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The purpose of this study is to determine the effects of grayanotoxin in mad honey on ovarian tissue folliculogenesis in terms of cell death and nitric oxide expression. Three groups of 18 female Sprague-Dawley rats were formed. The first group received mad honey (80 mg/kg), the second group received normal honey (80 mg/kg), and the third group was the control. The first and second groups received normal and mad honey by oral gavage for 30 days before being sacrificed under anesthesia. Caspase 3 immunostaining showed a moderate to strong response, particularly in the mad honey group. In the mad honey group, immunostaining for caspase 8 and caspase 9 revealed a moderate immunoreaction in the granulosa cells of the Graaf follicles. The majority of Graaf follicles exhibited TUNEL positive in the mad honey group. The iNOS immunoreaction revealed a high level of expression in the mad honey group. In all three groups, eNOS immunostaining showed weak reactivity. According to the findings of apoptotic and nitric oxide marker expression, it was determined that mad honey may result in an increase in follicular atresia in ovarian follicles when compared to normal honey and control groups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

In efforts to achieve the goal of reducing ship emissions in the fight against climate change, reducing fuel consumption by making ships lighter is stated as one of the solutions. In this study, the possibilities of making composite equivalents of propellers, which are the most complex ship elements and traditionally produced from metal materials, are investigated with the advantages of additive manufacturing, which offers a rapid production opportunity for such forms. In this way, a lighter composite propeller and, therefore, a lighter ship will be achieved, and negative environmental impacts, especially harmful emissions, will be reduced. In the study, a 1/14-scale ship propeller was produced through the material extrusion method of additive manufacturing using an HDPE composite containing long carbon fiber with a 15% weight fraction. An attempt to reduce flexibility with an epoxy-carbon fabric prepreg coating was made, as the flexibility has negative effects on the performance of the produced propeller. The propeller tunnel test showed that the applied carbon fabric epoxy prepreg helped to improve the propeller's performance by decreasing the flexibility of the propeller and reducing the deformation at the tips. At the same time, the propeller weight was decreased by 60% compared to its metal counterparts.

Background: Fragmented QRS (fQRS) might be associated with certain characteristics in ST-elevation myocardial infarction (STEMI) patients and inhospital adverse events., Materials and Methods: A sum of 500 patients were gone over retrospectively. Patients with STEMI, all undergone percutaneous coronary intervention, were grouped as fQRS (-) and fQRS (+). Characteristics of the patients, major adverse cardiac event (MACE), death in hospital, nonfatal myocardial infarction (MI), stent thrombosis, slow flow myocardial perfusion, development of ventricular tachycardia (VT) and fibrillation, cardiogenic shock and cardiopulmonary arrest were filtered., Results: FQRS (-) group was composed of 207 patients whose mean age was 61.1 ± 12.1, whereas 293 patients were there in fQRS (+) with a mean age of 66.7 ± 10.6 ( P < 0.001). Thrombolysis in MI (TIMI) ( P < 0.01), the global registry of acute coronary events (GRACE) ( P < 0.01) scores, white blood cell count, neutrophil/lymphocyte ratio, MACE and the ratio of death in hospital and VT in the hospital were significantly higher in fQRS (+) group ( P < 0.001, for remaining all). In multivariate logistic regression analysis, TIMI scores above 2 and GRACE scores above 109 were determined as independent predictors of MACE in the entire patient group (odds ratio [OR]: 2.022; 95% confidence interval [CI]; 1.321-3.424 , P = 0.003; OR: 1.712; 95% CI: 1.156-2.804 , P = 0.008)., Conclusion: FQRS (+) and fQRS (-) patients markedly differ from each other in terms of certain demographic and clinical features and TIMI and GRACE scores have a significant predictive value for MACE in all STEMI patients' group., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Research in Medical Sciences.)

Oligoanalgesia, the undertreatment of trauma-related pain using standard analgesics in prehospital and emergency departments, has been extensively documented as one of the major challenges affecting the effective treatment of trauma-related pain. When administered in low doses, methoxyflurane has been highlighted by numerous medical works of literature to provide an effective, nonopioid, nonnarcotic treatment alternative to standard analgesics for prehospital and emergency department use. Low-dose methoxyflurane has been associated with fast-pain relief in adult patients manifesting moderate-to-severe pain symptoms. This systematic review and meta-analysis aimed to assess the clinical implication of low-dose methoxyflurane use in prehospital and emergency departments in adult patients with moderate-to-severe trauma-related pain. Moreover, the review aimed at assessing the risk stratification associated with using low-dose methoxyflurane in prehospital and emergency departments. The systematic review and meta-analysis performed a comprehensive search for pertinent literature assessing the implications and risks of using low-dose methoxyflurane in adult patients exhibiting moderate-to-severe trauma-related pain in prehospital settings. A comparison between the use of low-dose methoxyflurane and standard-of-care analgesics, placebo, in prehospital settings was reported in four clinically conducted randomized controlled trials (RCTs). These RCTs included the STOP! trial, InMEDIATE, MEDIATA, and the PenASAP trials. A meta-analysis comparing the time taken to achieve first pain relief on initial treatment of patients with moderate-to-severe trauma-related pain favored the use of low-dose methoxyflurane to the standard-of-care analgesics (mean difference = -6.63, 95% confidence interval = -7.37, -5.09) on time taken to establish effective pain relief. Low-dose methoxyflurane has been associated with superior and faster pain relief in prehospital and emergency departments in adult patients exhibiting moderate-to-severe trauma-related pain compared to other standard analgesics., Competing Interests: None declared., (Copyright: © 2023 Turkish Journal of Emergency Medicine.)

Structural variants are a common cause of disease and contribute to a large extent to inter-individual variability, but their detection and interpretation remain a challenge. Here, we investigate 11 individuals with complex genomic rearrangements including germline chromothripsis by combining short- and long-read genome sequencing (GS) with Hi-C. Large-scale genomic rearrangements are identified in Hi-C interaction maps, allowing for an independent assessment of breakpoint calls derived from the GS methods, resulting in >300 genomic junctions. Based on a comprehensive breakpoint detection and Hi-C, we achieve a reconstruction of whole rearranged chromosomes. Integrating information on the three-dimensional organization of chromatin, we observe that breakpoints occur more frequently than expected in lamina-associated domains (LADs) and that a majority reshuffle topologically associating domains (TADs). By applying phased RNA-seq, we observe an enrichment of genes showing allelic imbalanced expression (AIG) within 100 kb around the breakpoints. Interestingly, the AIGs hit by a breakpoint (19/22) display both up- and downregulation, thereby suggesting different mechanisms at play, such as gene disruption and rearrangements of regulatory information. However, the majority of interpretable genes located 200 kb around a breakpoint do not show significant expression changes. Thus, there is an overall robustness in the genome towards large-scale chromosome rearrangements., (© 2022. The Author(s).)

Telomeres are repetitive nucleotide sequences at the ends of each chromosome. It has been hypothesized that telomere attrition evolved as a tumor suppressor mechanism in large long-lived species. Long telomeres can silence genes millions of bases away through a looping mechanism called telomere position effect over long distances (TPE-OLD). The function of this silencing mechanism is unknown. We determined a set of 2322 genes with high positional conservation across replicatively aging species that includes known and candidate TPE-OLD genes that may mitigate potentially harmful effects of replicative aging. Notably, we identified PPP2R2C as a tumor suppressor gene, whose up-regulation by TPE-OLD in aged human fibroblasts leads to dephosphorylation of p70S6 kinase and mammalian target of rapamycin suppression. A mechanistic link between telomeres and a tumor suppressor mechanism supports the hypothesis that replicative aging fulfills a tumor suppressor function and motivates previously unknown antitumor and antiaging strategies.

In acute myeloid leukemia, there is an ongoing debate on the prognostic value of the early bone marrow assessment in patients receiving intensive therapy. In this retrospective study, we analyzed the prognostic impact of the early response in 1,008 patients with newly diagnosed acute myeloid leukemia, who were treated at our institution with intensive chemotherapy followed by consolidation chemotherapy and/or allogeneic hematopoietic stem cell transplantation (HSCT). We found that early blast persistence has an independent negative prognostic impact on overall survival, eventfree survival and relapse-free survival. This negative prognostic impact may only be overcome in patients showing at least a partial remission at the early bone marrow assessment and who subsequently achieve blast clearance by additional induction chemotherapy prior to consolidation therapy with allogeneic HSCT. In accordance, we propose that the time slope of remission is an additional leukemia-related dynamic parameter that reflects chemosensitivity and thus may inform post-induction therapy decision-making. In addition to patient-related factors, European LeukemiaNet risk group, measurable residual disease monitoring and donor availability, this may particularly apply to European LeukemiaNet intermediate-risk patients, for whom a decision between consolidation chemotherapy and allogeneic HSCT remains challenging in many cases.

BRD4 is part of a multiprotein complex involved in loading the cohesin complex onto DNA, a fundamental process required for cohesin-mediated loop extrusion and formation of Topologically Associating Domains. Pathogenic variations in this complex have been associated with a growing number of syndromes, collectively known as cohesinopathies, the most classic being Cornelia de Lange syndrome. However, no cohort study has been conducted to delineate the clinical and molecular spectrum of BRD4-related disorder. We formed an international collaborative study, and collected 14 new patients, including two fetuses. We performed phenotype and genotype analysis, integrated prenatal findings from fetopathological examinations, phenotypes of pediatric patients and adults. We report the first cohort of patients with BRD4-related disorder and delineate the dysmorphic features at different ages. This work extends the phenotypic spectrum of cohesinopathies and characterize a new clinically relevant and recognizable pattern, distinguishable from the other cohesinopathies., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Nasal septum deviation is the leading cause of upper airway obstruction. Chronic upper airway obstruction may cause myocardial injury due to chronic hypoxia. Effects of septoplasty on left venticular diastolic and sistolic functions are not well known. The myocardial performance index is an easy-to-apply and reliable parameter that reflects systolic and diastolic cardiac functions., Objective: The present study aimed to investigate the effect of nasal septoplasty on the myocardial performance index in patients with nasal septal deviation., Methods: This prospective study consisted of 50 consecutive patients who underwent septoplasty due to symptomatic prominent C- or S-shaped nasal septal deviation. Transthoracic echocardiogarphy was performed in all patients before and 3 months after septoplasty. Calculated myocardial performance indices were compared., Results: Significantly higher left ventricular myocardial performance index (0.52 ± 0.06 vs. 0.41 ± 0.04, p <  0.001), longer isovolumic relaxation time (95.0 ± 12.5 vs. 78.0 ± 8.6 ms, p <  0.001), longer isovolumic contraction time (45.5 ± 7.8 vs. 39.5 ± 8.6 ms, p <  0.001), longer deceleration time (184.3 ± 32.5 vs. 163.6 ± 45.4 ms, p =  0.004), higher ratio of transmitral early to late peak velocities (E/A) (1.42 ± 0.4 vs. 1.16 ± 0.2, p =  0.006) and shorter ejection time (270.1 ± 18.3 vs. 286.5 ± 25.8 ms, p <  0.001) were observed before septoplasty when compared to values obtained 3 months after septoplasty. Left ventricular systolic ejection fraction was similar before and after septoplasty (63.8±2.8% vs. 64.6±3.2%, p  = 0.224)., Conclusion: Septoplasty surgery not only reduces nasal blockage symptoms in nasal septal deviation patients but also may improve left ventricular performance. Thus, treatment of nasal septal deviation without delay is suggested to prevent possible future cardiovascular events., (Copyright © 2020 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Gallbladder volvulus is a rare entity. The condition results in rotation of the gallbladder on its mesentery along the axis of cystic duct and artery. Gallbladder volvulus is a condition in which the organ twists on its long axis to the point where its vascular supply is compromised., Competing Interests: None declared., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Objective/introduction: Near-infrared spectroscopy (NIRS) is a non-invasive technique to detect cerebral ischemia by monitoring changes in regional cerebral oxygenation (rSO2) in the frontal lobes. However, there are no studies showing the changes in NIRS values in response to hemodynamic variations during stages of carotid endarterectomy (CEA) procedure and clinical implications of these changes. The aim of this study was to determine if hemodynamic changes affect NIRS values during carotid endarterectomy and if our results may help to provide strategies for hemodynamic management in these patients., Methods: A total of 50 consecutive patients undergoing CEA were prospectively included in the study. NIRS was measured at first minute after clamping of carotid artery, and then systolic blood pressure was increased above 150 mmHg. NIRS values from both hemispheres were recorded simultaneously at certain time points and were analyzed to evaluate the changes at different stages of operation and to assess correlations with hemodynamic parameters., Results: NIRS values on the right and left sides were correlated with systolic (right P<0.001, R2:0.24; left P=0.02, R2:0.10) diastolic (right P<0.001, R2:0.36; left P=0.001, R2:0.18) and mean (right P<0.001, R2:0.33; left P=0.003, R2:0.17) blood pressures when the patient was under general anaesthesia. NIRS values were significantly lower than pre-incision values just after clamping of carotid artery in both hemispheres (P=0.005 for the right and P<0.001 for the left side)., Conclusion: NIRS values measured in our study show that there is a correlation between hemodynamic changes and cerebral oxygenation. This effect is especially pronounced while the patient is asleep and intubated, which implies the importance of close monitoring of patients with carotid disease during any surgery requiring general anaesthesia.

Background: Fibroblasts can be isolated from skin biopsies using a chemical dissociation, a physical dissociation, or a combination of both techniques. They can be reprogrammed into induced pluripotent stem cells (iPSCs) through the introduction of defined sets of key transcription factors. This study aimed to identify the optimal protocol for skin biopsy dissociation, fibroblast culture, and fibroblast cryopreservation in the scope of reprogramming into iPSCs and in the context of biobank accreditation. Methods: First, four dissociation techniques typically used in the laboratory (explant based, enzymatic, and/or mechanical) and two cryopreservation media containing 10% dimethyl sulfoxide, either commercial or homemade, were evaluated in terms of post-thaw recovery, viability, growth curves, and karyotyping analyses of the fibroblasts. Next, the clones reprogrammed from the fibroblasts isolated with the two optimal dissociation methods and cryopreservation media were further assessed by reprogramming quality before cryopreservation and post-thaw pluripotency comparison. Results: Fibroblasts isolated from skin biopsies using an explant-based or enzymatic dissociation method showed higher viability, higher proliferative potential, and higher genome stability post-thaw compared to the other dissociation techniques. Fibroblasts obtained by the explant-based dissociation technique showed a slightly higher reprogramming quality. The iPSC reprogrammed from explant-based dissociated fibroblasts showed successful recovery of iPSC clones. No difference between the two cryopreservation media was detected for the tested endpoints, with the exception of a higher visual count of colonies at the end of the reprogramming for the explant-based dissociation method. Conclusions: This article presents a formal method optimization for biospecimen processing in the context of accreditation in laboratories and biobanks. We validated skin biopsy-derived fibroblast isolation, culture, and cryopreservation for downstream mRNA reprogramming into iPSCs. The explant-based dissociation technique and homemade medium are selected as optimal to isolate and cryopreserve fibroblasts from skin biopsies in the scope of reprogramming into iPSCs.

Patients who are affected with severe chronic illness or in need for end-of-life care ((EOLC), they are mainly treated in the emergency departments (EDs) to provide the utmost amount of care for their condition. The major aspects which impact the accessibility of care in the ED include the clinical, social, and economic factors in different regions of countries. In recent years as the EOLC has been provided, it has been observed that patients experiencing EOL and dealing with a dying process do not always achieve the experience what resonates with a good death. The main cause of concern for these patients is the problem that in the ED they do not have access to palliative care options, mainly the ones who are suffering from noncancer ailments. These patients are provided palliative care at a very later stage in the ED when they could have been provided with palliative management at home in an earlier manner. EOLC plays a very critical role in ensuring that terminally ill patients are given a proper and adequate amount of care. The present article aims to highlight the EOLC in the ED in the Middle-Eastern regions. We aim to present a broader view that has impacted the current situation of EOLC in the Middle East regions and demonstrate a description of the EOLC in an ED setting between the Middle Eastern regions and western culture focusing on the following five important factors: Situation acceptance in the ED, cultural compatibility of bioethics, treatment perspective, skills among clinical providers and physician's attitude. In this literature review, we present the evidence associated with the EOLC in the ED setting with respect to the Middle East countries and bring out their differences in the religious, clinical, social, ethical, and economic aspects in comparison with the Western countries. We also tried to determine the differences between the two regions in terms of the principle of explaining the fatal diagnosis or poor prognosis, family relations, and do-not-resuscitate decision. This comparative analysis will help to bring out the gaps in the quality of care in the ED in the Middle East countries and promote the development of well-assessed policies and strategies to improve EOLC. The findings of this study and the future interventions that can be implemented to improve the structure and design of the EOLC that will act as a guiding force to execute evidence-based quality improvement program., Competing Interests: Conflicts of interest None Declared., (Copyright: © 2022 Turkish Journal of Emergency Medicine.)