Search results for: acute lymphoblastic leukemia (ALL)

Authors: Hassan Ali Abood Nassrullah, Jabbar Fadeel Mahdi, Mohammed Salih Mahdi Alkurdi, Ali Al Mousawi, Saad Ibrahim Al-Ghabban, Abdul Amir H. Kadhum, Ahmed Al-Amiery

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Background: Q fever is a zoonotic disease characterized by its clinical polymorphism and can present acutely as fever, pneumonia, hepatitis, and chronically as infective endocarditis, arthritis, osteomyelitis, or hepatitis. Objective: The aim of this study is To estimate the prevalence of cases of Q fever in hospitalized febrile patients in Imam Al Hussain Teaching Medical City in Karbala. Methods: One hundred patients with pyrexia were admitted to the medical ward from 1st August to 31st December 2019. Serological procedures fortified by Enzyme-linked Immunosorbent Assay test. Patients were considered to have acute Q fever when the specific antibodies (IgM and IgG) of phase II of Coxiella burnetii were positive. Results: The mean age of the patients was 35.05±12.93 years; females constituted 60% of them. Eighteen patients (18%) showed positive results for IgM, a lower proportion (13% n=13) had positive IgG levels, and 9% showed equivocal results. Statistical analysis revealed a significant association between positive IgM levels of the female gender and in patients consuming unpasteurized milk. One patient (female aged 60 years) died in the hospital, while all other patients were discharged well. Two female patients were pregnant, and one of them had an abortion. Conclusions: Q fever is more common in febrile patients. The study indicates that this disease should not be overlooked in the differential diagnosis of acute fever. Serological testing should be performed in all patients with acute febrile illness with an unsettling diagnosis.

Keywords: antibodies, frequency, immunoglobulin IgM, Q fever

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Authors: Naim Izet Kajtazi

Abstract:

Context: Increased intracranial pressure and associated symptoms such as headache, papilledema, motor or sensory deficits, seizures, and conscious disturbance are well-known in acute CVT. However, visual loss is not commonly associated with this disease, except in the case of secondary IIH associated with it. Process: We report a case of a 40-year-old male with Behçet’s disease and cerebral venous thrombosis, and other multiple comorbidities admitted with a four-day history of increasing headache and rapidly progressive visual loss bilaterally. The neurological examination was positive for bilateral papilledema of grade 3 with light perception on the left eye and counting fingers on the right eye. Brain imaging showed old findings of cerebral venous thrombosis without any intraparenchymal lesions to suggest a flare-up of Behçet’s disease. The lumbar puncture, followed by the lumbar drain insertion, gave no benefit in headache or vision. However, he completely lost sight. The right optic nerve sheath fenestration did not result in vision improvement. The acute spinal shock complicated the lumbar drain removal due to epidural hematoma. An urgent lumbar laminectomy with hematoma evacuation undertook. Intra-operatively, the neurosurgeon noted suspicious abnormal vessels at conus medullaris with the possibility of an arteriovenous malformation. Outcome: In a few days following the spinal surgery, the patient vision started to improve. Further improvement was achieved after plasma exchange sessions followed by cyclophosphamide. In the recent follow-up in the clinic, he reported better vision, drove, and completed his Ph.D. studies. Relevance: Visual loss in patients with Behçet’s disease should always be anticipated and taken reasonable care of, ensuring that they receive well-combined immunosuppression with anticoagulation and agents to reduce intracranial pressure. This patient’s story is significant for a high disease burden and complicated hospital course by acute spinal shock due to spinal lumbar drain removal with a possible underlying spinal arteriovenous malformation.

Keywords: Behcet disease, optic neuritis, IIH, CVT

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Authors: Jiandong Ren, Lijun Zhao, Peng Chen

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Nafamostat (NA), a synthetic broad-spectrum serine protease inhibitor, has been routinely employed for the treatment of acute pancreatitis (AP) and other inflammatory-associated diseases in some East Asia countries. Although the potent inhibitory activity against inflammation-related proteases such as thrombin, trypsin, kallikrein, plasmin, coagulation factors and complement factors is generally considered to be responsible for the anti-inflammatory effects of NA, precise target and molecular mechanism underlying the anti-inflammatory activity in the treatment of AP remain largely unknown yet. As an intracellular inflammatory signaling platform, the NOD-like receptor protein 3 (NLRP3) inflammasome is recently identified to be involved in the development of AP. In present study, we have revealed that NA alleviated pancreatic injury in a caerulein-induced AP model by inhibiting the NLRP3 inflammasome activation in pancreas. Mechanistically, NA interacted with HDAC6, a cytoplasmic deacetylase implicated in the NLRP3 inflammasome pathway, and efficiently abrogated the function of HDAC6. This property enabled NA to influence HDAC6 dependent NF-κB transcriptional activity and thus block NF-κB-driven transcriptional priming of NLRP3 inflammasome. Moreover, NA exerted the potential to interfere HDAC6-mediated intracellular transport of NLRP3, thereby leading to the failure of NLRP3 inflammasome activation. Our current work has provided valuable insight into the molecular mechanism underlying the immunomodulatory effect of NA in treatment of AP, highlighting its promising application in prevention of NLRP3 inflammasome-associated inflammatory pathological damage.

Keywords: acute pancreatitis, HDAC6, nafamostat, NLRP3 inflammasome

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Abdulkareem M. Hamid, Yaseen Elhebshi, Adam Daïch

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Luotonins and its derivatives (Isoluotonins) are alkaloids from the aerial parts of Peganum nigellastrum Bunge that display three major skeleton types. Luotonins A, B, and E are pyrroloquinazolinoquinoline alkaloids. A few methods were known for the sysnthesis of Isoluotonin. All luotonins have shown promising cytotoxicities towards selected human cancer cell lines, especially against leukemia P-388 cells. Luotonin A is the most active one, with its activity stemming from topoisomerase I-dependent DNA-cleavage. Such intriguing biological activities and unique structures have led not only to the development of synthetic methods for the efficient synthesis of these compounds, but also to interest in structural modifications for improving the biological properties. Recent progress in the study of luotonins is covered.

Keywords: luotonin A, isoluotonin, pyrroloquiolines, alkaloids

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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

Abstract:

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: 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: Ilknur Kahriman, Hacer Kobya Bulut, Birsel C. Demirbag

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Introduction and Aim: One of the most challenging aspects of being parents of a child diagnosed with cancer is to balance their normal family life with the child's health needs and treatment requirements. Cancer covers an important part of family life and gets ahead of other matters. Families mostly feel that everything has changed in their lives with the cancer diagnosis and are obliged to make a number of adjustments in their lives. Their normal family life suddenly begins to include treatments, hospital appointments and hospitalizations. This study is a descriptive research conducted to determine the changes in the lives of families who had a child with cancer. Methods: This study was carried out with 65 families having children diagnosed with cancer in 0-17 age group at outpatient pediatric oncology clinic and polyclinic of a university hospital in Trabzon. Data were collected through survey method from August to November, 2015. In the analysis of the data, numbers, percentage and chi-square test were used. Findings: It was found out that the average age of mothers was 35.33 years, most of them were primary school graduates (44.6%) and housewives (89.2%) and the average age of fathers was 39.30 years, most of them were high school graduates (29.2%) and self-employed (43.8% ). The majority of their children were boys and their average age was 7.74 years and 77% had Acute lymphocytic leukemia (ALL) diagnosis. 87.5% of the mothers who had a child with cancer had increased fears in their lives, 84.4% had increased workload at home, 82.8% had more stressful life and 82.8% felt themselves physically tired. The mothers indicated that their healthy children could not do the social activities they had used to do before (56.5%), they no longer fed their healthy children with the food they loved eating so that the sick child did not aspire (52.3%) and their healthy children were more furious than before (53.2%). As for the fathers, the fundamental change they had was increased workload at home (82.3%), had more stressful life (80.6%) and could no longer allocate time to the activities they had been interested in and done before (77.8%). There was not a significant difference between the sick children gender and the changes in their parents lives. The communication between the mothers and their healthy children were determined to be positively affected in the families in which the sick child's disease duration was under 12 months (X2 = 6.452, p = 0.011). Conclusion: This study showed that parents having a child with cancer had more workload at home, had more stressful lives, could not allocate time to social activities, had increased fears, felt themselves tired and their healthy children became more furious and their social activities reduced.

Keywords: child, cancer, changes in lives, family

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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: 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: Sophia Shi

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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: Afia Naheed, Manmohan Singh, David Lucy

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This work is based on a mathematical as well as statistical study of an SEIJTR deterministic model for the interpretation of transmission of severe acute respiratory syndrome (SARS). Based on the SARS epidemic in 2003, the parameters are estimated using Runge-Kutta (Dormand-Prince pairs) and least squares methods. Possible graphical and numerical techniques are used to validate the estimates. Then effect of the model parameters on the dynamics of the disease is examined using sensitivity and uncertainty analysis. Sensitivity and uncertainty analytical techniques are used in order to analyze the affect of the uncertainty in the obtained parameter estimates and to determine which parameters have the largest impact on controlling the disease dynamics.

Keywords: infectious disease, severe acute respiratory syndrome (SARS), parameter estimation, sensitivity analysis, uncertainty analysis, Runge-Kutta methods, Levenberg-Marquardt method

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

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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: Steven G. Sclan

Abstract:

Background: Since December 2019, the world has been afflicted by the spread of the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2), which is responsible for the condition referred to as Covid-19. The illness has had a cataclysmic impact on the political, social, economic, and overall well-being of the population of the entire globe. While Covid-19 has had a substantial universal fatality impact, it may have an even greater effect on the socioeconomic, medical well-being, and healthcare planning for remaining societies. Significance: As these numbers illustrate, many more persons survive the infection than die from it, and many of those patients have noted ongoing, persistent symptoms after successfully enduring the acute phase of the illness. Recognition and understanding of these symptoms are crucial for developing and arranging efficacious models of care for all patients (whether or not having been hospitalized) surviving acute covid illness and plagued by post-acute symptoms. Furthermore, regarding Covid infection in children (< 18 y/o), although it may be that Covid “+” children are not major vectors of infective transmission, it now appears that many more children than initially thought are carrying the virus without accompanying obvious symptomatic expression. It seems reasonable to wonder whether viral effects occur in children – those children who are Covid “+” and now asymptomatic – and if, over time, they might also experience similar symptoms. An even more significant question is whether Covid “+” asymptomatic children might manifest increased multiple health problems as they grow – i.e., developmental complications (e.g., physical/medical, metabolic, neurobehavioral, etc.) – in comparison to children who had been consistently Covid “ - ” during the pandemic. Topics Addressed and Theoretical Importance: This review is important because of the description of both quantitative and qualitative methods for clinical and biomedical research. Topics reviewed will consider the importance of well-designed, comprehensive (i.e., quantitative and qualitative methods) longitudinal studies of Post Covid-19 symptoms in both adults and children. Also reviewed will be general characteristics of longitudinal studies and a presentation of a model for a proposed study. Also discussed will be the benefit of longitudinal studies for the development of efficacious interventions and for the establishment of cogent, practical, and efficacious community healthcare service planning for post-acute covid patients. Conclusion: Results of multi-dimensional, longitudinal studies will have important theoretical implications. These studies will help to improve our understanding of the pathophysiology of long COVID and will aid in the identification of potential targets for treatment. Such studies can also provide valuable insights into the long-term impact of COVID-19 on public health and socioeconomics.

Keywords: COVID-19, post-COVID-19, long COVID, longitudinal research, quantitative research, qualitative research

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

Abstract:

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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Authors: Nabil Jallouli, Luisa M. Pastrana-Martínez, Ana R. Ribeiro, Nuno F. F. Moreira, Joaquim L. Faria, Olfa Hentati, Adrián M. T. Silva, Mohamed Ksibi

Abstract:

Degradation and mineralization of ibuprofen (IBU) were investigated using Ultraviolet (UV) Light Emitting Diodes (LEDs) in TiO2 photocatalysis. Samples of ultrapure water (UP) and a secondary treated effluent of a municipal wastewater treatment plant (WWTP), both spiked with IBU, as well as a highly concentrated IBU (230 mgL-1) pharmaceutical industry wastewater (PIWW), were tested in the TiO2/UV-LED system. Three operating parameters, namely, pH, catalyst load and number of LEDs were optimized. The process efficiency was evaluated in terms of IBU removal using high performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Additionally, the mineralization was investigated by determining the dissolved organic carbon (DOC) content. The chemical structures of transformation products were proposed based on the data obtained using liquid chromatography with a high resolution mass spectrometer ion trap/time-of-flight (LC-MS-IT-TOF). A possible pathway of IBU degradation was accordingly proposed. Bioassays were performed using the marine bacterium Vibrio fischeri to evaluate the potential acute toxicity of original and treated wastewaters. TiO2 heterogeneous photocatalysis was efficient to remove IBU from UP and from PIWW, and less efficient in treating the wastewater from the municipal WWTP. The acute toxicity decreased by ca. 40% after treatment, regardless of the studied matrix.

Keywords: acute toxicity, Ibuprofen, UV-LEDs, wastewaters

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Authors: Saimir Heta, Kastriot Haxhirexha, Virtut Velmishi, Nevila Alliu, Ilma Robo

Abstract:

Background: Testicular rotation can occur at any age. The possibility to save the testicle is the fastest possible surgical intervention which is indicated by the presence of acute pain even at rest. The time element is more important to diagnose and proceed further with surgical intervention. Testicular damage is a consequence which mainly depends on the moment of onset of symptoms, at the time when the symptoms are diagnosed, the earliest action to be performed is surgical intervention. Sometimes medical tests are needed to confirm a diagnosis, or to help identify another cause for symptoms; for example, the urine test, that is used to check for infection, associated with the scrotal ultrasound test. Control of blood flow to the longitudinal supply vessels of the testicles is indicated. The sign that indicates testicular rotation is a reduction in blood flow. This is the element which is distinguished from ultrasound examination. Surgery may be needed to determine if the patient’s symptoms are caused by the rotation of the testis or any other condition. Discussion: As a surgical intervention of the emergency, the torsion of the test depends very much on the duration of the torsion, as the success in the life of the testicle depends on the fastest surgical intervention. From the previous clinic, it is noted that in any case presented to the pediatric patient diagnosed with testicular rotation, there is always a link with personal history that the patient refers to the presence of a previous episode of testicular trauma. Literature supports this fact very logically. Conclusions: Salvation without testicular atrophy depends closely on establishing the diagnosis of testicular rotation as soon as possible. Following the logic above, it can be said that the diagnosis for rotation should be performed as soon as possible, to avoid consequences that will not be favorable for the patient.

Keywords: acute scrotum, test torsion, newborns, clinical presentation

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Authors: M. G. R. S. Perera, B. S. Weerakoon, L. P. G. Sherminie, M. L. Jayatilake, R. D. Jayasinghe, W. Huang

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The aim of this study was to measure and evaluate the Longitudinal Relaxation Times (T1) in bone marrow of an Acute Myeloid Leukaemia (AML) patient in order to explore the potential for a prognostic biomarker using Magnetic Resonance Imaging (MRI) which will be a non-invasive prognostic approach to AML. MR image data were collected in the DICOM format and MATLAB Simulink software was used in the image processing and data analysis. For quantitative MRI data analysis, Region of Interests (ROI) on multiple image slices were drawn encompassing vertebral bodies of L3, L4, and L5. T1 was evaluated using the T1 maps obtained. The estimated bone marrow mean value of T1 was 790.1 (ms) at 3T. However, the reported T1 value of healthy subjects is significantly (946.0 ms) higher than the present finding. This suggests that the T1 for bone marrow can be considered as a potential prognostic biomarker for AML patients.

Keywords: acute myeloid leukaemia, longitudinal relaxation time, magnetic resonance imaging, prognostic biomarker.

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Authors: M. S. Raza, A. Kapil, Sonu Tyagi, H. Gautam, S. Mohapatra, R. Chaudhry, S. Sood, V. Goyal, R. Lodha, V. Sreenivas, B. K. Das

Abstract:

Background: Acute bacterial meningitis remains the major cause of mortality and morbidity. More than half of the survivors develop the significant lifelong neurological abnormalities. Diagnosis of the hospital acquired acute bacterial meningitis (HAABM) is challenging as it appears either in the post operative patients or patients acquire the organisms from the hospital environment. In both the situations, pathogens are exposed to high dose of antibiotics. Chances of getting multidrug resistance organism are very high. We have performed this experiment to find out the etiological agents of HAABM and its antibiotics susceptibility pattern. Methodology: A perspective study was conducted at the Department of Microbiology, All India Institute of Medical Sciences, New Delhi. From March 2015 to April 2018 total 400 Cerebro spinal fluid samples were collected aseptically. Samples were processed for cell count, Gram staining, and culture. Culture plates were incubated at 37°C for 18-24 hours. Organism grown on blood and MacConkey agar were identified by MALDI-TOF Vitek MS (BioMerieux, France) and antibiotic susceptibility tests were performed by Kirby Bauer disc diffusion method as per CLSI 2015 guideline. Results: Of the 400 CSF samples processed, 43 (10.75%) were culture positive for different bacteria. Out of 43 isolates, the most prevalent Gram-positive organisms were S. aureus 4 (9.30%) followed by E. faecium 3 (6.97%) & CONS 2 (4.65%). Similarly, E. coli 13 (30.23%) was the commonest Gram-negative isolates followed by A. baumannii 12 (27.90%), K. pneumonia 5 (11.62%) and P. aeruginosa 4(9.30%). Most of the antibiotics tested against the Gram-negative isolates were resistance to them. Colistin was most effective followed by Meropenem and Imepenim for all Gram-negative HAABM isolates. Similarly, most of antibiotics tested were susceptible to S. aureus and CONS. However, E. faecium (100%) were only susceptible to vancomycin and teicoplanin. Conclusion: Hospital acquired acute bacterial meningitis (HAABM) is becoming the emerging challenge as most of isolates are showing resistance to commonly used antibiotics. Gram-negative organisms are emerging as the major player of HAABM. Great care needs to be taken especially in tertiary care hospitals. Similarly, antibiotic stewardship should be followed and antibiotic susceptibility test (AST) should be performed regularly to update the antibiotic patter and to prevent from the emergence of resistance. Updated information of the AST will be helpful for the better management of the meningitis patient.

Keywords: CSF, MALDI-TOF, hospital acquired acute bacterial meningitis, AST

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Authors: Bayan Almofty, Yuto Yamaki, Tadamasa Terai, Sadahito Uto

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Culture techniques of skeletal muscle cells are advanced in the field of regenerative medicine and applied research of cultured muscle. As applied research of cultured muscle, myopathy (muscles disease) treatment is expected and development bio of actuator is also expected in biomedical engineering. Grayanotoxins (GTXs) is known as neurotoxins that enhance the permeability of cell membrane for Na ions. Grayanotoxins are extracted from a famous Pieris japonica and Ericaceae as well as a phytotoxin. In this study, we investigated the effect of GTXs on muscle cells (C2C12) contraction and membrane potential. Contraction of myotubes is induced by applied external electrical stimulation. Contraction and membrane potential change of skeletal muscle cells are induced by injection of current. We, therefore, concluded that effect of Grayanotoxins on contraction and membrane potential of C2C12 relate to acute toxicity of GTXs.

Keywords: skeletal muscle cells C2C12, grayanotoxins, contraction, membrane potential, acute toxicity, pytotoxin, motubes

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Authors: Leonardo Juan Ramírez López, Javier Oswaldo Rodriguez Velasquez

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We have designed a Holter that measures the heart´s activity for over 24 hours, implemented a prediction methodology, and generate alarms as well as indicators to patients and treating physicians. Various diagnostic advances have been developed in clinical cardiology thanks to Holter implementation; however, their interpretation has largely been conditioned to clinical analysis and measurements adjusted to diverse population characteristics, thus turning it into a subjective examination. This, however, requires vast population studies to be validated that, in turn, have not achieved the ultimate goal: mortality prediction. Given this context, our Insight Research Group developed a mathematical methodology that assesses cardiac dynamics through entropy and probability, creating a numerical and geometrical attractor which allows quantifying the normalcy of chronic and acute disease as well as the evolution between such states, and our Tigum Research Group developed a holter device with 12 channels and advanced computer software. This has been shown in different contexts with 100% sensitivity and specificity results.

Keywords: attractor , cardiac, entropy, holter, mathematical , prediction

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Authors: Amare Nigatu, Mågne Bratveit, Bente E. Moen

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Background: Pesticide exposure is an important public health concern in Ethiopia, but there is limited information on pesticide intoxications. Residents may have an increased risk of pesticide exposure through proximity of their homes to farms using pesticides. Also the pesticide exposure might be related to employment at these farms. This study investigated the prevalence of acute pesticide intoxications (API) by residence proximity to a nearby flower farm and assessed if intoxications are related to working there or not. Methods: A cross-sectional survey involving 516 persons was conducted. Participants were grouped according to their residence proximity from a large flower farm; living within 5 kilometers and 5-12 kilometers away, respectively. In a structured interview, participants were asked if they had health symptoms within 48 hours of pesticide exposure in the past year. Those, who had experienced this and reported two or more typical pesticide intoxication symptoms, were considered as having had API. Chi-square and independent t-tests were used to compare categorical and continuous variables, respectively. Confounding variables were adjusted by using binomial regression model. Results: The prevalence of API in the past year among the residents in the study area was 26%, and it was higher in the population living close to the flower farm (42%) compared to those living far away (11%), prevalence ratio (PR) = 3.2, 95% CI: 2.2-4.8, adjusted for age, gender & education. A subgroup living close to the farm & working there had significantly more API (56%) than those living close & did not work there (16%), adjusted PR = 3.0, 95% CI: 1.8-4.9. Flower farm workers reported more API (56%) than those not working there (13%,), adjusted PR = 4.0, 95% CI: 2.9-5.6. Conclusion: The residents living closer than 5 kilometers to the flower farm reported significantly higher prevalence of API than those living 5-12 kilometers away. This increased risk of API was associated with work at the flower farm.

Keywords: acute pesticide intoxications, self-reported symptoms, flower farm workers, living proximity

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Authors: Sara Ataei, Maryam Taghizadeh-Ghehi, Amir Sarayani, Asieh Ashouri, Amirhossein Moslehi, Molouk Hadjibabaie, Kheirollah Gholami

Abstract:

Background: Acute kidney injury (AKI) is common in hematopoietic stem cell transplantation (HSCT) patients with an incidence of 21–73%. Prevention and early diagnosis reduces the frequency and severity of this complication. Predictive biomarkers are of major importance to timely diagnosis. Neutrophil gelatinase associated lipocalin (NGAL) is a widely investigated novel biomarker for early diagnosis of AKI. However, no study assessed NGAL for AKI diagnosis in HSCT patients. Methods: We performed further analyses on gathered data from our recent trial to evaluate the performance of urine NGAL (uNGAL) as an indicator of AKI in 72 allogeneic HSCT patients. AKI diagnosis and severity were assessed using Risk–Injury–Failure–Loss–End-stage renal disease and AKI Network criteria. We assessed uNGAL on days -6, -3, +3, +9 and +15. Results: Time-dependent Cox regression analysis revealed a statistically significant relationship between uNGAL and AKI occurrence. (HR=1.04 (1.008-1.07), P=0.01). There was a relation between uNGAL day +9 to baseline ratio and incidence of AKI (unadjusted HR=.1.047(1.012-1.083), P<0.01). The area under the receiver-operating characteristic curve for day +9 to baseline ratio was 0.86 (0.74-0.99, P<0.01) and a cut-off value of 2.62 was 85% sensitive and 83% specific in predicting AKI. Conclusions: Our results indicated that increase in uNGAL augmented the risk of AKI and the changes of day +9 uNGAL concentrations from baseline could be of value for predicting AKI in HSCT patients. Additionally uNGAL changes preceded serum creatinine rises by nearly 2 days.

Keywords: acute kidney injury, hemtopoietic stem cell transplantation, neutrophil gelatinase-associated lipocalin, Receiver-operating characteristic curve

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Authors: Eman Merza, Stephen Pearson, Glen Lichtwark, Peter Malliaras

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The Achilles tendon (AT) exhibits volume changes related to fluid flow under acute load which may be linked to changes in stiffness. Fluid flow provides a mechanical signal for cellular activity and may be one mechanism that facilitates tendon adaptation. This study aimed to investigate whether isometric intervention involving a high level of load duration and intensity could maximize the immediate reduction in AT volume and stiffness compared to interventions involving a lower level of load duration and intensity. Sixteen healthy participants (12 males, 4 females; age= 24.4 ± 9.4 years; body mass= 70.9 ± 16.1 kg; height= 1.7 ± 0.1 m) performed three isometric interventions of varying levels of load duration (2 s and 8 s) and intensity (35% and 75% maximal voluntary isometric contraction) over a 3 week period. Freehand 3D ultrasound was used to measure free AT volume (at rest) and length (at 35%, 55%, and 75% of maximum plantarflexion force) pre- and post-interventions. The slope of the force-elongation curve over these force levels represented individual stiffness (N/mm). Large reductions in free AT volume and stiffness resulted in response to long-duration high-intensity loading whilst less reduction was produced with a lower load intensity. In contrast, no change in free AT volume and a small increase in AT stiffness occurred with lower load duration. These findings suggest that the applied load on the AT must be heavy and sustained for a long duration to maximize immediate volume reduction, which might be an acute response that enables optimal long-term tendon adaptation via mechanotransduction pathways.

Keywords: Achilles tendon, volume, stiffness, free tendon, 3d ultrasound

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Authors: Birendra Kumar Bista, Rhitik Bista, Prafulla Koirala, Lokendra Mandal, Nikrsh Raj Shrestha, Vivek Kattel

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Introduction: Poorly controlled diabetes is associated with cause and poor outcome of stroke. High blood sugar reduces cerebral blood flow, increases intracranial pressure, cerebral edema and neuronal death, especially among patients with poorly controlled diabetes.1 SGLT2 inhibitors are associated with 50% reduction in hemorrhagic stroke compared with placebo. SGLT2 inhibitors decrease cardiovascular events via reducing glucose, blood pressure, weight, arteriosclerosis, albuminuria and reduction of atrial fibrillation.2,3 No study has been documented in low income countries to see the role of post stroke SGLT2 inhibitors on diabetic patients at and after ICU admission. Aims: The aim of the study was to measure the 12 months outcome of diabetic patients with acute stroke admitted in ICU set up with naïve SGLT2 inhibitors add on therapy. Method: It was prospective cohort study carried out in a 250 bedded tertiary neurology care hospital at the province capital Biratnagar Nepal. Diabetic patient with acute stroke admitted in ICU from 1st January 2022 to 31st December 2022 who were not under SGLT2 inhibitors were included in the study. These patients were managed as per hospital protocol. Empagliflozin was added to the alternate enrolled patients. Empagliflozin was continued at the time of discharged and during follow up unless contraindicated. These patients were followed up for 12 months. Outcome measured were mortality, morbidity requiring readmission or hospital visit other than regular follow up, SGLT2 inhibitors related adverse events, neuropsychiatry comorbidity, functional status and biochemical parameters. Ethical permission was taken from hospital administration and ethical board. Results: Among 147 diabetic cases 68 were not treated with empagliflozin whereas 67 cases were started the SGLT2 inhibitors. HbA1c level and one year mortality was significantly low among patients on empaglifozin arm. Over a period of 12 months 427 acute stroke patients were admitted in the ICU. Out of them 44% were female, 61% hypertensive, 34% diabetic, 57% dyslipidemia, 26% smoker and with median age of 45 years. Among 427 cases 4% required neurosurgical interventions and 76% had hemorrhagic CVA. The most common reason for ICU admission was GCS<8 (51%). The median ICU stay was 5 days. ICU mortality was 21% whereas 1 year mortality was 41% with most common reason being pneumonia. Empaglifozin related adverse effect was seen in 11% most commonly lower urinary tract infection in 6%. Conclusion: Empagliflozin can safely be started among acute stroke with better Hba1C control and low mortality outcome compared to treatment without SGLT2 inhibitor.

Keywords: diabetes, ICU, mortality, SGLT2 inhibitors, stroke

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