Search results for: clinical pathway

Authors: Ergin Toros, Manar Aslan

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This study was planned as a descriptive study in order to learn the opinions of the students who are studying in nursing undergraduate program about their theoretical/practical lessons and departments. The education in the undergraduate nursing programs has great importance because it contains the knowledge and skills to prepare student nurses to the clinic in the future. In order to provide quality-nursing services in the future, the quality of nursing education should be measured, and opinions of student nurses about education should be taken. The research population was composed of students educated in a university with 1-4 years of theoretical and clinical education (N=550), and the sample was composed of 460 students that accepted to take part in the study. It was reached to 83.6% of target population. Data collected through a survey developed by the researchers. Survey consists of 48 questions about sociodemographic characteristics (9 questions), theoretical courses (9 questions), laboratory applications (7 questions), clinical education (14 questions) and services provided by the faculty (9 questions). It was determined that 83.3% of the nursing students found the nursing profession to be suitable for them, 53% of them selected nursing because of easy job opportunity, and 48.9% of them stayed in state dormitory. Regarding the theoretical courses, 84.6% of the students were determined to agree that the question ‘Course schedule is prepared before the course and published on the university web page.’ 28.7% of them were determined to do not agree that the question ‘Feedback is given to students about the assignments they prepare.’. It has been determined that 41,5% of the students agreed that ‘The time allocated to laboratory applications is sufficient.’ Students said that physical conditions in laboratory (41,5%), and the materials used are insufficient (44.6%), and ‘The number of students in the group is not appropriate for laboratory applications.’ (45.2%). 71.3% of the students think that the nurses view in the clinics the students as a tool to remove the workload, 40.7% of them reported that nurses in the clinic area did not help through the purposes of the course, 39.6% of them said that nurses' communication with students is not good. 37.8% of students stated that nurses did not provide orientation to students, 37.2% of them think that nurses are not role models for students. 53.7% of the students stated that the incentive and support for the student exchange program were insufficient., %48 of the students think that career planning services, %47.2 security services,%45.4 the advisor spent time with students are not enough. It has been determined that nursing students are most disturbed by the approach of the nurses in the clinical area within the undergraduate education program. The clinical area education which is considered as an integral part of nursing education is important and affect to student satisfaction.

Keywords: nursing education, student, clinical area, opinion

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Authors: Elham Shakerian, Reza Afarin

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The hepatic disease causes approximately 2 million deaths/year worldwide. Liver fibrosis is the last stage of numerous chronic liver diseases, and until now there is no definite cure or drug for it. Activation of hepatic stellate cells (HSCs) is the main reason for fibrosis. Transforming growth factor (TGF-β), as a main profibrogenic cytokine, if increased in these cells, leads to liver fibrosis through smad3 signaling pathways and increasing the expressions of Collagen type I and III, and actin-alpha smooth muscle (αSMA) genes. Curcumin (CUR) is a polyphenolic compound and an active ingredient derived from the rhizome of the turmeric plant that exerts effective antioxidant, anti-inflammatory, and antimicrobial activity. It has been shown that daily consumption of curcumin may have a protective effect on the liver against oxidative stress associated with alcohol consumption. In this study, we investigate the role of Curcumin in decreasing HSC activation and treating liver fibrosis. First, the human HSCs were treated with 2 ng/ml of (TGF-β) for 24 hours to become activated, then with Silibinin for 24 hours. Total RNAs were extracted, reversely transcribed into cDNA, Quantitative Real-time PCR, and western blot were performed. The mRNA expression levels of Collagen type I and III, αSMA genes, and the level of smad3 phosphorylation in TGF-β activated human HSCs treated with Curcumin were significantly reduced compared to human HSCs untreated with Curcumin. Curcumin is effective in reducing the expression of fibrogenic genes in the activated human HSCs treated with TGFB through downregulation of the TGF-β/smad3 signaling pathway. Therefore, Curcumin possesses significant antifibrotic properties in hepatic fibrosis

Keywords: hepatic fibrosis, human HSCs, curcumin, fibrogenic genes

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Authors: Charléa M. Smith, Raiden L. Schodowski, Arletty Pinel

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Due to the COVID-19 pandemic, the Faculty of Medical Sciences of The University of the West Indies (UWI) Mona in Kingston, Jamaica, had to rapidly migrate to digital and blended learning. Students in the preclinical stage of the program transitioned to full-time online learning, while students in the clinical stage experienced decreased daily patient contact and the implementation of a blend of online lectures and virtual clinical practice. Such sudden changes were coupled with the institutional pressure of the need to introduce a novel approach to education without much time for preparation, as well as additional strain endured by the faculty, who were overwhelmed by serving as frontline workers. During the period July 20 to August 23, 2021, this study surveyed preclinical and clinical students to capture their experiences with these changes and their recommendations for future use of digital modalities of learning to enhance medical education. It was conducted with a fellow student of the 2021 cohort of the MultiPod mentoring program. A questionnaire was developed and distributed digitally via WhatsApp to all medical students of the UWI Mona campus to assess students’ experiences and perceptions of the advantages, challenges, and impact on individual knowledge proficiencies brought about by the transition to predominantly digital learning environments. 108 students replied, 53.7% preclinical and 46.3% clinical. 67.6% of the total were female and 30.6 % were male; 1.8% did not identify themselves by gender. 67.2% of preclinical students preferred blended learning and 60.3% considered that the content presented did not prepare them for clinical work. Only 31% considered that the online classes were interactive and encouraged student participation. 84.5% missed socialization with classmates and friends and 79.3% missed a focused environment for learning. 80% of the clinical students felt that they had not learned all that they expected and only 34% had virtual interaction with patients, mostly by telephone and video calls. Observing direct consultations was considered the most useful, yet this was the least-used modality. 96% of the preclinical students and 100% of the clinical ones supplemented their learning with additional online tools. The main recommendations from the survey are the use of interactive teaching strategies, more discussion time with lecturers, and increased virtual interactions with patients. Universities are returning to face-to-face learning, yet it is unlikely that blended education will disappear. This study demonstrates that students’ perceptions of their experience during mobility restrictions must be taken into consideration in creating more effective, inclusive, and efficient blended learning opportunities.

Keywords: blended learning, digital learning, medical education, student perceptions

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Authors: Pureun-Haneul Lee, Byeong-Gon Kim, Sun-Hye Lee, An-Soo Jang

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Background: Nanoparticles may pose adverse health effects due to particulate matter inhalation. Nanoparticle exposure induces cell and tissue damage, causing local and systemic inflammatory responses. The inflammasome is a major regulator of inflammation through its activation of pro-caspase-1, which cleaves pro-interleukin-1β (IL-1β) into its mature form and may signal acute and chronic immune responses to nanoparticles. Objective: The aim of the study was to identify whether nanoparticles exaggerates inflammasome pathway leading to airway inflammation and hyperresponsiveness in an allergic mice model of asthma. Methods: Mice were treated with saline (sham), OVA-sensitized and challenged (OVA), or titanium dioxide nanoparticles. Lung interleukin 1 beta (IL-1β), interleukin 18 (IL-18), NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and caspase-1 levels were assessed with Western Blot. Caspase-1 was checked by immunohistochemical staining. Reactive oxygen species were measured for the marker 8-isoprostane and carbonyl by ELISA. Results: Airway inflammation and hyperresponsiveness increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. TiO2 nanoparticles treatment increased IL-1β and IL-18 protein expression in OVA-sensitized/challenged mice. TiO2 nanoparticles augmented the expression of NLRP3 and caspase-1 leading to the formation of an active caspase-1 in the lung. Lung caspase-1 expression was increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. Reactive oxygen species was increased in OVA-sensitized/challenged mice and in OVA-sensitized/challenged plus TiO2 exposed mice. Conclusion: Our data demonstrate that inflammasome pathway activates in asthmatic lungs following nanoparticles exposure, suggesting that targeting the inflammasome may help control nanoparticles-induced airway inflammation and responsiveness.

Keywords: bronchial asthma, inflammation, inflammasome, nanoparticles

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Authors: Mohamed Wahba

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Objective: To build a comparative arm for product (X) in specific gene mutated advanced gastrointestinal cancer using real world evidence to fulfill HTA requirements in drug evaluation. Methods: Data for product (X) were collected from phase II clinical trial while real world data for (Y) and (Z) were collected from US database. Real-world (RW) cohorts were matched to clinical trial base line characteristics using weighting by odds method. Outcomes included progression-free survival (PFS) and overall survival (OS) rates. Study location and participants: Internationally (product X, n=80) and from USA (Product Y and Z, n=73) Results: Two comparisons were made: trial cohort 1 (X) versus real-world cohort 1 (Z), trial cohort 2 (X) versus real-world cohort 2 (Y). For first line, the median OS was 9.7 months (95% CI 8.6- 11.5) and the median PFS was 5.2 months (95% CI 4.7- not reached) for real-world cohort 1. For second line, the median OS was 10.6 months (95% CI 4.7- 27.3) for real-world cohort 2 and the median PFS was 5.0 months (95% CI 2.1- 29.3). For OS analysis, results were statistically significant but not for PFS analysis. Conclusion: This study provided the clinical comparative outcomes needed for HTA evaluation.

Keywords: real world evidence, pharmacoeconomics, HTA agencies, oncology

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Authors: Ejovi Eghwubare Augustine

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This study delved into the traditional mechanisms of conflict resolution in Africa, a pathway to sustainable peace in Nigeria. It deployed the quantitative and qualitative methods of data collection and content analysis. The work adopted the Peace Process theory propounded by John Darby and Roger Macunity. It ascertained that disputes or disagreements are unarguably and necessarily an inevitable part of human existence, flowing directly from communication, interaction, and relationships which can occur at individual and national levels, even at international levels in view of the current trend of globalization. The alternative Dispute Resolution (ADR) mechanism is a basket of procedures outside the traditional process of litigation or strict determination of legal rights. It may also be elucidated as a range of procedures that serve as generally involve the intercession and assistance of a neutral and impartial third party. The traditional mechanisms of conflict resolution in Africa are alien to the Western world; this paper is of utmost importance to the Western world and also enriched their pool of literature. Nigeria is a country that is dominated by various ethnic groups anchored on diverse cultures, customs, and traditions. It is, therefore, not surprising to see conflicts arise, and despite the various attempts at resolving these conflicts through litigation, they still remained unabated. The paper investigated the lessons learned from Traditional Mechanisms of Conflict resolution; it also interrogated its impact and the way forward. In light of the lessons that were learned and the impact of the traditional mechanisms of conflict resolution, suggestions on how to attain a sustainable, peaceful society were proffered. In conclusion, the study crystallized reforms on the alternative dispute resolution introduced through the traditional mechanism, which includes, amongst others, that constitutional recognition should be given to traditional institutions of conflict resolution to enable quick dispensation of matters.

Keywords: traditional, conflict, peace, resolution

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Authors: Jitendra Jain, Cassandra Hidajat, Hansraj Riteesh Bookun

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Graft patency underpins long-term prognosis after coronary artery bypass grafting surgery (CABG). The benefits of the combined use of only the left internal mammary artery and radial artery, referred to as total arterial revascularisation (TAR), on long-term clinical outcomes and quality of life are relatively unknown. The aim of this study was to identify whether there were differences in long term clinical outcomes between recipients of TAR compared to a cohort of mostly arterial revascularization involving the left internal mammary, at least one radial artery and at least one saphenous vein graft. A retrospective analysis was performed on all patients who underwent TAR or were re-vascularized with supplementary saphenous vein graft from February 1996 to December 2004. Telephone surveys were conducted to obtain clinical outcome parameters including major adverse cardiac and cerebrovascular events (MACCE) and Short Form (SF-36v2) Health Survey responses. A total of 176 patients were successfully contacted to obtain postop follow up results. The mean follow-up length from time of surgery in our study was TAR 12.4±1.8 years and conventional 12.6±2.1. PCS score was TAR 45.9±8.8 vs LIMA/Rad/ SVG 44.9±9.2 (p=0.468) and MCS score was TAR 52.0±8.9 vs LIMA/Rad/SVG 52.5±9.3 (p=0.723). There were no significant differences between groups for NYHA class 3+ TAR 9.4% vs. LIMA/Rad/SVG 6.6%; or CCS 3+ TAR 2.35% vs. LIMA/Rad/SVG 0%.

Keywords: CABG; MACCEs; quality of life; total arterial revascularisation

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Authors: Fakhrosadat Sajjadian, Ramin Ghasemi Shayan

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The tumor microenvironment plays an fundamental part in tumor start, movement, metastasis, and treatment resistance. It varies from ordinary tissue in terms of its extracellular network, vascular and lymphatic arrange, as well as physiological conditions. The clinical application of atomic cancer imaging is regularly prevented by the tall commercialization costs of focused on imaging operators as well as the constrained clinical applications and little showcase measure of a few operators. . Since numerous cancer types share comparable characteristics of the tumor microenvironment, the capacity to target these biomarkers has the potential to supply clinically translatable atomic imaging advances for numerous types encompassing cancer and broad clinical applications. Noteworthy advance has been made in focusing on the tumor microenvironment for atomic cancer imaging. In this survey, we summarize the standards and methodologies of later progresses in atomic imaging of the tumor microenvironment, utilizing distinctive imaging modalities for early discovery and conclusion of cancer. To conclude, The tumor microenvironment (TME) encompassing tumor cells could be a profoundly energetic and heterogeneous composition of safe cells, fibroblasts, forerunner cells, endothelial cells, flagging atoms and extracellular network (ECM) components.

Keywords: molecular, imaging, TME, medicine

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Authors: Aniruddha Kulkarni

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In very few cases of external hernias we require imaging modalities as on most occasions clinical examination tests are good enough. Ultrasound will help in chronic abdominal or groin pain, equivocal clinical results & complicated hernias. Ultrasound is useful in assessment of cause of raised intrabdominal pressure. In certain cases will comment about etiology, complications and chronicicty of lesion. Screening of rest of abdominal organs too is important advantage being real time modality. Cost effectiveness, no radiation allows modality be used repeatedly in indicated cases. Sonography is better accepted by patients too as it is cost effective. Best advanced tissue harmonic equipment and increasing expertise making it popular. Ultrasound can define surgical anatomy, rent size, contents, etiological /recurrence factors in great detail and with authority hence accidental findings in a planned surgical procedure can be easily avoided. Clinical dynamic valselva and reducibility test can better documented by real time ultrasound study. In case of recurrence, Sonography will help in assessing the hernia details better as being dynamic real time investigation. Ultrasound signs in case of internal hernias are well comparable with CT findings.

Keywords: laparoscopic repair, Hernia, CT findings, chronic pain

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Authors: Inam Ridha, Christine L. Kuryla, Madhuranga Thilakasiri Madugoda Ralalage Don, Norman J. Kleiman, Yunro Chung, Jin Park, Vel Murugan, Joshua LaBaer

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To date, more than 275 million people worldwide have been diagnosed with COVID-19 and the rapid spread of the omicron variant suggests many millions more will soon become infected. Many infections are asymptomatic, while others result in mild to moderate illness. Unfortunately, some infected individuals exhibit more serious symptoms including respiratory distress, thrombosis, cardiovascular disease, multi-organ failure, cognitive difficulties, and, in roughly 2% of cases, death. Studies indicate other coronaviruses can alter the host cell's epigenetic profile and lead to alterations in the immune response. To better understand the mechanism(s) by which SARS-CoV-2 infection causes serious illness, DNA methylation profiles in peripheral blood mononuclear cells (PBMCs) from 90 hospitalized severely ill COVID-19 patients were compared to profiles from uninfected control subjects. Exploratory epigenome-wide DNA methylation analyses were performed using multiplexed methylated DNA immunoprecipitation (MeDIP) followed by pathway enrichment analysis. The findings demonstrated significant DNA methylation changes in infected individuals as compared to uninfected controls. Pathway analysis indicated that apoptosis, cell cycle control, Toll-like receptors (TLR), cytokine interactions, and T cell differentiation were among the most affected metabolic processes. In addition, changes in specific gene methylation were compared to SARS-CoV-2 induced changes in RNA expression using published RNA-seq data from 3 patients with severe COVID-19. These findings demonstrate significant correlations between differentially methylated and differentially expressed genes in a number of critical pathways.

Keywords: COVID19, epigenetics, DNA mathylation, viral infection

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Authors: L. B. Naves, L. Almeida

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The development of Drugs Delivery System (DDS), has been wildly investigated in the last decades. In this paper, first a general overview of traditional and modern wound dressing is presented. This is followed by a review of what scientist have done in the medical environment, focusing the possibility to develop a new alternative for DDS through transdermal pathway, aiming to treat melanoma skin cancer.

Keywords: cancer therapy, dressing polymers, melanoma, wound healing

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Authors: Evar C. Umeozor, Experience I. Nduagu, Ian D. Gates

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The energy requirements of carbon dioxide utilization (CDU) technologies/processes are diverse, so also are their environmental footprints. This paper explores the energy and environmental impacts of systems for CO₂ conversion to fuels, chemicals, and materials. Energy needs of the technologies and processes deployable in CO₂ conversion systems are met by one or combinations of hydrogen (chemical), electricity, heat, and light. Likewise, the environmental footprint of any CO₂ utilization pathway depends on the systems involved. So far, evaluation of CDU systems has been constrained to particular energy source/type or a subset of the overall system needed to make CDU possible. This introduces limitations to the general understanding of the energy and environmental implications of CDU, which has led to various pitfalls in past studies. A CDU system has an energy source, CO₂ supply, and conversion units. We apply a holistic approach to consider the impacts of all components in the process, including various sources of energy, CO₂ feedstock, and conversion technologies. The electricity sources include nuclear power, renewables (wind and solar PV), gas turbine, and coal. Heat is supplied from either electricity or natural gas, and hydrogen is produced from either steam methane reforming or electrolysis. The CO₂ capture unit uses either direct air capture or post-combustion capture via amine scrubbing, where applicable, integrated configurations of the CDU system are explored. We demonstrate how the overall energy and environmental impacts of each utilization pathway are obtained by aggregating the values for all components involved. Proper accounting of the energy and emission intensities of CDU must incorporate total balances for the utilization process and differences in timescales between alternative conversion pathways. Our results highlight opportunities for the use of clean energy sources, direct air capture, and a number of promising CO₂ conversion pathways for producing methanol, ethanol, synfuel, urea, and polymer materials.

Keywords: carbon dioxide utilization, processes, energy options, environmental impacts

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Authors: Chamtouri I., Kechida M.

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Background: Evaluation has a prominent role in medical education and graduation. This evaluation has usually done in face-to-face, by written or oral questions. Simulation is increasingly taking a part as a method of evaluation. Due to the Covid-19 pandemic, which disrupted face-to-face evaluation, simulation using serious games (SG) is emerging in the field of training and assessment of medical students. The aim of our study is to compare the results of the evaluation of medical students by virtual simulation by online serious games versus clinical case-multiple choice questions (MCQ) and to assess the degree of satisfaction from these two evaluation methods. Methods: Medical students from the same study level were voluntarily participated in this study. Groupe 1 had an evaluation by SG dealing with “diagnosis and management of ST-segment elevationmyocardialinfarction (STEMI)alreadyprepared on the website www.Mediactiv.com. Groupe 2 were evaluated by clinical case-MCQ having thes same topic as SG. Results of the two groups were compared. Satisfaction questionnaire was filled by the two groups. Satisfaction degree was compared between the two groups. Results. In this study, 64 medical students (G1:31 and G2: 33) were enrolled. Obtaining complete notes in the "questioning" and "clinical examination" parts is significantly more important in-group 1 compared to group 2. No significant difference detected between the two groups in terms of “ECG interpretation” and “diagnosis of STEMI” parts. A greater number of students of group 1 obtained the full note compared to group 2 in “the initial treatment part” (54.8% vs. 39.4%; p = 0.04). Thirty learners (96.8%) in-group 1 obtained a total score ≥ 50% versus 69.7% in-group 2 (p = 0.004). The full score of 100% was obtained in three learners in-group1, while no student scored 100% in-group2 (p = 0.027). Medical evaluation using SG was reported as more innovative, fun, and realistic compared to evaluation by clinical case-MCQ. No significant difference detected between the two methods in terms of stress. Conclusion: Simulation by SG can be considered as an innovative and effective method in evaluating medical students with a higher degree of satisfaction.

Keywords: evaluation, serious games, medical students, satisfaction

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Authors: Shanza Akram, Sameen Toor, Heba Harb Abu Alkass, Zainab Abdulsalam Altaha, Sara Taha Abdulla, Saleem Imran

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Acute pulmonary embolism (PE) is a common disease and can be fatal. The clinical presentation is variable and nonspecific, making accurate diagnosis difficult. Testing patients with suspected acute PE has increased dramatically. However, the overuse of some tests, particularly CT and D-dimer measurement, may not improve care while potentially leading to patient harm and unnecessary expense. CTPA is the investigation of choice for PE. Its easy availability, accuracy and ability to provide alternative diagnosis has lowered the threshold for performing it, resulting in its overuse. Guidelines have recommended the use of clinical pretest probability tools such as ‘Wells score’ to assess risk of suspected PE. Unfortunately, implementation of guidelines in clinical practice is inconsistent. This has led to low risk patients being subjected to unnecessary imaging, exposure to radiation and possible contrast related complications. Aim: To study the diagnostic yield of CT PA, clinical pretest probability of patients according to wells score and to determine whether or not there was an overuse of CTPA in our service. Methods: CT scans done on patients with suspected P.E in our hospital from 1st January 2014 to 31st December 2014 were retrospectively reviewed. Medical records were reviewed to study demographics, clinical presentation, final diagnosis, and to establish if Wells score and D-Dimer were used correctly in predicting the probability of PE and the need for subsequent CTPA. Results: 100 patients (51male) underwent CT PA in the time period. Mean age was 57 years (24-91 years). Majority of patients presented with shortness of breath (52%). Other presenting symptoms included chest pain 34%, palpitations 6%, collapse 5% and haemoptysis 5%. D Dimer test was done in 69%. Overall Wells score was low (<2) in 28 %, moderate (>2 - < 6) in 47% and high (> 6) in 15% of patients. Wells score was documented in medical notes of only 20% patients. PE was confirmed in 12% (8 male) patients. 4 had bilateral PE’s. In high-risk group (Wells > 6) (n=15), there were 5 diagnosed PEs. In moderate risk group (Wells >2 - < 6) (n=47), there were 6 and in low risk group (Wells <2) (n=28), one case of PE was confirmed. CT scans negative for PE showed pleural effusion in 30, Consolidation in 20, atelactasis in 15 and pulmonary nodule in 4 patients. 31 scans were completely normal. Conclusion: Yield of CT for pulmonary embolism was low in our cohort at 12%. A significant number of our patients who underwent CT PA had low Wells score. This suggests that CT PA is over utilized in our institution. Wells score was poorly documented in medical notes. CT-PA was able to detect alternative pulmonary abnormalities explaining the patient's clinical presentation. CT-PA requires concomitant pretest clinical probability assessment to be an effective diagnostic tool for confirming or excluding PE. . Clinicians should use validated clinical prediction rules to estimate pretest probability in patients in whom acute PE is being considered. Combining Wells scores with clinical and laboratory assessment may reduce the need for CTPA.

Keywords: CT PA, D dimer, pulmonary embolism, wells score

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Authors: Aya Al Masri, Stefaan Carpentier, Fabrice Leroy, Thibault Julien, Safoin Aktaou, Malorie Martin, Fouad Maaloul

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Introduction: During an 'Interventional Radiology (IR)' procedure, the patient's skin-dose may become very high for a burn, necrosis and ulceration to appear. In order to prevent these deterministic effects, an accurate calculation of the patient skin-dose mapping is essential. For most machines, the 'Dose Area Product (DAP)' and fluoroscopy time are the only information available for the operator. These two parameters are a very poor indicator of the peak skin dose. We developed a mathematical model that reconstructs the magnitude (delivered dose), shape, and localization of each irradiation field on the patient skin. In case of critical dose exceeding, the system generates warning alerts. We present the results of its comparison with clinical studies. Materials and methods: Two series of comparison of the skin-dose mapping of our mathematical model with clinical studies were performed: 1. At a first time, clinical tests were performed on patient phantoms. Gafchromic films were placed on the table of the IR machine under of PMMA plates (thickness = 20 cm) that simulate the patient. After irradiation, the film darkening is proportional to the radiation dose received by the patient's back and reflects the shape of the X-ray field. After film scanning and analysis, the exact dose value can be obtained at each point of the mapping. Four experimentation were performed, constituting a total of 34 acquisition incidences including all possible exposure configurations. 2. At a second time, clinical trials were launched on real patients during real 'Chronic Total Occlusion (CTO)' procedures for a total of 80 cases. Gafchromic films were placed at the back of patients. We performed comparisons on the dose values, as well as the distribution, and the shape of irradiation fields between the skin dose mapping of our mathematical model and Gafchromic films. Results: The comparison between the dose values shows a difference less than 15%. Moreover, our model shows a very good geometric accuracy: all fields have the same shape, size and location (uncertainty < 5%). Conclusion: This study shows that our model is a reliable tool to warn physicians when a high radiation dose is reached. Thus, deterministic effects can be avoided.

Keywords: clinical experimentation, interventional radiology, mathematical model, patient's skin-dose mapping.

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Authors: Siriporn Sikkaphun

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Food is essential for living, and receiving correct, suitable, and adequate food is advantageous to the body, especially for patients because it can enable good recovery. Feeding through a gastrostomy tube is one useful way that is widely used because it is easy, convenient, and economical.To compare the effectiveness of using the clinical guidelines for feeding through a gastrostomy tube in critically ill surgical patients.This is a pre-post quasi-experimental study on 15 critically ill surgical or accident patients who needed intubation and the gastrostomy tube from August 2011 to November 2012. The data were collected using the guidelines, and an evaluation form for effectiveness of guidelines for feeding through a gastrostomy tube in critically ill surgical patients. After using the guidelines for feeding through a gastrostomy tube in critically ill surgical patients, it was found that The average number of days from the admission date to the day the patients received food through the G-tube significantly reduced at the level .05. The number of personnel who practiced nursing activities correctly and suitably for patients with complications during feeding significantly increased at the level .05.The number of patients receiving energy to the target level significantly increased at the level .05. The results of this study indicated that the use of the guidelines for feeding through a gastrostomy tube in critically ill surgical patients was feasible in practice, and the outcomes were beneficial to the patients.

Keywords: clinical guidelines, feeding, gastrostomy tube, critically ill, surgical patients

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Authors: Caixiu Pu, Zhen Chen

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We present the rare case of umbilical arterial atresia, leading to a good outcome and provide clinical and pathological findings. A 27-year-old nulliparous first gravida with PGDM was found single umbilical artery(SUA) by routine ultrasound san at 30 weeeks of gestation. Fetal status was monitored weekly. A healthy male newborn was delivered by cesarean section at 39 weeks. The umbilical cord was overly twisted and no thrombus was found along the whole diseased vessel. The cause of umbilical arterial atresia was unclear, and the correct diagnosis was a challenge. Expected clinical management was recommended, in which sonographic diagnosis may play a very important part.

Keywords: pregnancy, single umbilical artery, umbilical arterial atresia, prenatal diagnosis

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Authors: Ilana Margalith, Yaron Niv

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One of the most important factors of professional health treatment is teamwork, in which each discipline contributes its expert knowledge, thus ensuring quality and a high standard of care as well as efficient communication (one of the International Patient Safety Goals). However, in most countries, students are educated separately by each health discipline. They are exposed to teamwork only during their clinical experience, which in some cases is short and skill-oriented. In addition, health organizations in most countries are hierarchical and although changes have occurred in the hierarchy of the medical system, there are still disciplines that underrate the unique contributions of other health professionals, thus, young graduates of health professions develop and base their perception of their peers from other disciplines on insufficient knowledge. In order to establish a wide-ranging perception among nursing students as to the contribution of different health professionals to the health of their patients, students at the Clalit Nursing Academy, Rabin Campus (Dina), Israel, participated in an interdisciplinary clinical discussion with students from several different professions, other than nursing, who were completing their clinical experience at Rabin Medical Center in medicine, health psychology, social work, audiology, physiotherapy and occupational therapy. The discussion was led by a medical-surgical nursing instructor. Their tutors received in advance, a case report enabling them to prepare the students as to how to present their professional theories and interventions regarding the case. Mutual stimulation and acknowledgment of the unique contribution of each part of the team enriched the nursing students' understanding as to how their own nursing interventions could be integrated into the entire process towards a safe and speedy recovery of the patient.

Keywords: health professions' students, interdisciplinary clinical discussion, nursing education, patient safety

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Authors: Marilena Fatigante

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Contemporary psychoanalysis is increasingly acknowledging the existential demands of clients in psychotherapy. A significant aspect of the personal crises that patients face today is often rooted in the difficulty to find meaning in their own existence, even after working through or resolving traumatic memories and experiences. Tracing back to the correspondence between Freud and Romain Rolland (1927), psychoanalysis could not ignore that investigation of the psyche also encompasses the encounter with deep, psycho-sensory experiences, which involve a sense of "being one with the external world as a whole", the well-known “oceanic feeling”, as Rolland posed it. Despite the recognition of Non-ordinary States of Consciousness (NSC) as catalysts for transformation in clinical practice, highlighted by neuroscience and results from psychedelic-assisted therapies, there is few research on how psychoanalytic knowledge can integrate with other treatment traditions. These traditions, commonly rooted in non -Western, unconventional, and non-formal psychological knowledge, emphasize the individual’s innate tendency toward existential integrity and transcendence of self-boundaries. Inspired by an autobiographical account, this paper examines narratives of 12 individuals, who engaged in psychoanalytic therapy and also underwent treatment involving a non-formal helping relationship with an expert guide in consciousness, which included experience of this nature. The guide relies on 35 yrs of experience in Psychological, multidisciplinary studies in Human Sciences and Art, and demonstrates knowledge of many wisdom traditions, ranging from Eastern to Western philosophy, including Psychoanalysis and its development in cultural perspective (e.g, Ethnopsychiatry). Analyses focused primarily on two dimensions that research has identified as central in assessing the degree of treatment “success” in the patients’ narrative accounts of their therapies: agency and coherence, defined respectively as the increase, expressed in language, of the client’s perceived ability to manage his/her own challenges and the capacity, inherent in “narrative” itself as a resource for meaning making (Bruner, 1990), to provide the subject with a sense of unity, endowing his /her life experience with temporal and logical sequentiality. The present study reports that, in all narratives from the participants, agency and coherence are described differently than in “common” psychotherapy narratives. Although the participants consistently identified themselves as responsible agentic subject, the sense of agency derived from the non-conventional guidance pathway is never reduced to a personal, individual accomplishment. Rather, the more a new, fuller sense of “Life” (more than “Self”) develops out of the guidance pathway they engage with the expert guide, the more they “surrender” their own sense of autonomy and self-containment. Something, which Safran (2016) identified as well talking about the sense of surrender and “grace” in psychoanalytic sessions. Secondly, narratives of individuals engaging with the expert guide describe coherence not as repairing or enforcing continuity but as enhancing their ability to navigate dramatic discontinuities, falls, abrupt leaps and passages marked by feelings of loss and bereavement. The paper ultimately explores whether valid criteria can be established to analyze experiences of non-conventional paths of self-evolution. These paths are not opposed or alternative to conventional ones, and should not be simplistically dismissed as exotic or magical.

Keywords: oceanic feeling, non conventional guidance, consciousness, narratives, treatment outcomes

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Authors: Siddharth Jain, Abhenil Mittal, Surendra Kumar Sharma

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Background: With its recent emergence and re-emergence, dengue has become a major international public health concern, imposing significant financial burden especially in developing countries. Despite aggressive control measures in place, India experienced one of its largest outbreaks in 2015 with Delhi being most severely affected. There is a lack of reliable predictors of disease severity and mortality in dengue. The present study was carried out to identify these predictors during the 2015 outbreak. Methods: This prospective observational study conducted at an apex tertiary care center in Delhi, India included confirmed adult dengue patients admitted between August-November 2015. Patient demographics, clinical details, and laboratory findings were recorded in a predesigned proforma. Appropriate statistical tests were used to summarize and compare the clinical and laboratory characteristics and derive predictors of mortality and severe disease, while developing a clinical risk score for mortality. Serotype analysis was also done for 75 representative samples to identify the dominant serotypes. Results: Data of 369 patients were analyzed (mean age 30.9 years; 67% males). Of these, 198 (54%) patients had dengue fever, 125 (34%) had dengue hemorrhagic fever (DHF Grade 1,2)and 46 (12%) developed dengue shock syndrome (DSS). Twenty two (6%) patients died. Late presentation to the hospital (≥5 days after onset) and dyspnoea at rest were identified as independent predictors of severe disease. Age ≥ 24 years, dyspnoea at rest and altered sensorium were identified as independent predictors of mortality. A clinical risk score was developed (12*age + 14*sensorium + 10*dyspnoea) which, if ≥ 22, predicted mortality with a high sensitivity (81.8%) and specificity (79.2%). The predominant serotypes in Delhi (2015) were DENV-2 and DENV-4. Conclusion: Age ≥ 24 years, dyspnoea at rest and altered sensorium were identified as independent predictors of mortality. Platelet counts did not determine the outcome in dengue patients. Timely referral/access to health care is important. Development and use of validated predictors of disease severity and simple clinical risk scores, which can be applied in all healthcare settings, can help minimize mortality and morbidity, especially in resource limited settings.

Keywords: dengue, mortality, predictors, severity

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Authors: Vesile Unver, Tulay Basak, Hatice Ayhan, Ilknur Cinar, Emine Iyigun, Nuran Tosun

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The aim of this study is to analyze the effects of the hybrid simulation. In this simulation, types standardized patients and task trainers are employed simultaneously. For instance, in order to teach the IV activities standardized patients and IV arm models are used. The study was designed as a quasi-experimental research. Before the implementation an ethical permission was taken from the local ethical commission and administrative permission was granted from the nursing school. The universe of the study included second-grade nursing students (n=77). The participants were selected through simple random sample technique and total of 39 nursing students were included. The views of the participants were collected through a feedback form with 12 items. The form was developed by the authors and “Patient intervention self-confidence/competence scale”. Participants reported advantages of the hybrid simulation practice. Such advantages include the following: developing connections between the simulated scenario and real life situations in clinical conditions; recognition of the need for learning more about clinical practice. They all stated that the implementation was very useful for them. They also added three major gains; improvement of critical thinking skills (94.7%) and the skill of making decisions (97.3%); and feeling as if a nurse (92.1%). In regard to the mean scores of the participants in the patient intervention self-confidence/competence scale, it was found that the total mean score for the scale was 75.23±7.76. The findings obtained in the study suggest that the hybrid simulation has positive effects on the integration of theoretical and practical activities before clinical activities for the nursing students.

Keywords: hybrid simulation, clinical practice, nursing education, nursing students

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Authors: Ashir Ahmed

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Generally, radicalization happens when a person's thinking and behaviour become significantly different from how most of the members of their society and community view social issues and participate politically. Radicalization often leads to violent extremism that refers to the beliefs and actions of people who support or use violence to achieve ideological, religious or political goals. Studies on radicalization negate the common myths that someone must be in a group to be radicalised or anyone who experiences radical thoughts is a violent extremist. Moreover, it is erroneous to suggest that radicalisation is always linked to religion. Generally, the common motives of radicalization include ideological, issue-based, ethno-nationalist or separatist underpinning. Moreover, there are number of factors that further augments the chances of someone being radicalised and may choose the path of violent extremism and possibly terrorism. Since there are numbers of factors (and sometimes quite different) contributing in radicalization and violent extremism, it is highly unlikely to devise a single solution that could produce effective outcomes to deal with radicalization, violent extremism and terrorism. The pathway to deradicalization, like the pathway to radicalisation, is different for everyone. Considering the need of having customized deradicalization resolution, this study proposes a multi-tier framework, called ‘pyramid of deradicalization’ that first help identifying the stage at which an individual could be on the radicalization pathway and then propose a customize strategy to deal with the respective stage. The first tier (tier 1) addresses broader community and proposes a ‘universal approach’ aiming to offer community-based design and delivery of educational programs to raise awareness and provide general information on possible factors leading to radicalization and their remedies. The second tier focuses on the members of community who are more vulnerable and are disengaged from the rest of the community. This tier proposes a ‘targeted approach’ targeting the vulnerable members of the community through early intervention such as providing anonymous help lines where people feel confident and comfortable in seeking help without fearing the disclosure of their identity. The third tier aims to focus on people having clear evidence of moving toward extremism or getting radicalized. The people falls in this tier are believed to be supported through ‘interventionist approach’. The interventionist approach advocates the community engagement and community-policing, introducing deradicalization programmes to the targeted individuals and looking after their physical and mental health issues. The fourth and the last tier suggests the strategies to deal with people who are actively breaking the law. ‘Enforcement approach’ suggests various approaches such as strong law enforcement, fairness and accuracy in reporting radicalization events, unbiased treatment by law based on gender, race, nationality or religion and strengthen the family connections.It is anticipated that the operationalization of the proposed framework (‘pyramid of deradicalization’) would help in categorising people considering their tendency to become radicalized and then offer an appropriate strategy to make them valuable and peaceful members of the community.

Keywords: deradicalization, framework, terrorism, violent extremism

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Authors: Fabio L. Vieira, Micaelle F. C. Lemos, Luciano C. Lemos, Rafaela S. Oliveira, Ian A. Cunha

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Brazil has some challenges ahead related to population oral health, most of them associated with the need of expanding into the local level its promotion and prevention activities, offer equal access to services and promote changes in the lifestyle of the population. The program implemented an oral health initiative in public schools in the city of Salvador, Bahia. The mission was to improve oral health among students on primary and secondary education, from 2 to 15 years old, using the school as a pathway to increase access to healthcare. The main actions consisted of a team's visit to the schools with educational sessions for dental cavity prevention and individual assessment. The program incorporated a clinical surveillance component through a dental evaluation of every student searching for dental disease and caries, standardization of the dentists’ team to reach uniform classification on the assessments, and the use of an online platform to register data directly from the schools. Sequentially, the students with caries were referred for free clinical treatment on the program’s Health Centre. The primary purpose of this study was to analyze the effects and outcomes of this school-based oral health program. The study sample was composed by data of a period of 3 years - 2015 to 2017 - from 13 public schools on the suburb of the city of Salvador with a total number of assessments of 9,278 on this period. From the data collected the prevalence of children with decay on permanent teeth was chosen as the most reliable indicator. The prevalence was calculated for each one of the 13 schools using the number of children with 1 or more dental caries on permanent teeth divided by the total number of students assessed for school each year. Then the percentage change per year was calculated for each school. Some schools presented a higher variation on the total number of assessments in one of the three years, so for these, the percentage change calculation was done using the two years with less variation. The results show that 10 of the 13 schools presented significative improvements for the indicator of caries in permanent teeth. The mean for the number of students with caries percentage reduction on the 13 schools was 26.8%, and the median was 32.2% caries in permanent teeth institution. The highest percentage of improvement reached a decrease of 65.6% on the indicator. Three schools presented a rise in caries prevalence (8.9, 18.9 and 37.2% increase) that, on an initial analysis, seems to be explained with the students’ cohort rotation among other schools, as well as absenteeism on the treatment. In conclusion, the program shows a relevant impact on the reduction of caries in permanent teeth among students and the need for the continuity and expansion of this integrated healthcare approach. It has also been evident the significative of the articulation between health and educational systems representing a fundamental approach to improve healthcare access for children especially in scenarios such as presented in Brazil.

Keywords: primary care, public health, oral health, school-based oral health, data management

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Authors: S. J. Yune, S. Y. Lee, S. J. Im, B. S. Kam, S. Y. Baek

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This study aimed to determine the reliability of clinical performance assessments, having been emphasized by ability-based education, and professors overall assessment methods. We addressed the following problems: First, we try to find out whether there is a difference in what we consider to be the main variables affecting the clinical performance test according to the evaluator’s working period and the number of evaluation experience. Second, we examined the relationship among the global rating score (G), analytic global rating score (Gc), and the sum of the analytical checklists (C). What are the main factors affecting clinical performance assessments in relation to the numbers of times the evaluator had administered evaluations and the length of their working period service? What is the relationship between overall assessment score and analytic checklist score? How does analytic global rating with 6 components in OSCE and 4 components in sub-domains (Gc) CPX: aseptic practice, precision, systemic approach, proficiency, successfulness, and attitude overall assessment score and task-specific analytic checklist score sum (C) affect the professor’s overall global rating assessment score (G)? We studied 75 professors who attended a 2016 Bugyeoung Consortium clinical skills performances test evaluating third and fourth year medical students at the Pusan National University Medical school in South Korea (39 prof. in OSCE, 36 prof. in CPX; all consented to participate in our study). Each evaluator used 3 forms; a task-specific analytic checklist, subsequent analytic global rating scale with sub-6 domains, and overall global scale. After the evaluation, the professors responded to the questionnaire on the important factors of clinical performance assessment. The data were analyzed by frequency analysis, correlation analysis, and hierarchical regression analysis using SPSS 21.0. Their understanding of overall assessment was analyzed by dividing the subjects into groups based on experiences. As a result, they considered ‘precision’ most important in overall OSCE assessment, and ‘precise accuracy physical examination’, ‘systemic approaches to taking patient history’, and ‘diagnostic skill capability’ in overall CPX assessment. For OSCE, there was no clear difference of opinion about the main factors, but there was for CPX. Analytic global rating scale score, overall rating scale score, and analytic checklist score had meaningful mutual correlations. According to the regression analysis results, task-specific checklist score sum had the greatest effect on overall global rating. professors regarded task-specific analytic checklist total score sum as best reflecting overall OSCE test score, followed by aseptic practice, precision, systemic approach, proficiency, successfulness, and attitude on a subsequent analytic global rating scale. For CPX, subsequent analytic global rating scale score, overall global rating scale score, and task-specific checklist score had meaningful mutual correlations. These findings support explanations for validity of professors’ global rating in clinical performance assessment.

Keywords: global rating, clinical performance assessment, medical education, analytic checklist

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Authors: Mathilde Blondon, Salla Aicha Dieng, Catherine Pfister

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In a paradoxical way, teenagers nowadays seem to use suicidal attempts to elaborate on their trauma abuses and regain some kind of control in their lives. As their behavior becomes life-threatening, the hospital offers a variety of expertise to address their need, with Child Protective Services also joining in, to a point when teenagers could have a feeling of losing control of their lives, which results in them making more suicidal attempts. Our goal here is to walk with these foster teenagers long enough to step therapy up first, then as their mental health is restored enough to step the therapy down in a way that is secure and will give them their life back. This would prevent them from making suicidal attempts to get a feeling of control over their life. We’ll present a clinical case of a 14-year-old girl named Sofia, who was suffering from parental deprivation, an identity disorder, and severe depression disorder. Our intervention took place in January 2024, after Sofia had undergone four hospitalizations, including a two-month period in a specialized clinic. In a stepping-up effort, a substantial setting has been built around Sofia. She was coming three days a week to therapeutic activities at the Child Psychiatry Day Hospital, she had one psychotherapy session a week at the Medical-Psychological Center, and she was meeting with the Adolescent Psychiatrist on a regular basis. However, her suicidal attempts frequency continued to increase to the point when she couldn’t stay more than four days outside the hospital unit without harming herself and being brought back to the Emergency Unit. We were all stuck in some kind of medical deadlock, writing to clinics that had no room for her while social workers were calling foster homes that wouldn’t even accept her either. At some point, a clinical decision was made by the psychiatrist to stop what appeared to be a global movement of traumatic repetition, which involved Sofia’s family, the medical team and the social workers as one. This decision to step therapy down created a surprise and put an end to the cycle. It provided a new path, a new solution where Sofia could securely settle without being unfaithful to her family. Her suicidal attempts stopped for four weeks. She had one relapse, then didn’t make another attempt so far. There is a fine line between too little and too much, a pathway with the right amount of care and support. We believe it is not a steady line but rather a path up and down the hill. It’s about building up this moment when medication and mental processes have improved the subject’s condition enough to allow the medical team to step therapy down and give more control back to the subject. These needed variations used to come from a change of hospital or medical team. Stepped care avoids any breaking of bonds and appears to be decisive in stopping teenagers’ suicidal attempts.

Keywords: child protection, adolescent psychiatry, teenager suicidal attempt, foster teenagers, parental deprivation, stepped care

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Authors: Panadda Rojpibulstit, Suthathip Kittisenachai, Songchan Puthong, Sirikul Manochantr, Pornpen Gamnarai, Sasichai Kangsadalampai, Sittiruk Roytrakul

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Hepatocellular carcinoma (HCC) is the most primary hepatic cancer worldwide. Nowadays a targeted therapy via monoclonal antibodies (mAbs) specific to tumor-associated antigen is continually developed in HCC treatment. In this regard, after establishing and consequently exploring Hep88 mAb’s tumoricidal effect on hepatocellular carcinoma cell line (HepG2 cell line), the Hep88 mAb’s specific Ag from both membrane and cytoplasmic fractions of HepG2 cell line was identified by 2-D gel electrophoresis and western blot analysis. After in-gel digestion and subsequent analysis by liquid chromatography-mass spectrometry (LC-MS), mortalin (HSPA9) and alpha-enolase were identified. The recombinant proteins specific to Hep88 mAb were cloned and expressed in E.coli BL21 (DE3). Moreover, alteration of HepG2 and Chang liver cell line after being induced by Hep88 mAb for 1-3 days was investigated using a transmission electron microscope. The result demonstrated that Hep88 mAb can bind to the recombinant mortalin (HSPA9) andalpha-enolase. In addition, gradual appearance of mitochondria vacuolization and endoplasmic reticulum dilatation were observed. Taken together, paraptosis-like programmed cell death (PCD) of HepG2 is induced by binding of mortalin (HSPA9) and alpha-enolase to Hep88 mAb. Mortalin depletion by formation of Hep88 mAb-mortalin (HSPA9) complex might initiate transcription-independent of p53-mediated apoptosis. Additionally, Hep88 mAb-alpha-enolase complex might initiate HepG2 cells energy exhaustion by glycolysis pathway obstruction. These results imply that Hep88 mAb might be a promising tool for development of an effective treatment of HCC in the next decade.

Keywords: Hepatocellular carcinoma, Monoclonal antibody, Paraptosis-like program cell death, Transmission electron microscopy, mortalin (HSPA9), alpha-enolase

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Authors: Ian McCulloh, Andrew Placona, Darren Stewart, Daniel Gause, Kevin Kiernan, Morgan Stuart, Christopher Zinner, Laura Cartwright

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An estimated 22-25% of viable deceased donor kidneys are discarded every year in the US, while waitlisted candidates are dying every day. As many as 85% of transplanted organs are refused at least once for a patient that scored higher on the match list. There are hundreds of clinical variables involved in making a clinical transplant decision and there is rarely an ideal match. Decision makers exhibit an optimism bias where they may refuse an organ offer assuming a better match is imminent. We propose a semi-parametric Cox proportional hazard model, augmented by an accelerated failure time model based on patient specific suitable organ supply and demand to estimate a time-to-next-offer. Performance is assessed with Cox-Snell residuals and decision curve analysis, demonstrating improved decision support for up to a 5-year outlook. Providing clinical decision makers with quantitative evidence of likely patient outcomes (e.g., time to next offer and the mortality associated with waiting) may improve decisions and reduce optimism bias, thus reducing discarded organs and matching more patients on the waitlist.

Keywords: decision science, KDPI, optimism bias, organ transplant

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Authors: Atitallah Sofien, Bouyahia Olfa, Hadj Salah Ibrahim, Ben Saleh Foued, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Carbon monoxide (CO) poisoning is a common pathology responsible for high morbidity and mortality worldwide. Aim: The purpose of this study was to determine the epidemiological profile of CO poisoning as well as its clinical, paraclinical, therapeutic, and evolutionary aspects. Methods: Our study included observations of CO poisoning in children hospitalized in the pediatric department C of the Children's Hospital in Tunis over a period of 3 years. Results: We have collected 199 cases of CO poisoning in children. The average age was 5.43 years, with a sex ratio of 0.98. The source of CO was inside the home in 73.2% of cases, and it was the gas bath heater in 68.8% of cases. The intoxication was collective in 93.5% of the cases, and it occurred during the month of January in 35.8% of the cases. The clinical manifestations were headaches in 69.5% of cases. The rate of carboxyhemoglobin was pathological in 73.9% of cases. All patients received normobaric oxygen therapy, and only 3.6% of patients had a hyperbaric oxygen therapy session. We did not deplore any case of death in our study. Conclusion: CO poisoning remains a public health problem in Tunisia with high morbidity. The risk of secondary complications, particularly neuropsychiatric, requires clinical and possibly neuroradiological monitoring of these victims.

Keywords: poisoning, carbon monoxide, children, hyperbaric oxygenation

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Authors: Katarína Koňariková, Georgios A. Perdikaris, Lucia Andrezálová, Zdeňka Ďuračková, Lucia Laubertová, Helena Gbelcová, Ingrid Žitňanová

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Introduction: The continuous demand for new anti-cancer drugs has stimulated chemotherapeutic research based on the use of essential metalloelements with the aim to develop potential drugs with lower toxicity and higher antiproliferative activity against tumors. Copper(II) and its complexes play an important role as suitable species for antiproliferative tests. Objectives: The central objective of the current study was to investigate the potential in vitro anti-proliferative effects of N-salicylidene-L-glutamato copper (II) complexes and molecular mechanism of apoptosis induced by tested complexes. In our project we tested N-salicylidene-L-glutamato copper (II) complexes ZK1 - [Cu(N-salicylidene-L-glutamato)(H2O)2].H2O; MK0 - ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O); MK1 - [Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O; MK3 - transbis(ethanol)tetrakis(imidazol)Cu(II)(2+)bis(N-salicylidene-D,L-glutamato-N,O)-KO:KO´-(imidazol); MK5 - [Cu(N-salicylidene-D,L- glutamato)(2-methylimidazol] at concentration range 0.001-100 µmol/L against human colon carcinoma cell line HT-29 and human breast carcinoma cell line MCF-7. Methods: Viability was assessed by direct counting of 0.4% trypan blue dye-excluding cells after 24, 48 and 72 hour cultivations with or without copper complex and by MTT assay. To analyze the type of cell death and its mechanism induced by our copper complex we used different methods. To distinguish apoptosis from necrosis we used electrophoretic analysis, to study the activity of caspases 8 and 9 – luminometric analysis and caspase activity 3 colorimetric assay. Results: The observed anti-proliferative effect of the copper complexes appeared to be dose-, time- and cell line- dependent. Human colon carcinoma cells HT-29 appeared to be more sensitive to the complex MK0 ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O) than to ZK1 ([Cu(N-salicylidene-L-glutamato)(H2O)2].H2O) and MK1 ([Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O)). Human colon carcinoma cells HT-29 appeared to be more sensitive to the complex than human breast carcinoma cells MCF-7. IC50 decreased with time of incubation (24, 48 and 72h) for HT-29, but increased for MCF-7. By electrophoresis we found apoptotic cell death induced by our copper complexes in HT-29 at concentrations 1, 10, 50 and 100 µmol/L after 48h (ZK1) and 72h (MK0, MK1) and in MCF-7 we did not find apoptosis. We also studied molecular mechanism of apoptosis in HT-29 induced by copper complexes. We found active caspase 9 in HT-29 after ZK1 ([Cu(N-salicylidene-L-glutamato)(H2O)2].H2O) and MK1 ([Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O)) influence and active caspase 8 after MK0 ([Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O) influence. Conclusion: Our copper complexes showed cytotoxic activities against human colon carcinoma cells HT-29 and breast cancer cell line MCF-7 in vitro. Apoptosis was activated by mitochondrial pathway (intrinsic pathway) in case of ZK1 [Cu(N-salicylidene-L-glutamato)(H2O)2].H2O; MK1 [Cu(N-salicylidene-5-methyl-L-glutamato)(H2O)].H2O; MK3 - transbis(ethanol)tetrakis(imidazol)Cu(II)(2+)bis(N-salicylidene-D,L-glutamato-N,O)-KO:KO´-(imidazol) and MK5 - [Cu(N-salicylidene-D,L- glutamato)(2-methylimidazol] copper complexes and by death receptors (extrinsic pathway) in case of MK0 [Cu2(N-sal-D,L-glu)2(isoquinoline)2].2H2O copper complex in HT-29.

Keywords: apoptosis, copper complex, cancer, carcinoma cell line

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Authors: Shi-xia Xu, Zai-wen Zhang, Ru-xue Chen, Shan Zhou, Xiang-feng Tang

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Objective: The clinical influence of HLA-DPB1 mismatches on clinical outcome of HSCT is less clear. This is the first meta-analysis to study the HLA-DPB1 matching statues on clinical outcomes after unrelated donor HSCT. Methods: We searched the CIBMTR, Cochrane Central Register of Controlled Trials (CENTRAL) and related databases (1995.01–2017.06) for all relevant articles. Comparative studies were used to investigate the HLA-DPB1 loci mismatches on clinical outcomes after unrelated donor HSCT, such as the disease-free survival (DFS), overall survival, GVHD, relapse, and transplant-related mortality (TRM). We performed meta-analysis using Review Manager 5.2 software and funnel plot to assess the bias. Results: At first, 1246 articles were retrieved, and 18 studies totaling 26368 patients analyzed. Pooled comparisons of studies found that the HLA-DPB1 mismatched group had a lower rate of DFS than the DPB1-matched group, and lower OS in non-T cell depleted transplantation. The DPB1 mismatched group has a higher incidence of aGVHD and more severe ( ≥ III degree) aGvHD, lower rate of relapse and higher TRM. Moreover, compared with 1-antigen mismatch, 2-antigen mismatched led to a higher risk of TRM and lower relapse rate. Conclusions: This meta-analysis indicated HLA-DPB1 has important influence on survival and transplant-related complications during unrelated donor HSCT and HLA-DPB1 donor selection strategies have been proposed based on a personalized algorithm.

Keywords: human leukocyte antigen, DPB1, transplant, meta-analysis, outcome

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