beauty service industry could be underestimated due to their temporary job position. Further studies evaluating the status and the incidence of viral infection among the workers with consideration of the vertical transmission would be required.

Keywords: beauty service, viral hepatitis, blood-borne infection, viral infection

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Authors: Asit K. Sikary, O. P. Murty

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Adipocere formation is a modification of the process of putrefaction. It consists mainly of saturated fatty acids, formed by the post-mortem hydrolysis and hydrogenation of body fats with the help of bacterial enzymes in the presence of warmth, moisture and anaerobic bacteria. In temperate climate, it takes weeks to develop while in India it starts to begin within 4-5 days. In this study, we have collected cases with adipocere formation, which were from the South Delhi region (average room temperature 27-390C) and autopsied at our centre. Details of the circumstances of the death, cause and time of death, surrounding environment and demographic profile of the deceased were taken into account. Total 16 cases were included in this study. Adipocere formation was predominantly present over cheeks, shoulder, breast, flanks, buttocks, and thighs. Out of 16, 11 cases were found in a dry atmosphere, 5 cases were brought from the water. There were 5 cases in which adipocere formation was seen in less than 2 days, and among them, in 1 case, as early as one day. This study showed that adipocere formation can be seen as early as 1 day in a hot and humid environment.

Keywords: adipocere, drowning, hanging, humid environment, strangulation, subtropical climate

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Authors: Maria L. G. Lourenço, Keylla H. N. P. Pereira, Viviane Y. Hibaru, Fabiana F. Souza, João C. P. Ferreira, Simone B. Chiacchio, Luiz H. A. Machado

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The neonatal mortality rates in dogs are considered high, varying between 5.7 and 21.2% around the world, and the causes of the deaths are often unknown. Data regarding canine neonatal mortality are scarce in Brazil. This study aims at describing the neonatal mortality rates in dogs, as well as the main causes of death. The study included 152 litters and 669 neonates admitted to the São Paulo State University (UNESP) Veterinary Hospital, Botucatu, São Paulo, Brazil between January 2018 and September 2019. The overall mortality rate was 16.7% (112/669), with 40% (61/152) of the litters presenting at least one case of stillbirth or neonatal mortality. The rate of stillbirths was 7.7% (51/669), while the neonatal mortality rate was 9% (61/669). The early mortality rate (0 to 2 days) was 13.7% (92/669), accounting for 82.1% (92/112) of all deaths. The late mortality rate (3 to 30 days) was 2.7% (18/669), accounting for 16% (18/112) of all deaths. Infection was the causa mortis in 51.8% (58/112) of the newborns, of which 30.3% (34/112) were caused by bacterial sepsis, and 21.4% (24/112) were caused by other bacterial, viral or parasite infections. Other causes of death included congenital malformations (15.2%, 17/112), of which 5.3% (6/112) happened through euthanasia due to malformations incompatible with life; asphyxia/hypoxia by dystocia (9.8%, 11/112); wasting syndrome in debilitated newborns (6.2%, 7/112); aspiration pneumonia (3.6%, 4/112); agalactia (2.7%, 3/112); trauma (1.8%, 2/112); administration of contraceptives to the mother (1.8%, 2/112) and unknown causes (7.1%, 8/112). The neonatal mortality rate was considered high, but they may be even higher in locations without adequate care for the mothers and neonates. Therefore, prenatal examinations and early neonatal care are of utmost importance for the survival of these patients.

Keywords: neonate dogs, puppies, mortality rate, neonatal death

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Authors: Neha Singh, Anuj Ranjan, Tanu Jindal

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Over the last decade, the exponential growth of mobile communication has been accompanied by a parallel increase in density of electromagnetic fields (EMF). The continued expansion of mobile phone usage raises important questions as EMF, especially radio frequency (RF), have long been suspected of having biological effects. In the present experiments, we studied the effects of RF-EMF on cell death (apoptosis) and DNA damage of a well- tested biological model, Drosophila melanogaster exposed to 2400 MHz frequency for different time duration i.e. 2 hrs, 4 hrs, 6 hrs,8 hrs, 10 hrs, and 12 hrs each day for five continuous days in ambient temperature and humidity conditions inside an exposure chamber. The flies were grouped into control, sham-exposed, and exposed with 100 flies in each group. In this study, well-known techniques like Comet Assay and TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) Assay were used to detect DNA damage and for apoptosis studies, respectively. Experiments results showed DNA damage in the brain cells of Drosophila which increases as the duration of exposure increases when observed under the observed when we compared results of control, sham-exposed, and exposed group which indicates that EMF radiation-induced stress in the organism that leads to DNA damage and cell death. The process of apoptosis and mutation follows similar pathway for all eukaryotic cells; therefore, studying apoptosis and genotoxicity in Drosophila makes similar relevance for human beings as well.

Keywords: cell death, apoptosis, Comet Assay, DNA damage, Drosophila, electromagnetic fields, EMF, radio frequency, RF, TUNEL assay

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Authors: Dursun Kalebaşi

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When we examine the history of mankind (from the past up to the present), we see that millions of people died because of the wars. Especially, since the beginning of 19th century, the increase of the human death rate is caused mostly by the regional conflicts and natural disasters rather than the wars. From that point of view, the biggest threat humanity face today is temperature increase and climate change that started to emerge in recent years. When we take into account the natural disasters on one hand and refuges that flee from regional conflicts on the other, it stands out as a dramatic situation because of the huge human losses. In this context, most of the countries started to give more importance to Search and Rescue (SAR) operations to stop the loss of lives or decrease the death rate. This article will tell about the SAR activities in Turkey since 2000 and discuss the Turkey’s contributions to Rescue Missions after the natural disasters in different parts of the world. Moreover, there will be some new highlights to a more habitable and more peaceful world through the SAR missions.

Keywords: search and rescue, natural disasters, migration and world peace, Turkish army forces

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Authors: Pratima Tatke, Archana Avhad, Bhanu Duggal, Meeta Rajivlochan, Sujata Saunik, Pradip Vyas, Nidhi Pandey, Aditee Dalvi, Jyothi Subramanian

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Background: Smoking is well established risk factor for the development and progression of coronary artery disease. It is strongly related to morbidity and mortality from cardiovascular causes. The aim of this study is to observe effect of smoking status on percutaneous coronary intervention(PCI) after 1 year. Methods: 2527 patients who underwent PCI at different hospital of Maharashtra(India) from 2012 to 2015 under the health insurance scheme which is launched by Health department, Government of Maharashtra for below poverty line(BPL) families which covers cardiology. Informed consent of patients was taken .They were followed by telephonic survey after 6months to 1year of PCI . Outcomes of interest included myocardial infarction, restenosis, cardiac rehospitalization, death, and a composite of events after PCI. Made group of two non smokers-1861 and smokers (including patients who quit at time of PCI )-659. Results: Statistical Analysis using Pearson’s chi square test revealed that there was trend seen of increasing incidence of death, Myocardial infarction and Restenosis in smokers than non smokers .Smokers had a greater death risk compared to nonsmoker; 5.7% and 5.1% respectively p=0.518. Also Repeat procedures (2.1% vs. 1.5% p=0.222), breathlessness (17.8% vs. 18.20% p=0.1) and Myocardial Infarction (7.3% vs. 10%) high in smoker than non smokers. Conclusion: Major adverse cardiovascular events (MACE) were observed even after successful PCI in smokers. Patients undergoing percutaneous coronary intervention should be encouraged to stop smoking.

Keywords: coronary artery diseases, major adverse cardiovascular events, percutaneous coronary intervention, smoking

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Authors: Madan Khadka, Dhruba Uprety, Rubina Rai

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Background and objective: In 2011, around 273,465 women died worldwide during pregnancy, childbirth or within 42 days after childbirth. Near-miss is recognized as the predictor of the level of care and maternal death. The objective of the study was to evaluate the associated risk factors of near-miss obstetric cases and maternal death. Material and Methods A Prospective Observational Study was done from August 1, 2014, to June 30, 2015, in Department of Obstetrics and Gynecology at BPKIHS hospital, tertiary care hospital in Eastern Nepal, Dharan. Case eligible by the 5-factor scoring system and WHO near miss criteria were evaluated. Risk factors included severe hemorrhage, hypertensive disorders, and a complication of abortion, ruptured uterus, medical/surgical condition and sepsis. Results: A total of 9,727 delivery were attended during the study period from August 2014 to June 2014. There were 6307 (71.5%) vaginal delivery and 2777(28.5%) caesarean section and 181 perinatal death with a total of 9,546 live birth. A total of 162 near miss was identified, and 16 maternal death occurred during the study. Maternal near miss rate of 16.6 per 1000 live birth, Women with life-threatening conditions (WLTC) of 172, Severe maternal outcome ratio of 18.64 per 1000 live birth, Maternal near-miss mortality ratio (MNM: 1 MD) 10.1:1, Mortality index (MI) of 8.98%. Risk factors were obstetric hemorrhage 27.8%, abortion/ectopic 27.2%, eclampsia 16%, medical/surgical condition 14.8%, sepsis 13.6%, severe preeclamsia 11.1%, ruptured uterus 3.1%, and molar pregnancy 1.9%. 19.75% were prim gravidae, with mean age 25.66 yrs, and cardiovascular and coagulation dysfunction as a major life threatening condition and sepsis (25%) was the major cause of mortality. Conclusion: Hemorrhage and hypertensive disorders are the leading causes of near miss event and sepsis as a leading cause of mortality. As near miss analysis indicates the quality of health care, it is worth presenting in national indices.

Keywords: abortion, eclampsia, hemorrhage, maternal mortility, near miss

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Authors: Kimiyo Shimomai, Mihoko Harada

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This study is a literature review of the psychological reactions that occur in end-of-life cancer patients who are nearing death. It searched electronic databases and selected literature related to psychological studies of end-of-life patients. There was no limit on the search period, and the search was conducted until the second week of December 2021. The keywords were specified as “death and dying”, “terminal illness”, “end-of-life”, “palliative care”, “psycho-oncology” and “research”. These literatures referred to Holly (2017): Comprehensive Systematic Review for Advanced Practice Nursing, P268 Figure 10.3 to ensure quality. These literatures were selected with a dissertation score of 4 or 5. The review was conducted in two stages with reference to the procedure of George (2002). First, these references were searched for keywords in the database, and then relevant references were selected from the psychology and nursing studies of end-of-life patients. The number of literatures analyzed was 76 for overseas and 17 for domestic. As for the independent variables, "physical variable" was the most common in 36 literatures (66.7%), followed by "psychological variable" in 35 literatures (64.8%), "spiritual variable" in 21 literatures (38%), and "social variable" in 17 literatures. (31.5%), "Variables related to medical care / treatment" were 16 literatures (29.6%). To summarize the relationship between these independent variables and the dependent variable, when the dependent variable is "psychological variable", the independent variables are "psychological variable", "social variable", and "physical variable". Among the independent variables, the physical variables were the most common. The psychological responses that occur in end-stage cancer patients who are nearing death are mutually influenced by psychological, social, and physical variables. Therefore, it supported the "total pain" advocated by Cicely Saunders.

Keywords: cancer patient, end-of-life, literature review, psychological process

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Authors: Tianjiao Chu, Carla Rios Luci, Christy Maksoudian, Ara Sargsian, Bella B. Manshian, Stefaan J. Soenen

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Nanomaterials have gained high interest in their use as potent anticancer agents. Apart from delivering chemotherapeutic agents in order to reduce off-target effects, molecular agents have also been widely explored. The advances in our understanding of cell biology and cell death mechanisms1 has generated a broad library of potential therapeutic targets by siRNA, mRNA, or pDNA complexes. In the present study, we explore the ability of pDNA-polyplexes to induce tumor-specific necroptosis. This results in a cascade of effects, where immunogenic cell death potentiates anti-tumor immune responses and results in an influx of dendritic cells and cytotoxic T cells, rendering the tumor more amenable to immune checkpoint inhibition. This study aims to explore whether the induction of necroptosis in a subpopulation of tumor cells can be used to potentiate immune checkpoint inhibition studies.

Keywords: nanoparticle, MLKL, necroptosis, immunotherapy

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Authors: G. I. Onwuka, A. Danbaba, S. U. Gulumbe

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This study investigated of Infant Mortality Rate as observed at a general hospital in Kaduna-South, Kaduna State, North West Nigeria. The causes of infant Mortality were examined. The data used for this analysis were collected at the statistics unit of the Hospital. The analysis was carried out on the data using Multiple Linear regression Technique and this showed that there is linear relationship between the dependent variable (death) and the independent variables (malaria, measles, anaemia, and coronary heart disease). The resultant model also revealed that a unit increment in each of these diseases would result to a unit increment in death recorded, 98.7% of the total variation in mortality is explained by the given model. The highest number of mortality was recorded in July, 2005 and the lowest mortality recorded in October, 2009.Recommendations were however made based on the results of the study.

Keywords: infant mortality rate, multiple linear regression, diseases, serial correlation

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Authors: H. Y. Al-Matubsi, G. A. Oriquat, M. Abu-Samak, O. A. Al Hanbali, M. Salim

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Background: Uncontrolled diabetes mellitus (DM) is an etiological factor for recurrent pregnancy loss and major congenital malformations in the offspring. Antioxidant therapy has been advocated to overcome the oxidant-antioxidant disequilibrium inherent in diabetes. The aims of this study were to evaluate the protective effect of lipoic acid (LA) on fetal outcome and to elucidate changes that may be involved in the mechanism(s) implicit diabetic fetopathy. Methods: Female rats were rendered hyperglycemic using streptozocin and then mated with normal male rat. Pregnant non-diabetic (group1; n=9; and group2; n=7) or pregnant diabetic (group 3; n=10; and group 4; n=8) rats were treated daily with either lipoic acid (LA) (30 mg/kg body weight; groups 2 and 4) or vehicle (groups 1 and 3) between gestational days 0 and 15. On day 15 of gestation, the rats were sacrificed, and the fetuses, placentas and membranes dissected out of the uterine horns. Following morphological examination, the fetuses, placentas and membranes were homogenized, and used to measure cyclooxygenases (COX) activities and metabolisms of prostaglandin (PG) E2 (PGEM) and PGF2 (PGFM) levels. Maternal liver and plasma total glutathione levels were also determined. Results: Supplementation of diabetic rats with LA was found to significantly (P<0.05) reduce resorption rates in diabetic rats and increased mean fetal weight compared to diabetic group. Treatment of diabetic rats with LA leads to a significant (P<0.05) increase in liver and plasma total glutathione, in comparison with diabetic rats. Decreased levels of PGEM and elevated levels of PGFM in the fetuses, placentas and membranes were characteristic of experimental diabetic gestation associated with malformation. LA treatment to diabetic mothers failed to normalize levels of PGEM to the non-diabetic control rats. However, the levels of PGEM in malformed fetuses from LA-treated diabetic mothers was significantly (P < 0.05) higher than those in malformed fetuses from diabetic rats. Conclusions: We conclude that LA can reduce congenital malformations in the offspring of diabetic rats at day 15 of gestation. However, LA treatment did not completely prevent the occurrence of malformations, other factors, such as arachidonic acid deficiency and altered prostaglandin metabolismmay be involved in the pathogenesis of diabetes-induced congenital malformations.

Keywords: diabetes, lipoic acid, pregnancy, prostaglandins

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Authors: B. Kulaga, A. Cinti, F. J. Mazzocchini

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Despite the fact that growing academic attention on dark tourism is a fairly recent phenomenon, among the various reasons for travelling death-related ones, are very ancient. Furthermore, the darker side of human nature has always been fascinated and curious regarding death, or at least, man has always tried to learn lessons from death. This study proposes to describe the phenomenon of dark tourism related to the 2016 earthquake in Central Italy, deadly for 302 people and highly destructive for the rural areas of Lazio, Marche, and Umbria Regions. The primary objective is to examine the motivation-experience relationship in a dark tourism site, using the structural equation model, applied for the first time to a dark tourism research in 2016, in a study conducted after the Beichuan earthquake. The findings of the current study are derived from the calculations conducted on primary data compiled from 350 tourists in the areas mostly affected by the 2016 earthquake, including the town of Amatrice, near the epicenter, Castelluccio, Norcia, Ussita and Visso, through conducting a Likert scale survey. Furthermore, we use the structural equation model to examine the motivation behind dark travel and how this experience can influence the motivation and emotional reaction of tourists. Expected findings are in line with the previous study mentioned above, indicating that: not all tourists visit the thanatourism sites for dark tourism purpose, tourists’ emotional reactions influence more heavily the emotional tourist experience than cognitive experiences do, and curious visitors are likely to engage cognitively by learning about the incident or related issues.

Keywords: dark tourism, emotional reaction, experience, motivation, structural equation model

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Authors: Vaibhavi Birle

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Posterior reversible encephalopathy syndrome is a rare clinic-radiological syndrome associated with acute changes in blood pressure during pregnancy. It is characterized symptomatically by headache, seizures, altered mental status, and visual blurring with radiological changes of white matter (vasogenic oedema) affecting the posterior occipital and parietal lobes of the brain. It is being increasingly recognized due to increased institutional deliveries and advances in imaging particularly magnetic resonance imaging (MRI). In spite of the increasing diagnosis the prediction of PRES and patient factors affecting susceptibility is still not clear. Hence, we conducted the retrospective study to analyse the factors associated with PRES at our tertiary centre.

Keywords: pres syndrome, eclampsia, maternal outcome, fetal outcome

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Authors: Shu-Pin Huang, Pai-Chi Teng, Hao-Han Chang, Chia-Hsin Liu, Yung-Lun Lin, Shu-Chi Wang, Hsin-Chih Yeh, Chih-Pin Chuu, Jiun-Hung Geng, Li-Hsin Chang, Wei-Chung Cheng, Chia-Yang Li

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The emergence of immune checkpoint inhibitors (ICIs) targeting proteins like PD-1 and PD-L1 has changed the treatment paradigm of bladder cancer. However, not all patients benefit from ICIs, with some experiencing early death. There's a significant need for biomarkers associated with the PD-1 pathway in bladder cancer. Current biomarkers focus on tumor PD-L1 expression, but a more comprehensive understanding of PD-1-related biology is needed. Our study has developed a seven-gene risk score panel, employing a comprehensive bioinformatics strategy, which could serve as a potential prognostic and predictive biomarker for bladder cancer. This panel incorporates the FYN, GRAP2, TRIB3, MAP3K8, AKT3, CD274, and CD80 genes. Additionally, we examined the relationship between this panel and immune cell function, utilizing validated tools such as ESTIMATE, TIDE, and CIBERSORT. Our seven-genes panel has been found to be significantly associated with bladder cancer survival in two independent cohorts. The panel was also significantly correlated with tumor infiltration lymphocytes, immune scores, and tumor purity. These factors have been previously reported to have clinical implications on ICIs. The findings suggest the potential of a PD-1 pathway-based transcriptomic panel as a prognostic and predictive biomarker in bladder cancer, which could help optimize treatment strategies and improve patient outcomes.

Keywords: bladder cancer, programmed cell death protein 1, prognostic biomarker, immune checkpoint inhibitors, predictive biomarker

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Authors: Dugeree Otgongerel, Kyong Jin Cho, Yu-Han Kim, Sangmee Ahn Jo

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Excessive activation of glutamate receptor is thought to be involved in retinal ganglion cell (RGC) death after ischemia- reperfusion damage. Glutamate carboxypeptidase II (GCPII) is an enzyme responsible for the synthesis of glutamate. Several studies showed that inhibition of GCPII prevents or reduces cellular damage in brain diseases. Thus, in this study, we examined the expression of GCPII in rat retina and the role of GCPII in acute high IOP ischemia-reperfusion damage of eye by using a GCPII inhibitor, 2-(phosphonomethyl) pentanedioic acid (2-PMPA). Animal model of ischemia-reperfusion was induced by raising the intraocular pressure for 60 min and followed by reperfusion for 3 days. Rats were randomly divided into four groups: either intra-vitreous injection of 2-PMPA (11 or 110 ng per eye) or PBS after ischemia-reperfusion, 2-PMPA treatment without ischemia-reperfusion and sham-operated normal control. GCPII immunoreactivity in normal rat retina was detected weakly in retinal nerve fiber layer (RNFL) and retinal ganglionic cell layer (RGL) and also inner plexiform layer (IPL) and outer plexiform layer (OPL) strongly where are co-stained with an anti-GFAP antibody, suggesting that GCPII is expressed mostly in Muller and astrocytes. Immunostaining with anti-BRN antibody showed that ischemia- reperfusion caused RGC death (31.5 %) and decreased retinal thickness in all layers of damaged retina, but the treatment of 2-PMPA twice at 0 and 48 hour after reperfusion blocked these retinal damages. GCPII level in RNFL layer was enhanced after ischemia-reperfusion but was blocked by PMPA treatment. This result was confirmed by western blot analysis showing that the level of GCPII protein after ischemia- reperfusion increased by 2.2- fold compared to control, but this increase was blocked almost completely by 110 ng PMPA treatment. Interestingly, GFAP immunoreactivity in the retina after ischemia- reperfusion followed by treatment with PMPA showed similar pattern to GCPII, increase after ischemia-reperfusion but reduction to the normal level by PMPA treatment. Our data demonstrate that increase of GCPII protein level after ischemia-reperfusion injury is likely to cause glial activation and/or retinal cell death which are mediated by glutamate, and GCPII inhibitors may be useful in treatment of retinal disorders in which glutamate excitotoxicity is pathogenic.

Keywords: glutamate carboxypepptidase II, glutamate excitotoxicity, ischemia-reperfusion, retinal ganglion cell

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Authors: Pranav Vaidya

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The recent upheaval of a ballot initiative taken place in California & Los Angeles‘s newspapers shows how the concept of giving Death Penalty obliterates the very soul basis of community and society which rests upon the tripod of values, ethics, and morality. This paper goes on with examining how, by giving death penalties we are, on one hand trying to wipe out those heinous offenders committing such unspeakable crimes against the public; while on the other hand it comes with a devastating effect of corroding and eluding the existence of ethics and morality which is in the very nature of “protecting the life of humankind”. As it can be stated that, by giving capital punishment, we are trying to legitimize an irreversible act of violence by the authority of state and target innocent victims because as long as the human justice is fallible, the risk of executing an innocent can never be eliminated. However, scholars in the legalization of Capital Punishment have argued that the courts should impose punishment befitting the crime so that they could reflect public abhorrence of the crime, create deterrent or rehabilitating effects & deliver the truest form of justice.

Keywords: ethics, heinous offenders, morality, unspeakable crimes

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Authors: Kai Way Li, Lang Gan

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Slip &Fall are common in Taiwan. They could result in injuries and even fatalities. Official statistics indicate that more than 15% of all occupational incidences were slip/fall related. All the workers in Taiwan are required by the law to join the worker’s insurance program administered by the Bureau of Labor Insurance (BLI). The BLI is a government agency under the supervision of the Ministry of Labor. Workers claim with the BLI for insurance compensations when they suffer fatalities or injuries at work. Injuries statistics based on worker’s compensation claims were rarely studied. The objective of this study was to quantify the injury statistics and financial cost due to slip-fall incidences based on the BLI compensation records. Compensation records in the BLI during 2007 to 2013 were retrieved. All the original application forms, approval opinions, results for worker’s compensations were in hardcopy and were stored in the BLI warehouses. Xerox copies of the claims, excluding the personal information of the applicants (or the victim if passed away), were obtained. The content in the filing forms were coded in an Excel worksheet for further analyses. Descriptive statistics were performed to analyze the data. There were a total of 35,024 claims including 82 deaths, 878 disabilities, and 34,064 injuries/illnesses which were slip/fall related. It was found that the average losses for the death cases were 40 months. The total dollar amount for these cases paid was 86,913,195 NTD. For the disability cases, the average losses were 367.36 days. The total dollar amount for these cases paid was almost 2.6 times of those for the death cases (233,324,004 NTD). For the injury/illness cases, the average losses for the illness cases were 58.78 days. The total dollar amount for these cases paid was approximately 13 times of those of the death cases (1134,850,821 NTD). For the applicants/victims, 52.3% were males. There were more males than females for the deaths, disability, and injury/illness cases. Most (57.8%) of the female victims were between 45 to 59 years old. Most of the male victims (62.6%) were, on the other hand, between 25 to 39 years old. Most of the victims were in manufacturing industry (26.41%), next the construction industry (22.20%), and next the retail industry (13.69%). For the fatality cases, head injury was the main problem for immediate or eventual death (74.4%). For the disability case, foot (17.46%) and knee (9.05%) injuries were the leading problems. The compensation claims other than fatality and disability were mainly associated with injuries of the foot (18%), hand (12.87%), knee (10.42%), back (8.83%), and shoulder (6.77%). The slip/fall cases studied indicate that the ratios among the death, disability, and injury/illness counts were 1:10:415. The ratios of dollar amount paid by the BLI for the three categories were 1:2.6:13. Such results indicate the significance of slip-fall incidences resulting in different severity. Such information should be incorporated in to slip-fall prevention program in industry.

Keywords: epidemiology, slip and fall, social burden, workers’ compensation

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Authors: Jeewantha Ranawaka, Gunawardane Kapila, Wijethunaga Mudiyanselage B. G. Jayathilake

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Introduction: Sweeping of the membranes is a fairly simple technique that may positively influence the shift from maintenance of pregnancy to the beginning of labor. Objective: To assess the effectiveness and acceptability of twice versus once-only membrane sweeping in uncomplicated primi gravid at 40 weeks of gestational age in a tertiary care hospital in Sri Lanka. Methods: A randomized controlled clinical trial was done in Ward 05 of Teaching Hospital, Kandy. The participants were primi-gravida with a singleton live fetus who was at 40 weeks of gestation with intact fetal membranes and with a Modified Bishop’s score <5. After randomization both groups received membrane sweeping at 40 weeks of gestation and the experimental group received membrane sweeping after 48 hours (40+2 days). The modified Bishop Score was assessed at 40+5 days. In two groups who did not go into natural labor at 40+5 days were managed according to the ward policy of cervical ripening and with labor induction at 40+5 days. Two different methods were used to assess discomfort and pain. Patient acceptability was assessed using recommendation to another patient and acceptance during next pregnancy. Perinatal, maternal and labour outcomes were assessed. Results: A change of the Bishops score was 67.3% (n= 31 of 46) in experimental group whereas in control group it was 57.5% (n= 38 of 66). (p = 0.21, OR-1.52, CI = 0.6 -3.34). Mean (SD) of Modified Bishop score was 6.36 (1.94) in experimental group and 6.03 (.84) in control group (p = 0.354). The probability of having the spontaneous onset of labour in experimental group was 61.6% (n=74 of 120) whereas in control group it was 45% (n= 54 of 120) (p=0.01, OR-1.966, CI = 1.17 – 3.28 NNT = 5.99). Recommending the method to another among experimental group was 75% (n= 90 of 120) whereas in control group it was 79.2% (n= 95 of 120) (p= 0.443). Accepting membrane Sweeping for subsequent pregnancy among experimental was 72.5% (n=87 of 120) whereas in control group was 72.5% (n=87 of 120) (p= 1.00) Need of formal induction of labour at 40+ 5 days in experimental group was 38.4% (n=46 of 120) whereas in control group was 61.6% (n=66 of 120) (p=0.01, OR=0.5, CI= 0.3 – 0.8, NNT=6). Neonatal outcome, labour outcome such as Cesarean -section rate, need for augmentation and maternal complications such as fever, Premature rupture of membrane, bleeding were comparable in two groups. Conclusions and Recommendations: It can be concluded that twice sweeping of membrane was effective to reduce the need of formal induction of labour and increase the chances of having spontaneous onset of labour (SOL) at 40+5 days without increasing maternal or fetal morbidity. Acceptability of twice sweeping is not different from sweeping once. Hence we recommend consideration of multiple membranes sweeping as first line for women at 40 weeks of gestation.

Keywords: acceptability, induction, labour, membrane sweeping

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Authors: Lingxia Li, Frédéric Schnell, Shuzhe Ding, Solène Le Douairon Lahaye

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Background: The risk of sudden cardiac arret/death (SCA/D) in athletes is controversial. There is a lack of meta-analyses assessing the sex differences in the risk of SCA/D in competitive athletes. Purpose: The aim of the present study was to evaluate sex differences in the incidence of SCA/D in competitive athletes using meta-analyses. Methods: The systematic review was registered in the PROSPERO database (registration ID: CRD42023432022) and was conducted according to the PRISMA guidelines. PubMed, Embase, Scopus, SPORT Discus and Cochrane Library were searched up to July 2023. To avoid systematic bias in data pooling, only studies with data for both sexes were included. Results: From the 18 included studies, 2028 cases of SCA/D were observed (males 1821 (89.79%), females 207 (10.21%)). The age ranges from the adolescents (<26 years) to the elderly (>45 years). The incidence in male athletes was 1.32/100,000 AY (95% CI: [0.90, 1.93]) and in females was 0.26/100,000 AY (95% CI: [0.16, 0.43]), the incidence rate ratio (IRR) was 6.43 (95% CI: [4.22, 9.79]). The subgroup synthesis showed a higher incidence in males than in females in both age groups <25 years and ≤35 years, the IRR was 5.86 (95% CI: [4.69, 7.32]) and 5.79 (95% CI: [4.73, 7.09]), respectively. When considering the events, the IRR was 6.73 (95%CI: [3.06, 14.78]) among studies involving both SCA/D events and 7.16 (95% CI: [4.93, 10.40]) among studies including only cases of SCD. The available clinical evidence showed that cardiac events were most frequently seen in long-distance running races (26, 35.1%), marathon (16, 21.6%) and soccer (10, 13.5%). Coronary artery disease (14, 18.9%), hypertrophic cardiomyopathy (8, 10.8%), and arrhythmogenic right ventricular cardiomyopathy (7, 9.5%) are the most common causes of SCA/D in competitive athletes. Conclusion: The meta-analysis provides evidence of sex differences in the incidence of SCA/D in competitive athletes. The incidence of SCA/D in male athletes was 6 to 7 times higher than in females. Identifying the reasons for this difference may have implications for targeted the prevention of fatal evets in athletes.

Keywords: incidence, sudden cardiac arrest, sudden cardiac death, sex difference, athletes

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Authors: Isaura Esther Solano Núñez, David Suarez

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The main purpose of this research is to discover what causes death in children of the Wayuu community, and deeply analyze those results in order to take corrective measures to properly control infant mortality. We consider important to determine the reasons that are producing early death in this specific type of population, since they are the most vulnerable to high risk environmental conditions. In this way, the government, through competent authorities, may develop prevention policies and the right measures to avoid an increase of this tragic fact. The methodology used to develop this investigation is data mining, which consists in gaining and examining large amounts of data to produce new and valuable information. Through this technique it has been possible to determine that the child population is dying mostly from malnutrition. In short, this technique has been very useful to develop this study; it has allowed us to transform large amounts of information into a conclusive and important statement, which has made it easier to take appropriate steps to resolve a particular situation.

Keywords: malnutrition, data mining, analytical, descriptive, population, Wayuu, indigenous

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Authors: Sudeshna Mukherjee, Leena Fageria, R. Venkataramana Dilip, Rajdeep Chowdhury, Jitendra Panwar

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Metal nanoparticles in recent years have gained importance in cancer therapy due to their enhanced permeability retention effect. Among various nanomaterials, silver nanoparticles (AgNPs) have received considerable attention due to their unique properties like conductivity, chemical stability, relative lower toxicity and outstanding therapeutic potential, such as anti-inflammatory, antimicrobial and anti-cancerous activities. In this study, we took a greener approach to synthesize silver nanoparticle from fungus and analyze its effects on both epithelial and mesenchymal derived cancer cells. Much research has been done on nanoparticle-induced apoptosis, but little is known about its role in autophagy. In our study, the silver nanoparticles were seen to induce autophagy which was analyzed by studying the expression of several autophagy markers like, LC3B-II and ATG genes. Monodansylcadaverine (MDC) assay also revealed the induction of autophagy upon treatment with AgNPs. Inhibition of autophagy by chloroquine resulted in increased cell death suggesting autophagy as a survival strategy adopted by the cells. In parallel to autophagy induction, silver nanoparticles induced ROS accumulation. Interestingly, autophagy inhibition by chloroquine increased ROS level, resulting in enhanced cell death. We further analyzed MAPK signaling upon AgNP treatment. It was observed that along with autophagy, activation of JNK signaling served as pro-survival while ERK signaling served as a pro-death signal. Our results provide valuable insights into the role of autophagy upon AgNP exposure and provide cues to probabilistic strategies to effectively sensitize cancer cells.

Keywords: autophagy, JNK signalling, reactive oxygen species, silver nanoparticles

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Authors: Kinneret Segal

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The work of a midwife is emotionally challenging, both positively and negatively. Midwives share moments of joy when a baby is welcomed into the world, and also attend difficult events of loss and trauma. The relationship that develops with the maternity is the essence of the midwife's care, and it is a fundamental source of motivation and professional satisfaction. This close relationship with the maternity may be used as a double-edged sword in cases of exposure to traumatic events at birth. Birth problems, exposure to emergencies and traumatic events, and loss can affect the professional quality of life and the Compassion satisfaction of the midwife. It seems that the issue of traumatic experiences in the work of midwives, has not been sufficiently explored. The present study examined the associations between exposure to traumatic events, personal resilience and post-traumatic symptoms, professional quality of life and organizational commitment among midwifery nurses in Israeli hospitals. 131 midwives from three hospitals in the country's center in Israel participated in this study. The data were collected during 2021 using a self-report questionnaire that examined sociodemographic characteristics, the degree of exposure to traumatic events in the delivery room, personal resilience, post-traumatic symptoms, professional quality of life, and organizational commitment. The three most difficult traumatic events for the midwives were death or fear of death of a newborn, death or fear of the death of a mother and a quiet birth. The higher the frequency of exposure to traumatic events, the more numerous and intense the onset of post-trauma symptoms. The more numerous and powerful the post-trauma symptoms, the higher the level of professional burnout and/or compassion fatigue, and the lower the level of compassion satisfaction. High levels of compassion satisfaction and/or low professional burnout were expressed in a heightened sense of organizational commitment. Personal resilience, country of birth, traumatic symptoms and organizational commitment, predicted satisfaction from compassion. Midwives are exposed to traumatic events associated with dissatisfaction and impairment of the professional quality of life that accompanies burnout and compassion fatigue. Exposure to traumatic events leads to the appearance of traumatic symptoms, a decrease in organizational commitment, and psychological and mental well-being. The issue needs to be addressed by implementing training programs, organizational support, and policies to improving well-being and quality of care among midwives.

Keywords: traumatic experirnces, midwives, quality of life, burnout, organizational commitment, personal resilience

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Authors: Yasaswi Vengalasetti, Jacob Eisenach, Jay Bhattacharya

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Seroprevalence studies can provide an estimation of the Infection Fatality Rate (IFR), the probability of death given infection. Measuring the seroprevalence and reported deaths of an area within a given time frame an IFR can be estimated. With this IFR calculation, we can then observe COVID-19 death figures in different countries around the world and estimate the number of cases since the onset of the pandemic. There is a large range for estimated COVID-19 infections across different countries. This ranged from 0.659 million infections in Hong Kong to 277 million infections in India. The largest estimated share of the population infected is 63% in Peru and the lowest is 3% in Norway. For younger populations, COVID-19 is most fatal in South America; for older populations, it is most fatal in North America. The Asian regions stand out with significantly lower IFRs in older populations: at 80 years old, COVID-19 is about three times as fatal than in South Asia and about twelve times as fatal than in East Asia. The weighted average for the share of the population infected, the sum of infections divided by the sum of populations across all countries, is 23%.

Keywords: epidemiology, seroprevalence, covid-19, infection fatality rate

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Authors: Mayuva Youngsabanant, Chanikarn Srinark, Supanyika Sengsai, Soratorn Kerdkriangkrai, Nongnuch Gumlungpat, Mayuree Pumipaiboon

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The follicular fluid proteins of healthy medium size follicles (4-6 mm in diameters) and large size follicles (7-8 mm in diameter) of large white pig ovaries were collected by using sterile technique. They were used for testing the effect on primary in vitro cell culture growth of porcine oviductal epithelial cells (pOEC). Porcine oviductal epithelial cells of luteal phase was culture in M199 and added with 10% fetal calf serum 2.2 mg/mL, NaHCO₃, 0.25 mM pyruvate, 15 µg/mL and 50 µg/mL, gentamycin sulfate at high humidified atmosphere with 5% CO₂ in 95% air atmosphere at 37°C for 96 h before testing. The optimized concentration of pFF of two follicle sizes (at concentration of 2, 4, 20, 40, 200, 400, 500, and 600 µg proteins) in culture medium was observed for 24 h using MTT assay. Results were analyzed with a one-way ANOVA in SPSS statistic. Moreover, pOEC was also studied in morphological characteristic on long-term culture. The results of long-term study revealed that pOEC showed 70-80 percentage of healthy morphology on epithelial-like character and contained 30 percentage of an elongated shape (fibroblast-like morphology) at 4 weeks of culture time. MTT assay reviewed an increase in the percentage of viability of pOEC in 2 treated of follicular fluid groups. Two treatment concentration groups were higher than control group (p < 0.05) but not in positive control group. Interestingly, at 200 µg protein of 2 treated follicular fluid groups were reached the highest cell viability which is higher than a positive control and it is significantly different form control group (P < 0.05). These cells are developed and had fibroblast elongate shape which is longer than the cells in control group and positive control group. This report implies that pFF of medium follicle size at 200 µg proteins and large follicle size at 200 and 500 µg proteins could be optimized concentration for using as a supplement in culture medium to promote cell growth and development instead of growth hormone from fetal calf serum. It could be applied in cell biotechnology researches. Acknowledgements: The project was funded by a grant from Silpakorn University Research and Development Institute (SURDI) and Faculty of Science, Silpakorn University, Thailand.

Keywords: in vitro, porcine follicular fluid protein (pFF), porcine oviductal epithelial cells (pOEC), MTT

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Authors: Mawong R., Bussracumpakorn C.

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Millions of young people around the world have been affected by COVID-19 to their psychological and social effects. Millennials’ stresses have been shaped by a few global issues, including climate change, political instability, and financial crisis. In particular, the spread of COVID-19 has become laying psychological and socioeconomic scars on them. When end-of-life planning turns into more widely discussed, the stigma and taboos around this issue are greatly lessened. End-of-life planning is defined as a future life plan, such as financial, legacy, funeral, and memorial planning. This plan would help millennials to discover the value and meaning of life. This study explores the attitudes of Thai Millennials toward end-of-life planning as a new normal awareness of life in order to initiate an innovative service concept to fit with their value and meaning. The study conducts an in-depth interview with 12 potential participants who have awareness or action on the plan. The framework of the customer journey map is used to analyze the responses to examine trigger points, barriers, beliefs, and expectations. The findings pointed to a service concept that is suggested for a new end-of-life planning service that is suited to Thai Millennials in 4 different groups, which are 1. Social -Conscious as a socially aware who to donate time and riches to make the world and society a better place, their end-of-life planning value is inspired by the social impact of giving something or some action that they will be able to do after life or during life which provides a variety of choice based on their preference to give to society, 2. Life Fulfillment who make a life goal for themselves and attempt to achieve it before the time comes to their value will be to inspire life value with a customized plan and provide guidance to suggest, 3. Prevention of the After-Death Effect who want to plan to avoid the effects of their death as patriarch, head of the family, and anchor of someone, so they want to have a plan that brings confidence and feel relief while they are still alive and they want to find some reliable service that they can leave the death will or asset, and 4. No Guilty Planning who plan for when they wish to be worry-free as a self-responsible they want to have the plan which is easy to understand and easy to access. The overall finding of the study is to understand the new service concept of end-of-life planning which to improve knowledge of significant life worth rather than death planning, encouraging people to reassess their lives in a positive way, leading to higher self-esteem and intrinsic motivation for this generation in this time of global crisis.

Keywords: design management, end-of-life planning, millennial generation, service design solution

Procedia PDF Downloads 163

Authors: Ana M. Lara, Manuela Llano, Felipe Gaitán, Rosa H. Bustos, Ana Maria Perdomo-Arciniegas, Ximena Bonilla

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Umbilical cord blood is used as a source of progenitor and stem cells for the regeneration of the hematopoietic and immune system to treat patients with different hematological or non-hematological diseases. This stem cell source represents an advantage over the use of bone marrow or mobilized peripheral blood because it has a lower incidence rate of graft-versus-host disease, probably due to fewer immunological compatibility restrictions. However, its low cellular dose limits its use in pediatric patients. This work proposes the standardization of a cell expansion technique to compensate for the dose of infused cells through the ex-vivo manipulation of hematopoietic progenitor cells from umbilical cord blood before transplantation. The expansion model is carried out through co-cultures with mesenchymal stem cells (MSC) from bone marrow (BM) and less explored fetal tissues such as Wharton's jelly (WJ) and umbilical cord blood (UCB). Initially, a master cell bank of primary mesenchymal stem cells isolated from different sources was established and characterized following International Society of Cell Therapies (ISCT) indications. Additionally, we assessed the effect of a short 25 Gy cycle of gamma irradiation on cell cycle arrest of mesenchymal cells over the support capacity for the expansion of hematopoietic stem cells from umbilical cord blood was evaluated. The results show that co-cultures with MSC from WJ and UCB allow the cellular dose of HSPC to be maximized between 5 and 16 times having a similar support capacity as BM. In addition, was evaluated the hematopoietic stem progenitor cell's HSPC functionality through the evaluation of migration capacity, their differentiation capacity during culture time by flow cytometry to evaluate the expression of membrane markers associated with lineage-committed progenitors, their clonogenic potential, and the evaluation of secretome profile in the expansion process was evaluated. So far, the treatment with gamma irradiation maintains the hematopoietic support capacity of mesenchymal stem cells from the three sources studied compared to treatments without irradiation, favoring the use of fetal tissues that are generally waste to obtain mesenchymal cell lines for ex-vivo expansion systems. With the results obtained, a standardized protocol that will contribute to the development of ex-vivo expansion with MSC on a larger scale will be achieved, enabling its clinical use and expanding its application in adults.

Keywords: ex-vivo expansion, hematopoietic stem cells, hematopoietic stem cell transplantation, mesenchymal stem cells, umbilical cord blood

Procedia PDF Downloads 83

Authors: Aizati N. A. Daud, Jorieke E. H. Bergman, Wilhelmina S. Kerstjens-Frederikse, Pieter Van Der Vlies, Eelko Hak, Rolf M. F. Berger, Henk Groen, Bob Wilffert

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Prenatal use of SRIs was previously associated with Congenital Heart Anomalies (CHA). The aim of the study is to explore whether pharmacogenetics plays a role in this teratogenicity using a gene-environment interaction study. A total of 33 case-mother dyads and 2 mother-only (children deceased) registered in EUROCAT Northern Netherlands were included in a case-only study. Five case-mother dyads and two mothers-only were exposed to SRIs (paroxetine=3, fluoxetine=2, venlafaxine=1, paroxetine and venlafaxine=1) in the first trimester of pregnancy. The remaining 28 case-mother dyads were not exposed to SRIs. Ten genes that encode the enzymes or proteins important in determining fetal exposure to SRIs or its mechanism of action were selected: CYPs (CYP1A2, CYP2C9, CYP2C19, CYP2D6), ABCB1 (placental P-glycoprotein), SLC6A4 (serotonin transporter) and serotonin receptor genes (HTR1A, HTR1B, HTR2A, and HTR3B). All included subjects were genotyped for 58 genetic variations in these ten genes. Logistic regression analyses were performed to determine the interaction odds ratio (OR) between genetic variations and SRIs exposure on the risk of CHA. Due to low phenotype frequencies of CYP450 poor metabolizers among exposed cases, the OR cannot be calculated. For ABCB1, there was no indication of changes in the risk of CHA with any of the ABCB1 SNPs in the children and their mothers. Several genetic variations of the serotonin transporter and receptors (SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 & rs6298, HTR3B rs1176744) were associated with an increased risk of CHA, but with too limited sample size to reach statistical significance. For SLC6A4 genetic variations, the mean genetic scores of the exposed case-mothers tended to be higher than the unexposed mothers (2.5 ± 0.8 and 1.88 ± 0.7, respectively; p=0.061). For SNPs of the serotonin receptors, the mean genetic score for exposed cases (children) tended to be higher than the unexposed cases (3.4 ± 2.2, and 1.9 ± 1.6, respectively; p=0.065). This study might be among the first to explore the potential gene-environment interaction between pharmacogenetic determinants and SRIs use on the risk of CHA. With small sample sizes, it was not possible to find a significant interaction. However, there were indications for a role of serotonin receptor polymorphisms in fetuses exposed to SRIs on fetal risk of CHA which warrants further investigation.

Keywords: gene-environment interaction, heart defects, pharmacogenetics, serotonin reuptake inhibitors, teratogenicity

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