Search results for: chronic obstructive

Authors: Somayeh Negahdari, Mohsen Ghanbarzadeh, Masoud Nikbakht, Heshmatolah Tavakol

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Asthma, obesity and overweight are the main factors causing change within the heart and respiratory airways. Asthma symptoms are normally observed during exercising. Epidemiological studies have indicated asthma symptoms occurring due to certain lifestyle habits; for example, a sedentary lifestyle. In this study, eight weeks of aerobic exercises resulted in a positive effect overall in overweight women experiencing mild chronic asthma. The quasi-experimental applied research has been done based on experimental and control groups. The experimental group (seven patients) and control group (n = 7) were graded before and after the test. According to the Borg dyspnea and fatigue Perception Index, the training intensity has determined. Participants in the study performed a sub-maximal aerobic activity schedule (45% to 80% of maximum heart rate) for two months, while the control group (n = 7) stayed away from aerobic exercise. Data evaluation and analysis of covariance compared both the pre-test and post-test with paired t-test at significance level of P≤ 0.05. After eight weeks of exercise, the results of the experimental group show a significant decrease in resting heart rate, systolic blood pressure, minute ventilation, while a significant increase in maximal oxygen uptake and tolerance activity (P ≤ 0.05). In the control group, there was no significant difference in these parameters ((P ≤ 0.05). The results indicate the aerobic activity can strengthen the respiratory muscles, while other physiological factors could result in breathing and heart recovery. Aerobic activity also resulted in favorable changes in cardiovascular parameters, and exercise tolerance of overweight women with chronic asthma.

Keywords: asthma, respiratory cardiac index, exercise tolerance, aerobic, overweight

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Authors: B. J. Mahen, N. E. Lloyd-Gale, S. Johnson, W. P. Rakowicz, M. J. Harris, A. D. Miller

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Background: Migraine is a leading cause of disability in the world. Calcitonin gene-related peptide (CGRP) receptor antagonists offer an approach to migraine prophylaxis by inhibiting the inflammatory and vasodilatory effects of CGRP. In recent years, NICE licensed the use of three CGRP-receptor antagonists: Fremanezumab, Galcanezumab, and Erenumab. Here, we present the outcomes of CGRP-antagonist treatment in a cohort of patients who suffer from episodic or chronic migraine and have failed at least three oral prophylactic therapies. Methods: We offered CGRP antagonists to 86 patients who met the NICE criteria to start therapy. We recorded the number of headache days per month (HDPM) at 0 weeks, 3 months, and 12 months. Of those, 26 patients were switched to an alternative treatment due to poor response or side effects. Of the 112 total cases, 9 cases did not sufficiently maintain their headache diary, and 5 cases were not followed up at 3 months. We have therefore included 98 sets of data in our analysis. Results: Fremanezumab achieved a reduction in HDPM by 51.7% at 3 months (p<0.0001), with 63.7% of patients meeting NICE criteria to continue therapy. Patients trialed on Galcanezumab attained a reduction in HDPM by 47.0% (p=0.0019), with 51.6% of patients meeting NICE criteria to continue therapy. Erenumab, however, only achieved a reduction in HDPM by 17.0% (p=0.29), and this was not statistically significant. Furthermore, 34.4%, 9.7%, and 4.9% of patients taking Fremanezumab, Galcanezumab, and Erenumab, respectively, continued therapy beyond 12 months. Of those who attempted drug holidays following 12 months of treatment, migraine symptoms relapsed in 100% of cases. Conclusion: We observed a significant improvement in HDPM amongst episodic and chronic migraine patients following treatment with Fremanezumab or Galcanezumab.

Keywords: migraine, CGRP, fremanezumab, galcanezumab, erenumab

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Authors: Yongrong Liu, Xin Tang

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Background: Persistent atrial fibrillation is a common arrhythmia closely related to heart failure. Heart rate control is an essential strategy for treating persistent atrial fibrillation. Still, the understanding of the relationship between different heart rate control levels and the risk of heart failure rehospitalization is limited. Objective: The objective of the study is to determine the relationship between different levels of heart rate control in patients with persistent atrial fibrillation and the risk of readmission for heart failure. Methods: We conducted a retrospective dual-centre cohort study, collecting data from patients with persistent atrial fibrillation who received outpatient treatment at two tertiary hospitals in central and western China from March 2019 to March 2020. The collected data included age, gender, body mass index (BMI), medical history, and hospitalization frequency due to heart failure. Patients were divided into three groups based on their heart rate control levels: Group I with a resting heart rate of less than 80 beats per minute, Group II with a resting heart rate between 80 and 100 beats per minute, and Group III with a resting heart rate greater than 100 beats per minute. The readmission rates due to heart failure within one year after discharge were statistically analyzed using propensity score matching in a 1:1 ratio. Differences in readmission rates among the different groups were compared using one-way ANOVA. The impact of varying levels of heart rate control on the risk of readmission for heart failure was assessed using the Cox proportional hazards model. Binary logistic regression analysis was employed to control for potential confounding factors. Results: We enrolled a total of 1136 patients with persistent atrial fibrillation. The results of the one-way ANOVA showed that there were differences in readmission rates among groups exposed to different levels of heart rate control. The readmission rates due to heart failure for each group were as follows: Group I (n=432): 31 (7.17%); Group II (n=387): 11.11%; Group III (n=317): 90 (28.50%) (F=54.3, P<0.001). After performing 1:1 propensity score matching for the different groups, 223 pairs were obtained. Analysis using the Cox proportional hazards model showed that compared to Group I, the risk of readmission for Group II was 1.372 (95% CI: 1.125-1.682, P<0.001), and for Group III was 2.053 (95% CI: 1.006-5.437, P<0.001). Furthermore, binary logistic regression analysis, including variables such as digoxin, hypertension, smoking, coronary heart disease, and chronic obstructive pulmonary disease as independent variables, revealed that coronary heart disease and COPD also had a significant impact on readmission due to heart failure (p<0.001). Conclusion: The correlation between the heart rate control level of patients with persistent atrial fibrillation and the risk of heart failure rehospitalization is positive. Reasonable heart rate control may significantly reduce the risk of heart failure rehospitalization.

Keywords: heart rate control levels, heart failure rehospitalization, persistent atrial fibrillation, retrospective cohort study

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Authors: Nehal Adel Khalil, Amel Foad Ketat, Fairouz Elsayed Mohamed Ali, Nahla Abdelmoneim Hamid, Hazem Farag Manaa

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Background: Chronic myeloid leukemia (CML) represents 15% of adult leukemias. Imatinib Mesylate (IM) is the gold standard treatment for new cases of CML. Treatment with IM results in improvement of the majority of cases. However, about 25% of cases may develop resistance. Sensitive and specific early predictors of IM resistance in CML patients have not been established to date. Aim: To investigate the value of miR-451 in CML as an early predictor for IM resistance in Egyptian CML patients. Methods: The study employed Real time Polymerase Reaction (qPCR) technique to investigate the leucocytic expression of miR-451 in fifteen newly diagnosed CML patients (group I), fifteen IM responder CML patients (group II), fifteen IM resistant CML patients (group III) and fifteen healthy subjects of matched age and sex as a control group (group IV). The response to IM was defined as < 10% BCR-ABL transcript level after 3 months of therapy. The following parameters were assessed in subjects of all the studied groups: 1- Complete blood count (CBC). 2- Measurement of plasma level of miRNA 451 using real-time Polymerase Chain Reaction (qPCR). 3- Detection of BCR-ABL gene mutation in CML using qPCR. Results: The present study revealed that miR-451 was significantly down-regulated in leucocytes of newly diagnosed CML patients as compared to healthy subjects. IM responder CML patients showed an up-regulation of miR- 451 compared with IM resistant CML patients. Conclusion: According to the data from the present study, it can be concluded that leucocytic miR- 451 expression is a useful additional follow-up marker for the response to IM and a promising prognostic biomarker for CML.

Keywords: chronic myeloid leukemia, imatinib resistance, microRNA 451, Polymerase Chain Reaction

Procedia PDF Downloads 294

Authors: Andrew Anis Fakhrey Mosaad

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Introduction: There are many different types of sleep disorders, each with serious implications for a person's health and a large financial burden on society. Method: This review offers a framework based on the International Classification of Sleep Disorders to aid in the diagnosis and treatment of sleep disorders. Differentiating between primary and secondary insomnia is covered, along with pharmacological and nonpharmacological therapy options. Common abnormalities of the circadian rhythm are mentioned along with their therapies, such as light therapy and chronotherapy. This article discusses the identification and management of periodic limb movement disorder and restless legs syndrome. The therapy of upper airway resistance syndrome and obstructive sleep apnea are the main topics of discussion. Conclusion: The range of narcolepsy symptoms and results, as well as diagnostic procedures and treatment, are discussed. The causes, outcomes, and treatments of many types of insomnias, such as sleep terrors, somnambulism, and rapid eye movement (REM) behavior sleep disorders, are discussed.

Keywords: diagnosis, treatment, sleep disorders, insomnia

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Authors: Joao Paulo Matheus, Renan Fangel

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Rheumatoid arthritis is a chronic, inflammatory, systemic and progressive disease that affects the synovial joints bilaterally, causing definitive orthopedic damage. It has a higher prevalence in postmenopausal female patients. It is a disabling disease that causes joint deformities that may compromise the functionality of the affected segment. The aim of this study was to evaluate the influence of low-intensity therapeutic laser on the perception of pain and quality of life in patients with rheumatoid arthritis. This is a randomized clinical study involving 6 women with a mean age of 56.8+6.3 years. Exclusion criteria: patients with acute pain, chronic infectious disease, underlying acute or chronic underlying disease. An AsGaAl laser with 808nm wavelength, 100mW power, beam output area of 0.028cm2, power density of 3.57W/cm2 was used. The laser was applied at pre-defined points in the interphalangeal and metacarpophalangeal joints, totaling 24 points, 2 times a week, for 4 weeks, totaling 8 sessions. The Pain Inventory (IBD) and Visual Analogue Scale (VAS) were used for the analysis of pain and for the WHOQOL-bref quality of life assessment. There was no statistical difference between the onset (5.67±2.66) and the final (4.67±3.78) of treatments (p=0.70). There was also no statistical difference between the beginning (5.67±2.66) and the final (4.67±3.78) of the treatments in the VAS analysis (p=0.68). The overall mean quality of life obtained by the questionnaire at the start of treatment was 42.3±7.6, while at the end of treatment it was 58.5±7.6 (p=0.01) and the domains of the questionnaire with significant differences were: psychological domain 42.9±6.8 and 66.7±12.9 (p=0.004), social domain 39.9±5.7 and 68.1±6.3 (p=0,0005) and environmental domain 36.3±7.3 and 56.3±12.5 (p=0.003). It can be concluded that the low-intensity therapeutic laser did not produce significant changes in the painful period of rheumatoid arthritis patients. However, there was an improvement in patients' quality of life in the psychological, social and environmental aspects.

Keywords: laser therapy, pain, quality of life, rheumatoid arthritis

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Authors: Dana El-Mughayyar, Neil Manson, Erin Bigney, Eden Richardson, Dean Tripp, Edward Abraham

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Use of narcotics to treat pain has increased over the past two decades and is a contributing factor to the current public health crisis. Understanding the pre-operative risks of chronic narcotic use may be aided through investigation of psychological measures. The objective of the reported study is to determine predictors of narcotic use two years post-surgery in a thoracolumbar spine surgery population, including an array of psychological factors. A prospective observational study of 191 consecutively enrolled adult patients having undergone thoracolumbar spine surgery is presented. Baseline measures of interest included the Pain Catastrophizing Scale (PCS), Tampa Scale for Kinesiophobia, Multidimensional Scale for Perceived Social Support (MSPSS), Chronic Pain Acceptance Questionnaire (CPAQ-8), Oswestry Disability Index (ODI), Numeric Rating Scales for back and leg pain (NRS-B/L), SF-12’s Mental Component Summary (MCS), narcotic use and demographic variables. The post-operative measure of interest is narcotic use at 2-year follow-up. Narcotic use is collapsed into binary categories of use and no use. Descriptive statistics are run. Chi Square analysis is used for categorical variables and an ANOVA for continuous variables. Significant variables are built into a hierarchical logistic regression to determine predictors of post-operative narcotic use. Significance is set at α < 0.05. Results: A total of 27.23% of the sample were using narcotics two years after surgery. The regression model included ODI, NRS-Leg, time with condition, chief complaint, pre-operative drug use, gender, MCS, PCS subscale helplessness, and CPAQ subscale pain willingness and was significant χ² (13, N=191)= 54.99; p = .000. The model accounted for 39.6% of the variance in narcotic use and correctly predicted in 79.7% of cases. Psychological variables accounted for 9.6% of the variance over and above the other predictors. Conclusions: Managing chronic narcotic usage is central to the patient’s overall health and quality of life. Psychological factors in the preoperative period are significant predictors of narcotic use 2 years post-operatively. The psychological variables are malleable, potentially allowing surgeons to direct their patients to preventative resources prior to surgery.

Keywords: narcotics, psychological factors, quality of life, spine surgery

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Authors: Subramaniam Iyer

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The most common disease that is pertaining to all human beings is heart-related. The reasons for coronary artery disease are due to lifestyle and eating habits. Due to this, many people mentally become sick, feeling that soon they will die due to their heart problems. This results in stress and anxiety, which has become common amongst all the Indians. Medicines are the commonest curative remedy in India, but it is proposed through this article some remedies through yoga. This article does not guarantee a 100% result, but it is a preventive remedy for coronary artery disease. Yoga is giving a new lease of life to many, so to tackle chronic diseases, it provides remedies that will be lifelong. It is brought to many people by Patanjali. Yoga will provide support to patients having coronary artery disease through its various relevant postures (asanas), which can be done very easily. Yoga does not send a message that if you do it regularly, you will be relieved from a particular disease. If it is performed every day, it will add vital energy for a smooth life, even if you are suffering from any chronic disease. In this article, we will be providing 6 postures (asanas), which can be performed at any time in the day, but the early morning will always be preferred (empty stomach) to get a good result. Secondly, these postures must be implemented after due consultation with your physician. If your physician disapproves, don’t do these postures as it will be harmful to your body.

Keywords: coronary artery, yoga, disease, remedy, medicine

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Authors: Keivan Jamshidi, Afshin Zahedi

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Reactive amyloidosis is a condition that complicates a long list of chronic inflammation, chronic infectious, malignant, and hereditary disorders. In the present study the propensity for amyloidogenesis in male and female rats on spatio-temporal pattern was evaluated. For this purpose a total of 40 male and female Swiss mice, obtained from Pasteur Institute Tehran, after being weighted were randomly divided into 4 groups including 2 treatment groups [ 10 male (Group A1) and 10 female (Group B1) each], and 2 control groups [10 male (Group A2) and 10 female (Group B2) each]. At the end of 3rd, 5th and 7th weeks of experiment 3 mice were randomly selected and euthnised. Spleen samples of each animal were obtained and preserved in 10% neutral buffer formalin. Sample were then processed through different stages of dehydration, clearing and impregnation and finally embedded in paraffin blocks. Sections of 5µm thickness then cut and stained by alkaline Congo red techniques. The data obtained from polarized microscopic quantitative analysis did show significant differences between groups A1 and B1. A preferential expression of reactive amyloidosis is concluded in male, indicating sex differences in amyloidosis.

Keywords: amyloidosis, amyloidogenesis, mice, gender

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Authors: Tahira Hyder, Saima Quraeshi, Zohaib Akram

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Salvadora Persica (SP) is known to have anti-inflammatory, antioxidant, anti-coagulant and anti-bacterial properties that may provide therapeutic benefits in the treatment of chronic periodontitis (CP). The current clinical trial was designed to investigate the clinical and anti-microbial effects of SP gel as an adjunct to scaling and root planning (SRP) in subjects with generalized CP. Sixty-six subjects with CP were randomized allocated into two groups: SRP + SP gel (test group) and SRP only (control group). Clinical parameters (periodontal pocket depth, gingival recession, clinical attachment level, bleeding score and plaque score) were recorded at baseline before SRP and at 6 weeks. At baseline and 6 weeks subgingival plaque samples were collected and periodontopathogen Porphyromonas Gingivalis (Pg) quantified using Real-time Polymerase Chain Reaction (RT-PCR). Both therapies reduced the mean periodontal pocket depth (PPD), plaque score (PS) and bleeding score (BOP) and improved the mean clinical attachment level (CAL) between baseline and 6 weeks. In subjects receiving adjunctive SP gel a statistically significant improvement was observed in BOP at follow-up compared to control group (15.01±3.47% and 22.81±6.81% respectively, p=0.001), while there was no statistically significant difference in periodontal pocket depth, gingival recession, clinical attachment level and plaque score between both groups. The test group displayed significantly greater Pg reduction compared to the control group after 6 weeks. The current study establishes that local delivery of SP gel into periodontal pocket in CP stimulated a significant reduction in bacteria Pg level and an improvement in gingival health, as evident from a reduced bleeding score, when used as an adjunct to SRP.

Keywords: miswak, scaling and root planing, porphyromonas gingivalis, chronic periodontitis

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Authors: Anna Mirczak

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Introduction: In connection with the aging of the population and the increase in the number of people with chronic illnesses, the priority objective for public health has become not only lengthening life, but also improving quality of life in older persons, as well as maintenance of their relative independence and active participation in social life. The most important determinant of a person’s quality of life is health. According to the literature, older people with chronic illness who live in rural settings are at greater risk for poor outcomes than their urban counterparts. Furthermore research characterizes the rural elderly as having a higher incidence of sickness, dysfunction, disability, restricted mobility, and acute and chronic conditions than their urban citizens. It is dictated by the overlapping certain specific socio-economic factors typical for rural areas which include: social and geography exclusion, limited access to health care centers, and low socioeconomic status. Aim of the study: The objective of this study was to recognize health status and needs of older people living in selected rural areas in Poland and evaluate the impacts of working in the farm on their health status. Material and methods: The study was performed personally, using interviews based on the structural questionnaires, during the period from March 2011 to October 2012. The group of respondents consisted 203 people aged 65 years and over living in selected rural areas in Poland. The analysis of collected research material was performed using the statistical package SPSS 19 for Windows. The level of significance for the tested the hypotheses assumed value of 0.05. Results: The mean age of participants was 75,5 years (SD=5,7) range from 65 to 94 years. Most of the interviewees had children (89.2%) and grandchildren (83.7) and lived mainly with family members (75.9%) mostly in double (46.8%) and triple (20.8%) household. The majority of respondents (71,9%) were physical working on the farm. At the time of interview, each of the respondents reported that they had been diagnosed with at least one chronic diseases by their GP. The most common were: hypertension (67,5%), osteoarthritis (44,8%), atherosclerosis (43,3%), cataract (40,4%), arrhythmia (28,6%), diabetes mellitus (19,7%) and stomach or duodenum ulcer diseases (17,2%).The number of diseases occurring of the sample was dependent on gender and age. Significant associations were observed between working on the farm and frequency of occurrence cardiovascular diseases, the gastrointestinal tract dysfunction and sensory disorders. Conclusions: The most common causes of disability among older citizens were: chronic diseases, malnutrition and complaints about access to health services (especially to cardiologist and an ophthalmologist). Health care access and health status are a particular concern in rural areas where the population is older, has lower education and income levels, and is more likely to be living in medically underserved areas than is the case in urban areas.

Keywords: ageing, health status, older people, rural

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Authors: Svitlana Antonenko, Gennady Telegeev

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Introductive statement: The development of chronic myeloid leukemia (CML) is caused by Bcr-Abl oncoprotein. Modern treatments with tyrosine kinase inhibitors are greatly complicated by the mutational variability of the Bcr-Abl oncoprotein, which causes drug resistance. Therefore, there is an urgent need to develop new approaches to the treatment of the disease, which will allow modeling the level of Bcr-Abl oncoprotein in the cell. Promising in this direction is the identification of proteases that can selectively promote cellular proteolysis of oncoproteins. The aim of the study was to study the effect of the interaction of Bcr-Abl with deubiquitinase USP1 on the level of oncoprotein in CML cells. Methodology: K562 cells were selected for the experiment. Сells were incubated with ML323 inhibitor for 24 hours. Precipitation of endogenous proteins from K562 cell lysate was performed using anti-Bcr-Abl antibodies. Cell lysates and precipitation results were studied by Western blot. Subcellular localization of proteins was studied by immunofluorescence analysis followed by confocal microscopy. The results were analyzed quantitatively and statistically. Major findings: The Bcr-Abl/USP1 protein complex was detected in CML cells, and it was found that inhibition of USP1 deubiquitinating activity by the compound ML323 leads to disruption of this protein complex and a decrease in the level of Bcr-Abl oncoprotein in cells. The interaction of Bcr-Abl with USP1 may result in deubiquitination of the oncoprotein, which disrupts its proteasomal degradation and leads to the accumulation of CML in cells. Conclusion: We believe that the interaction of oncoprotein with USP1 may be one of the prerequisites that contribute to malignant cell transformation due to the deubiquitination of oncoprotein, which leads to its accumulation and disease progression. A correlation was found between the deubiquitinating activity of USP1 and the level of oncoprotein in CML cells. Thus, we identify deubiquitinase USP1 as a promising therapeutic target for the development of a new strategy for the treatment of CML by modulating the level of Bcr-Abl in the cell.

Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, deubiquitination Bcr-Abl, K562 cell

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Authors: Natcha Lueangapapong, Chariya Chuthapisith, Lunliya Thampratankul

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Background: There is a need to find an appropriate tool to help healthcare providers determine sleep problems in children for early diagnosis and management. The Japanese Sleep Questionnaire for Preschoolers (JSQ-P) is a parent-reported sleep questionnaire that has good psychometric properties and can be used in the context of Asian culture, which is likely suitable for Thai children. Objectives: This study aimed to translate and validate the Japanese Sleep Questionnaire for Preschoolers (JSQ-P) into a Thai version and to evaluate factors associated with sleep disorders in preschoolers. Methods: After approval by the original developer, the cross-cultural adaptation process of JSQ-P was performed, including forward translation, reconciliation, backward translation, and final approval of the Thai version of JSQ-P (TH-JSQ-P) by the original creator. This study was conducted between March 2021 and February 2022. The TH-JSQ-P was completed by 2,613 guardians whose children were aged 2-6 years twice in 10-14 days to assess its reliability and validity. Content validity was measured by an index of item-objective congruence (IOC) and a content validity index (CVI). Face validity, content validity, structural validity, construct validity (discriminant validity), criterion validity and predictive validity were assessed. The sensitivity and specificity of the TH-JSQ-P were also measured by using a total JSQ-P score cutoff point 84, recommended by the original JSQ-P and each subscale score among the clinical samples of obstructive sleep apnea syndrome. Results: Internal consistency reliability, evaluated by Cronbach’s α coefficient, showed acceptable reliability in all subscales of JSQ-P. It also had good test-retest reliability, as the intraclass correlation coefficient (ICC) for all items ranged between 0.42-0.84. The content validity was acceptable. For structural validity, our results indicated that the final factor solution for the Th-JSQ-P was comparable to the original JSQ-P. For construct validity, age group was one of the clinical parameters associated with some sleep problems. In detail, parasomnias, insomnia, daytime excessive sleepiness and sleep habits significantly decreased when the children got older; on the other hand, insufficient sleep was significantly increased with age. For criterion validity, all subscales showed a correlation with the Epworth Sleepiness Scale (r = -0.049-0.349). In predictive validity, the Epworth Sleepiness Scale was significantly a strong factor that correlated to sleep problems in all subscales of JSQ-P except in the subscale of sleep habit. The sensitivity and specificity of the total JSQ-P score were 0.72 and 0.66, respectively. Conclusion: The Thai version of JSQ-P has good internal consistency reliability and test-retest reliability. It passed 6 validity tests, and this can be used to evaluate sleep problems in preschool children in Thailand. Furthermore, it has satisfactory general psychometric properties and good reliability and validity. The data collected in examining the sensitivity of the Thai version revealed that the JSQ-P could detect differences in sleep problems among children with obstructive sleep apnea syndrome. This confirmed that the measure is sensitive and can be used to discriminate sleep problems among different children.

Keywords: preschooler, questionnaire, validation, Thai version

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Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov

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Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.

Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development

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Authors: Azza A. Ali, Doaa M. Abd El-Latif, Amany M. Gad, Yasser M. A. Elnahas, Karema Abu-Elfotuh

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Background: Exposure to Aluminium (Al) has been increased recently. It is found in food products, food additives, drinking water, cosmetics and medicines. Chronic consumption of Al causes oxidative stress and has been implicated in several chronic disorders. Liver is considered as the major site for detoxification while kidney is involved in the elimination of toxic substances and is a target organ of metal toxicity. Social isolation (SI) or protein malnutrition (PM) also causes oxidative stress and has negative impact on Al-induced nephrotoxicity as well as hepatotoxicity. Coenzyme Q10 (CoQ10) is a powerful intracellular antioxidant with mitochondrial membrane stabilizing ability while wheat grass is a natural product with antioxidant, anti-inflammatory and different protective activities, cocoa is also potent antioxidants and can protect against many diseases. They provide different degrees of protection from the impact of oxidative stress. Objective: To study the impact of social isolation together with Protein malnutrition on nephro- and hepato-toxicity induced by chronic Al exposure in rats as well as to investigate the postulated protection using a combination of Co Q10, wheat grass and cocoa. Methods: Eight groups of rats were used; four served as protected groups and four as un-protected. Each of them received daily for five weeks AlCl3 (70 mg/kg, IP) for Al-toxicity model groups except one group served as control. Al-toxicity model groups were divided to Al-toxicity alone, SI- associated PM (10% casein diet) and Al- associated SI&PM groups. Protection was induced by oral co-administration of CoQ10 (200mg/kg), wheat grass (100mg/kg) and cocoa powder (24mg/kg) combination together with Al. Biochemical changes in total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) were measured in serum of all groups. Specimens of kidney and liver were used for assessment of oxidative parameters (MDA, SOD, TAC, NO), inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3) and DNA fragmentation in addition to evaluation of histopathological changes. Results: SI together with PM severely enhanced nephro- and hepato-toxicity induced by chronic Al exposure. Co Q10, wheat grass and cocoa combination showed clear protection against hazards of Al exposure either alone or when associated with SI&PM. Their protection were indicated by the significant decrease in Al-induced elevations in total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels as well as ALT, AST, ALP, LDH. Liver and kidney of the treated groups also showed significant decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation, together with significant increase in total proteins, SOD and TAC. Biochemical results were confirmed by the histopathological examinations. Conclusion: SI together with PM represents a risk factor in enhancing nephro- and hepato-toxicity induced by Al in rats. CoQ10, wheat grass and cocoa combination provide clear protection against nephro- and hepatotoxicity as well as the consequent degenerations induced by chronic Al-exposure even when associated with the risk of SI together with PM.

Keywords: aluminum, nephrotoxicity, hepatotoxicity, isolation and protein malnutrition, coenzyme Q10, wheatgrass, cocoa, nutrients combinations

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Authors: Maedeh Gharazi

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Distinguishing proof of entrepreneurial open doors in the field of nutrition counseling is a focal issue in utilizing nutrition experts and addressing the needs of patients with chronic diseases better. To this end, this review has been directed keeping in mind the end goal to investigate the supply and interest patterns of diabetes sustenance advising as a fundamental stride toward recognizing the entrepreneurial open doors for nutrition advisors in Tehran, Iran. To execute this expressive overview concentrate on, a survey in light of Likert scale was sent via email to 100 dynamic experts in the field of nutrition counseling services in Tehran, of whom 52 reacted to its inquiries. At that point, the mean estimations of members' reactions were ascertained utilizing SPSS programming and contrasted to each other. The outcome acquired in view of members' reactions uncovered that the requirement for "healthful guiding as a treatment group" was basically not met in diverse age, training and salary gatherings of diabetic patients. Along these lines, nutrition counseling as a treatment group can be considered as a suitable field for entrepreneurial exercises.

Keywords: nutrition counseling, chronic diseases, diabetes, likert scale, SPSS programming

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Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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Authors: Nagat M. Saeed, Mabruka S. Elashheb, Fatma M. Ben Rabaha, Aisha M Edrah

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The aim of the study was to determine the type and pattern of antibiotic susceptibility of the pathogenic microorganisms causing chronic suppurative otitis media (CSOM), which could lead to better therapeutic decisions and consequently avoidance of appearance of resistance to specific antibiotics. Most frequently isolated agents were Pseudomonas aeruginosa 28.5%; followed by Staphylococcus aureus 18.2%; proteus mirabilis 13.9%; Providencia stuartti 6.7%; Bacteroides melaninogenicus, Aspergillus sp., candida sp., 4.2% each; and other microorganisms were represented in 3-0.2%. Drug sensitivities pattern of Pseudomonas aeruginosa showed that ciprofloxacin was active against the majority of isolates (93.9%) followed by ceftazidime 86.2%, amikacin 76.2% and gentamicin 40.8%. However, Staphylococcus aureus isolates were resistant to penicillin 72.7%, erythromycin 28.6%, cephalothin 18.2%, cloxacillin 8.3% and ciprofloxacin was active against 96.2% of isolates. The resistance pattern of proteus mirabilis was 55.6% to ampicillin, 47.1% to carbencillin, 29.4% to cephalothin, 14.3% to gentamicin and 4.8% to amikacin while 100% were sensitive to ciprofloxacin. We conclude that ciprofloxacin is the best drug of choice in the treatment of CSOM caused by the common microorganisms.

Keywords: otitis media, chronic suppurative otitis media (CSOM), microorganisms, drug sensitivity

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Authors: Mohamed Abdel-Hamid, Olfat Gamil Shaker, Doha El-Sayed Ellakwa, Eman Fathy Abdel-Maksoud

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Introduction: Despite advances in the knowledge of the molecular virology of hepatitis C virus (HCV), the mechanisms of hepatocellular injury in HCV infection are not completely understood. Hepatitis C viral infection (HCV) influences the susceptibility to apoptosis. This could lead to insufficient antiviral immune response and persistent viral infection. Aim of this study: was to examine whether BCL-2 gene polymorphism at codon 43 (+127G/A or Ala43Thr) has an impact on development of hepatocellular carcinoma caused by chronic hepatitis C Egyptian patients. Subjects and Methods: The study included three groups; group 1: composing of 30 patients with hepatocellular carcinoma (HCC), group 2 composing of 30 patients with HCV, group 3 composing of 30 healthy subjects matching the same age and socioeconomic status were taken as a control group. Gene polymorphism of BCL2 (Ala43Thr) were evaluated by PCR-RFLP technique and measured for all patients and controls. Results: The summed 43Thr genotype was more frequent and statistically significant in HCC patients as compared to control group. This genotype of BCL2 gene may inhibit the programmed cell death which leads to disturbance in tissue and cells homeostasis and reduction in immune regulation. This result leads to viral replication and HCV persistence. Moreover, virus produces variety of mechanisms to block genes participated in apoptosis. This mechanism proves that HCV patients who have 43Thr genotype are more susceptible to HCC. Conclusion: The data suggest for the first time that the BCL2 polymorphism is associated with the susceptibility to HCC in Egyptian populations and might be used as molecular markers for evaluating HCC risk. This study clearly demonstrated that Chronic HCV exhibit a deregulation of apoptosis with the disease progression. This provides an insight into the pathogenesis of chronic HCV infection, and may contribute to the therapy.

Keywords: BCL2 gene, Hepatitis C Virus, Hepatocellular carcinoma, sensitivity, specificity, apoptosis

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Authors: Astrid Tannert, Anuradha Ramoji, Christina Ebert, Frederike Gladigau, Lorena Tuchscherr, Jürgen Popp, Ute Neugebauer

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Staphylococcus aureus is a facultative intracellular pathogen, which by entering host cells may evade immunologic host response as well as antimicrobial treatment. In that way, S. aureus can cause persistent intracellular infections which are difficult to treat. Depending on the strain, S. aureus may persist at different intracellular locations like the phagolysosome. The first barrier invading pathogens from the blood stream that they have to cross are the endothelial cells lining the inner surface of blood and lymphatic vessels. Upon proceeding from an acute to a chronic infection, intracellular pathogens undergo certain biochemical and structural changes including a deceleration of metabolic processes to adopt for long-term intracellular survival and the development of a special phenotype designated as small colony variant. In this study, the endothelial cell line Ea.hy 926 was used as a model for acute and chronic S. aureus infection. To this end, Ea.hy 926 cells were cultured on QIAscout™ Microraft Arrays, a special graded cell culture substrate that contains around 12,000 microrafts of 200 µm edge length. After attachment to the substrate, the endothelial cells were infected with GFP-expressing S. aureus for 3 weeks. The acute infection and the development of persistent bacteria was followed by confocal laser scanning microscopy, scanning the whole Microraft Array for the presence and for detailed determination of the intracellular location of fluorescent intracellular bacteria every second day. After three weeks of infection representative microrafts containing infected cells, cells with protruded infections and cells that did never show any infection were isolated and fixed for Raman micro-spectroscopic investigation. For comparison, also microrafts with acute infection were isolated. The acquired Raman spectra are correlated with the fluorescence microscopic images to give hints about a) the molecular alterations in endothelial cells during acute and chronic infection compared to non-infected cells, and b) metabolic and structural changes within the pathogen when entering a mode of persistence within host cells. We thank Dr. Ruth Kläver from QIAGEN GmbH for her support regarding QIAscout technology. Financial support by the BMBF via the CSCC (FKZ 01EO1502) and from the DFG via the Jena Biophotonic and Imaging Laboratory (JBIL, FKZ PO 633/29-1, BA 1601/10-1) is highly acknowledged.

Keywords: correlative image analysis, intracellular infection, pathogen-host adaption, Raman micro-spectroscopy

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Authors: Lukman Ahmad Jamil, Heather M. Wallace

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Introduction: Numerous epidemiological studies have shown a positive as well as negative association and no association in some cases between chronic use of calcium channel blockers and the increased risk of developing cancer. However, these associations were enmeshed with controversies in the absence of laboratory based studies to back up those claims. Aim: The aim of this study was to determine in mechanistic terms the association between the long-term administration of nifedipine and diltiazem and increased risk of developing cancer using the human embryonic kidney (HEK293) cell line. Methods: Cell counting using the Trypan blue dye exclusion and 3-4, 5-Dimethylthiazol-2-yl-2, 5-diphenyl-tetrazolium bromide (MTT) assays were used to investigate the effect of nifedipine and diltiazem on the growth pattern of HEK293 cells. Protein assay using modified Lowry method and analysis of intracellular polyamines concentration using Liquid Chromatography – Tandem Mass Spectrometry (LC-MS) were performed to ascertain the mechanism through which chronic use of nifedipine increases the risk of developing cancer. Results: Both nifedipine and diltiazem significantly increased the proliferation of HEK293 cells dose and time dependently. This proliferative effect after 24, 48 and 72-hour incubation period was observed at 0.78, 1.56 and 25 µM for nifedipine and 0.39, 1.56 and 25 µM for diltiazem, respectively. The increased proliferation of the cells was found to be statistically significantly (p<0.05). Furthermore, the increased proliferation of the cells induced by nifedipine was associated with the increase in the protein content and elevated intracellular polyamines concentration level. Conclusion: The chronic use of nifedipine is associated with increased proliferation of cells with concomitant elevation of polyamines concentration and elevated polyamine levels have been implicated in many malignant transformations and hence, these provide a possible explanation on the link between long term use of nifedipine and development of some human cancers. Further studies are needed to evaluate the cause of this association.

Keywords: cancer, nifedipine, polyamine, proliferation

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Authors: Parthasarathi Pramanik

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Body packing is a way of transfer drugs across the international border or any drug prohibited area. The drugs are usually hidden in body packets inside the anatomical body cavities like mouth, intestines, rectum, ear, vagina etc. Cocaine is a very common drug for body packing across the world. A 48 year old male was reported dead in his hotel after complaining of chest pain and vomiting. At autopsy, there were eighty-two white cylindrical body packs in the stomach, small and large intestines. Seals of few of the packets were opened. Toxicological examination revealed presence of cocaine in the stomach, liver, kidney and hair samples. Microscopically, presence of myocardial necrosis with interstitial oedema along with hypertrophy and fibrosis of the myocardial fibre suggested heart failure due to cocaine cardio toxicity. However, focal lymphocyte infiltration and perivascular fibrosis in the myocardium also indicated chronic cocaine toxicity of the deceased. After careful autopsy examination it was considered the victim was died due congestive heart failure secondary to acute and chronic cocaine poisoning.

Keywords: cardiac failure, cocaine, body packer, sudden death

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Authors: Hadeer E. Eliwa, Naglaa S. Bazan, Ebtissam A. Darweesh, Nagwa A. Sabri

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Background: Generic substitution of brand ivabradine prescriptions can reduce drug expenditures and improve adherence. However, the distrust of generic medicines by practitioners and patients due to doubts regarding their quality and fear of counterfeiting compromise the acceptance of this practice. Aim: The goal of this study is to compare the therapeutic equivalence of brand product versus the generic product of ivabradine in adult patients with chronic heart failure with reduced ejection fraction (≤ 40%) (HFrEF). Methodology: Thirty-two Egyptian patients with chronic heart failure with reduced ejection fraction (HFrEF) were treated with branded ivabradine (Procrolan ©) and generic (Bradipect ©) during 24 (2x12) weeks. Primary outcomes were resting heart rate (HR), NYHA FC, Quality of life (QoL) using Minnesota Living with Heart Failure (MLWHF) and EF. Secondary outcomes were the number of hospitalizations for worsening HFrEF and adverse effects. The washout period was not allowed. Findings: At the 12th week, the reduction in HR was comparable in the two groups (90.13±7.11 to 69±11.41 vs 96.13±17.58 to 67.31±8.68 bpm in brand and generic groups, respectively). Also, the increase in EF was comparable in the two groups (27.44 ±4.59 to 33.38±5.62 vs 32±5.96 to 39.31±8.95 in brand and generic groups, respectively). The improvement in NYHA FC was comparable in both groups (87.5% in brand group vs 93.8% in the generic group). The mean value of the QOL improved from 31.63±15.8 to 19.6±14.7 vs 35.68±17.63 to 22.9±15.1 for the brand and generic groups, respectively. Similarly, at end of 24 weeks, no significant changes were observed from data observed at 12th week regarding HR, EF, QoL and NYHA FC. Only minor side effects, mainly phosphenes, and a comparable number of hospitalizations were observed in both groups. Conclusion: The study revealed no statistically significant differences in the therapeutic effect and safety between generic and branded ivabradine. We assume that practitioners can safely interchange between them for economic reasons.

Keywords: bradipect©, heart failure, ivabradine, Procrolan ©, therapeutic equivalence

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Authors: Alakija Temitope Olufunmilayo, Akinyemi, Yagba Joy

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Hepatitis is the inflammation of the liver tissue that can cause whiteness of the eyes (Jaundice), lack of appetite, vomiting, tiredness, abdominal pain, diarrhea. Hepatitis is acute if it resolves within 6 months and chronic if it last longer than 6 months. Acute hepatitis can resolve on its own, lead to chronic hepatitis or rarely result in acute liver failure. Chronic hepatitis may lead to scarring of the liver (Cirrhosis), liver failure and liver cancer. Modelling Hepatitis B may become necessary in order to reduce its spread. So, dynamic SIR model can be used. This model consists of a system of three coupled non-linear ordinary differential equation which does not have an explicit formula solution. It is an epidemiological model used to predict the dynamics of infectious disease by categorizing the population into three possible compartments. In this study, a five-compartment dynamic model of Hepatitis B disease was proposed and developed by adding control measure of sensitizing the public called awareness. All the mathematical and statistical formulation of the model, especially the general equilibrium of the model, was derived, including the nonlinear least square estimators. The initial parameters of the model were derived using nonlinear least square embedded in R code. The result study shows that the proportion of Hepatitis B patient in the study population is 1.4 per 1,000,000 populations. The estimated Hepatitis B induced death rate is 0.0108, meaning that 1.08% of the infected individuals die of the disease. The reproduction number of Hepatitis B diseases in Nigeria is 6.0, meaning that one individual can infect more than 6.0 people. The effect of sensitizing the public on the basic reproduction number is significant as the reproduction number is reduced. The study therefore recommends that programme should be designed by government and non-governmental organization to sensitize the entire Nigeria population in order to reduce cases of Hepatitis B disease among the citizens.

Keywords: hepatitis B, modelling, non-linear ordinary differential equation, sihar model, sensitization

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Authors: Azar Sharafianpor, Hossein Rassi, Fahimeh Nemati Mansur

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Cardiovascular diseases (CVD) are the most important cause of death in industrialized and developing countries such as Iran. The most important risk factors for the CVD, genetic factors and chronic infectious agents, such as Helicobacter pylori, can be mentioned. The TNFα gene is one of the most important anti-inflammatory cytokines that can affect the sensitivity, efficacy, and ability of the immune response to chronic infections. Some TNF-α gene polymorphisms, including the replacement of the G nucleotide G with A at position 308 in the promoter region of TNF-α, increase the transcription of cytokines in the target cells and thus predispose a person to chronic infections. This study examines the TNF-α 308 polymorphism and its association with Helicobacter pylori infection in this disease. This study was a case-control study in which 154 patients were examined as cases or patients with symptoms of myocardial infarction or angina and 160 as controls or healthy subjects. All of the subjects at different ages were given venous blood and age, BMI, cholesterol, LDL, and HDL were determined. DNA was extracted from the specimens, and the cagA gene from H. pylori and the TNF-α-308 polymorphism were determined by PCR in patients and healthy subjects. Statistical analysis was performed with Epi Info software. The results showed that the frequency of H. pylori infection in the patients and healthy group were 53.23% (82 out of 154) and 47.5% (76 out of 160). There was no significant difference in H. pylori outbreak between the two groups. The frequencies of TNF-α-308 genotype for GG, GA, and AA in patients were 0.17, 0.49, and 0.34, respectively, whereas for controls 0.47, 0.35, and 0.18 for GG, GA, and AA, respectively. The frequency of genotype analysis of TNF-α-308 polymorphisms in both patients and healthy groups showed that there was a significant difference in the frequency of genotypes and the AA genotype was higher in the affected individuals. Also, there was a significant relationship between the genotype and the contamination with H. pylori and changes in cholesterol, LDL, and HDL levels were observed. The results of the study indicate that H. pylori detection in individuals with AA genotype in people under 50 years of age can play an important role in early diagnosis and treatment of cardiovascular disease.

Keywords: Helicobacter pylori, TNFα gene, cardiovascular diseases, TNFα-308 polymorphism

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Authors: Afshin Zahedi, Keivan Jmahidi

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Acrylamide (AA) has been shown to cause neurotoxic effects in humans and neurotoxic, genotoxic, reproductive, and carcinogenic effects in laboratory animals. To investigate the nephrotoxic effect of acrylamide (ACR) 50 adult male rats (Wistar, approximately 250 g) were randomly assigned in 4 groups; including 3 treatment groups and 1 control group named as A, B, C, and D respectively. Rats in treatment groups were exposed to 0.1, 1, and 10 mg/kg ACR per day×90 days p.o (gavage) respectively. The remaining 10 rats in control group received daily p.o (gavage) of 0.9% saline (3ml/kg). On day 91, two rats were randomly selected, perfused, dissected and proper samples were collected from their kidneys. Results of histopathological studies based on H&E technique did not show morphologic changes in kidneys of rats belong to groups A, B and D, while moderate to severe morphologic changes including glomerular hypercellularity, global pattern of proliferative glomerulonephritis, occupation of capsular space, and tubular cell swelling and hyaline cast formation, were observed in different stained sections obtained from the kidneys of rats belong to group, C. This finding, beside neurotoxic, reproductive and carcinogenic effects, indicates for the first time another important aspect of toxic effect of ACR, ie, chronic nephrotoxicity.

Keywords: acrylamide, nephrotoxicity, glomerulonephritis, rats

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Authors: Vikneswaran Murugaiyah, Sultan Ayesh Mohammed Saghir, Kisantini Murugesu, Mohd. Zaini Asmawi, Amirin Sadikun

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Gynura procumbens is a popular medicinal plant used as a folk medicine in Southeast Asia to treat kidney diseases, diabetes mellitus and hyperlipidemia. The present study aims to investigate the antihyperlipidemic potential of phenolic acids rich fraction (PARF) from G. procumbens in chemically-induced acute and high fat diet-induced chronic hyperlipidemic rats. Ethanolic extract of G. procumbens leaves exhibited significant reductions in total cholesterol (TC) and triglycerides (TG) levels (P < 0.01 and P < 0.001, respectively) of poloxamer 407-induced rats compared to hyperlipidemic control after 58 h of treatment. Upon bioactivity guided fractionation the antihyperlipidemic activity was found to be concentrated in the PARF, which significantly reduced the TC and TG levels (P < 0.001). HPLC analysis revealed that 3,5-dicaffeoylquinic acid; 4,5-dicaffeoylquinic acid and chlorogenic acid are the major compounds in the PARF. Likewise, chlorogenic acid (60 mg/kg) exhibited significant reductions in TC and TG levels of hyperlipidemic rats (P < 0.001). Both chlorogenic acid and PARF significantly reduced LDL, VLDL and atherogenic index (P<0.01), while PARF increased the HDL (P < 0.01) compared to hyperlipidemic control. Both were found to be not cytotoxic against normal and cancer cell lines. In addition, LD50 of orally administered PARF was more than 5,000 mg/kg. Further investigation in high fat diet-induced chronic hyperlipidemic rats revealed that chronic administration of PARF dose-dependently restored the increase in lipids parameters. In summary, the phenolic acids rich fraction of G. procumbens leaves showed promising antihyperlipidemic effect in both chemically- and diet-induced hyperlipidemic rats that warrants further elucidation on its mechanisms of action.

Keywords: Antihyperlipidemic, Gynura procumbens, phenolic acids, chlorogenic acid, poloxamer-407, high fat diet

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Authors: Upasana Sharma, Jayanti Dutta, Amarjeet Singh

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Background: Ayurveda is a comprehensive natural health care system. It is widely used in India as a system of primary health care, and interest in it is growing worldwide. Objectives: 1) To assess the extent and pattern of use of Ayurvedic medicines/ products by the people of Chandigarh. 2) To assess the perceived impact of use of Ayurvedic medicines/ products among the users. Methods: A cross-sectional community based study was conducted in a city of North India. Overall 371 households were covered from rural, urban and slum areas from December 2010 to April 2011. Respondents were interviewed regarding practices about Ayurveda products. Results: Around 160 (43%; 95% CI= 38.15, 47.85) of the respondents were using Ayurvedic products in one form or the other. Out of them, 91 (57%) had used Ayurvedic medicines in combination with some other system of medicine rather than as a standalone therapy. Most of them (81%) preferred Ayurveda products for chronic digestive system related problems. Conclusion: The present study revealed that respondents had keen interest in Ayurveda. A section of population was taking Ayurvedic treatment for their health ailments. There was a great level of satisfaction among the users but high cost bothered them at times.

Keywords: ayurveda, alternative medicine, chronic diseases, complimentary medicine

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Authors: A. Seham A. Elgamal, Reham H. Saleh

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Chronic kidney disease became a global health problem worldwide. Therefore, in order to maintain a patient’s life and improve the survival rate, hemodialysis is essential to replace the function of their kidneys. However, those patients may complain about multiple physical and psychological stressors due to the nature of the disease and the need for frequent hemodialysis sessions. So, those patients use various strategies to cope with the stressors related to their disease and the treatment procedures. Cross-sectional, descriptive study was carried out to achieve the aim of the study. A convenient sample including all adult patients was recruited for this study. Hemodialysis Stressors Scale (HSS) and Jalowiec Coping Scale (JCS) were used to investigate the stressors and coping strategies of 89 hemodialysis patients, at a governmental hospital (King Khalid Hospital-Jeddah). Results of the study revealed that 50.7% experienced physiological stressors and 38% experienced psychosocial stressors. Also, optimistic, fatalistic, and supportive coping strategies were the most common coping strategies used by the patients with mean scores (2.88 + 0.75, 2.87 + 0.75, and 1.82 + 0.71), respectively. In conclusion, being familiar with the types of stressors and the effective coping strategies of hemodialysis patients and their families are important in order to enhance their adaptation with chronic kidney diseases.

Keywords: copying strategies, hemodialysis, physiological stressors, psychological stressors

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Authors: Blessing A. Aderibigbe

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Combination therapy is a treatment approach that is used to prevent the emergence of drug resistance. This approach is used for the treatment of many chronic and infectious diseases. Potentiating agents are currently explored in combination therapy, resulting in excellent therapeutic outcomes. Breast cancer and malaria are two chronic conditions responsible globally for high death rates. In this research, a class of polymer-drug conjugates containing potentiating agents with either antimalarial or anticancer drugs were prepared by Michael Addition Polymerization reaction and ring-opening polymerization reaction. Conjugation of potentiating agents with bioactive compounds into the polymers resulted in conjugates with good water solubility, highly selective and non-toxic. In vitro cytotoxicity and in vitro antiplasmodial evaluation on the conjugates revealed that the conjugates were more effective when compared to the free drugs. The drug release studies further showed that the release profile of the drugs from the conjugates was sustained. The findings revealed the potential of polymer-drug conjugates to overcome drug toxicity and drug resistance, which is common with the currently used antimalarial and anticancer drugs.

Keywords: anticancer, antimalarials, combination therapy, polymer-drug conjugates

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