“Endogenous Melatonin Concentration Along with the Expression of Mitochondrial Regulator Genes is Elevated by the Serum Shock Process in the U87-MG Cell Line”

According to the World Health Organization, glioblastoma, also known as the fourth grade in the development of astrocytoma, is a glial tumor limited to the central nervous system with a strong ability to invade the brain parenchyma. Melatonin can be generated outside of the pineal gland tissue, according to new research. Melatonin is produced by mitochondria independently but in concert with cell demands, and it plays an important function in cell cycle and metabolism regulation. As a result, we set out to investigate the association between cell metabolism and the serum shock-induced increase in endogenous melatonin, as well as the percentage of cell proliferation.Background: Melatonin can be produced in the mitochondria organelle of glioblastoma cells without the involvement of the pineal gland, according to new research. Regarding the physiological function of melatonin secreted by the pineal gland in the regulation of rhythmicity, the goal of this study was to see if the glioblastoma cell's melatonin production ability could be influenced using a typical serum shock technique established for cellular rhythm regulator.Material and methods: First, U87-MG glioblastoma cells were cultured in a DMEM medium containing 10% FBS and then cells were treated with a standard serum shock process (no FBS, 8h). The concentration of melatonin was measured using ELISA method in supernatant and cell extracts of Shock and control groups. The cell proliferation was measured by using BrdU staining and flow cytometry assessment. The gene expression levels of some mitochondria or circadian related genes including TFAM, BMAL1, PPARGC1A(PGC1-α), and DNM1L(DRP1) were measured, using qRT-PCR method.Results: In comparison to the control group, serum shock treated U87-MG glioblastoma cells had higher concentrations of cellular and released endogenous melatonin (two times). At the mRNA level, we discovered considerable upregulation of mitochondrial or circadian regulator genes (TFAM, BMAL1, PPARGC1A, and DNM1L); in the shock group compared to the control group (P <0.0002). Furthermore, although the percentage of proliferative cells (Brdu positive) was higher in the shock group, it was not statistically significant.Conclusion: The serum shock procedure has a significant impact on the U87-MG cell line's cellular activity. In terms of the study's findings, it's worth noting that an increase in endogenous melatonin concentration influences several signaling pathways within the U87-MG cell line, as seen by the increased expression of candidate genes.In light of the findings of this study, it's worth noting that further research into the role of endogenous melatonin and its effects on cancer cells is critical, and that comparing the results of normal and cancer cells can reveal the hotspots of the signaling pathways involved, which could facilitate in better understanding the biology of glioblastoma.

Combined, Converted, and Prophylactic Use of Resuscitative Endovascular Balloon Occlusion of the Aorta for Severe Torso Trauma: A Retrospective Study

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used as an intra-aortic balloon occlusion method in Japan; however, the protocols for its effective use in different pathological conditions remain unclear. This study aimed to summarise the strategies of REBOA use in severe torso trauma.Methods: Twenty-nine cases of REBOA for torso trauma treated at our hospital over 5 years were divided into the shock (n=12), cardiopulmonary arrest (CPA) (n=13), and non-shock (n=4) groups. We retrospectively examined patient characteristics, trauma mechanism, injury site, severity score, intervention, survival rates at 24 hours, and intervention details in each group.Results: In the shock group, 9 and 3 patients survived and died within 24 hours, respectively; time to intervention (56.6 vs 130.7 min, p=0.346) and total occlusion time (40.2 vs 337.7 min, p=0.009) were both shorter in surviving patients than in the casualties. In the CPA group, 10 patients were converted from resuscitative thoracotomy with aortic cross-clamp (RTACC); a single patient survived. Four patients in the non-shock group survived, having received prophylactic REBOA.Conclusions: The efficacy of REBOA for severe torso trauma depends on patient condition. In the shock group, time to intervention and total occlusion time correlated with survival. The use of REBOA with definitive haemostasis and minimum delays to intervention may improve outcomes. Patients with CPA are at a high risk of mortality; however, conversion from RTACC may be effective in some cases. Prophylactic intervention in the non-shock group may help achieve immediate definitive haemostasis.

Soluble vascular cell adhesion molecule-1 levels and severity of dengue hemorrhagic fever in children

Background The clinical manifestations of dengue infection vary widely, ranging from asymptomatic to severe forms that can cause death. In severe infections, the expression of soluble vascular cell adhesion molecule-1 (sVCAM-1) in endothelial cells is reportedly excessive, causing endothelial cell gaps through VE-cadherin and plasma leakage, which is the basic mechanism for shock in dengue hemorrhagic fever (DHF). Objective To determine the association between sVCAM-1 levels and severity of dengue hemorrhagic fever in children. Methods This cross-sectional study was done in children with DHF at Dr. M. Djamil Hospital, Padang, West Sumatera. Subjects were diagnosed according to the 2011 WHO criteria and selected by consecutive sampling. They were grouped as DHF with or without shock. Examination of sVCAM-1 levels was done by ELISA method. Mann-Whitney test with a significance of P<0.05 was used for statistical analysis. Results A total of 66 patients were collected from January 2018 to December 2019, but 2 patients were excluded. The 64 subjects who met the inclusion criteria consisted of 32 (50%) DHF without shock and 32 (50%) DHF with shock. Median sVCAM-1 was significantly higher in the DHF with shock group (840 ng/mL) than in DHF without shock group (598 ng/mL) (P<0.05). Conclusion There was a significant association between higher sVCAM-1 levels and greater severity of dengue hemorrhagic fever in children.

Prognostic value of changes in the cardiac arrest rhythms from the prehospital stage to the emergency department in out-of-hospital cardiac arrest patients without prehospital returns of spontaneous circulation: A nationwide observational study

Background This study aimed to assess the prognostic value of the changes in cardiac arrest rhythms from the prehospital stage to the ED (emergency department) in out-of-hospital cardiac arrest (OHCA) patients without prehospital returns of spontaneous circulation (ROSC). Methods This retrospective analysis was performed using nationwide population-based OHCA data from South Korea between 2012 and 2016. Patients with OHCA with medical causes and without prehospital ROSC were included and divided into four groups according to the nature of their cardiac arrest rhythms (shockable or non-shockable) in the prehospital stage and in the ED: (1) the shockable and shockable (Shock-Shock) group, (2) the shockable and non-shockable (Shock-NShock) group, (3) the non-shockable and shockable (NShock-Shock) group, and (4) the non-shockable and non-shockable (NShock-NShock) group. The presence of a shockable rhythm was confirmed based on the delivery of an electrical shock. Propensity score matching and multivariate logistic regression analyses were used to assess the effect of changes in the cardiac rhythms on patient outcomes. The primary outcome was sustained ROSC in the ED; the secondary outcomes were survival to hospital discharge and good neurological outcomes at hospital discharge. Results After applying the exclusion criteria, 51,060 eligible patients were included in the study (Shock-Shock, 4223; Shock-NShock, 3060; NShock-Shock, 11,509; NShock-NShock, 32,268). The propensity score-matched data were extracted from the six comparative subgroups. For sustained ROSC in the ED, Shock-Shock showed a higher likelihood than Shock-NShock (P <0.01) and NShock-NShock (P <0.01), Shock-NShock showed a lower likelihood than NShock-Shock (P <0.01) and NShock-NShock (P <0.01), NShock-Shock showed a higher likelihood NShock-NShock (P <0.01). For survival to hospital discharge, Shock-Shock showed a higher likelihood than Shock-NShock (P <0.01), NShock-Shock (P <0.01), and NShock-NShock (P <0.01), Shock-NShock showed a higher likelihood than NShock-Shock (P <0.01) and NShock-NShock (P <0.01), of sustained ROSC in the ED. For good neurological outcomes, Shock-Shock showed higher likelihood than Shock-NShock (P <0.01), NShock-Shock (P <0.01), and NShock-NShock (P <0.01), Shock-NShock showed better likelihood than NShock-NShock (P <0.01), NShock-Shock showed a better likelihood than NShock-NShock (P <0.01). Conclusion Sustained ROSC in the ED may be expected for patients with shockable rhythms in the ED compared with those with non-shockable rhythms in the ED. For the clinical outcomes, survival to hospital discharge and neurological outcomes, patients with Shock-Shock showed the best outcome, whereas patients with NShock-NShock showed the poorest outcome and Shock-NShock showed a higher likelihood of achieving survival to hospital discharge with no significant differences in the neurological outcomes compared with NShock-Shock.

Estimation of short-term and medium-term survival from sudden cardiac death based on the initial rhythm

Introduction: Sudden cardiac death (SCD) is a clinical syndrome defined as: sudden, premature, natural death from cardiogenic causes in a cardiac patient or a person without known cardiac disease, preceded by sudden loss of consciousness and occurring within one hour of the onset of acute symptoms. (3). According to published literature, the incidence of sudden cardiac death ranges widely (15-48%), depending on geographical and demographic indicators. Objective: The aim of our study was to investigate short-term and medium-term survival after resuscitation in patients with sudden cardiac death. Methods: data from patients in two groups of sudden cardiac death were compared at hospital discharge and at 1 and 3 months after hospital discharge. We compared data from 92 patients who suffered a SCD between 1 January 2016 and 31 December 2017. Data from patients who had a proven shockable (I) or non-shockable (II) incipient rhythm following SCD were included. The main endpoint was the comparison of mortality between the two groups. For statistical analysis, we used a T-test and ANOVA to compare the data. Our exclusion criteria included inaccurate documentation and uncertain rhythm. Results: 62% of patients in the shock group had a significantly higher survival at all three observed time points than in the non-shock group. Conclusion: In our study population, the hypothesis that patients with a shockable rhythm in SCD have significantly better survival than those without shockable rhythm was confirmed by several studies. Our patients had significantly higher survival both at hospital discharge and at day 30 survival. Introducción: La muerte súbita cardíaca (MSC) es un síndrome clínico que se define como: la muerte súbita, prematura y natural por causas cardiogénicas en un paciente cardíaco o en una persona sin enfermedad cardíaca conocida, precedida de una pérdida súbita de conciencia y que se produce en la hora siguiente al inicio de los síntomas agudos. (3). Según la literatura publicada, la incidencia de la muerte súbita cardíaca varía ampliamente (15-48%), dependiendo de indicadores geográficos y demográficos. Objetivo: El objetivo de nuestro estudio fue investigar la supervivencia a corto y medio plazo tras la reanimación en pacientes con muerte súbita cardíaca. Métodos: Se compararon los datos de los pacientes de dos grupos de muerte súbita cardíaca al alta hospitalaria y a los 1 y 3 meses del alta hospitalaria. Se compararon los datos de 92 pacientes que sufrieron una MSC entre el 1 de enero de 2016 y el 31 de diciembre de 2017. Se incluyeron los datos de los pacientes que tenían un ritmo incipiente demostrable (I) o no demostrable (II) tras la MSC. El criterio de valoración principal fue la comparación de la mortalidad entre los dos grupos. Para el análisis estadístico, se utilizó una prueba T y un ANOVA para comparar los datos. Nuestros criterios de exclusión incluyeron la documentación inexacta y el ritmo incierto. Resultados: El 62% de los pacientes del grupo de choque tuvo una supervivencia significativamente mayor en los tres puntos temporales observados que en el grupo de no choque. Conclusión: En nuestra población de estudio, la hipótesis de que los pacientes con ritmo desfibrilable en la ECF tienen una supervivencia significativamente mayor que los que no tienen ritmo desfibrilable fue confirmada por varios estudios. Nuestros pacientes tuvieron una supervivencia significativamente mayor tanto al alta hospitalaria como al día 30 de supervivencia.

Comparison of Resuscitation Outcomes Between 2‐ or 3‐Stacked Defibrillation Strategies With Minimally Interrupted Chest Compression and the Single Defibrillation Strategy: A Swine Cardiac Arrest Model

Background There is controversy over whether the number and mode of electrical shock are optimal for successful defibrillation. Methods and Results Fifty‐four pigs were randomly assigned to 3 groups. After inducing ventricular fibrillation and a 2‐minute downtime, basic life support was initiated with a 30:2 compression/ventilation ratio for 8 minutes. Subsequently, 20 minutes of advanced life support, including asynchronous ventilation, every 10 chest compressions with 15 L/min of oxygen, was delivered. Animals of the single shock group received a single shock, animals of the 2‐stacked shock group received 2 consecutive shocks, and animals of the 3‐stacked shock group received 3 consecutive shocks. Animals with the return of spontaneous circulation underwent post–cardiac arrest care for 12 hours. The rates of successful defibrillation, return of spontaneous circulation, 24‐hour survival, and 48‐hour survival and neurological deficit score were compared between the groups. Hemodynamic parameters, arterial blood gas profiles, troponin I, and cardiac output were not different between the groups. There was a significant difference in chest compression fraction between the single and 3‐stacked shock groups ( P <0.001), although there was no difference between the single and 2‐stacked shock groups ( P =0.022) or the 2‐stacked and 3‐stacked shock groups ( P =0.040). The rates of successful defibrillation, return of spontaneous circulation, 24‐hour survival, and 48‐hour survival were higher in the 2‐ and 3‐stacked shock groups than in the single shock group ( P =0.021, P =0.015, and P =0.021, respectively). Neurological deficit score at 48 hours was not different between the groups. Conclusions A stacked shock strategy was superior to a single shock strategy for successful defibrillation and better resuscitation outcomes in treating ventricular fibrillation.

Endogenous Melatonin Concentration Along With the Expression of Mitochondrial Regulator Genes Is Elevated by the Serum Shock Process in the U87-MG Cell Line

Glioblastoma, also known as the fourth grade in the development of astrocytoma according to the World Health Organization, is a tumor in the glial region confined to the central nervous system with high invasion capability to the parenchyma of the brain. Recent findings suggest that melatonin can be synthesized outside the pineal gland tissue. Mitochondria can produce melatonin independently but in coordination with cell demands which plays a critical role in regulating the cell cycle and cell metabolism. hence, we aimed to examine the relationship between cell metabolism and the induction of endogenous melatonin increase induced by the serum shock process, then, determine the percentage of cell proliferation.Background: glioblastoma is a highly invasive tumor of glial cell of brain tissue. Recently it was reported that melatonin can be produced in mitochondria organelle of the glioblastoma cells independent to pineal gland. Regarding the physiological function of melatonin released from pineal gland in regulation of rhythmicity, here we aimed to investigate if serum shock standard protocol known for cellular rhythm regulator can change the melatonin production ability of the glioblastoma cell.Material and methods: First, U87-MG glioblastoma cells were cultured in a DMEM medium containing 10% FBS and then cells were treated with a standard serum shock process (no FBS, 8h). The concentration of melatonin was measured using ELISA method in supernatant and cell extracts of Shock and control groups. The cell proliferation was measured by using BrdU staining and flow cytometry assessment. The gene expression levels of some mitochondria or circadian related genes including TFAM, BMAL1, PGC-1α, and DRP1 were measured, using qRT-PCR method.Results: our findings showed increased (two times) concentration of cellular and released endogenous melatonin in the FBS shock treated U87-MG glioblastoma cells compared to the control group. we found significant up-regulation of the mitochondria or circadian regulator genes (TFAM, BMAL1, PGC-1α, and DRP1) at mRNA level; in the FBS shock group compared to the control group (P <0.0002). Moreover, the percent of proliferative cell (Brdu positive) was also elevated in FBS shock group however it was not statistically significant. Conclusion: the serum shock process has a far effect on the cellular behavior of the U87-MG cell line. regard to the results of the study, it is worth mentioning that an increase in the concentration of endogenous melatonin affects many signaling pathways within the U87-MG cell line, and the elevated expression of the candidate genes was the proof of this fact.by considering the results of this study it also should be noted that detailed investigating the role of endogenous melatonin and its effects on cancer cells is pivotal and by comparing the results of the normal cells with cancer cells we can find the hotspots of the involved signaling pathways that could help better understanding the biology of glioblastoma.

Features of Patients Receiving Extracorporeal Membrane Oxygenation Relative to Cardiogenic Shock Onset: A Single-Centre Experience

Background and Objectives: Extracorporeal membrane oxygenation (ECMO) can be helpful in patients with cardiogenic shock associated with myocardial infarction, and its early use can improve the patient survival rate. In this study, we report a mortality rate-difference analysis that examined the time and location of shock occurrence. Materials and Methods: We enrolled patients who underwent ECMO due to cardiogenic shock related to myocardial infarction and assigned them to either a pre- or post-admission shock group. The primary outcome was the 1-month mortality rate; a subgroup analysis was conducted to assess the effect of bailout ECMO. Results: Of the 113 patients enrolled, 67 (38 with pre-admission shock, 29 with post-admission shock) were analysed. Asystole was more frequently detected in the pre-admission shock group than in the post-admission group. In both groups, the commonest culprit lesion location was in the left anterior descending artery. Cardiopulmonary resuscitation was performed significantly more frequently and earlier in the pre-admission group. The 1-month mortality rate was significantly lower in the pre-admission group than in the post-admission group. Male sex and ECMO duration (≥6 days) were factors significantly related to the reduced mortality rate in the pre-admission group. In the subgroup analysis, the mortality rate was lower in patients receiving bailout ECMO than in those not receiving it; the difference was not statistically significant. Conclusions: ECMO application resulted in lower short-term mortality rate among patients with out-of-hospital cardiogenic shock onset than with in-hospital shock onset; early cardiopulmonary resuscitation and ECMO might be helpful in select patients.

Machine Learning for Early Warning of Septic Shock in Children With Hematological Malignancies Accompanied by Fever or Neutropenia: A Single Center Retrospective Study

ObjectivesThe purpose of this article was to establish and validate clinically applicable septic shock early warning model (SSEW model) that can identify septic shock in hospitalized children with onco-hematological malignancies accompanied with fever or neutropenia.MethodsData from EMRs were collected from hospitalized pediatric patients with hematological and oncological disease at Shanghai Children’s Medical Center. Medical records of patients (&gt;30 days and &lt;19 years old) with fever (≥38°C) or absolute neutrophil count (ANC) below 1.0 × 109/L hospitalized with hematological or oncological disease between January 1, 2017 and August 1, 2019 were considered. Patients in whom septic shock was diagnosed during the observation period formed the septic shock group, whereas non-septic-shock group was the control group. In the septic shock group, the time points at 4, 8, 12, and 24 hours prior to septic shock were taken as observation points, and corresponding observation points were obtained in the control group after matching. We employed machine learning artificial intelligence (AI) to filter features and used XGBoost algorithm to build SSEW model. Area under the ROC curve (AU-ROC) was used to compare the effectiveness among the SSEW Model, logistic regression model, and pediatric sequential organ failure score (pSOFA) for early warning of septic shock.Main ResultsA total of 64 observation periods in the septic shock group and 2191 in the control group were included. AU-ROC of the SSEW model had higher predictive value for septic shock compared with the pSOFA score (0.93 vs. 0.76, Z = −2.73, P = 0.006). Further analysis showed that the AU-ROC of the SSEW model was superior to the pSOFA score at the observation points 4, 8, 12, and 24 h before septic shock. At the 24 h observation point, the SSEW model incorporated 14 module root features and 23 derived features.ConclusionThe SSEW model for hematological or oncological pediatric patients could help clinicians to predict the risk of septic shock in patients with fever or neutropenia 24 h in advance. Further prospective studies on clinical application scenarios are needed to determine the clinical utility of this AI model.

The State of the Structure of the Brain Cortex at Different Times of the Postmortal Period after Massive Blood Loss and Blood Loss Complicated by Hemorrhagic Shock

Determine the time of death based on these characteristics. Aims: The aim of the study was to identify the features of changes in the structure of the cerebral cortex in different periods of the post - mortem period after massive blood loss and blood loss complicated by hemorrhagic shock, and to determine the age of death based on these data. Study Design: Cross-sectional study. Place and Duration of Study: Department of Medicine and Department of Forensic Medicine 2020 between. Methodology: The structures of the cortex from the Brodman sixth field of the large hemispheres of the brain were studied from 73 corpses of individuals who died from massive blood loss (MB) - 61 and blood loss complicated by hemorrhagic shock -12. The study of corpses with MB (group 1) was carried out in the period: 6-8 h (26), 8-10 h (6), 10-12 h (4), 12-14 h (6), 14-16 h ( 12), 16-24 h (5), 24-28 h (2) postmortem period. Research of corpses after hemorrhagic shock (group 2) were carried out after 6-8 hours (3), 12-14 (3), 18-20 (2), 24-28 (4). Histological preparations of the brain were first examined qualitatively, then quantitatively. Quantitative study of structures was carried out by the point method according To G. G. Avtandilov, the digital material was statistically processed by the Student – Fisher method. Results: Thus, at death from massive blood loss, as the post-mortem period increases, there is an increase in structural changes in cortical neurons,as well as an expansion of pericellular space. The vascular component of the cerebral cortex is also involved in destructive processes associated with an increase in the postmortem period, and an increase in perivascular spaces is observed. Conclusion: Comparative analysis of the data obtained showed that in the postmortem period after hemorrhagic shock (group 2), destructive changes in the cerebral cortex appear earlier and are more pronounced than in the case of death from massive blood loss (group 1). Similar expansion of perineuronal and perivascular spaces in the cerebral cortex reflects the persistence of thanatogenesis manifestations in different periods of the post-mortal period after death from massive blood loss and hemorrhagic shock.