Search results for: swine respiratory disease

Authors: Moussa Majed, Omar Yaser

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The main objective of this experiment was to study the impact of Probiotic compound on the specific immunity as the case study of infectious bursal disease. Total of 8000 one-day old Ross 108 broiler were randomly divided into two experimental groups; control group (4500 birds) and experimental group (3500 birds). Birds in two groups were reared under similar environmental conditions. Birds in control group received basal diets without probiotic whereas the birds in experimental one were fed basal diets supplemented with a commercial probiotic mixture) probiotic lacting k, which contains bacteria cells beyond to lactobacillus, Streptococcus and bifidobacterium genus that are isolated from gut microflora in healthy chickens(. The commercial probiotic were used according to the manufacturer instruction. 400 blood samples for each group were collected from wing vein every 5-7 days as interval period till 42 days old. Indirect Enzyme-Linked Immunosorbent Assay (ELISA) test was performed to detect the level of infectious bursal disease virus (IBDV) antibodies. The results clearly showed that the mean of immune titers was significantly (p= 0.03) higher in trail group than control one. The coefficient of variance percentages were 55% and 39% for control and trial groups respectively, this illustrates that homogeneity of immunity titers in the trail group was much better comparing with control group. The values of geometric means of titers in the control group and trial group were reported 3820 and 8133, respectively. The crude mortality rate in the experimental group was two times lower comparing with control group (14% and 28% respectively, p = 0.005

Keywords: probiotic, broiler chicken, infectious bursal disease, immunity, ELISA test

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Authors: Maria Giovanna Lupo, Marina Camera, Marcello Rattazzi, Nicola Ferri

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A complex interplay among chronic kidney disease, lipid metabolism and aortic calcification has been recognized starting from results of many clinical and experimental studies. Here we investigated the influence of kidney function on PCSK9 levels, both in uremic rats and in clinical observation study, and its potential direct action on cultured smooth muscle cells (SMCs) calcification. In a cohort of 594 subjects enrolled in a single centre, observational, cross-sectional and longitudinal study, a negative association between GFR and plasma PCSK9 was found. Atherosclerotic cardiovascular disease (ASCVD), as co-morbidity, further increased PCSK9 plasma levels. Diet-induced uremic condition in rats, induced aortic calcification and increased total cholesterol and PCSK9 levels in plasma, livers and kidneys. Immunohistochemical analysis confirmed PCSK9 expression in aortic SMCs. SMCs overexpressing PCSK9 (SMCsPCSK9), cultured for 7-days in a pro-calcification environment (2.0mM or 2.4mM inorganic phosphate, Pi) showed a significantly higher extracellular calcium (Ca2+) deposition compared to mocked SMCs. Under the same experimental conditions, the addition of exogenous recombinant PCSK9 did not increase the extracellular calcification of SMCs. By flow cytometry analysis we showed that SMCsPCSK9, in response to 2.4mM Pi, released higher number of extracellular vesicles (EVs) positive for three tetraspanin molecules, such as CD63, CD9, and CD81. EVs derived from SMCsPCSK9 tended to be more enriched in calcium and alkaline phosphatase (ALPL), compared to EVs from mocks SMCs. In conclusion, our study reveals a direct role of PCSK9 on vascular calcification induced by higher inorganic phosphate levels associated to CKD condition. This effect appears to be mediated by a positive effect of endogenous PCSK9 on the release of EVs containing Ca2+ and ALP, which facilitate the deposition inorganic calcium phosphate crystals.

Keywords: PCSK9, calcification, extracellular vesicles, chronic kidney disease

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Authors: David Ming Liu, Benjamin Hirsch, Bashir Aden

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Syndromic surveillance is to detect or predict disease outbreaks through the analysis of medical sources of data. Using social media data like tweets to do syndromic surveillance becomes more and more popular with the aid of open platform to collect data and the advantage of microblogging text and mobile geographic location features. In this paper, a Syndromic Surveillance Framework is presented with machine learning kernel using tweets data analytics. Influenza and the three cities Abu Dhabi, Al Ain and Dubai of United Arabic Emirates are used as the test disease and trial areas. Hospital cases data provided by the Health Authority of Abu Dhabi (HAAD) are used for the correlation purpose. In our model, Latent Dirichlet allocation (LDA) engine is adapted to do supervised learning classification and N-Fold cross validation confusion matrix are given as the simulation results with overall system recall 85.595% performance achieved.

Keywords: Syndromic surveillance, Tweets, Machine Learning, data mining, Latent Dirichlet allocation (LDA), Influenza

Procedia PDF Downloads 116

Authors: Yahya Ibrahim Harande

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The purpose of this study was to identify the journals that published articles on malaria disease in Africa and to determine the core of productive journals from the identified journals. The data for the study were culled out from African Index Medicus (AIM) database. A total of 529 articles was gathered from 115 journal titles from 1979-2011. In order to obtain the core of productive journals, Bradford`s law was applied to the collected data. Five journal titles were identified and determined as core journals. The data used for the study was analyzed and that, the subject matter used, Malaria was in conformity with the Bradford`s law. On the aspect dispersion of the literature, English was found to be the dominant language of the journals. (80.9%) followed by French (16.5%). Followed by Portuguese (1.7%) and German (0.9%). Recommendation is hereby proposed for the medical libraries to acquire these five journals that constitute the core in malaria literature for the use of their clients. It could also help in streamlining their acquision and selection exercises. More researches in the subject area using Bibliometrics approaches are hereby recommended.

Keywords: productive journals, malaria disease literature, Bradford`s law, core journals, African scholars

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Authors: Anita Paddy, Millicent Obodai, Lebbaeus Asamani

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The management of sickle cell disease requires a multidisciplinary team for better outcomes. Thus, literature on the application of the biopsychosocial model for the management and explanation of chronic pain in sickle cell disease (SCD) and other chronic diseases abound. However, there is limited research on the use of the biopsychosocial model, together with a spiritual component (biopsychosocial-spiritual model). The study investigated the extent to which healthcare providers utilized the biopsychosocial-spiritual model in the management of chronic pain to improve the quality of life (QoL) of patients with SCD. This study employed the descriptive survey design involving a consecutive sampling of 261 patients with SCD who were between the ages of 18 to 79 years and were accessing hematological services at the Clinical Genetics Department of the Korle Bu Teaching Hospital. These patients willingly consented to participate in the study by appending their signatures. The theory of integrated quality of life, the gate control theory of pain and the biopsychosocial(spiritual) model were tested. An instrument for the biopsychosocial-spiritual model was developed, with a basis from the literature reviewed, while the World Health Organisation Quality of Life BREF (WHOQoLBref) and the spirituality rating scale were adapted and used for data collection. Data were analyzed using descriptive statistics (means, standard deviations, frequencies, and percentages) and partial least square structural equation modeling. The study revealed that healthcare providers had a great leaning toward the biological domain of the model compared to the other domains. Hence, participants’ QoL was not fully improved as suggested by the biopsychosocial(spiritual) model. Again, the QoL and spirituality of patients with SCD were quite high. A significant negative impact of spirituality on QoL was also found. Finally, the biosocial domain of the biopsychosocial-spiritual model was the most significant predictor of QoL. It was recommended that policymakers train healthcare providers to integrate the psychosocial-spiritual component in health services. Also, education on SCD and its resultant impact from the domains of the model should be intensified while health practitioners consider utilizing these components fully in the management of the condition.

Keywords: biopsychosocial (spritual), sickle cell disease, quality of life, healthcare, accra

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Authors: Po-Jung Huang, Chi-Ching Lee, Bertrand Chin-Ming Tan, Yuan-Ming Yeh, Julie Lichieh Chu, Tin-Wen Chen, Cheng-Yang Lee, Ruei-Chi Gan, Hsuan Liu, Petrus Tang

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Whole-exome sequencing focuses on the protein coding regions of disease/cancer associated genes based on a priori knowledge is the most cost-effective method to study the association between genetic alterations and disease. Recent advances in high throughput sequencing technologies and proteomic techniques has provided an opportunity to integrate genomics and proteomics, allowing readily detectable mutated peptides corresponding to mutated genes. Since sequence database search is the most widely used method for protein identification using Mass spectrometry (MS)-based proteomics technology, a mutant proteome database is required to better approximate the real protein pool to improve disease-associated mutated protein identification. Large-scale whole exome/genome sequencing studies were launched by National Cancer Institute (NCI), Broad Institute, and The Cancer Genome Atlas (TCGA), which provide not only a comprehensive report on the analysis of coding variants in diverse samples cell lines but a invaluable resource for extensive research community. No existing database is available for the collection of mutant protein sequences related to the identified variants in these studies. CMPD is designed to address this issue, serving as a bridge between genomic data and proteomic studies and focusing on protein sequence-altering variations originated from both germline and cancer-associated somatic variations.

Keywords: TCGA, cancer, mutant, proteome

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Authors: Farah Amalina Mohamed Affandi, Redhwan Ahmad Al-Naggar, Seok Mui Wang, Thanikasalam Kathiresan

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Gestational choriocarcinoma is a condition in which there is an abnormal growth or a tumor inside the women’s uterus after conception. It is a type of gestational trophoblastic disease which is relatively rare and malignant. The current epidemiological data of this disease are inadequate. The purposes of this study are to examine the epidemiology of choriocarcinoma and their risk factors based on all available population-based and hospital-based data of the disease. In this study, we searched The MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases using the keywords ‘choriocarcinoma’, ‘gestational’, ‘gestational choriocarcinoma’ and ‘epidemiology’. We included only human studies published in English between 1995 and 2015 to ensure up to date evidence. Case studies, case reports, animal studies, letters to the editor, news, and review articles were excluded. Retrieved articles were screened in three phases. In the first phase, any articles that did not match the inclusion criteria based solely on titles were excluded. In the second phase, the abstracts of remaining articles were screened thoroughly; any articles that did not meet our inclusion criteria were excluded. In the final phase, full texts of the remaining articles were read and assessed to exclude articles that did not meet the inclusion criteria or any articles that fulfilled the exclusion criteria. Duplicates articles were also removed. Systematic reviews and meta-analysis were excluded. Extracted data were summarized in table and figures descriptively. The reference lists of included studies were thoroughly reviewed in search for other relevant studies. A total of ten studies met all the selection criteria. Nine were retrospective studies and one was cohort study. Total numbers of 4563 cases of choriocarcinoma were reviewed from several countries which are Korea, Japan, South Africa, USA, New Mexico, Finland, Turkey, China, Brazil and The Netherlands. Different studies included different range of age with their mean age of 28.5 to 30.0 years. All studies investigated on the disease’s incidence rate, only two studies examined on the risk factors or associations of the disease. Approximately 20% of the studies showed a reduction in the incidence of choriocarcinoma while the other 80% showed inconsistencies in rate. Associations of age, fertility age, occupations and socio-demographic with the status remains unclear. There is limited information on the epidemiological aspects of gestational choriocarcinoma. The observed results indicated there was a decrease in the incidence rate of gestational choriocarcinoma globally. These could be due to the reduction in the incidence of molar pregnancy and the efficacy of the treatment, mainly by chemotherapy.

Keywords: epidemiology, gestational choriocarcinoma, incidence, prevalence, risk factor

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Authors: Noorulain Khalid, Unsaar Hayat, Muhammad Chaudhary, Christos Iosifidis, Felipe Dhawahir-Scala, Fiona Carley

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Dry eye disease (DED) is a common condition seen in the emergency eye department (EED) at Manchester Royal Eye Hospital (MREH). However, there is variability in the prescription of lubricating eye drops among different healthcare providers. The aim of this study was to develop an up-to-date, standardized algorithm for the prescription of lubricating eye drops in the EED at MREH based on international and national guidelines. The study also aimed to assess the impact of implementing the guideline on the rate of inappropriate lubricant prescriptions. Primarily, the impact was to be assessed in the form of the appropriateness of prescriptions for patients’ DED. The impact was secondary to be assessed through analysis of the cost to the hospital. Data from 845 patients who attended the EED over a 3-month period were analyzed, and 157 patients met the inclusion and exclusion criteria. After conducting a review of the literature and collaborating with the corneal team, an algorithm for the prescription of lubricants in the EED was developed. Three plan-do-study-act (PDSA) cycles were conducted, with interventions such as emails, posters, in-person reminders, and education for incoming trainees. The appropriateness of prescriptions was evaluated against the guidelines. Data were collected from patient records and analyzed using statistical methods. The appropriateness of prescriptions was assessed by comparing them to the guidelines and by clinical correlation with a specialized registrar. The study found a substantial improvement in the number of appropriate prescriptions, with an increase from 55% to 93% over the three PDSA cycles. There was additionally a 51% reduction in expenditure on lubricant prescriptions, resulting in cost savings for the hospital (approximate saving of £50/week). Theoretical importance: Appropriate prescription of lubricating eye drops improves disease management for patients and reduces costs for the hospital. The development and implementation of a standardized guideline facilitate the achievement of these goals. Conclusion: This study highlights the inconsistent management of DED in the EED and the potential lack of training in this area for healthcare providers. The implementation of a standardized, easy-to-follow guideline for lubricating eye drops can help to improve disease management while also resulting in cost savings for the hospital.

Keywords: lubrication, dry eye disease, guideline, prescription

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Authors: Atitallah Sofien, Bouyahia Olfa, Krifi farah, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Subcutaneous fat necrosis of the newborn (SCFN) is a rare acute hypodermatitis characterized by skin lesions in the form of infiltrated, hard plaques and subcutaneous nodules, with a purplish-red color, occurring between the first and sixth week of life. SCFN is generally a benign condition that spontaneously regresses without sequelae, but it can be complicated by severe hypercalcemia. Methodology: This is a retrospective case report of neonatal subcutaneous fat necrosis complicated with severe hypercalcemia and nephrocalcinosis. Results: This is a case of a female newborn with a family history of a hypothyroid mother on Levothyrox, born to non-consanguineous parents and from a well-monitored pregnancy. The newborn was delivered by cesarean section at 39 weeks gestation due to severe preeclampsia. She was admitted to the Neonatal Intensive Care Unit at 1 hour of life for the management of grade 1 perinatal asphyxia and immediate neonatal respiratory distress related to transient respiratory distress. Hospitalization was complicated by a healthcare-associated infection, requiring intravenous antibiotics for ten days, with a good clinical and biological response. On the 20th day of life, she developed skin lesions in the form of indurated purplish-red nodules on the back and on both arms. A SCFN was suspected. A calcium level test was conducted, which returned a result of 3 mmol/L. The rest of the phosphocalcic assessment was normal, with early signs of nephrocalcinosis observed on renal ultrasound. The diagnosis of SCFN complicated by nephrocalcinosis associated with severe hypercalcemia was made, and the condition improved with intravenous hydration and corticosteroid therapy. Conclusion: SCFN is a rare and generally benign hypodermatitis in newborns with an etiology that is still poorly understood. Despite its benign nature, SCFN can be complicated by hypercalcemia, which can sometimes be life-threatening. Therefore, it is important to conduct a thorough skin examination of newborns, especially those with risk factors, to detect and correct any potential hypercalcemia.

Keywords: subcutaneous fat necrosis, newborn, hypercalcemia, nephrocalcinosis

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Authors: Peng Guo

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Objective: This study investigates the clinical characteristics of sleep disorders (SD) in patients with Alzheimer's disease (AD) and their relationship with cognitive impairment. Methods: According to the inclusion and exclusion criteria of AD, 460 AD patients were consecutively included in Beijing Tiantan Hospital from January 2016 to April 2022. Demographic data, including gender, age, age of onset, course of disease, years of education and body mass index, were collected. The Pittsburgh sleep quality index (PSQI) scale was used to evaluate the overall sleep status. AD patients with PSQI ≥7 was divided into AD with SD (AD-SD) group, and those with PSQI < 7 were divided into AD with no SD (AD-nSD) group. The overall cognitive function of AD patients was evaluated by the scales of Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA), memory was evaluated by the AVLT-immediate recall, AVLT-delayed recall and CFT-delayed memory scales, the language was evaluated by BNT scale, visuospatial ability was evaluated by CFT-imitation, executive function was evaluated by Stroop-A, Stroop-B and Stroop-C scales, attention was evaluated by TMT-A, TMT-B, and SDMT scales. The correlation between cognitive function and PSQI score in AD-SD group was analyzed. Results: Among the 460 AD patients, 173 cases (37.61%) had SD. There was no significant difference in gender, age, age of onset, course of disease, years of education and body mass index between AD-SD and AD-nSD groups (P>0.05). The factors with significant difference in PSQI scale between AD-SD and AD-nSD groups include sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance, use of sleeping medication and daytime dysfunction (P<0.05). Compared with AD-nSD group, the total scores of MMSE, MoCA, AVLT-immediate recall and CFT-imitation scales in AD-SD group were significantly lower（P＜0.01，P＜0.01，P＜0.01，P＜0.05）. In AD-SD group, subjective sleep quality was significantly and negatively correlated with the scores of MMSE, MoCA, AVLT-immediate recall and CFT-imitation scales (r=-0.277，P=0.000; r=-0.216，P=0.004; r=-0.253，P=0.001; r=-0.239, P=0.004), daytime dysfunction was significantly and negatively correlated with the score of AVLT-immediate recall scale (r=-0.160，P=0.043). Conclusion The incidence of AD-SD is 37.61%. AD-SD patients have worse subjective sleep quality, longer time to fall asleep, shorter sleep time, lower sleep efficiency, severer nighttime SD, more use of sleep medicine, and severer daytime dysfunction. The overall cognitive function, immediate recall and visuospatial ability of AD-SD patients are significantly impaired and are closely correlated with the decline of subjective sleep quality. The impairment of immediate recall is highly correlated with daytime dysfunction in AD-SD patients.

Keywords: Alzheimer's disease, sleep disorders, cognitive impairment, correlation

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Authors: Mohammed S. Bhader, Abdullah A. Ghaddaf, Anas Alamoudi, Amal Abualola, Renad Kalantan, Noura Alkhulaifi, Ibrahim Halawani, Mohammed Alhindi

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Background: Noninvasive neurally adjusted ventilatory assist (NAVA) is a relatively new mode of noninvasive ventilation with promising clinical and patient-ventilator outcomes for preterm infants. The aim of this systematic review was to compare NAVA to nasal continuous or positive airway pressure (NCPAP) or intermittent positive airway pressure (NIPP) for preterm infants. Methods: We searched the online databases Medline, Embase, and CENTRAL. We included randomized controlled trials (RCTs) that compared NAVA to NCPAP or NIPP for preterm infants < 37 weeks gestational age. We sought to evaluate the following outcomes: noninvasive intubation failure rate, desaturation rate, the fraction of inspired oxygen (FiO2), and length of stay in the neonatal intensive care unit (NICU). We used the mean difference (MD) to represent continuous outcomes, while the odds ratio (OR) was used to represent dichotomous outcomes. Results: A total of 11 RCTs that enrolled 429 preterm infants were deemed eligible. NAVA showed similar clinical outcomes to NCPAP or NIPP with respect to noninvasive intubation failure (RR for NAVA versus NCPAP: 0.82, 95% confidence interval (CI): 0.49 to 1.37), desaturation rate (RR for NAVA versus NCPAP: 0.69, 95%CI: 0.36 to 1.29; RR for NAVA versus NIPP: 0.58, 95%CI: 0.08 to 4.25), FiO2 (MD for NAVA versus NCPAP: –0.01, 95%CI: –0.04 to 0.02; MD for NAVA versus NIPP: –7.16, 95%CI: –22.63 to 8.31), and length of stay in the NICU (MD for NAVA versus NCPAP: 1.34, 95%CI: –4.17 to 6.85). Conclusion: NAVA showed similar clinical and ventilator-related outcomes compared to the usual care noninvasive respiratory support measures NCPAP or NIPP for preterm infants.

Keywords: preterm infants, noninvasive neurally adjusted ventilatory assist, NIV-NAVA, non-invasive ventilation, nasal continuous or positive airway pressure, NCPAP, intermittent positive airway pressure ventilation, NIPP, respiratory distress syndrome, RDS

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Authors: Chander Shekhar, Jeetendra Yadav, Shaziya Allarakha

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Hypertension has been described as an 'iceberg disease' as those who suffered are ignored and hence usually seek healthcare services at a very late stage. It is estimated that more than 2 million Indians are suffering from hypertensive heart disease that contributed to above 0.13 million deaths in 2016. The paper study aims to know the prevalence of Hypertension in India and its variation by socioeconomic backgrounds and to find out risk factors discriminating hypertension with special emphasis on consumption of tobacco and alcohol among men aged 15-54 years in India. The paper uses NFHS (2015-16) data. The paper used binary logistic regression and discriminant analysis to find significant predictors and discriminants of interest. The prevalence of hypertension was 16.5% in the study population. The results suggest that consumption of alcohol and tobacco are significant discriminant characteristics in carrying hypertension irrespective of what socioeconomic background characteristic he possesses.

Keywords: hypertention, alcohol, tobacco, discriminant

Procedia PDF Downloads 146

Authors: Rima Al Garni, Emad Al Shdaifat, Sahar Elmetwalli, Mohammad Alzaid, Abdulrahman Alghothayyan, Sara Al Abd Al Hai, Seham Al Rashidi

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Aim: To investigate the prevalence of non-adherence of patients on haemodialysis and explore their perception of the importance of adherence to the therapeutic regime and estimate the predictors for adherence to the therapeutic regime. Background: End-stage renal disease is commonly treated by haemodialysis. Haemodialysis treatment alone is not effective in replacing kidney function. Diet and fluid restrictions, along with supplementary medications, are mandatory for the survival and well-being of patients. Hence, adherence to this therapeutic regimen is essential. However, non-adherence to diet and fluid restrictions, medications, and dialysis is common among patients on haemodialysis. Design: Descriptive cross-sectional method was applied to investigate the prevalence of non-adherence to treatment, including adherence to diet and fluid restrictions, medications, and dialysis sessions. Methods: Structured interviews were conducted using the Arabic version of the End-Stage Renal Disease Adherence Questionnaire. The sample included 230 patients undergoing haemodialysis in the Eastern Region of Saudi Arabia. Data were analysed using descriptive statistics and multiple regressions. Results/Findings: Most patients had good adherence (71.3%), and only 3.9% had poor adherence. The divorced or widowed patient had higher adherence compared with single (P=0.011) and married participants (P=0.045) through using the post hoc test. Patients above 60 years had higher adherence compared to patients below 40 years old (P=0.016) using the post hoc test. For the perception of the importance of adherence to the therapeutic regime subscale, two-thirds of the patients had lower scores (<=11). Conclusion: Adherence to therapeutic regime is high for three fourth of patients undergoing haemodialysis in the Eastern Region of Saudi Arabia; this finding is similar to results abstracted from the local literature. This result would help us highlight the needs of patients who are not compliant with their treatment plans and investigate the consequences of non-adherence on their well-being and general health. Hence, plan individualised therapeutic programmes that could raise their awareness and influence their adherence to therapeutic regimes.

Keywords: adherence to treatment, haemodialysis, end stage renal disease, diet and fluid restrictions

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Authors: Siti Khairunniza-Bejo, Yusnida Yusoff, Nik Salwani Nik Yusoff, Idris Abu Seman, Mohamad Izzuddin Anuar

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Most of the oil palm plantations have been threatened by Basal Stem Rot (BSR) disease which causes serious economic impact. This study was conducted to identify the healthy and BSR-infected oil palm tree using thirteen color indices. Multispectral and thermal camera was used to capture 216 images of the leaves taken from frond number 1, 9 and 17. Indices of normalized difference vegetation index (NDVI), red (R), green (G), blue (B), near infrared (NIR), green – blue (GB), green/blue (G/B), green – red (GR), green/red (G/R), hue (H), saturation (S), intensity (I) and thermal index (T) were used. From this study, it can be concluded that G index taken from frond number 9 is the best index to differentiate between the healthy and BSR-infected oil palm trees. It not only gave high value of correlation coefficient (R=-0.962), but also high value of separation between healthy and BSR-infected oil palm tree. Furthermore, power and S model developed using G index gave the highest R2 value which is 0.985.

Keywords: oil palm, image processing, disease, leaves

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Authors: Jitendra Pratap, Daphne Prybyszcuk, Luke Elliott, Arnold Ng

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Introduction: Coronary CT angiography is a non-invasive imaging technique for the assessment of coronary artery disease and has high sensitivity and negative predictive value. However, the correlation between the degree of CT coronary stenosis and the significance of hemodynamic obstruction is poor. The assessment of myocardial perfusion has mostly been undertaken by Nuclear Medicine (SPECT), but it is now possible to perform stress myocardial CT perfusion (CTP) scans quickly and effectively using CT scanners with high temporal resolution. Myocardial CTP is in many ways similar to neuro perfusion imaging technique, where radiopaque iodinated contrast is injected intravenously, transits the pulmonary and cardiac structures, and then perfuses through the coronary arteries into the myocardium. On the Siemens Force CT scanner, a myocardial perfusion scan is performed using a dynamic axial acquisition, where the scanner shuffles in and out every 1-3 seconds (heart rate dependent) to be able to cover the heart in the z plane. This is usually performed over 38 seconds. Report: A CT myocardial perfusion scan can be utilised to complement the findings of a CT Coronary Angiogram. Implementing a CT Myocardial Perfusion study as part of a routine CT Coronary Angiogram procedure provides a ‘One Stop Shop’ for diagnosis of coronary artery disease. This case study demonstrates that although the CT Coronary Angiogram was within normal limits, the perfusion scan provided additional, clinically significant information in regards to the haemodynamics within the myocardium of a patient with Hypertrophic Obstructive Cardio Myopathy (HOCM). This negated the need for further diagnostics studies such as cardiac ECHO or Nuclear Medicine Stress tests. Conclusion: CT coronary angiography with adenosine stress myocardial CTP was utilised in this case to specifically exclude coronary artery disease in conjunction with accessing perfusion within the hypertrophic myocardium. Adenosine stress myocardial CTP demonstrated the reduced myocardial blood flow within the hypertrophic myocardium, but the coronary arteries did not show any obstructive disease. A CT coronary angiogram scan protocol that incorporates myocardial perfusion can provide diagnostic information on the haemodynamic significance of any coronary artery stenosis and has the potential to be a “One Stop Shop” for cardiac imaging.

Keywords: CT, cardiac, myocardium, perfusion

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Authors: Tara Gurung, Suprina Prajapati

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Health and well being of people is a crucial for accomplishing sustainable development goals of any country. The present study focuses on quality of life of patients undergoing hemodialysis. Hemodialysis is a life sustaining treatment for patients with end stage renal disease (ESRD). Hemodialysis can bring about significant impairment in health related quality of life (HRQOL). The purpose of this study was to assess the quality of life of hemodialysis patients undergoing hemodialysis. A descriptive cross-sectional research design was utilized in total 100 samples using random sampling technique. The findings revealed that the total quality of life of the patients was 30.41±3.99 out of 100. The total physical component score was statistically significant with education status of the patients where p value for t test was 0.03 (p=0.03) and occupation of the patients where p value for the ANOVA test was 0.007 (p=0.007). The study recommended that it would be better if awareness programs regarding chronic kidney disease and life style modification in hemodialysis patients is given to the patients so that it would help patients to maintain the HRQOL.

Keywords: health and well bing, hemodialysis, patients quality of life

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Authors: Donya Ashtiani Haghighi, Amirali Baniasadi

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Coronavirus (COVID-19) disease has spread abruptly all over the world since the end of 2019. Computed tomography (CT) scans and X-ray images are used to detect this disease. Different Deep Neural Network (DNN)-based diagnosis solutions have been developed, mainly based on Convolutional Neural Networks (CNNs), to accelerate the identification of COVID-19 cases. However, CNNs lose important information in intermediate layers and require large datasets. In this paper, Capsule Network (CapsNet) is used. Capsule Network performs better than CNNs for small datasets. Accuracy of 0.9885, f1-score of 0.9883, precision of 0.9859, recall of 0.9908, and Area Under the Curve (AUC) of 0.9948 are achieved on the Capsule-based framework with hyperparameter tuning. Moreover, different dropout rates are investigated to decrease overfitting. Accordingly, a dropout rate of 0.1 shows the best results. Finally, we remove one convolution layer and decrease the number of trainable parameters to 146,752, which is a promising result.

Keywords: capsule network, dropout, hyperparameter tuning, classification

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Authors: Mohammad Jamal

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Non-alcoholic fatty liver disease (NAFLD) has become one of the most chronic liver diseases, prevalent among people with morbid obesity. NAFLD does not develop clinically significant liver disease, however cirrhosis and liver cancer develop in subset and currently there are no approved therapies for the treatment of NAFLD. The study is aimed to understand the various key genes involved in the mechanism of NAFLD which can be valuable for developing diagnostic and predictive biomarkers based on their histologic stage of liver. The study was conducted on 16 male Sprague Dawley rats. The animals were divided in two groups: control group (n=8) fed on ad libitum normal chow and regular water and the cafeteria group (CAF)) (n=8) fed on high fatty/ carbohydrate diet. The animals received their respective diet from 4 weeks onwards from D.O.B until 25 weeks. Liver was extracted and RT² Profiler PCR Array was used to assess the NAFLD related genes. Histological evaluation was performed using H&E stain in liver tissue sections. Our PCR array results showed that genes involved in anti-inflammatory activity (Ifng, IL10), fatty acid uptake/oxidation (Fabp5), apoptosis (Fas), lipogenesis (Gck and Srebf1), Insulin signalling (Igfbp1) and metabolic pathway (pdk4) were upregulated in the liver of cafeteria fed obese rats. Bloated hepatocytes, displaced nucleus and higher lipid content were seen in the liver of cafeteria fed obese rats. Although Liver biopsies remain the gold standard in evaluating NAFLD, however an approach towards non-invasive markers could be used in understanding the physiology, therapeutic potential, and the targets to combat NAFLD.

Keywords: biomarkers, cafeteria diet, obesity, NAFLD

Procedia PDF Downloads 143

Authors: Hsiu-Chuan Hsueh, Kuei-Feng Shen Jr., Chia-Ling Chao, Hui-Chuan Pan

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This article described a 75 years old woman who has suffered from intestinal perforation and accepted surgery with temporary enterostomy, the operation makes her depressed, refused relatives and friend's care, facing low willingness to participate in various activities due to fear of changing body appearance caused by surgery and leave enterostomy. The author collected information through observation talks, physical evaluation, and medical records during the period of care from November 14 to November 30, 2016, we used the four aspects of physiology, psychology, society and spirituality as a whole sexual assessment to establish the nursing problems of patient, included of acute pain, disturbance of body image,coping ineffective individual. For patient care issues, to encouraged case to express their inner feelings and take part in self-care programs through providing good therapeutic interpersonal relationships with their families. However, it provided clear information about the disease and follow-up treatment plan, give compliments in a timely manner, enhanced self-confidence of individual cases and their motivation to participate in self-care of stoma, further face the disease in a positive manner. At the same time, cross-section team care model and individual care measures were developed to enhance the care skills after returning home and at the same time assist the individual in facing the psychological impact caused by stoma. Hope to provide this experience, as a reference for the future care of the disease.

Keywords: enterostomy, intestinal perforation, nursing experience, ostomy

Procedia PDF Downloads 139

Authors: O. O. Sufyani, M. E. Oraiby, S. A. Qumaiy, A. I. Alaamri, Z. M. Eisa, A. M. Hakami, M. A. Attafi, O. M. Alhassan, W. M. Elsideeg, E. M. Noureldin, Y. A. Hobani, Y. Q. Majrabi, I. A. Khardali, A. B. Maashi, A. A. Al Mane, A. H. Hakami, I. M. Alkhyat, A. A. Sahly, I. M. Attafi

Abstract:

According to the Food and Agriculture Organization (FAO) Pesticides Use Database, pesticide use in agriculture in Saudi Arabia has more than doubled from 4539 tons in 2009 to 10496 tons in 2019. Among pesticides, pyrethroids is commonly used in Saudi Arabia. Pesticides may increase susceptibility to a variety of diseases, particularly among pesticide workers, due to their extensive use, indiscriminate use, and long-term exposure. Therefore, analyzing blood chemo-profiles and evaluating the detected substances as biomarkers for pyrethroid pesticide exposure may assist to identify and predicting adverse effects of exposure, which may be used for both preventative and risk assessment purposes. The purpose of this study was to (a) analyze chemo-profiling by Gas Chromatography-Mass Spectrometry (GC-MS) analysis, (b) identify the most commonly detected chemicals in a time-exposure-dependent manner using a Venn diagram, and (c) identify their associated disease among pesticide workers using analyzer tools on the Comparative Toxicogenomics Database (CTD) website, (250 healthy male volunteers (20-60 years old) who deal with pesticides in the Jazan region of Saudi Arabia (exposure intervals: 1-2, 4-6, 6-8, more than 8 years) were included in the study. A questionnaire was used to collect demographic information, the duration of pesticide exposure, and the existence of chronic conditions. Blood samples were collected for biochemistry analysis and extracted by solid-phase extraction for gas chromatography-mass spectrometry (GC-MS) analysis. Biochemistry analysis reveals no significant changes in response to the exposure period; however, an inverse association between the albumin level and the exposure interval was observed. The blood chemo-profiling was differentially expressed in an exposure time-dependent manner. This analysis identified the common chemical set associated with each group and their associated significant occupational diseases. While some of these chemicals are associated with a variety of diseases, the distinguishing feature of these chemically associated disorders is their applicability for prevention measures. The most interesting finding was the identification of several chemicals; erucic acid, pelargonic acid, alpha-linolenic acid, dibutyl phthalate, diisobutyl phthalate, dodecanol, myristic Acid, pyrene, and 8,11,14-eicosatrienoic acid, associated with pneumoconiosis, asbestosis, asthma, silicosis and berylliosis. Chemical-disease association study also found that cancer, digestive system disease, nervous system disease, and metabolic disease were the most often recognized disease categories in the common chemical set. The hierarchical clustering approach was used to compare the expression patterns and exposure intervals of the chemicals found commonly. More study is needed to validate these chemicals as early markers of pyrethroid insecticide-related occupational disease, which might assist evaluate and reducing risk. The current study contributes valuable data and recommendations to public health.

Keywords: occupational, toxicology, chemo-profiling, pesticide, pyrethroid, GC-MS

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Authors: Choppala Pratheek, Vineet Ahuja

Abstract:

Background: Crohn's disease (CD) recurrence following surgery is a common challenge, and current detection methods rely on risk factors identified in Western populations. This study aimed to investigate the risk factors and rates of postoperative CD recurrence in a tuberculosis-endemic region like India. Retrospective data was collected from a structured database from a specialty IBD clinic by reviewing case files from January 2005 to December 2021. Inclusion criteria involved CD patients diagnosed based on the ECCO-ESGAR consensus guidelines, who had undergone at least one intestinal resection and had a minimum follow-up period of one year at the IBD clinic. Results: A total of 90 patients were followed up for a median period of 45 months (IQR, 20.75 - 72.00). Out of the 90 patients, 61 received ATT prior to surgery, with a mean delay in diagnosis of 2.5 years, although statistically non-significant (P=0.078). Clinical recurrence occurred in 50% of patients, with the cumulative rate increasing from 13.3% at one year to 40% at three years. Among 63 patients who underwent endoscopy, 65.7% showed evidence of endoscopic recurrence, with the cumulative rate increasing from 31.7% at one year to 55.5% at four years. Smoking was identified as a significant risk factor for early endoscopic recurrence (P=0.001) by Cox regression analysis, but no other risk factors were identified. Initiating post-operative medications prior to clinical recurrence delayed its onset (P=0.004). Subgroup analysis indicated that endoscopic monitoring aided in the early identification of recurrence (P=0.001). The findings contribute to enhancing post-operative CD management strategies in such regions where the disease burden is escalating.

Keywords: crohns, post operative, tuberculosis-endemic, risk factors

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Authors: I. Hua Chu, Hsiang-Chi Yu, Hsuan Su

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Purpose: To examine the associations between self-determined motivation and physical activity in patients with coronary heart disease (CHD) in a longitudinal study. Methods: Patients with CHD were recruited for this study. Their motivations for exercise were measured by the Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2). Physical activity was assessed using the 7-day physical activity recall questionnaire. Duration and energy expenditure of moderate to vigorous physical activity (MVPA) were used in data analysis. All outcome measures were assessed at baseline and 12 months follow up. Data were analyzed using Pearson correlation analysis and regression analysis. Results: The results of the 45 participants (mean age 60.24 yr; 90.2% male) revealed that there were significant negative correlations between amotivation at baseline and duration (r=-.295, p=.049) and energy expenditure (r=-.300, p=.045) of MVPA at 12 months. In contrast, there were significant positive correlations between calculated relative autonomy index (RAI) at baseline and duration (r=.377, p=.011) and energy expenditure (r=.382, p=.010) of MVPA at 12 months. There was no significant correlation between other subscales of the BREQ-2 and duration or energy expenditure of MVPA. Regression analyses revealed that RAI was a significant predictor of duration (p=.011) and energy expenditure (p=.010) of MVPA at 12 months follow-up. Conclusions: These results suggest that the relative degree of self-determined motivation could predict long-term MVPA behaviors in CHD patients. Physical activity interventions are recommended to target enhancing one’s identified and intrinsic motivation to increase the likelihood of physical activity participation in this population.

Keywords: self-determined motivation, physical activity, coronary heart disease, relative autonomy index (RAI)

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Authors: Hanane Boutaj, Abdelilah Meddich, Said Wahbi, Zainab El Alaoui-Talibi, Allal Douira, Abdelkarim Filali-Maltouf, Cherkaoui El Modafar

Abstract:

The present work aims to investigate the effect of arbuscular mycorrhizal fungi (AMF) in improving the olive tree resistance to Verticillium wilt caused by Verticillium dahliae. Inoculated plants with a mycorrhizal autochthonous consortium 'Rhizolive consortium' and pure strain 'Glomus irregulare' were infected after three months with V. dahliae. The improving of olive tree resistance was determined through disease severity, incidence, and defoliation. On the other hand, the defense mechanisms of olive plants were evaluated through lignin content, phenylalanine ammonia lyase (PAL) activity, and polyphenol content. The results revealed that both AMF significantly (p < 0.05) reduced disease development and the rate of defoliation in infected olive plants. Moreover, the contents of lignin were boosted after mycorrhizal inoculation in both the roots and the stems of olive plants, which remained significantly (p < 0.001) higher after the 90th days of V. dahliae inoculation. PAL activity was increased after V. dahliae inoculation in the stems of 'Rhizolive consortium' treatment that were 17 times higher than those in the roots of olive plants. The polyphenol content in the stems was about twice higher than those in the roots. The reduction of disease severity was accompanied by increased levels of lignin content, PAL activity, and polyphenol content, particularly in the stems of olive plants, indicating the strengthening of the olive plant immune system against V. dahliae.

Keywords: olive tree, Mycorrhizal autochthonous consortium, Glomus irregulare, Verticillium dahliae, defense mechanisms

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Authors: Shireen Ibish

Abstract:

Physical inactivity and unhealthy diets have contributed to a global burden of disease with increased relation to non-communicable diseases, increased risk of colon and breast cancer, high prevalence of depression, reduced quality of life and early death. The World Health Organisation’s facts on Obesity show a tripling in prevalence across the European Region since the 1980s. This has lead to a huge public health burden, being responsible for and 10-13% of deaths (fourth largest cause of global mortality) and 2-8% of health costs in the Region. In the UK alone, the present cost of physical inactivity has been estimated to be £8.2 billion. In 2002 a paper published in the International Journal of Epidemiology on ‘sedentary’ lifestyle, put into figures the increasingly worrying statistics across European countries. “Percentages of sedentary lifestyles across European countries ranged between 43.3% (Sweden) and 87.8% (Portugal)”. This was especially so amongst obese subjects, less- educated people, and smokers. While in the UK’s “50% of adult population in the UK is predicted to be obese by 2050.” Sports and Exercise Medicine, as a specialty, has a lot to offer in targeting this globally increasing epidemic. The worrying figures and the increasing knowledge of combating and preventing this issue have lead to increased awareness amongst the medical profession and more targeted interventions to reduce the burden of disease. “The public health element of the specialty is critical – this is not simply a specialty for the management of elite athletes’ medical conditions – it is central to the promotion of exercise as a means of disease prevention, to enhance well-being and in the management of disease.” WHO advised on creating National policies, encouraging and providing opportunities for greater physical activity, and improve the affordability, availability and accessibility of healthy foods. In the UK various different movements have been established to target this problem. The Motivate2Move, Move Eat Treat and guidelines advising specialties on targeting and encouraging exercise in the population (Sport and Exercise Medicine A Fresh Approach).

Keywords: sedentary lifestyle, obesity, public health burden, medicine

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Authors: Elidrissi Laila, El Rhaoussi Fatima-Zahra, Haddad Fouad, Tahiri Mohamed, Hliwa Wafaa, Bellabah Ahmed, Badre Wafaa

Abstract:

Introduction: Metabolic Dysfunction Associated with Non-Alcoholic Fatty Liver Disease (MASLD), formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD), is the leading cause of chronic liver disease. The cardiometabolic risk factors associated with MASLD represent common health issues and significant public health challenges. Medical students, being active participants in the healthcare system and a young demographic, are particularly relevant for understanding this entity to prevent its occurrence on a personal and collective level. The objective of our study is to assess the level of knowledge among medical students regarding MASLD, its risk factors, and its long-term consequences. Materials and Methods: We conducted a descriptive cross-sectional study using an anonymous questionnaire distributed through social media over a period of 2 weeks. Medical students from various faculties in Morocco answered 22 questions about MASLD, its etiological factors, diagnosis, complications, and principles of treatment. All responses were analyzed using the Jamovi software. Results: A total of 124 students voluntarily provided complete responses. 59% of our participants were in their 3rd year, with a median age of 21 years. Among the respondents, 27% were overweight, obese, or diabetic. 83% correctly answered more than half of the questions, and 77% believed they knew about MASLD. However, 84% of students were unaware that MASLD is the leading cause of chronic liver disease, and 12% even considered it a rare condition. Regarding etiological factors, overweight and obesity were mentioned in 93% of responses, and type 2 diabetes in 84%. 62% of participants believed that type 1 diabetes could not be implicated in MASLD. For 83 students, MASLD was considered a diagnosis of exclusion, while 41 students believed that a biopsy was mandatory for diagnosis. 12% believed that MASLD did not lead to long-term complications, and 44% were unaware that MASLD could progress to hepatocellular carcinoma. Regarding treatment, 85% included weight loss, and 19% did not consider diabetes management as a therapeutic approach for MASLD. At the end of the questionnaire, 89% of the students expressed a desire to learn more about MASLD and were invited to access an informative sheet through a hyperlink. Conclusion: MASLD represents a significant public health concern due to the prevalence of its risk factors, notably the obesity pandemic, which is widespread among the young population. There is a need for awareness about the seriousness of this emerging and long-underestimated condition among young future physicians.

Keywords: MASLD, medical students, obesity, diabetes

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Authors: Huimin Zhao, Xiaoquan Liu, Haochen Liu

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The major challenge facing Alzheimer's Disease (AD) drug development is how to effectively improve cognitive function in clinical practice. Growing evidence indicates that stimulating hippocampal neurogenesis is a strategy for restoring cognition in animal models of AD. The mitogen-activated protein kinase (MAPK) pathway is a crucial factor in neurogenesis, which is negatively regulated by Dual-specificity phosphatase 16 (DUSP16). Transcriptome analysis of post-mortem brain tissue revealed up-regulation of DUSP16 expression in AD patients. Additionally, DUSP16 was involved in regulating the proliferation and neural differentiation of neural progenitor cells (NPCs). Nevertheless, whether the effect of DUSP16 on ameliorating cognitive disorders by influencing NPCs differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, we found that increased DUSP16 expression in both 3×Tg and SAMP8 models of AD led to NPC differentiation impairments. By silencing DUSP16, cognitive benefits, the induction of AHN and synaptic plasticity, were observed in AD mice. Furthermore, we found that DUSP16 is involved in the process of NPC differentiation by regulating c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, the increased DUSP16 may be regulated by the ETS transcription factor (ELK1), which binds to the promoter region of DUSP16. Loss of ELK1 resulted in decreased DUSP16 mRNA and protein levels. Our data uncover a potential regulatory role for DUSP16 in adult hippocampal neurogenesis and provide a possibility to find the target of AD intervention.

Keywords: alzheimer's disease, cognitive function, DUSP16, hippocampal neurogenesis

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Authors: Yan Lu, Song Hong, Janakiraman Udaiyappan, Aarti Nagayach, Quoc-Viet A. Duong, Masao Morita, Shun Saito, Yuichi Kobayashi, Yuhai, Zhao, Hongying Peng, Nicholas B. Pham, Walter J Lukiw, Christopher A. Vuong, Nicolas G. Bazan

Abstract:

Aims: Neurodegeneration and behavior dysfunction occurs in patients with Alzheimer's Disease (AD), and as the disease progresses many patients develop cognitive impairment. 5XFAD mouse model of AD is widely used to study AD pathogenesis and treatment. This study aimed to investigate the effect of maresin like 1 (MaR-L1) treatment in AD pathology using 5XFAD mice. Methods: We tested 12-month-old male 5XFAD mice and wild type control mice treated with MaR-L1 in a battery of behavioral tasks. We performed open field test, beam walking test, clasping test, inverted grid test, acetone test, marble burring test, elevated plus maze test, cross maze test and novel object recognition test. We also studied neuronal loss, amyloid β burden, and inflammation in the brains of 5XFAD mice using immunohistology and Western blotting. Results: MaR-L1 treatment to the 5XFAD mice showed improved cognitive function of 5XFAD mice. MaR-L1 showed decreased anxiety behavior in open field test and marble burring test, increased muscular strength in the beam walking test, clasping test and inverted grid test. Cognitive function was improved in MaR-L1 treated 5XFAD mice in the novel object recognition test. MaR-L1 prevented neuronal loss and aberrant inflammation. Conclusion: Our finding suggests that behavioral abnormalities were normalized by the administration of MaR-L1 and the neuroprotective role of MaR-L1 in the AD. It also indicates that MaR-L1 treatment is able to prevent and or ameliorate neuronal loss and aberrant inflammation. Further experiments to validate the results are warranted using other AD models in the future.

Keywords: Alzheimer's disease, motor and cognitive behavior, 5XFAD mice, Maresin Like 1, microglial cell, astrocyte, neurodegeneration, inflammation, resolution of inflammation

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Authors: Junaid Mahmood Alam, Sana Anwar, Sarah Sughra Asghar

Abstract:

Chronic hepatitis or Hepatitis C viral (HCV) infection has been identified as one of the factors that could elicit autoimmune disease resulting in the development of auto-antibodies. Furthermore, HCV is implicated in contravening of forbearance to antigens, therefore, inciting auto-reactivity. In this regard, several near and past studies noted the prevalence of thyroid dysfunction and production of anti-thyroid antibodies (ATAb) such as anti-thyroid peroxidase (AntiTPO) and anti-thyroglobulin (AntiTG) in patients with HCV. Likewise, one of the etiologies of augmentation of thyroid disease is basically interferon therapy for HCV infections, for which a number of autoimmune diseases have been noted including Grave’s disease, Hishimoto thyroiditis. A prospectively case-control study was therefore carried out at department of clinical biochemistry lab services and chemical pathology in collaboration with department of clinical microbiology, at Liaquat National Hospital and Medical College, Karachi Pakistan for the period January 2015 to December 2017. Two control groups were inducted for comparison purpose, control group 1 = without HCV infection and with thyroid disorders (n = 20), control group 2 = with HCV infection and without thyroid disorders (n = 20), whereas HCV infected were n = 40 where more than half were noted to be positive for either of HCV IgG and Ag. In HCV group, patients with existing sub-clinical hypothyroidism and clinical hyperthyroidism were less than 5%. Analysis showed the presence of AntiTG in 12 HCV patients (30%), AntiTPO in 15 (37.5%) and both AntiTG and antiTPO in 10 patients (25%). Only 3 patients were found with the history of anti-thyroid auto-antibodies (7.5%) and one with parents and relatives with auto-immune disorders (2.5%). Patients that remained untreated were 12 (30%), under treatment 18 (45%) and with complete-course of treatment 10 (25%). As per review of the literature, meta-analysis of evident data and cross-sectional studies of selective cohorts (as studied in presented research), thyroid connection is designated as one of the most recurrent endocrine ailment associated with chronic HCV infection. Moreover, it also represents an extrahepatic disease in the continuum of HCV syndrome. In conclusion, HCV patients were more likely to encompass thyroid disorders especially related to development of either of ATAb or both antiTG and AntiTPO.

Keywords: Hepatitis C viral (HCV) infection, anti-thyroid antibodies, anti-thyroid peroxidase antibodies, anti-thyroglobulin antibodies

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Authors: Neslihan Demirci, Serdar Durdağı

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Mycobacterium tuberculosis is still a worldwide disease-causing agent that, according to WHO, led to the death of 1.5 million people from tuberculosis (TB) in 2020. The bacteria reside in macrophages located specifically in the lung. There is a known quadruple drug therapy regimen for TB consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Over the past 60 years, there have been great contributions to treatment options, such as recently approved delamanid (OPC67683) and bedaquiline (TMC207/R207910), targeting mycolic acid and ATP synthesis, respectively. Also, there are natural compounds that can block the tryptophanyl-tRNA synthetase (TrpRS) enzyme, chuangxinmycin, and indolmycin. Yet, already the drug resistance is reported for those agents. In this study, the newly released TrpRS enzyme structure is investigated for potential inhibitor drugs from already synthesized molecules to help the treatment of resistant cases and to propose an alternative drug for the quadruple drug therapy of tuberculosis. Maestro, Schrodinger is used for docking and molecular dynamic simulations. In-house library containing ~8000 compounds among FDA-approved indole-containing compounds, a total of 57 obtained from the ChemBL were used for both ATP and tryptophan binding pocket docking. Best of indole-containing 57 compounds were subjected to hit expansion and compared later with virtual screening workflow (VSW) results. After docking, VSW was done. Glide-XP docking algorithm was chosen. When compared, VSW alone performed better than the hit expansion module. Best scored compounds were kept for ten ns molecular dynamic simulations by Desmond. Further, 100 ns molecular dynamic simulation was performed for elected molecules according to Z-score. The top three MMGBSA-scored compounds were subjected to steered molecular dynamic (SMD) simulations by Gromacs. While SMD simulations are still being conducted, ponesimod (for multiple sclerosis), vilanterol (β₂ adrenoreceptor agonist), and silodosin (for benign prostatic hyperplasia) were found to have a significant affinity for tuberculosis TrpRS, which is the propulsive force for the urge to expand the research with in vitro studies. Interestingly, top-scored ponesimod has been reported to have a side effect that makes the patient prone to upper respiratory tract infections.

Keywords: drug repurposing, molecular dynamics, tryptophanyl-tRNA synthetase, tuberculosis

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Authors: Sina Mahdavi

Abstract:

Background and Objective: Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelination process in the CNS. Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially Epstein-Barr virus (EBV) and MS, is one potential cause that is not well understood. In this study, we aim to summarize the available data on EBV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis," "Epstein-Barr virus," and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched, and 14 articles were chosen, studied, and analyzed. Results: Demyelinated lesions isolated from MS patients contain EBNAs from EBV proteins. The EBNA1 domain contains a pentapeptide fragment identical to B-crystallin, a heat shock peptide, that is increased in peripheral B cells in response to B-crystallin infection, resulting in myelin-directed autoimmunity mediated by proinflammatory T cells. EBNA2, which is involved in the regulation of viral transcription, may enhance transcription from MS risk loci. A 7-fold increase in the risk of MS has been observed in EBV infection with HLA-DR15 synergy. Conclusion: EBV infection along with a variety of specific genetic risk alleles, cause inflammatory cascades in the CNS by infected B cells. There is a high expression of EBV during the course of MS, which indicates the relationship between EBV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of EBV may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, Epstein-Barr virus, central nervous system, EBNAs

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