Search results for: chronic kidney disease

Authors: Roop Kiran, Muhammad Shoaib Zafar, Nazish Idrees Chaudhary

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Depression is known to be the second most frequently occurring comorbid mental illness among patients suffering from chronic physical conditions. Around the world, depression is associated with chronic liver diseases as one of the dominant symptoms. This evidence brings attention to the research about various predictors for short life expectancy and poor quality of life in patients suffering from comorbid depression and CLD. Following are the objectives of this study i) measure the occurrence rate of comorbid depression among patients with CLD and ii) find the frequency of risk factors between patients with and without depression comorbid with CLD. This is a quantitative study with a cross-sectional design. The research data was collected through a measure called Hamilton Depression Rating Scale (HDRS) with a demographic Performa from 100 patients who visited the Department of Psychiatry for consultation at Mayo Hospital Lahore with a diagnosed CLD from the last four years. There were (42%) patients with CLD who had comorbid depression. Among depressed and non-depressed patients, significant differences were found (p<0.05) for unemployment in 25 (59.5%) males and 20 (34.5%) female patients, for co-morbidity in 25 (59.5%) males and 18 (31.0%) female patients, for illiteracy in 18 (42.9%) males and 13 (22.4%) female patients, for the history of CLD for more than the last 2years in 41 (97.6%) males and 47 (81.0%) female patients, for severity of CLD in 26 (61.9%) males and 20 (34.5%) female patients. This concludes that depression frequently occurs among patients with CLD. This study recommends considerable attention to plan preventative measures in the future and develop such intervention protocols that consider the management of risk factors that significantly influence comorbid depression with CLD.

Keywords: psychiatry, comorbid, health, quality of life

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

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

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

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Authors: Soumaya Mrabet, Imen Akkari, Amira Atig, Elhem Ben Jazia

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Introduction: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease of unknown cause. Concomitant autoimmune disorders have been described in 30–50% of patients with AIH. The aim of our study is to determine the prevalence and the type of autoimmune disorders associated with AIH. Material and Methods: It is a retrospective study over a period of 16 years (2000-2015) including all patients followed for AIH. The diagnosis of AHI was based on the criteria of the revised International AIH group scoring system (IAIHG). Results: Twenty-for patients (21 women and 3 men) followed for AIH were collected. The mean age was 39 years (17-65 years). Among these patients, 11 patients(45.8%) had at least one autoimmune disease associated to AIH. These diseases were Hashimoto's thyroiditis (n = 5), Gougerot Sjogren syndrome (n=5), Primary biliary cirrhosis (n=2), Primitive sclerosant Cholangitis (n=1), Addison disease (n = 1) and systemic sclerosis (n=1). Patients were treated with corticosteroids alone or with azathioprine associated to the specific treatment of associated diseases with complete remission of AIH in 90% of cases and clinical improvement of other diseases. Conclusion: In our study, the prevalence of autoimmune diseases in AIH patients was 45.8%. These diseases were dominated by autoimmune thyroiditis and Gougerot Sjogren syndrome. The investigation of autoimmune diseases in autoimmune hepatitis must be systematic because of their frequency and the importance of adequate management.

Keywords: autoimmune diseases, autoimmune hepatitis, autoimmune thyroiditis, gougerot sjogren syndrome

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Authors: Josiah Damisa, Michelle Louise Richardson, Morenike Adewuyi

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Lower back pain is a significant cause of disability worldwide and associated with great implications in terms of the well-being of affected individuals and society as a whole due to its undeniable socio-economic impact. With its prevalence on the increase as a result of an aging global population, the need for novel forms of pain management is ever paramount. This review aims to provide further insight into current research regarding a role for the endocannabinoid signaling pathway as a target in the treatment of chronic pain, with particular emphasis on its potential use as part of the treatment of lower back pain. Potential advantages and limitations of cannabis-based medicines over other forms of analgesia currently licensed for medical use are discussed in addition to areas that require ongoing consideration and research. To evaluate the efficacy of cannabis-based medicines in chronic pain, studies pertaining to the role of medical cannabis in chronic disease were reviewed. Standard searches of PubMed, Google Scholar and Web of Science databases were undertaken with peer-reviewed journal articles reviewed based on the indication for pain management, cannabis treatment modality used and study outcomes. Multiple studies suggest an emerging role for cannabis-based medicines as therapeutic agents in the treatment of chronic back pain. A potential synergistic effect has also been purported if these medicines are co-administered with opiate analgesia due to the similarity of the opiate and endocannabinoid signaling pathways. However, whilst recent changes to legislation in the United Kingdom mean that cannabis is now licensed for medicinal use on NHS prescription for a number of chronic health conditions, concerns remain as to the efficacy and safety of cannabis-based medicines. Research is lacking into both their side effect profiles and the long-term effects of cannabis use. Legal and ethical considerations to the use of these products in standardized medical practice also persist due to the notoriety of cannabis as a drug of abuse. Despite this, cannabis is beginning to gain traction as an alternative or even complementary drug to opiates, with some preclinical studies showing opiate-sparing effects. Whilst there is a paucity of clinical trials in this field, there is scope for cannabinoids to be successful anti-nociceptive agents in managing chronic back pain. The ultimate aim would be to utilize cannabis-based medicines as alternative or complementary therapies, thereby reducing opiate over-reliance and providing hope to individuals who have exhausted all other forms of standard treatment.

Keywords: endocannabinoids, cannabis-based medicines, chronic pain, lower back pain

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Authors: Aya Gamal Khattab

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Chronic infection with the hepatitis C virus (HCV) is now the leading cause of liver-related morbidity and mortality; Currently, alanine aminotransferase ALT measurement is not only widely used in detecting the incidence, development, and prognosis of liver disease with obvious clinical symptoms, but also provides reference on screening the overall health status during health check-ups. Exercise is a low-cost, reliable and sustainable therapy for many chronic diseases. Low-volume high intensity interval training HIT is time efficient while also having wider application to different populations including people at risk for chronic inflammatory diseases. Purpose of this study was to investigate the effect of low volume high intensity interval training on ALT, AST in HCV patients. All practical work was done in outpatient physiotherapy clinic of Suez Canal Authority Hospitals. Forty patients both gender (27 male, 13 female), age ranged (40-60) years old submitted to low volume high intensity interval training on treadmill for two months three sessions per week. Each session consisting of five min warming up, two bouts for 10 min each bout consisting of 30 sec - 1 min of high intensity (75%-85%) HRmax then two to four min active recovery at intensity (40%-60%) HRmax, so the sum of high intensity intervals was one to two min for each session and four to eight min active recovery, and ends with five min cooling down. ALT and AST were measured before starting exercise session and 2 months later after finishing the total exercise sessions through blood samples. Results showed significant decrease in ALT, AST with improvement percentage (18.85%), (23.87%) in the study, so the study concluded that low volume high intensity interval training had a significant effect in lowering the level of circulating liver enzymes (ALT, AST) which means protection of hepatic cells and restoration of its function.

Keywords: alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis C (HCV), low volume high intensity interval training

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Authors: T. Heikkinen, J. Oksman, T. Bragge, A. Nurmi, O. Kontkanen, T. Ahtoniemi

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Motor impairment is an inherent phenotypic feature of several chronic neurodegenerative diseases, and pharmacological therapies aimed to counterbalance the motor disability have a great market potential. Animal models of chronic neurodegenerative diseases display a number deteriorating motor phenotype during the disease progression. There is a wide array of behavioral tools to evaluate motor functions in rodents. However, currently existing methods to study motor functions in rodents are often limited to evaluate gross motor functions only at advanced stages of the disease phenotype. The most commonly applied traditional motor assays used in CNS rodent models, lack the sensitivity to capture fine motor impairments or improvements. Fine motor skill characterization in rodents provides a more sensitive tool to capture more subtle motor dysfunctions and therapeutic effects. Importantly, similar approach, kinematic movement analysis, is also used in clinic, and applied both in diagnosis and determination of therapeutic response to pharmacological interventions. The aim of this study was to apply kinematic gait analysis, a novel and automated high precision movement analysis system, to characterize phenotypic deficits in three different chronic neurodegenerative animal models, a transgenic mouse model (SOD1 G93A) for amyotrophic lateral sclerosis (ALS), and R6/2 and Q175KI mouse models for Huntington’s disease (HD). The readouts from walking behavior included gait properties with kinematic data, and body movement trajectories including analysis of various points of interest such as movement and position of landmarks in the torso, tail and joints. Mice (transgenic and wild-type) from each model were analyzed for the fine motor kinematic properties at young ages, prior to the age when gross motor deficits are clearly pronounced. Fine motor kinematic Evaluation was continued in the same animals until clear motor dysfunction with conventional motor assays was evident. Time course analysis revealed clear fine motor skill impairments in each transgenic model earlier than what is seen with conventional gross motor tests. Motor changes were quantitatively analyzed for up to ~80 parameters, and the largest data sets of HD models were further processed with principal component analysis (PCA) to transform the pool of individual parameters into a smaller and focused set of mutually uncorrelated gait parameters showing strong genotype difference. Kinematic fine motor analysis of transgenic animal models described in this presentation show that this method isa sensitive, objective and fully automated tool that allows earlier and more sensitive detection of progressive neuromuscular and CNS disease phenotypes. As a result of the analysis a comprehensive set of fine motor parameters for each model is created, and these parameters provide better understanding of the disease progression and enhanced sensitivity of this assay for therapeutic testing compared to classical motor behavior tests. In SOD1 G93A, R6/2, and Q175KI mice, the alterations in gait were evident already several weeks earlier than with traditional gross motor assays. Kinematic testing can be applied to a wider set of motor readouts beyond gait in order to study whole body movement patterns such as with relation to joints and various body parts longitudinally, providing a sophisticated and translatable method for disseminating motor components in rodent disease models and evaluating therapeutic interventions.

Keywords: Gait analysis, kinematic, motor impairment, inherent feature

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Authors: Barun K. De

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Acquired immunodeficiency syndrome (AIDS) is caused by two types of human immunodeficiency viruses, collectively designated HIV. HIV infection is spreading globally particularly in developing countries. Before an individual is diagnosed with HIV, the disease goes through different phases. First there is an acute early phase that is followed by an established or chronic phase. Subsequently, there is a latency period after which the individual becomes immunodeficient. It is in the acute phase that an individual is highly infectious due to a high viral load. Presently, HIV diagnosis involves use of tests that do not detect the acute phase infection during which both the viral RNA and p24 antigen are expressed. Instead, these less sensitive tests detect antibodies to viral antigens which are typically sero-converted later in the disease process following acute infection. These antibodies are detected in both asymptomatic HIV-infected individuals as well as AIDS patients. Studies indicate that early diagnosis and treatment of HIV infection can reduce medical costs, improve survival, and reduce spreading of infection to new uninfected partners. Newer 4th generation combination antigen/antibody tests are highly sensitive and specific for detection of acute and established HIV infection (HIV1 and HIV2) enabling immediate linkage to care. The CDC (Center of Disease Control, USA) recently recommended an algorithm involving three different tests to screen and diagnose acute and established infections of HIV-1 and HIV-2 in a general population. Initially a 4th generation combo test detects a viral antigen p24 and specific antibodies against HIV -1 and HIV-2 envelope proteins. If the test is positive it is followed by a second test known as a differentiation assay which detects antibodies against specific HIV-1 and HIV-2 envelope proteins confirming established infection of HIV-1 or HIV-2. However if it is negative then another test is performed that measures viral load confirming an acute HIV-1 infection. Screening results of a Phoenix area population detected 0.3% new HIV infections among which 32.4% were acute cases. Studies in the U.S. indicate that this algorithm effectively reduces HIV infection through immediate treatment and education following diagnosis.

Keywords: new algorithm, HIV, diagnosis, infection

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Authors: Asim Abbasi, Amer Habib, Sajid Hussain, Muhammad Sufyan, Iqra, Hasnain Sajjad

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Except for few scattered cases, powdery mildew disease was not a big problem for watermelon in the past but with the outbreaks of its pathotypes, races 1W and 2W, this disease becomes a serious issue all around the globe. The severe outbreak of this disease also increased the rate of fungicide application for its proper management. Twelve varieties of watermelon were screened in Research Area of Department of Plant pathology, University of Agriculture, Faisalabad to check the incidence of powdery mildew disease. Disease inoculum was prepared and applied with the help of foliar spray method. Fungicides and plants extracts were also applied after the disease incidence. Percentage leaf surface area diseased was assessed visually with a modified Horsfall-Barratt scale. The results of the experiment revealed that among all varieties, WT2257 and Zcugma F1 were highly resistant showing less than 5% disease incidence while Anar Kali and Sugar baby were highly susceptible with disease incidence of more than 65%. Among botanicals neem extract gave best results with disease incidence of less than 20%. Besides neem, all other botanicals also gave significant control of powdery mildew disease than the untreated check. In case of fungicides, Gemstar showed least disease incidence i.e. < 10%, however besides control maximum disease incidence was observed in Curzate (> 30%).

Keywords: botanicals, fungicides, pathotypes, powdery mildew

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Authors: Haolin Li, Eric Bair, Jane Monaco, Quefeng Li

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The temporomandibular disorder (TMD) is a series of musculoskeletal disorders ranging from jaw pain to chronic debilitating pain, and the risk factors for the onset and maintenance of TMD are still unclear. Prior researches have shown that the potential risk factors for chronic TMD are related to psychosocial factors, autonomic functions, and pain sensitivity. Using data from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study’s baseline case-control study, we examine whether the risk factors identified by prior researches are still statistically significant after taking all of the risk measures into account in one single model, and we also compare the relative influences of the risk factors in three different perspectives (psychosocial factors, autonomic functions, and pain sensitivity) on the chronic TMD. The statistical analysis is conducted by using ridge logistic regression and bootstrapping, in which the performance of the algorithms has been assessed using extensive simulation studies. The results support most of the findings of prior researches that there are many psychosocial and pain sensitivity measures that have significant associations with chronic TMD. However, it is surprising that most of the risk factors of autonomic functions have not presented significant associations with chronic TMD, as described by a prior research.

Keywords: autonomic function, OPPERA study, pain sensitivity, psychosocial measures, temporomandibular disorder

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Authors: A. K. Putri, A.Fitri, C. A. Batubara

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Diabetes Mellitus (DM) is a chronic disease that could cause complications. The complication can be Peripheral Arterial Disease (PAD) or Diabetic Neuropathy (DN). Peripheral Arterial Disease is checked by Ankle Brachial Index (ABI), DN is checked by Diabetic Neuropathy Examination (DNE) score. To determine the association of ABI and DNE score in DM type 2. This study uses a cross-sectional design. The subjects were DM patients at the neurology and endocrinology polyclinic at Haji Adam Malik Hospital Medan and its network hospital and this study subjects were examined for ABI and DNE scores. The data were analysed using the Fisher Exact statistics test. Demographics characteristic showed most of subject are female (51,6%), age range ≥ 60 (45.2% ; average 57,6 ± 9,8 years ), and history of DM 5-10 years (45,2%). The most patient ABI characteristics were mild PAD (42%) and moderate PAD (29%). The most patient DNE Score characteristics were≥ 3 (51,6%). There’s a significant relationship between ABI and DNE score in DM type 2 (p =0.016). Conclusion: There is a significant association between ABI and DNE scores in DM type 2 patients

Keywords: diabetic neuropathy, diabetes mellitus, ankle-brachial index, diabetic neuropathy examination

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Authors: Syed Dawood M. Taimur

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Background: Peripheral arterial disease (PAD) is under diagnosed in primary care practices, yet the extent of unrecognized PAD in patients with coronary artery disease (CAD) is unknown. Objective: To assess the prevalence of previously unrecognized PAD in patients undergoing coronary angiogram and to determine the relationship between the presence of PAD and severity of CAD. Material & Methods: This five years retrospective study was conducted at an invasive lab of the department of Cardiology, Ibrahim Cardiac Hospital & Research Institute from January 2010 to December 2014. Total 77 patients were included in this study. Study variables were age, sex, risk factors like hypertension, diabetes mellitus, dyslipidaemia, smoking habit and positive family history for ischemic heart disease, coronary artery and peripheral artery profile. Results: Mean age was 56.83±13.64 years, Male mean age was 53.98±15.08 years and female mean age was 54.5±1.73years. Hypertension was detected in 55.8%, diabetes in 87%, dyslipidaemia in 81.8%, smoking habits in 79.2% and 58.4% had a positive family history. After catheterization 88.3% had peripheral arterial disease and 71.4% had coronary artery disease. Out of 77 patients, 52 had both coronary and peripheral arterial disease which was statistically significant (p < .014). Coronary angiogram revealed 28.6% (22) patients had triple vessel disease, 23.3% (18) had single vessel disease, 19.5% (15) had double vessel disease and 28.6% (22) were normal coronary arteries. The peripheral angiogram revealed 54.5% had superficial femoral artery disease, 26% had anterior tibial artery disease, 27.3% had posterior tibial artery disease, 20.8% had common iliac artery disease, 15.6% had common femoral artery disease and 2.6% had renal artery disease. Conclusion: There is a strong and definite correlation between coronary and peripheral arterial disease. We found that cardiovascular risk factors were in fact risk factors for both PAD and CAD.

Keywords: coronary artery disease (CAD), peripheral artery disease(PVD), risk, factors, correlation, cathetarization

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Authors: Kelly E. Tow, Peter Caputi, Claudia Rogge, Thomas Lee, Simon R. Knowles

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Inflammatory Bowel Disease (IBD) is a serious chronic health condition, characterised by inflammation of the gastrointestinal tract. Individuals with active IBD experience severe abdominal symptoms, which can adversely impact their physical and mental health, as well as their quality of life (QoL). Given that stress may exacerbate IBD symptoms and is frequently highlighted as a contributing factor for the development of psychological difficulties and poorer QoL, it is vital to investigate stress-management strategies aimed at improving the lives of those with IBD. The present study extends on the limited research in IBD cohorts by exploring the role of dispositional mindfulness and its impact on psychological well-being and QoL. The study examined how disease activity and dispositional mindfulness were related to psychological distress and QoL in a cohort of IBD patients. The potential role of dispositional mindfulness as a moderator between stress and anxiety, depression and QoL in these individuals was also examined. Participants included 47 patients with a clinical diagnosis of IBD. Each patient completed a series of psychological questionnaires and was assessed by a gastroenterologist to determine their disease activity levels. Correlation analyses indicated that disease activity was not significantly related to psychological distress or QoL in the sample of IBD patients. However, dispositional mindfulness was inversely related to psychological distress and positively related to QoL. Furthermore, moderation analyses demonstrated a significant interaction between stress and dispositional mindfulness on anxiety. These findings demonstrate that increased levels of dispositional mindfulness may be beneficial for individuals with IBD. Specifically, the results indicate positive links between dispositional mindfulness, general psychological well-being and QoL, and suggest that dispositional mindfulness may attenuate the negative impacts of stress on levels of anxiety in IBD patients. While further research is required to validate and expand on these findings, the current study highlights the importance of addressing psychological factors in IBD and indicates support for the use of mindfulness-based interventions for patients with the disease.

Keywords: anxiety, depression, dispositional mindfulness, inflammatory bowel disease, quality of life, stress

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Authors: Kriti Upadhyay, Ashraf Ali, Puja Sohal, Randeep Guleria

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Background: In Chronic Obstructive Pulmonary diseases (COPD) pathogenesis oxidative stress plays an important role. Hypoxia-Inducible factor (HIF-1α) is a dimeric protein complex which Functions as a master transcriptional regulator of the adaptive response to hypoxiaand is a risk factor that increases when oxidative stress triggers. The role ofHIF-1αin COPD due to smoking is lacking. Aim: This study aims to evaluate the role of HIF-1α in smoker COPD patients comparing its association with diseases severity. Method: In this cross-sectional study, we recruited 87 subjects, 57 were smokers with COPD,15 were smokers without COPD and other 15 were non-smoker healthy controls. The mean age was 54.6± 9.32 (cases 57.08±8.15; controls 50.0± 9.8). There were 62%smokers, 25% non-smokers,7% tobacco chewers and 6% ex-smokers. Enzyme-linked immune sorbent assay (ELISA) method was used for analyzing serum samples wherein HIF-1α was analyzed by Sandwich-ELISA. Results: In smoker COPD patients, a significantly higher HIF-1α level showed positive association with hypoxia, smoking status and severity of disease (p=0.03). The mean value of HIF-1α was not significantly different in smokers without COPD and healthy controls. Conclusion: It is found that HIF-1α level was increased in smoker COPD, but not in smokers without COPD. This suggests that development of COPD drive the HIF-1α pathway and it correlates with the severity of diseases.

Keywords: COPD, chronic obstructive pulmonary diseases, smokers, nonsmokers, hypoxia

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Authors: Lídia E. O. Cruz, Adriano P. C. Calvo, Renato J. Soares, Regiane A. Carvalho

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Individuals with non-specific chronic low back pain may present altered movement patterns during functional activities. However, muscle behavior before and after performing a functional task with different load conditions is not yet fully understood. The aim of this study is to analyze lumbar muscle activity before and after performing the functional task of picking up and placing an object on the ground (with and without load) in individuals with nonspecific chronic low back pain. 20 subjects with nonspecific chronic low back pain and 20 healthy subjects participated in this study. A surface electromyography was performed in the ilio-costal, longissimus and multifidus muscles to evaluate lumbar muscle activity before and after performing the functional task of picking up and placing an object on the ground, with and without load. The symptomatic participants had greater lumbar muscle activation compared to the asymptomatic group, more evident in performing the task without load, with statistically significant difference (p = 0,033) between groups for the right multifidus muscle. This study showed that individuals with nonspecific chronic low back pain have higher muscle activation before and after performing a functional task compared to healthy participants.

Keywords: chronic low back pain, functional task, lumbar muscles, muscle activity

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Authors: Yahia Massinissa, Melakhessou Med Akram, Mezahdia Mehdi, Marref Salah Eddine

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Cytokines are natural proteins which act as true intercellular communication signals in immune and inflammatory responses. Reverse signaling pathways that activate cytokines help to regulate different functions at the target cell, causing its activation, its proliferation, the differentiation, its survival or death. It was shown that malfunctioning of the cytokine regulation, particularly over-expression, contributes to the onset and development of certain serious diseases such as chronic rheumatoid arthritis, Crohn's disease, psoriasis, lupus. The action mode of Kinoid® technology is based on the principle vaccine: The patient's immune system is activated so that it neutralizes itself and the factor responsible for the disease. When applied specifically to autoimmune diseases, therapeutic vaccination allows the body to neutralize cytokines (proteins) overproduced through a highly targeted stimulation of the immune system.

Keywords: cytokines, Kinoid tech, auto-immune diseases, vaccination

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Authors: Huafeng Wei

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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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Authors: Ali Fuad Ashour

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Introduction: Multiple sclerosis (MS) is a chronic, progressive and degenerative disease that affects the central nervous system (CNS). MS has been described to result in the debilitating symptom of the disease. It is reported to have a negative impact on the patient’s mental activities, brings a lower quality of life, leads to unemployment, causes distress and psychological disorders, generates low levels of motivation and self-esteem, and result in disability and neurological impairment. The aim of this study was to compare the effects of MS on patients from Britain and Kuwait. Methodology: A questionnaire was distributed to 200 individuals with MS (100 Kuwaiti and 100 British). The questionnaire consists of three parts; 1. General demographics, 2. Disease-specific data (symptoms, severity levels, relapse frequency, and support system), and 3. Attitudes towards physical exercise. Results: A response rate of 62% from the British sample and 50% from the Kuwaiti sample was achieved. 84% of the sample (n=52) were 41 years old or over. The duration of the disease was less than 10 years in 43.4% of British and 68% of Kuwaiti respondents. The majority of British respondents (56.5%) reported the disease severity to be moderate, while the majority of Kuwaitis was mild (72%). The annual relapse rates in Kuwait were relatively low, with 82% of the Kuwaiti sample had one relapse per year, compared to the 64.5% of British. The most common symptoms reported by British respondents were balance (75.8%), fatigue (74.2%), and weakness (71%), and by Kuwaiti respondents were fatigue (86%), balance (76%), and weakness (66%). The help and support for MS were by far more diverse for the British than Kuwaiti respondents. Discussion: The results unveiled marked differences between two groups of British and Kuwaiti MS patients in terms of patients’ age and disease duration, and severity. The overwhelming majority of Kuwaiti patients are young individuals who have been with the disease for a relatively short period of time, and their MS in most cases was mild. On the other hand, British patients were relatively older, many have been with the disease for a long period of time, and their average MS condition was more serious than that of their Kuwaiti counterparts. The main support in Kuwait comes from the neurologist, who primarily prescribe medications and advise patients to try to be active. The Kuwaiti respondents thought that lack of encouragement was the main reason for them not to engage in social activities.

Keywords: multiple sclerosis, Kuwait, exercise, demographic

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Authors: Saleh N. Maodaa

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Perinatal exposure to nicotine imbalances the redox status in newborns. This study investigated the effect of Anethum graveolens (dill) extract on oxidative stress and tissue injury in the liver and kidney of mice newborns exposed to nicotine perinatally. Pregnant mice received nicotine (0.25 mg/kg) on gestational day 12 to day 5 after birth and/or A. graveolens extract on a gestational day 1 to day 15 after birth. Newborn mice exposed to nicotine showed multiple histopathological alterations in the kidney and liver, including inflammatory cell infiltration and degenerative changes. Nicotine exposure increased hepatic and renal reactive oxygen species (ROS), lipid peroxidation, tumor necrosis factor (TNF-_), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) (p < 0.001), and decreased antioxidant defenses (p < 0.001). A. graveolens supplementation significantly prevented liver and kidney injury, suppressed ROS generation (p < 0.001), lipid peroxidation (p < 0.001), and inflammatory response (p < 0.001), and enhanced antioxidant defenses. In addition, A. graveolens upregulated hepatic and renal Nrf2 and HO-1 mRNA and increased HO-1 activity in normal and nicotine-exposed mice. In conclusion, A. graveolens protects against perinatal nicotine-induced oxidative stress, inflammation, and tissue injury in the liver and kidney of newborn mice. A. graveolens upregulated hepatic and renal Nrf2/HO-1 signaling and enhanced antioxidant defenses in mice.

Keywords: dill, oxidative stress, cytokines, nicotine

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Authors: Dylan Treger, Lujia Zhang, Xiaoxiao Jia, Jessica H. Hui, Munkh-Amgalan Gantumur, Mizhou Hui, Li Liu

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Hyaluronic acid (HA) is involved in wound healing via inflammation, granulation, and re-epithelialization mechanisms. The poor physical properties of natural high-molecular-weight polymers limit their direct use in the medical field. In this clinical study, we investigated whether the local injection of a tissue-permeable 35 kDa HA fragment (HA35) could favor the healing process in patients with chronic wounds accompanied by neuropathic pain. The HA35 fragments were freshly manufactured by degradation of high-molecular-weight HA with bovine testis-derived hyaluronidase PH20. Twenty patients in this study had nonhealing wounds and wound-related pain for more than 3 months. Freshly produced HA35 was locally injected into healthy skin immediately surrounding chronic wounds once a day for 10 days. Wound-associated pain and the degree of wound healing were evaluated. The injection of HA35 relieved the pain associated with chronic wounds in 24 hours. HA35 treatment significantly promoted the healing of chronic wounds, including expanded fresh granulation tissue on the wounds; reduced darkness or redness, dryness, and damaged areas on the surface of the skin surrounding the wounds; and decreased the size of the wound area. It can be concluded that the topical injection of tissue-permeable HA35 around chronic wounds has great potential to promote wound healing.

Keywords: 35 kDa hyaluronan fragment HA35, chronic wound, wound healing, tissue permeability

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Authors: Magdalena B. Kaziuk, Waldemar Kosiba

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Background: In the XXI century we have to deal with the epidemic of obesity which is important risk factor for the cardiovascular and kidney diseases. Lipo proteins are directly involved in the atherosclerotic process. Non-high-density lipo protein (non-HDL) began following widespread recognition of its superiority over LDL as a measurement of vascular event risk. Non-HDL includes residual risk which persists in patients after achieved recommended level of LDL. Materials and Methods: The study covered 111 patients (52 females, 59 males, age 51,91±14 years), hospitalized on the intern department. Body composition was assessed using the bioimpendance method and anthropometric measurements. Physical activity data were collected during the interview. The nutritional status and the obesity type were determined with the Waist to Height Ratio and the Waist to Hip Ratio. A function of the kidney was evaluated by calculating the estimated glomerular filtration rate (eGFR) using MDRD formula. Non-HDL was calculated as a difference between concentration of the Total and HDL cholesterol. Results: 10% of patients were found to be underweight; 23.9 % had correct body weight; 15,08 % had overweight, while the remaining group had obesity: 51,02 %. People with the android shape have higher non-HDL cholesterol versus with the gynoid shape (p=0.003). The higher was non-HDL, the lower eGFR had studied subjects (p < 0.001). Significant correlation was found between high non-HDL and incorrect dietary habits in patients avoiding eating vegetables, fruits and having low physical activity (p < 0.005). Conclusions: Android type of figure raises the residual risk of the heart disease associated with higher levels of non-HDL. Increasing physical activity in these patients reduces the level of non-HDL. Non-HDL seems to be the best predictor among all cholesterol measures for the cardiovascular events and worsening eGFR.

Keywords: obesity, non-HDL cholesterol, glomerular filtration rate, lifestyle

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Authors: Rahil Sahragard, Mahmoud Hatami, Rostam Bahadori Khalili

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Diabetes is one of the most important health problems in the world and a chronic disease requiring continuous care and therefore, it is necessary for patients to undergo self-care and nutrition education. This study was conducted to evaluate the effect of nutrition education on the metabolic control of diabetic patients in Tehran in 2015. An experimental study was conducted on 100 patients who had previously been approved by a specialist physician for diabetes and at least one year after their onset. At first, patients without any knowledge of the educational program were selected as sample and from them a checklist containing demographic and specific information about diabetes was filled and were taken three fasting blood glucose and three times fasting blood glucose (5 p.m.) Then, the patients received face-to-face training in the same conditions for 2 weeks in a Mehregan hospital of Tehran, and received 3 months of training, while they were fully monitored and during this time, samples that had a cold or blood pressure-related disease or were admitted to the hospital were excluded from the study. After the end of the study, the checklist was filled again and 3 fasting blood glucose and 3 fasting blood glucose samples were taken, the results were statistically analyzed by MC Nemar's statistical test. The research findings were performed on 100 patients 41.7% male and 58.3% women, the range of age was between 22 and 60 years old, with a duration of diabetes ranging from 1 to 15 years. Abnormal fasting blood glucose from 95% to 48.3% (P <0.0001) and non-fasting blood glucose decreased from 91.6% to 71.2% (P <0.001). Research has shown that training on blood glucose control has been successful, therefore, it is recommended that more research is done in the field of education to help patients with diabetes more comfortable.

Keywords: nutrition education, diabetes, function, insulin, chronic, metabolic control

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Authors: Yenni Anggrayni

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The lack of awareness of the significant prevalence of school absenteeism in Indonesia, which ultimately results in high rates of school dropouts, is an unresolved issue. Therefore, this study aims to investigate the root causes of chronic absenteeism qualitatively and quantitatively using the bioecological systems paradigm in secondary schools for any reason. This study used an open-ended questionnaire to collect data from 1,148 students in six West Java Province districts/cities. Univariate and stepwise multiple logistic regression analyses produced a prediction model for the components. Analysis results show that poor teacher-student relationships, bullying by peers or teachers, negative perception of education, and lack of parental involvement in learning activities are the leading causes of chronic absenteeism. Another finding is to promote home-school partnerships to improve school climate and parental involvement in learning to address chronic absenteeism.

Keywords: bullying, chronic absenteeism, dropout of school, home-school partnerships, parental involvement

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Authors: Ayşe Defne Öz, Özlem Bozkurt

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Alzheimer's Disease (AD) is counted as one of the most important global health problems and the main cause of dementia. The term dementia refers to a wide spectrum of disorders characterized by global, chronic, and generally irreversible cognitive deterioration. It is estimated that %60 % to 80 of the cases of dementia are because of AD. Alzheimer's is a slowly progressive brain disease. The reason for AD is unknown to the author's best knowledge, yet it is one of the topics that is most researched. AD shows the histopathologically abnormal accumulation of the protein beta-amyloid (plague) outside neurons and twisted strands of the protein tau (tangles) inside neurons in the brain. These changes are accompanied by damage to the brain tissue and the death of neurons. AD causes people to have difficulty remembering names or conversations. Some of the later symptoms are difficulty in talking and walking. Alzheimer's Disease is elevated by the illness and mortality of COVID-19. COVID-19 has affected many lives globally and had profound effects on human lives. COVID-19 is caused by SARS-CoV-2, which is a virus that attacks the respiratory and central nervous system and has neuroinvasive potential. More than %80 of COVID-19 patients have ageusia or anosmia, representing the pathognomic features of the disease. Patients with dementia are frail, and with the COVID-19 pandemic, including isolation, cognitive decline may exacerbate. Furthermore, patients with AD can be unable to follow the directions, such as covering their mouth and nose while coughing and can live in nursing homes which makes them more open to being infected. As COVID-19 is highly infectious and its management requires isolation and quarantine, the need for caregivers for AD management conflicts with that of COVID-19 and adds an extra burden on AD patients, caregivers, families, society, and the economy. Due to the entry of SARS-CoV-2 into the central nervous system, inflammation caused by COVID-19, prolonged hospitalization, and delirium, it has been reported that COVID-19 causes many neurological disorders and predisposition to AD.

Keywords: Alzheimer's disease, COVID-19, dementia, SARS-CoV-2

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Authors: Basma Hassabo, Sarah Ahmed, Aisha Hameed

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Aims and Objectives: To determine the incidence of maternal mortality amongst pregnant women with sickle cell disease (SCD) in the United Kingdom and to determine exact cause of death in these women. Background: SCD is caused by the ‘sickle’ gene and is characterized by episodes of severe bone pain and other complications like acute chest syndrome, chronic pulmonary hypertension, stroke, retinopathy, chronic renal failure, hepato-splenic crises, avascular bone necrosis, sepsis and leg ulcers. SCD is a continual cause of maternal mortality and fetal complications, and it comprises 1.5% of all Direct and Indirect deaths in the UK. Sepsis following premature rupture of membranes with ascending infection, post-partum infection and pre-labour overwhelming septic shock is one of its leading causes of death. Over the last fifty years of maternal mortality reports in UK, between 1 to 4 pregnant women died in each triennium. Material and Method: This is a retrospective study that involves pregnant women who died from SCD complications in the UK between 1952-2012. Data were collected from the UK Confidential Enquiries into Maternal Death and its causes between 1952–2012. Prior to 1985, exact cause of death in this cohort was not recorded. Results: 33 deaths reported between 1964 and 1984. 17 deaths were reported due to sickle cell disease between 1985 and 2012. Five women in this group died of sickle cell crisis, one woman had liver sequestration crisis, two women died of venous thromboembolism, two had myocardial fibrosis and three died of sepsis. Remaining women died of amniotic fluid embolism, SUDEP, myocardial ischemia and intracranial haemorrhage. Conclusion: The leading causes of death in sickle cell sick pregnant women are sickle cell crises, sepsis, venous thrombosis and thromboembolism. Prenatal care for women with SCD should be managed by a multidisciplinary team that includes an obstetrician, nutritionist, primary care physician, and haematologist. In every sick Sickle Cell woman Sickle Cell crises should be on the top of the list of differential diagnosis. Aggressive treatment of complications with low threshold to commence broad-spectrum antibiotics and LMWH contribute to better outcomes.

Keywords: incidence, maternal mortality, sickle cell disease (SCD), uk

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Authors: Ibtisam Al-Zaru

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Background: Worldwide, depression among coronary artery disease (CAD) patients is considered a serious problem that may cause many complications and negative consequences; particularly serious being increased mortality and morbidity rate. Studying depression among CAD patients in Jordan has not been investigated thoroughly and thus a need for further studies has been a priority. Aims: To assess depression in non-hospitalized Jordanian patients with CAD; to describe the relationship between socio-demographic data, health related factors, and depression; and to examine the best predictors of depression in non-hospitalized Jordanian patients with CAD. Method: A cross-sectional-descriptive design was used to collect data from 174 non-hospitalized Jordanian patients diagnosed with CAD in outpatients’ cardiac clinics, using a self- administered questionnaires and Cardiac Depression Scale. Results: 53.4% of CAD patients reported mild/moderate, and severe depressive symptoms. Significant relationships between depressive symptoms and some demo-clinical characteristics (i.e. being female gender; having of chronic disease and surgical history; being physically inactive, and perceived their sexual activity, physical and psychological as poor). The preceding factors are also found to be statistically significant predictors for depression among this patients’ group. Conclusion: Jordanian patients with CAD had various levels of severity regarding their depressive symptoms. Therefore, health care providers need to introduce depression assessment and treatment in cardiac rehabilitation to control depression and its impact on the patient. Consequently, such control will reduce co-morbidity, mortality, complications and health costs among CAD patients and enhance the quality of their lives.

Keywords: coronary artery disease, predictors, depression, prevalence

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Authors: Arati Inamdar, Siddharth Bhattacharyya, Kester Haye

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Collision tumors are rare entities characterized by neoplasms of two different cell populations with distinct separating boundaries. Such tumors could be benign, malignant, or a combination of both. The exact mechanism of origin for collision tumors is predicted to be tumor heterogeneity or concurrent occurrence of neoplasm in the same organ. We present two cases of plasmacytoma presenting as a collision tumor, one with a tumor of hematological origin and another with a non-hematological origin, namely Chronic Lymphocytic Leukemia and Adenocarcinoma of the colon, respectively. The immunohistochemical stains and flowcytometry analysis performed on the specimens aided incorrect diagnosis. Interestingly, neoplastic cells of plasmacytoma in the first case demonstrated strong cytokeratin along with weak Epithelial Specific Antigen/ Epithelial cell adhesion molecule Monoclonal Antibody (MOC31) positivity, indicating that the tumor may influence the microenvironment of the tumor in the vicinity. Furthermore, the next-generation sequencing studies performed on the specimen with plasmacytoma and chronic lymphocytic lymphoma demonstrated BReast CAncer gene (BRCA2) and Tumor Necrosis Factor Alpha Induced Protein 3 (TNFAIP3) as a disease associated variants suggestive of risk for multiple tumors including collision tumors. Our reports highlight the unique collision tumors involving plasmacytoma, which have never been reported previously, as well as provide necessary insights about the underline genetic aberrations and tumor heterogeneity through sequencing studies and allow clonality assessment for subsequent tumors.

Keywords: BRCA2, collision tumor, chronic lymphocytic leukemia, plasmacytoma

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Authors: Vivian Isaac, A. T. Joteeshwaran, Craig McLachlan

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The University of New South Wales (UNSW) Rural Clinical School has a strategic collaborative focus on chronic disease and public health. Our objectives are to understand rural environmental and biological interactions in vulnerable community populations. The UNSW Rural Clinical School translational model is a spoke and hub network. This spoke and hub model connects rural data and biological specimens with city based collaborative public health research networks. Similar spoke and hub models are prevalent across research centers in India. The Australia-India Council grant was awarded so we could establish sustainable public health and community research collaborations. As part of the collaborative network we are developing strategies around data and biological sharing platforms between Indian Institute of Public Health, Public Health Foundation of India (PHFI), Hyderabad and Rural Clinical School UNSW. The key objective is to understand how research collaborations are conducted in India and also how data can shared and tracked with external collaborators such as ourselves. A framework to improve data sharing for research collaborations, including DNA was proposed as a project outcome. The complexities of sharing biological data has been investigated via a visit to India. A flagship sustainable project between Rural Clinical School UNSW and PHFI would illustrate a model of data sharing platforms.

Keywords: data sharing, collaboration, public health research, chronic disease

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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: W. Soufi, F. Boukli Hacene, S. Ghalem

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Alzheimer's disease (AD) is a neurodegenerative disease that leads to a progressive and permanent deterioration of nerve cells. This disease is progressively accompanied by an intellectual deterioration leading to psychological manifestations and behavioral disorders that lead to a loss of autonomy. It is the most frequent of degenerative dementia. Alzheimer's disease (AD), which affects a growing number of people, has become a major public health problem in a few years. In the context of the study of the mechanisms governing the evolution of AD disease, we have found that natural flavonoids are good acetylcholinesterase inhibitors that reduce the rate of ßA secretion in neurons. This work is to study the inhibition of acetylcholinesterase (AChE) which is an enzyme involved in Alzheimer's disease, by methods of molecular modeling. These results will probably help in the development of an effective therapeutic tool in the fight against the development of Alzheimer's disease. Our goal of the research is to study the inhibition of acetylcholinesterase (AChE) by molecular modeling methods.

Keywords: Alzheimer's disease, acetylcholinesterase, flavonoids, molecular modeling

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Authors: Diriba Dereje

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Background: Cardiac and renal disease are the most prevalent chronic non-communicable diseases (CNCD) affecting the community in a significant manner. The best and recommended method in halting CNCD is by working on prevention as early as possible. This is only possible if early surrogate markers are identified. As part of the stated solution, this study will identify an association between microalbuminuria (an early surrogate marker of renal and cardiac disease) and lung function test among adult in the community. Objective: The main aim of this study was to assess an association between microalbuminuria (an early surrogate marker of renal and cardiac disease) and lung function test among adult in the community. Methodology: Community based cross sectional study was conducted among 384 adult in Jimma town. A systematic sampling technique was used in selecting participants to the study. In searching for the possible association, binary and multivariate logistic regression and t-test was conducted. Finally, the association between microalbuminuria and lung function test was well stated in the form of figures and written description. Result and Conclusion: A significant association was found between microalbuminuria and different lung function test parameters.

Keywords: microalbuminuria, lung function, association, test

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