Search results for: acute aortic syndrome

Authors: Adrian Reynaldo Sudirman, Siti Farida, Aisyah Aminy Maulidina, Caren Andika Surbakti

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Sedentary lifestyle and imbalance consumption pattern has made metabolic syndrome as the global time bomb phenomenon in the world. The increasing tendency of people in consuming high amount of fructose and cholesterol food has worsened this issue in the society. Pancreas steatosis become one of the most comorbid when early diagnosis and prompt treatment has not been applied on hyperglycemic and hyperlipidemic condition in metabolic syndrome patient. Gemfibrozil become the drug of choice to prevent this issue, yet the efficacy of this regiment was still questionable. Acalypha indica Linn. is the herb that has protective effect on hyperlipidemic and hyperglycemic condition. This study was aimed to compare therapeutic effect of gemfibrozil (G) and Acalypha indica Linn. (AI) on high fructose and cholesterol diet-induced pancreas steatosis in Sprague-Dawley mice. The post induction mice were divided into four groups: control, gemfibrozil, AI extract, and G+AI combination regiment. Each group received four weeks intervention. The result of statistical analysis using the One-Way ANOVA test and Tukey Post Hoc test showed significant decrease in pancreatic steatosis between the control group and administered Acalypha indica group (p = 0.004, 95% CI: 0.170-0.959) and the group administered with a combination of Gemfibrozil-Acalypha indica (p = 0.023, 95% CI: 0.537-0.813). The protective effect of Acalypha indica Linn. shows that this plant has the potential as therapeutic option in overcoming the condition of pancreas steatosis in metabolic syndrome.

Keywords: Acalypha Indica Linn., Cholesterol, Fructose, Gemfibrozil, Pancreas Steatosis

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Authors: Hager Elsheikh

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Context: Pancreatitis is a condition characterized by inflammation in the pancreas, which can lead to serious complications if untreated. Both acute and chronic pancreatitis are associated with immune reactions and fibrosis, which further damage the pancreas. The type 2 immune response, primarily driven by alternative activated macrophages (AAMs), plays a significant role in the development of fibrosis. The IL-4/STAT6 pathway is a crucial signaling pathway for the activation of M2 macrophages. Pancreatic fibrosis is induced by dysregulated inflammatory responses and can result in the autodigestion and necrosis of pancreatic acinar cells. Research Aim: The aim of this study is to investigate the impact of STAT6, a crucial molecule in the IL-4/STAT6 pathway, on the severity and development of fibrosis during acute and chronic pancreatitis. The research also aims to understand the influence of the JAK/STAT6 signaling pathway on the balance between fibrosis and regeneration in the presence of different macrophage populations. Methodology: The research utilizes murine models of acute and chronic pancreatitis induced by cerulean injection. Animal models will be employed to study the effect of STAT6 knockout on disease severity and fibrosis. Isolation of acinar cells and cell culture techniques will be used to assess the impact of different macrophage populations on wound healing and regeneration. Various techniques such as PCR, histology, immunofluorescence, and transcriptomics will be employed to analyze the tissues and cells. Findings: The research aims to provide insights into the mechanisms underlying tissue fibrosis and wound healing during acute and chronic pancreatitis. By investigating the influence of the JAK/STAT6 signaling pathway and different macrophage populations, the study aims to understand their impact on tissue fibrosis, disease severity, and pancreatic regeneration. Theoretical Importance: This research contributes to our understanding of the role of specific signaling pathways, macrophage polarization, and the type 2 immune response in pancreatitis. It provides insights into the molecular mechanisms underlying tissue fibrosis and the potential for targeted therapies. Data Collection and Analysis Procedures: Data will be collected through the use of murine models, isolation and culture of acinar cells, and various experimental techniques such as PCR, histology, immunofluorescence, and transcriptomics. Data will be analyzed using appropriate statistical methods and techniques, and the findings will be interpreted in the context of the research objectives. Conclusion: By investigating the mechanisms of tissue fibrosis and wound healing during acute and chronic pancreatitis, this research aims to enhance our understanding of the disease progression and potential therapeutic targets. The findings have theoretical importance in expanding our knowledge of pancreatic fibrosis and the role of macrophage polarization in the context of the type 2 immune response.

Keywords: immunity in chronic diseases, pancreatitis, macrophages, immune response

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Authors: Lucia Salvioni, Pietro Giorgio Lovaglio, Valerio Leoni, Miriam Colombo, Luisa Fiandra

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The involvement of plasmatic surfactant protein-D (SP-D) in pulmonary diseases has been long investigated, and over the last two years, more interest has been directed to determine its role as a marker of COVID-19. In this direction, several studies aimed to correlate pulmonary surfactant proteins with the clinical manifestations of the virus indicated SP-D as a prognostic biomarker of COVID-19 pneumonia severity. The present work has performed a retrospective study on a relatively large cohort of patients of Hospital Pio XI of Desio (Lombardia, Italy) with the aim to assess differences in the hematic SP-D concentrations among COVID-19 patients and healthy donors and the role of SP-D as a prognostic marker of severity and/or of mortality risk. The obtained results showed a significant difference in the mean of log SP-D levels between COVID-19 patients and healthy donors, so as between dead and survived patients. SP-D values were significantly higher for both hospitalized COVID-19 and dead patients, with threshold values of 150 and 250 ng/mL, respectively. SP-D levels at admission and increasing differences among follow-up and admission values resulted in the strongest significant risk factors of mortality. Therefore, this study demonstrated the role of SP-D as a predictive marker of SARS-CoV-2 infection and its outcome. A significant correlation of SP-D with patient mortality indicated that it is also a prognostic factor in terms of mortality, and its early detection should be considered to design adequate preventive treatments for COVID-19 patients.

Keywords: SARS-CoV-2 infection, COVID-19, surfactant protein-D (SP-D), mortality, biomarker

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Authors: Iman M. Mansour, Rania A. Zayed, Fadwa S. Abdel-Azim, Lamyaa H. Abdel-Latif

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Background and Objectives: The microenvironment of acute myeloid leukemia (AML) is suppressive for immune cells. Regulatory T cells (Tregs) have been recognized to play a role in helping leukemic cells to evade immunesurveillance. The mesenchymal stem cells (MSCs) are essential contributors in immunomodulation of the microenvironment as they can promote differentiation of Tregs via the indoleamine 2,3-dioxygenase (IDO) pathway. The aim of the present work was to evaluate the expression of IDO in bone marrow derived MSCs and to study its correlation to percentage of Tregs. Methods: 37 adult bone marrow samples were cultured in appropriate culture medium to isolate MSCs. Successful harvest of MSCs was determined by plastic adherence, morphology and positive expression of CD271 and CD105; negative expression of CD34 and CD45 using flowcytometry. MSCs were examined for IDO expression by immunocytochemistry using anti-IDO monoclonal antibody. CD4+ CD25+ cells (Tregs) were measured in bone marrow samples by flowcytometry. Results: MSCs were successfully isolated from 20 of the 37 bone marrow samples cultured. MSCs showed higher expression of IDO and Tregs percentage was higher in AML patients compared to control subjects (p=0.002 and p<0.001 respectively). A positive correlation was found between IDO expression and Tregs percentage (p value=0.012, r=0.5). Conclusion: In this study, we revealed an association between high IDO expression in MSCs and elevated levels of Tregs which has an important role in the pathogenesis of AML, providing immunosuppressive microenvironment.

Keywords: acute myeloid leukemia, indoleamine 2, 3-dioxygenase, mesenchymal stem cells, T regulatory cells

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Authors: Zahra Heydari

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Introduction: One of the major clinical issues is acute renal failure, which is caused by ischemia-reperfusion of the kidney and is associated with high mortality. Despite advances in this area, important issues such as tissue necrosis, cell apoptosis, and so on in damaged tissue are suggestive for more researches and study on this subject. Objective: Evaluation of the potential utility of Ezetimibe in reducing injuries and cell death induced by kidney ischemia/ reperfusion through inducing expression changes of different cellular pathways in adult Sprague-Dawley rats. Materials and methods: Forty rats weighing 180-200g were divided into 4 groups. For this purpose, the first right kidneys of the rats were removed during surgery. After 20 days, the left renal artery was closed with a soft clamp and reperfusion was performed. After 24 hours, blood samples were collected and sent to the laboratory with kidneys to measure bax and bcl-2 by Western blotting and histopathological tests. Results: Quantitative damage reviews of Kidney tissue indicates damage Acute and severe tubular lesions were observed in the ischemia group. Also, the amount of injury was significantly reduced in the treatment group. There was also a significant difference between the ischemia and sham groups. In general, the results show that a single dose of 1.2 mg/kg of ezetimibe can reduce the bax/ bcl-2 ratio compared to the ischemia group. In general, the results showed Ezetimibe is effective in reducing cell damage and death due to ischemia/ reperfusion after renal ischemia through changes in the expression of various cellular pathways in rats.

Keywords: acute renal failure, renal ischemia-reperfusion injury, ezetimibe, apoptosis

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Authors: Hasanpasha N. Sholapur, Basanagouda M.Patil

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Alcoholic extract of the bark of Moringa oleifera Lam. (MO), (Moringaceae), has been evaluated experimentally in the past for its insulin sensitizing potentials. In order to explore the possibility of the class of phytochemical(s) responsible for this experimental claim, the alcoholic extract was fractionated into non-polar [petroleum ether (PEF)], moderately non-polar [ethyl acetate (EAF)] and polar [aqueous (AQF)] fractions. All the fractions and pioglitazone (PIO) as standard (10mg/kg were p.o., once daily for 11 d) were investigated for their chronic effect on fasting plasma glucose, triglycerides, total cholesterol, insulin, oral glucose tolerance and acute effect on oral glucose tolerance in dexamethasone-induced (1 mg/kg s.c., once daily for 11 d) chronic model and acute model (1 mg/kg i.p., for 4 h) respectively for insulin resistance (IR) in rats. Among all the fractions tested, chronic treatment with EAF (140 mg/kg) and PIO (10 mg/kg) prevented dexamethasone-induced IR, indicated by prevention of hypertriglyceridemia, hyperinsulinemia and oral glucose intolerance, whereas treatment with AQF (95 mg/kg) prevented hepatic IR but not peripheral IR. In acute study single dose treatment with EAF (140 mg/kg) and PIO (10 mg/kg) prevented dexamethasone-induced oral glucose intolerance, fraction PEF did not show any effect on these parameters in both the models. The present study indicates that the triterpenoidal and the phenolic class of phytochemicals detected in EAF of alcoholic extract of MO bark may be responsible for the prevention of dexamethasone-induced insulin resistance in rats.

Keywords: Moringa oleifera, insulin resistance, dexamethasone, serum triglyceride, insulin, oral glucose tolerance test

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Authors: Paria Soleimani, Arezoo Neshati

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Myocardial infarction is one of the leading causes of ‎death in the world. Some of these deaths occur even before the patient ‎reaches the hospital. Myocardial infarction occurs as a result of ‎impaired blood supply. Because the most of these deaths are due to ‎coronary artery disease, hence the awareness of the warning signs of a ‎heart attack is essential. Some heart attacks are sudden and intense, but ‎most of them start slowly, with mild pain or discomfort, then early ‎detection and successful treatment of these symptoms is vital to save ‎them. Therefore, importance and usefulness of a system designing to ‎assist physicians in the early diagnosis of the acute heart attacks is ‎obvious.‎ The purpose of this study is to determine how well a predictive ‎model would perform based on the only patient-reportable clinical ‎history factors, without using diagnostic tests or physical exams. This ‎type of the prediction model might have application outside of the ‎hospital setting to give accurate advice to patients to influence them to ‎seek care in appropriate situations. For this purpose, the data were ‎collected on 711 heart patients in Iran hospitals. 28 attributes of clinical ‎factors can be reported by patients; were studied. Three logistic ‎regression models were made on the basis of the 28 features to predict ‎the risk of heart attacks. The best logistic regression model in terms of ‎performance had a C-index of 0.955 and with an accuracy of 94.9%. ‎The variables, severe chest pain, back pain, cold sweats, shortness of ‎breath, nausea, and vomiting were selected as the main features.‎

Keywords: Coronary heart disease, Acute heart attacks, Prediction, Logistic ‎regression‎

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Authors: D. F. Zeynalov, T. V. Kartseva, O. V. Sorokin

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Currently, approaches to assess cardiointervalography are based on the calculation of data variance intervals RR. However, they do not allow the evaluation of features related to a period of the cardiac cycle, so how electromechanical phenomena during cardiac subphase are characterized by differently directed changes. Therefore, we have proposed a method of subphase analysis of the cardiac cycle, developed in the department of hominal physiology Novosibirsk State Medical University to identify the features of the dispersion subphase of the cardiac cycle. In the present paper we have examined the 5-minute intervals cardiointervalography (CIG) to isolate RR-, QT-, ST-ranges in healthy children and children with acute respiratory diseases (ARD) in comparison. It is known that primary school-aged children suffer at ARD 5-7 times per year. Consequently, it is one of the most relevant problems in pediatrics. It is known that the spectral indices and indices of temporal analysis of heart rate variability are highly sensitive to the degree of intoxication during immunological process. We believe that the use of subphase analysis of heart rate will allow more thoroughly evaluate responsiveness of the child organism during the course of ARD. The study involved 60 primary school-aged children (30 boys and 30 girls). In order to assess heart rhythm regulation, the record CIG was used on the "VNS-Micro" device of Neurosoft Company (Ivanovo) for 5 minutes in the supine position and 5 minutes during active orthostatic test. Subphase analysis of variance QT-interval and ST-segment was performed on the "KardioBOS" software Biokvant Company (Novosibirsk). In assessing the CIG in the supine position and in during orthostasis of children with acute respiratory diseases only RR-intervals are observed typical trend of general biological reactions through pressosensitive compensation mechanisms to lower blood pressure, but compared with healthy children the severity of the changes is different, of sick children are more pronounced indicators of heart rate regulation. But analysis CIG RR-intervals and analysis subphase ST-segment have yielded conflicting trends, which may be explained by the different nature of the intra- and extracardiac influences on regulatory mechanisms that implement the various phases of the cardiac cycle.

Keywords: acute respiratory diseases, cardiointervalography, subphase analysis, cardiac cycle

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Authors: Ihtisham Bukhari

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In the current study, we enrolled a 46, XY phenotypically female patient bearing testes in her inguinal canal. DNA sequencing of the AR gene detected a missense mutation C.1715A > G (p. Y572C) in exon 2 which is already known to cause Complete androgen insensitivity syndrome (CAIS). We further studied the effects of this mutation on the testicular histopathology of the patient. No spermatocytes were seen in the surface spreading of testicular tissues while H&E staining showed that seminiferous tubules predominantly have only Sertoli cells. To confirm this meiotic failure is likely due to the current AR mutation we performed mRNA expression of genes associated with AR pathway, expression and location of the associated proteins in testicular tissues. Western blot and real-time PCR data showed that the patient had high levels of expression of AMH, SOX9, and INNB in testis. Tubules were stained with SOX9 and AMH which revealed Sertoli cell maturation arrest. Therefore, we suggest that AR mutation enhances AMH expression which ultimately leads to failure in the maturation of Sertoli cells and failure in spermatogenesis.

Keywords: androgen receptor, spermatogenesis, infertility, Sertoli cell only syndrome

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Authors: Susan Evans, Janna Gordon-Elliott, Katarzyna Wyka, Virginia Mutch

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During the rise of the COVID-19 pandemic, healthcare workers needed an intervention that could address their profound acute stress. Mindfulness-based stress reduction (MBSR) is a program that has long established effectiveness for mental and physical health outcomes. In recent years, MBSR has been modified such that the duration of both class time and number of sessions has been abbreviated, and its delivery has been adapted for online dissemination, thus increasing the likelihood that individuals who could most benefit from the program would do so. We sought to investigate whether a brief, online version of MBSR could be feasible and acceptable for health care workers (HCW) in acute stress in response to the COVID-19 pandemic. Participants were recruited via an email sent to all hospital employees, which spans residents, physicians, nurses, housekeeping, lab technicians, administrators, and others. Participating HCW were asked about their previous experience with mindfulness and asked to commit to a minimum of 3 sessions. They were then provided with four weekly 1-hour sessions online that included the major mindfulness exercises taught during traditional MBSR programs (i.e., body scan, sitting meditation, mindful eating, and yoga). Participants were provided with supporting slides, videos, demonstrations and asked to track their practice. Hospital staff enrolled in the program; by the end of the first day of recruitment, 40 had applied; by the start date, about 100 were enrolled, and n attended a minimum of 3 sessions, supporting feasibility. Hospital staff also participated and practiced the mindfulness exercises (n=42), thus supporting acceptability. Participants reported that the program was logical, successful, and worth recommending both before starting the program and after completing it (M= 22.02 and M=21.76, respectively, possible range 0-27). There was a slight decline in the belief in improvement in health and well-being due to the program (ES=.37, p=.021). Secondary hypotheses regarding participants’ self-reported stress and levels of mindfulness were also supported, such that participants reported improvements in perceived stress (ES=.45, p=.006), compassion satisfaction, burnout, and secondary traumatic stress (ES=.41, ES=.31, ES=.35, respectively, p<.05). Participants reported significant improvements in the describing facet of mindfulness (ES=.49, p=.004), while all other facets (observing, acting with awareness, nonjudging of inner experience, nonreactivity to inner experience) remained unchanged pre- to post-program. Results from this study suggest that an abridged, online version of MBSR is feasible and accessible to health care workers in acute stress and provides benefits expected from traditional MBSR programs. The lack of a randomized control group limits generalizability. We intend to provide a structure, framework, and lessons learned to hospital administrators and clinical staff seeking to support their employees in acute stress.

Keywords: acute stress, health care workers, mindfulness, online interventions

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Authors: Nouha Bouayed Abdelmoula, Rim Louati, Nawel Abdellaoui, Balkiss Abdelmoula, Oldez Kaabi, Walid Smaoui, Samir Aloulou

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Background and Aims: Cardiofaciocutaneous syndrome (CFC) is an autosomal dominant disorder with the vast majority of cases arising by a new mutation of BRAF, MEK1, MEK2, or rarely, KRAS genes. Here, we report a rare Tunisian case of CFC syndrome for whom we identify SOS1 mutation. Methods: Genomic DNA was obtained from peripheral blood collected in an EDTA tube and extracted from leukocytes using the phenol/chloroform method according to standard protocols. High resolution melting (HRM) analysis for screening of mutations in the entire coding sequence of PTPN11 was conducted first. Then, HRM assays to look for hot spot mutations coding regions of the other genes of the RAS-MAPK pathway (RAt Sarcoma viral oncogene homolog Mitogen-Activated Protein Kinases Pathway): SOS1, SHOC2, KRAS, RAF1, KRAS, NRAS, CBL, BRAF, MEK1, MEK2, HRAS, and RIT1, were applied. Results: Heterozygous SOS1 point mutation clustered in exon 10, which encodes for the PH domain of SOS1, was identified: c.1655 G > A. The patient was a 9-year-old female born from a consanguineous couple. She exhibited pulmonic valvular stenosis as congenital heart disease. She had facial features and other malformations of Noonan syndrome, including macrocephaly, hypertelorism, ptosis, downslanting palpebral fissures, sparse eyebrows, a short and broad nose with upturned tip, low-set ears, high forehead commonly associated with bitemporal narrowing and prominent supraorbital ridges, short and/or webbed neck and short stature. However, the phenotype is also suggestive of CFC syndrome with the presence of more severe ectodermal abnormalities, including curly hair, keloid scars, hyperkeratotic skin, deep plantar creases, and delayed permanent dentition with agenesis of the right maxillary first molar. Moreover, the familial history of the patient revealed recurrent brain malignancies in the paternal family and epileptic disease in the maternal family. Conclusions: This case report of an overlapping RASopathy associated with SOS1 mutation and familial history of brain tumorigenesis is exceptional. The evidence suggests that RASopathies are truly cancer-prone syndromes, but the magnitude of the cancer risk and the types of cancer partially overlap.

Keywords: cardiofaciocutaneous syndrome, CFC, SOS1, brain cancer, germline mutation

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Authors: Firouz Amani, Adalat Hoseinian, Sajjad Hakimian

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Background: The mortality due to Myocardial Infarction (MI) is often occur during the first hours after onset of symptom. So, for taking the necessary treatment and decreasing the mortality rate, timely visited of the hospital could be effective in this regard. The aim of this study was to investigate the impact of effective factors in mortality of MI patients by using Linear Logistic Regression. Materials and Methods: In this case-control study, all patients with Acute MI who referred to the Ardabil city hospital were studied. All of died patients were considered as the case group (n=27) and we select 27 matched patients without Acute MI as a control group. Data collected for all patients in two groups by a same checklist and then analyzed by SPSS version 24 software using statistical methods. We used the linear logistic regression model to determine the effective factors on mortality of MI patients. Results: The mean age of patients in case group was significantly higher than control group (75.1±11.7 vs. 63.1±11.6, p=0.001).The history of non-cardinal diseases in case group with 44.4% significantly higher than control group with 7.4% (p=0.002).The number of performed PCIs in case group with 40.7% significantly lower than control group with 74.1% (P=0.013). The time distance between hospital admission and performed PCI in case group with 110.9 min was significantly upper than control group with 56 min (P=0.001). The mean of delay time from Onset of symptom to hospital admission (patient delay) and the mean of delay time from hospital admissions to receive treatment (system delay) was similar between two groups. By using logistic regression model we revealed that history of non-cardinal diseases (OR=283) and the number of performed PCIs (OR=24.5) had significant impact on mortality of MI patients in compare to other factors. Conclusion: Results of this study showed that of all studied factors, the number of performed PCIs, history of non-cardinal illness and the interval between onset of symptoms and performed PCI have significant relation with morality of MI patients and other factors were not meaningful. So, doing more studies with a large sample and investigated other involved factors such as smoking, weather and etc. is recommended in future.

Keywords: acute MI, mortality, heart failure, arrhythmia

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Authors: Merve Begum Terzi, Orhan Arikan, Adnan Abaci, Mustafa Candemir

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Acute myocardial infarction is a major cause of death in the world. Therefore, its fast and reliable diagnosis is a major clinical need. ECG is the most important diagnostic methodology which is used to make decisions about the management of the cardiovascular diseases. In patients with acute myocardial ischemia, temporary chest pains together with changes in ST segment and T wave of ECG occur shortly before the start of myocardial infarction. In this study, a technique which detects changes in ST/T sections of ECG is developed for the early diagnosis of acute myocardial ischemia. For this purpose, a database of real ECG recordings that contains a set of records from 75 patients presenting symptoms of chest pain who underwent elective percutaneous coronary intervention (PCI) is constituted. 12-lead ECG’s of the patients were recorded before and during the PCI procedure. Two ECG epochs, which are the pre-inflation ECG which is acquired before any catheter insertion and the occlusion ECG which is acquired during balloon inflation, are analyzed for each patient. By using pre-inflation and occlusion recordings, ECG features that are critical in the detection of acute myocardial ischemia are identified and the most discriminative features for the detection of acute myocardial ischemia are extracted. A classification technique based on support vector machine (SVM) approach operating with linear and radial basis function (RBF) kernels to detect ischemic events by using ST-T derived joint features from non-ischemic and ischemic states of the patients is developed. The dataset is randomly divided into training and testing sets and the training set is used to optimize SVM hyperparameters by using grid-search method and 10fold cross-validation. SVMs are designed specifically for each patient by tuning the kernel parameters in order to obtain the optimal classification performance results. As a result of implementing the developed classification technique to real ECG recordings, it is shown that the proposed technique provides highly reliable detections of the anomalies in ECG signals. Furthermore, to develop a detection technique that can be used in the absence of ECG recording obtained during healthy stage, the detection of acute myocardial ischemia based on ECG recordings of the patients obtained during ischemia is also investigated. For this purpose, a Gaussian mixture model (GMM) is used to represent the joint pdf of the most discriminating ECG features of myocardial ischemia. Then, a Neyman-Pearson type of approach is developed to provide detection of outliers that would correspond to acute myocardial ischemia. Neyman – Pearson decision strategy is used by computing the average log likelihood values of ECG segments and comparing them with a range of different threshold values. For different discrimination threshold values and number of ECG segments, probability of detection and probability of false alarm values are computed, and the corresponding ROC curves are obtained. The results indicate that increasing number of ECG segments provide higher performance for GMM based classification. Moreover, the comparison between the performances of SVM and GMM based classification showed that SVM provides higher classification performance results over ECG recordings of considerable number of patients.

Keywords: ECG classification, Gaussian mixture model, Neyman–Pearson approach, support vector machine

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Authors: Lee Rui, Rajeev Ramachandran

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The approach to recurrent fevers in the paediatric or adolescent age group is not a straightforward one. Causes range from infectious diseases to rheumatological conditions to endocrinopathies, and are usually accompanied by weight loss rather than weight gain. We present an interesting case of a 16-year-old girl brought by her mother to the General Pediatrics Clinic for concerns of recurrent fever paired with significant weight gain over 1.5 years, with no identifiable cause found despite extensive work-up by specialists ranging from Rheumatologists to Oncologists. This case provides a learning opportunity on the approach to weight gain paired with persistent fevers in a paediatric population, one which is not commonly encountered and prompts further evaluation and consideration of less common diagnoses. In a span of 2 years, the girl’s weight had increased from 55 kg at 13 years old (75th centile) to 73.9 kg at 16 years old (>97th centile). About 1 year into her rapid weight gain, she started developing recurrent fevers of documented temperatures > 37.5 – 38.6 every 2-3 days, resulting in school absenteeism when she was sent home after temperature-taking in school found her to be febrile. The rapid onset of weight gain paired with unexplained fevers prompted the treating physician to consider the diagnosis of ROHHAD syndrome. Rapid onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) syndrome is a rare disorder first described in 2007. It is characterized by dysfunction of the autonomic and endocrine system, characterized by hyperphagia and rapid-onset weight gain. This rapid weight gain is classically followed by hypothalamic manifestations with neuroendocrine deficiencies, hypo-ventilatory breathing abnormalities, and autonomic dysregulation. ROHHAD is challenging to diagnose with and diagnosis is made based mostly on clinical judgement. However if truly diagnosed, the condition is characterized by high morbidity and mortality rates. Early recognition of sleep disorders breathing and targeted therapeutic interventions helps limit morbidity and mortality associated with ROHHAD syndrome. This case poses an interesting diagnostic challenge and a diagnosis of ROHHAD has to be considered, given the serious complications that can come with disease progression while conditions such as Munchausen’s or drug fever remain as diagnoses of exclusion until we have exhausted all other possible conditions.

Keywords: pediatrics, endocrine, weight gain, recurrent fever, adolescent

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Authors: Khadidja Bellifa, Sidi Mohamed Mekelleche

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Phenols and especially halogenated phenols represent a substantial part of the chemicals produced worldwide and are known as aquatic pollutants. Quantitative structure–toxicity relationship (QSTR) models are useful for understanding how chemical structure relates to the toxicity of chemicals. In the present study, the acute toxicities of 45 halogenated phenols to Tetrahymena Pyriformis are estimated using no cost semi-empirical quantum chemistry methods. QSTR models were established using the multiple linear regression technique and the predictive ability of the models was evaluated by the internal cross-validation, the Y-randomization and the external validation. Their structural chemical domain has been defined by the leverage approach. The results show that the best model is obtained with the AM1 method (R²= 0.91, R²CV= 0.90, SD= 0.20 for the training set and R²= 0.96, SD= 0.11 for the test set). Moreover, all the Tropsha’ criteria for a predictive QSTR model are verified.

Keywords: halogenated phenols, toxicity mechanism, hydrophobicity, electrophilicity index, quantitative stucture-toxicity relationships

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Authors: Hasan Frookh Jamal

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This is a case of a 36-year-old Bahraini gentleman diagnosed to have Cushing's Syndrome with a large anterior mediastinal mass. He was sent abroad to the Speciality hospital in Jordan, where he underwent diagnostic video-assisted thoracoscopy, partial thymectomy and pericardial fat excision. Histopathology of the mass was reported to be an Atypical carcinoid tumor with a low Ki67 proliferation index of 5%, the mitotic activity of 4 MF/10HPF and pathological stage classification(pTNM): pT1aN1. MRI of the pituitary gland showed an ill-defined non-enhancing focus of about 3mm on the Rt side of the pituitary on coronal images, with a similar but smaller one on the left side, which could be due to enhancing pattern rather than a real lesion as reported. The patient underwent Ga68 Dotate PET/CT scan post-operatively, which showed multiple somatostatin receptor-positive lesions seen within the tail, body and head of the pancreas and positive somatostatin receptor lymph nodes located between the pancreatic head and IVC. There was no uptake detected at the anterior mediastinum nor at the site of thymic mass resection. There was no evidence of any positive somatostatin uptake at the soft tissue or lymph nodes. The patient underwent IPSS, which proved that the source is, in fact, an ectopic source of ACTH secretion. Unfortunately, the patient's serum cortisol remained elevated after surgery and failed to be suppressed by 1 mg ODST and by 2 days LLDST with a high ACTH value. The patient was started on Osilodrostat for treatment of hypercortisolism for the time being and his future treatment plan with Lutetium-177 Dotate therapy vs. bilateral adrenalectomy is to be considered in an MDT meeting.

Keywords: cushing syndrome, neuroendocrine tumur, carcinoid tumor, Thymoma

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Authors: Treder Natalia, Siemiński Mariusz

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Takotsubo cardiomyopathy (TC) is a recently defined clinical entity. First described by Japanese researchers, today is diagnosed worldwide in 1-2% of patients admitted with the preliminary diagnosis of Acute Coronary Syndrome. The etiology of takotsubo cardiomyopathy remains still largely unknown. Currently, the most likely cause of takotsubo is direct cytotoxicity caused by catecholamine surge triggered by emotional stress. There is a strong relation between recent severe emotional stress and TC. The aim of this study was to analysis the role of stress and personality as a risk factor of TT. The presented research involves 35 people who are diagnosed TC. All patients were women, mean age 60 years. The methods used in the research are popular psychological tests: Perceived Stress Scale, DS14 scale to measure type D personality, The Neo-Five Factor Inventory of Personality and psychological interview. The obtained results prove that stress events may directly precede or even release TC. The stressful events occurred directly before the symptoms in 75% examined. 65% assessed their family life as very stressful. Examiners have also a high level of experienced stress. Only 25% of the TC were classified as having type D personality but they have a high level of negative affectivity. The subjects had a high level of extraversion, openness to experiences and an average level of neuroticism. The results suggested that such a type of personality profile may predispose to the development of takotsubo cardiomyopathy. Patients with TT are the individuals who reveal joint tendency to the experience of negative emotions and very stressful family life.

Keywords: stress, personality trails, familiar problems, Takotsubo cardiomyopathy

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Authors: Mohamed Abo El Nasr, Mohamed Shoeib, Abdelhamid Abdelkhalik, Amro Serag

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Background: Early assessment of severity of chest trauma, either blunt or penetrating is of critical importance in prediction of patient outcome. Different trauma scoring systems are widely available and are based on anatomical or physiological parameters to expect patient morbidity or mortality. Up till now, there is no ideal, universally accepted trauma score that could be applied in all trauma centers and is suitable for assessment of severity of chest trauma patients. Aim: Our aim was to compare various trauma scoring systems regarding their predictability of morbidity and mortality in chest trauma patients. Patients and Methods: This study was a prospective study including 400 patients with chest trauma who were managed at Tanta University Emergency Hospital, Egypt during a period of 2 years (March 2014 until March 2016). The patients were divided into 2 groups according to the mode of trauma: blunt or penetrating. The collected data included age, sex, hemodynamic status on admission, intrathoracic injuries, and associated extra-thoracic injuries. The patients outcome including mortality, need of thoracotomy, need for ICU admission, need for mechanical ventilation, length of hospital stay and the development of acute respiratory distress syndrome were also recorded. The relevant data were used to calculate the following trauma scores: 1. Anatomical scores including abbreviated injury scale (AIS), Injury severity score (ISS), New injury severity score (NISS) and Chest wall injury scale (CWIS). 2. Physiological scores including revised trauma score (RTS), Acute physiology and chronic health evaluation II (APACHE II) score. 3. Combined score including Trauma and injury severity score (TRISS ) and 4. Chest-Specific score Thoracic trauma severity score (TTSS). All these scores were analyzed statistically to detect their sensitivity, specificity and compared regarding their predictive power of mortality and morbidity in blunt and penetrating chest trauma patients. Results: The incidence of mortality was 3.75% (15/400). Eleven patients (11/230) died in blunt chest trauma group, while (4/170) patients died in penetrating trauma group. The mortality rate increased more than three folds to reach 13% (13/100) in patients with severe chest trauma (ISS of >16). The physiological scores APACHE II and RTS had the highest predictive value for mortality in both blunt and penetrating chest injuries. The physiological score APACHE II followed by the combined score TRISS were more predictive for intensive care admission in penetrating injuries while RTS was more predictive in blunt trauma. Also, RTS had a higher predictive value for expectation of need for mechanical ventilation followed by the combined score TRISS. APACHE II score was more predictive for the need of thoracotomy in penetrating injuries and the Chest-Specific score TTSS was higher in blunt injuries. The anatomical score ISS and TTSS score were more predictive for prolonged hospital stay in penetrating and blunt injuries respectively. Conclusion: Trauma scores including physiological parameters have a higher predictive power for mortality in both blunt and penetrating chest trauma. They are more suitable for assessment of injury severity and prediction of patients outcome.

Keywords: chest trauma, trauma scores, blunt injuries, penetrating injuries

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Authors: Azadeh Mottaghi, Zeynab Shakeri

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Background: Eating disorders (ED) are group of psychological disorders that significantly impair physical health and psychosocial function. EDconsists wide range of morbidity such as loss of eating control, binge eating disorder(BED), night eating syndrome (NES), and bulimia nervosa. Eating behavior is a wide range term that includes food choices, eating patterns, eating problems. In this study, current knowledge will be discussed aboutcomparison of eating disorders and eating behaviors in morbid obese women with and without type 2 diabetes. Methods: 231 womenwith morbid obesity were included in the study.Loss of eating control, Binge eating disorder and Bulimia nervosa, Night eating syndrome, and eating behaviors and psychosocial factorswere assessed. SPSS version 20 was used for statistical analysis. A p-value of <0.05 was considered significant. Results: There was a significant difference between women with and without diabetes in case of binge eating disorder (76.3% vs. 47.3%, p=0.001). Women with the least Interpersonal support evaluation list (ISEL) scores had a higher risk of eating disorders, and it is more common among diabetics (29.31% vs. 30.45%, p= 0.050). There was no significant difference between depression level and BDI score among women with or without diabetes. Although 38.5% (n=56) of women with diabetes and 50% (n=71) of women without diabetes had minimal depression. The logistic regression model has shown that women without diabetes had lower odds of exhibiting BED (OR=0.28, 95% CI 0.142-0.552).Women with and without diabetes with high school degree (OR=5.54, 95% CI 2.46-9.45, P= 0.0001 & OR=6.52, 95% CI 3.15-10.56, respectively) and moderate depression level (OR=2.03, 95% CI 0.98-3.95 & OR=3.12, 95% CI 2.12-4.56, P= 0.0001) had higher odds of BED. Conclusion: The result of the present study shows that the odds of BED was lower in non-diabetic women with morbid obesity. Women with morbid obesity who had high school degree and moderate depression level had more odds for BED.

Keywords: eating disorders binge eating disorder, night eating syndrome, bulimia nervosa, morbid obesity

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Authors: Emmanuel K. Aziz Saba, Sarah S. El-Tawab

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Objectives: Carpal tunnel syndrome (CTS) was found to be associated with high pressure within the Guyon’s canal. The aim of this study was to assess the involvement of sensory and/or motor ulnar nerve fibers in patients with CTS and whether this affects the accuracy of the median versus ulnar sensory and motor comparative tests. Patients and methods: The present study included 145 CTS hands and 71 asymptomatic control hands. Clinical examination was done for all patients. The following tests were done for the patients and control: (1) Sensory conduction studies: median nerve, ulnar nerve, dorsal ulnar cutaneous nerve and median versus ulnar digit (D) four sensory comparative study; (2) Motor conduction studies: median nerve, ulnar nerve and median versus ulnar motor comparative study. Results: There were no statistically significant differences between patients and control group as regards parameters of ulnar motor study and dorsal ulnar cutaneous sensory conduction study. It was found that 17 CTS hands (11.7%) had ulnar sensory abnormalities in 17 different patients. The median versus ulnar sensory and motor comparative studies were abnormal among all these 17 CTS hands. There were statistically significant negative correlations between median motor latency and both ulnar sensory amplitudes recording D5 and D4. There were statistically significant positive correlations between median sensory conduction velocity and both ulnar sensory nerve action potential amplitude recording D5 and D4. Conclusions: There is ulnar sensory nerve abnormality among CTS patients. This abnormality affects the amplitude of ulnar sensory nerve action potential. The presence of abnormalities in ulnar nerve occurs in moderate and severe degrees of CTS. This does not affect the median versus ulnar sensory and motor comparative tests accuracy and validity for use in electrophysiological diagnosis of CTS.

Keywords: carpal tunnel syndrome, ulnar nerve, median nerve, median versus ulnar comparative study, dorsal ulnar cutaneous nerve

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Authors: Wu Liching

Abstract:

Aim This case aims to discuss the pathogenesis, clinical manifestations and medical treatment of strokes caused by mitochondrial gene mutations. Methods Diagnosis of ischemic stroke caused by mitochondrial gene defect by means of "next-generation sequencing mitochondrial DNA gene variation detection", imaging examination, neurological examination, and medical history; this study took samples from the neurology ward of a medical center in northern Taiwan cases diagnosed with acute cerebral infarction as the research objects. Result This case is a 49-year-old married woman with a rare disease, mitochondrial gene mutation inducing ischemic stroke. She has severe hearing impairment and needs to use hearing aids, and has a history of diabetes. During the patient’s hospitalization, the blood test showed that serum Lactate: 7.72 mmol/L, Lactate (CSF) 5.9 mmol/L. Through the collection of relevant medical history, neurological evaluation showed changes in consciousness and cognition, slow response in language expression, and brain magnetic resonance imaging examination showed subacute bilateral temporal lobe infarction, which was an atypical type of stroke. The lineage DNA gene has m.3243A>G known pathogenic mutation point, and its heteroplasmic level is 24.6%. This pathogenic point is located in MITOMAP and recorded as Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) , Leigh Syndrome and other disease-related pathogenic loci, this mutation is located in ClinVar and recorded as Pathogenic (dbSNP: rs199474657), so it is diagnosed as a case of stroke caused by a rare disease mitochondrial gene mutation. After medical treatment, there was no more seizure during hospitalization. After interventional rehabilitation, the patient's limb weakness, poor language function, and cognitive impairment have all improved significantly. Conclusion Mitochondrial disorders can also be associated with abnormalities in psychological, neurological, cerebral cortical function, and autonomic functions, as well as problems with internal medical diseases. Therefore, the differential diagnoses cover a wide range and are not easy to be diagnosed. After neurological evaluation, medical history collection, imaging and rare disease serological examination, atypical ischemic stroke caused by rare mitochondrial gene mutation was diagnosed. We hope that through this case, the diagnosis of rare disease mitochondrial gene variation leading to cerebral infarction will be more familiar to clinical medical staff, and this case report may help to improve the clinical diagnosis and treatment for patients with similar clinical symptoms in the future.

Keywords: acute stroke, MELAS, lactic acidosis, mitochondrial disorders

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Authors: Waseem Al Talalwah, Shorok Al Dorazi, Roger Soames

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Persistent sciatic artery is a rare anatomical vascular variation resulting from a lack of regression of the embryonic dorsal axial artery. The axial artery is the main artery supplying the lower limb during development in the first trimester. The current research includes 206 sciatic artery cases in 171 patients between 1864 and 2012. It aims to identify the risk factor of sciatic artery aneurysm in congenital limb anomalies. Sciatic artery aneurysm was diagnosed incidentally in amniotic band syndrome (ABS) existing with no congenital anomaly in 0.7% or with double knee in 0.7%, with the tibia in 0.7% and with hemihypertrophy or soft tissue hypertrophy in 1.4%. Therefore, the current study indicates a relationship the same gene responsible for the congenital limb deformities may be responsible for non-regression of the sciatic artery. Furthermore, pediatricians should refer cases of congenital limb anomalies for vascular evaluation prior to corrective surgical intervention.

Keywords: amniotic band syndrome, congenital limb deformities, double knee, sciatic artery, sciatic artery aneurysm , soft tissue hypertrophy

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Authors: Sophia Shi

Abstract:

Acute kidney injury (AKI) is the sudden onset of kidney damage in which the kidneys cannot filter waste from the blood, requiring emergency hospitalization. AKI patient mortality rate is high in the ICU and is virtually impossible for doctors to predict because it is so unexpected. Currently, there is no hybrid model predicting AKI that takes advantage of two types of data. De-identified patient data from the MIMIC-III database and de-identified kidney images and corresponding patient records from the Beijing Hospital of the Ministry of Health were collected. Using data features including serum creatinine among others, two numeric models using MIMIC and Beijing Hospital data were built, and with the hospital ultrasounds, an image-only model was built. Convolutional neural networks (CNN) were used, VGG and Resnet for numeric data and Resnet for image data, and they were combined into a hybrid model by concatenating feature maps of both types of models to create a new input. This input enters another CNN block and then two fully connected layers, ending in a binary output after running through Softmax and additional code. The hybrid model successfully predicted AKI and the highest AUROC of the model was 0.953, achieving an accuracy of 90% and F1-score of 0.91. This model can be implemented into urgent clinical settings such as the ICU and aid doctors by assessing the risk of AKI shortly after the patient’s admission to the ICU, so that doctors can take preventative measures and diminish mortality risks and severe kidney damage.

Keywords: Acute kidney injury, Convolutional neural network, Hybrid deep learning, Patient record data, ResNet, Ultrasound kidney images, VGG

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Authors: Kheireddine El-Boubbou

Abstract:

Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC₅₀ values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.

Keywords: magnetic nanoparticles, drug delivery, acute myeloid leukemia, iron oxide, cancer nanotherapy

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Authors: H. A. Algahtani, A. S. Khan, O. Alzahrani, N. Hussein, M. A. Khan, Loudhi Y. I. Soliman

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Objective: To report on the Saudi experience (developing country) of neurological complications from bariatric surgery. The literature on the subject is reviewed. Method: This is a cross sectional study done in King Abdul Aziz Medical City Jeddah, WR, where we reviewed all charts of the patients who underwent bariatric surgery between January 1st, 2009 to December 31st , 2014. Personal and clinical data including age, sex, BMI, comorbidities, type of procedure, duration of stay in hospital, complications and postoperative follow up were collected. In addition follow up visit and remote complication if present were collected. All patients with neurological complications were reviewed in details including their clinical examination, laboratory and imaging results, treatment and prognosis. This report is essentially descriptive with no statistical analysis performed. Results: Fifteen cases were collected in this study (3%). Axonal polyneuropathy was the most frequent neurological complica¬tion, but cases of Wernicke syndrome, vitamin B12 deficiency, Guillain-Barre syndrome and cupper deficiency were also identified. Fourteen patients (93.3%) had full recovery from the neurological signs and symptoms but unfortunately one patient died. Conclusion: Bariatric surgery, a procedure that is continuously increasing in popularity, is not free of potential neurological complications. A clear education, guidelines and follow-up program should be planned and practiced. Facts should be clearly presented to the individual undergoing this type of surgery. Although a clear cause-effect relation cannot be established for the present cases, the cumulative literature on the subject makes it important to warn the patient of the potential risks of this procedure.

Keywords: bariatric surgery, neurological complications, neuropathy, Wenicke syndrome

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Authors: R. R. Billones, N. Lukkahatai, L. N. Saligan

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Mindfulness based interventions (MBIs) have been used in medically unexplained symptoms (MUS). This systematic review describes the literature investigating the general effect of MBIs on MUS and identifies the effects of specific MBIs on specific MUS conditions. The preferred reporting items for systematic reviews and meta-analysis guidelines (PRISMA) and the modified Oxford quality scoring system (JADAD) were applied to the review, yielding an initial 1,556 articles. The search engines included PubMed, ScienceDirect, Web of Science, Scopus, EMBASE, and PsychINFO using the search terms: mindfulness, or mediations, or mindful or MBCT or MBSR and medically unexplained symptoms or MUS or fibromyalgia or FMS. A total of 24 articles were included in the final systematic review. MBIs showed large effects on socialization skills for chronic fatigue syndrome (d=0.65), anger in fibromyalgia (d=0.61), improvement of somatic symptoms (d=1.6) and sleep (d=1.12) for painful conditions, physical health for chronic back pain (d=0.51), and disease intensity for irritable bowel disease/syndrome (d=1.13). A manualized MBI that applies the four fundamental elements present in all types of interventions were critical to efficacy. These elements were psycho-education sessions specific to better understand the medical symptoms, the practice of awareness, the non-judgmental observance of the experience at the moment, and the compassion to ones’ self. The effectiveness of different mindfulness interventions necessitates giving attention to improve the gaps that were identified related to home-based practice monitoring, competency training of mindfulness teachers, and sound psychometric properties to measure the mindfulness practice.

Keywords: mindfulness-based interventions, medically unexplained symptoms, mindfulness-based cognitive therapy, mindfulness-based stress reduction, fibromyalgia, irritable bowel syndrome

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Authors: Eda Jazexhiu-Postoli, Gladiola Hoxha, Ada Simeoni, Sonila Biba

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Background Neonatal hypotonia represents a commonly encountered issue in the Neonatal Intensive Care Unit and newborn nursery. The differential diagnosis is broad, encompassing chromosome abnormalities, primary muscular dystrophies, neuropathies and inborn errors of metabolism. Aim of study Our study describes some of the main clinical features of hypotonia in newborns and presents clinical cases of neonatal hypotonia we treated in our Neonatal unit in the last 3 years. Case reports Four neonates born in our hospital presented with hypotonia after birth, one preterm newborn 35-36 weeks of gestational age and three other term newborns (38-39 weeks of gestational age). Prenatal data revealed a decrease in fetal movements in both cases. Intrapartum meconium-stained amniotic fluid was found in 75% of our hypotonic newborns. Clinical features included inability to establish effective respiratory movements and need for resuscitation in the delivery room, respiratory distress syndrome, feeding difficulties and need for oro-gastric tube feeding, dysmorphic features, hoarse voice and moderate to severe muscular hypotonia. The genetic workup revealed the diagnosis of Autosomal Recessive Congenital Myasthenic Syndrome 1-B, Sotos Syndrome, Spinal Muscular Atrophy Type 1 and Transient Hypotonia of the Newborn. Two out of four hypotonic neonates were transferred to the Pediatric Intensive Care Unit and died at the age of three to five months old. Conclusion Hypotonia is a concerning finding in neonatal care and it is suggested by decreased intrauterine fetal movements, failure to establish first breaths, respiratory distress and feeding difficulties in the neonate. Prognosis is determined by its etiology and time of diagnosis and intervention.

Keywords: hypotonic neonate, respiratory distress, feeding difficulties, fetal movements

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Authors: Christina Williams, Mehari Weldemariam, Ann M. Farese, Thomas J. MacVittie, Maureen A. Kane

Abstract:

Radiation exposure results in dose-dependent and time-dependent multi-organ damage. Drug development of medical countermeasures (MCM) for radiation-induced injury occurs under the FDA Animal Rule because human efficacy studies are not ethical or feasible. The FDA Animal Rule requires the representation of both sexes and describes several uses for biomarkers in MCM drug development studies. Currently, MCMs are limited and there is no FDA-approved biomarker for any radiation injury. Sex as a variable is essential to identifying biomarkers and developing effective MCMs for acute radiation exposure (ARS) and delayed effects of acute radiation exposure (DEARE). These studies aim to address the death of information on sex differences that have not been determined by studies that included only male, single-sex cohorts. Studies have reported differences in radiosensitivity according to sex. As such, biomarker discovery for radiation-induced damage must consider sex as a variable. This study evaluated the plasma proteomic profile of Rhesus macaque non-human primates after different exposures and doses, as well as time points after radiation. Exposures and doses included total body irradiation between 5-7.5 Gy and partial body irradiation with 5% bone marrow sparing at 9, 9.5 and 10 Gy. Timepoints after irradiation included days 1, 3, 60, and 180, which encompassed both acute radiation syndromes and delayed effects of acute radiation exposure. Bottom-up proteomic analyses of plasma included equal numbers of males and females. In the control animals, few proteomic differences are observed between the sexes. In the irradiated animals, there are a few sex differences, with changes mostly consisting of proteins upregulated in the female animals. Multiple canonical pathways were upregulated in irradiated animals relative to the control animals when subjected to pathway analysis, but differential responses between the sexes are limited. These data provide critical baseline differences according to sex and establish sex differences in non-human primate models relevant to drug development of MCM under the FDA Animal Rule.

Keywords: ionizing radiation, sex differences, plasma proteomics, biomarker discovery

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Authors: Joshua Chew, Vesa Cheng, David Thomson

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Background: Hereditary angioedema (HAE) or C1 esterase deficiency is a relatively rare entity that has a potential for significant anesthetic complications. Methods: A literature review was performed of published cases of surgery in patients with HAE. Results were limited to English language only and cases were examined for management strategies and successful prevention of acute attacks. Results: The literature revealed the successful use of C1 esterase inhibitors as the most common agent in surgical prophylaxis therapy. Other therapeutic targets described included kallikrein inhibitors and bradykinin B2 receptor antagonists. Conclusions: Therapeutic targets that exist for the management of acute attacks in HAE have been successfully employed in the setting of surgery. The data is currently limited and could not be used as a firm evidence base, but the limited outcomes seen are positive and reassuring for the prospective anesthetic management of this potentially fatal condition.

Keywords: anesthesia, C1 esterase deficiency, hereditary angioedema, surgical prophylaxis

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Authors: Chaoge Wang, Xiquan Weng, Yan Meng, Wentao Lin

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Objective: Cold exposure and exercise serve as two physiological stimuli to glycolipid metabolism and insulin sensitivity. So far, it remains to be elucidated whether exercise plus cold exposure can produce an addictive effect on promoting glycolipid metabolism and insulin sensitivity. Methods: 64 SD rats were subjected to high-fat and high-sugar diets for 9-week and sucessfully to establish an obesity model. They were randomly divided into 8 groups: normal control group (NC), normal exercise group (NE), continuous cold control group (CC), continuous cold exercise group (CE), acute clod control group (AC), acute cold exercise group (AE), intermittent cold control group (IC) and intermittent cold exercise group (IE). For continuous cold exposure, the rats stayed in a cold environment all day; for acute cold exposure, the rats were exposed to cold for only 4h before the end of the experiment; for intermittent cold exposure, the rats were exposed to cold for 4h per day. The protocol for treadmill runnings were as follows: 25m/min (speed), 0°C (slope), 30 mins each time, an interval for 10 mins between two runnings, twice/two days, lasting for 5 weeks. Sampling were conducted on the 5th weekend. Blood lipids, free fatty acids, blood glucose (FBG), and serum insulin (FINS) were examined, and the insulin resistance index (HOMA-IR = FBG (mmol/L)×FINS(mIU/L)/22.5) was calculated. SPSS 22.0 was used for statistical analysis of the experimental results, and the ANOVA analysis was performed between groups (p < 0.05 was significant). Results: (1) Compared with the NC group, the FBG of the rats was significantly declined in the NE, CE, AC, AE, and IE groups (p < 0.05), the FINS of the rats was significantly declined in the AE group (p < 0.05), the HOMA-IR of the rats was significantly declined in the NE, CE, AC, AE and IE groups (p < 0.05). Compared with the NE group, the FBG of the rats was significantly declined in the CE, AE, and IE groups (p < 0.05), the FINS and HOMA-IR of the rats were significantly declined in the AE group (p < 0.05). (2) Compared with the NC group, the CHO, TG, LDL-C, and FFA of the rats were significantly declined in CE and IE groups (p < 0.05), the HDL-C of the rats was significantly higher in NE, CC, CE, AE, and IE groups (p < 0.05). Compared with the NE group, the HDL-C of the rats was significantly higher in the CE and IE groups (p < 0.05). Conclusions: Sedentariness or exercise in the acute cold doesn't make sense in the treatment of type 2 diabetes, which led to one-off increases of the body's insulin sensitivity. Exercise in the continuous and intermittent cold can effectively decline the FBG, TC, TG, LDL-C, and FFA levels and increase the HDL-C level and insulin sensitivity in obese rats. These results can impact the prevention and treatment of type 2 diabetes.

Keywords: cold, exercise, insulin sensitivity, obesity

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