Search results for: vascular dysfunction

Authors: Zohreh Rostami, Arezoo Khosravi, Mohammad Nikpoor Aghdam, Mahmood Salesi

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Background: Cardiovascular mortality in chronic kidney disease (CKD) and end stage renal disease (ESRD) patients have a strong relationship with baseline or progressive left ventricular hypertrophy (LVH) meanwhile in hemodialysis patients 10% decrement in left ventricular mass was associated with 28% reduction in cardiovascular mortality risk. In consonance with these arguments, we designed a study to measure morphological and functional echocardiographic variations early after transplantation. Method: The patients with normal renal function underwent two advanced echocardiographic studies to examine the structural and functional changes in left ventricular mass before and 3-month after transplantation. Results: From a total of 23 participants 21(91.3%) presented with left ventricular hypertrophy, 60.9% in eccentric and 30.4% in concentric group. Diastolic dysfunction improved in concentric group after transplantation. Both in pre and post transplantation global longitudinal strain (GLS)- average in eccentric group was more than concentric (-17.45 ± 2.75 vs -14.3 ± 3.38 p=0.03) and (-18.08 ± 2.6 vs -16.1 ± 2.7 p= 0.04) respectively. Conclusion: Improvement and recovery of left ventricular function in concentric group was better and sooner than eccentric after kidney transplantation. Although fractional shortening and diastolic function and GLS-4C in pre-transplantation in concentric group was worse than eccentric, but therapeutic response to kidney transplantation in concentric was more and earlier than eccentric group.

Keywords: chronic kidney disease, end stage renal disease, left ventricular hypertrophy, global longitudinal strain

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Authors: Zi-Han Li, Lu Fang, Liang Wu, Dong-Yuan Chang, Manyuan Dong, Liang Ji, Qi Zhang, Ming-Hui Zhao, Sydney C.W. Tang, Lemin Zheng, Min Chen

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Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance, and hyperglycemia, which were risk factors for diabetic nephropathy (DN). Recently, it was found that annexin A1(ANXA1) could improve mitochondrial function to mitigate DN progression. However, the underlying mechanism is not fully clear yet. Here, it was identified that uncoupling protein 1 (UCP1), an inner membrane protein of mitochondria, as a key to mitochondrial homeostasis improved by ANXA1. Specifically, ANXA1 attenuated mitochondrial dysfunction via appropriately upregulating UCP1 by stabilizing its transcription factor GATA binding protein 3 (GATA3) through combining with thioredoxin. Moreover, specific overexpression of UCP1 in renal cortex rescued renal injuries in diabetic Anxa1-KO mice. UCP1 deletion aggravated renal injuries in HFD/STZ-induced diabetic mice. Mechanistically, UCP1 reduced mitochondrial fission through the aristaless-related homeobox (ARX)/cardiolipin synthase 1 (CRLS1) pathway. Therapeutically, CL316243, a UCP1 agonist, could attenuate established DN in db/db mice. This work established a novel principle to harness the power of uncouplers for the treatment of DN.

Keywords: diabetic nephropathy, uncoupling protein 1, mitochondrial homeostasis, cardiolipin metabolism

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Authors: Muhammad Mazhar, Yong Zhu, Likang Qin

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Foods contain endogenous components known as dietary fibers, which are classified into soluble and insoluble forms. Dietary fibers are resistant to gut digestive enzymes, modulating anaerobic intestinal microbiota (AIM) and fabricating short-chain fatty acids (SCFAs). Acetate, butyrate, and propionate dominate in the gut, and different pathways, including Wood-Ljungdahl and acrylate pathways, generate these SCFAs. In pancreatic dysfunction, the release of insulin/glucagon is impaired, which leads to hyperglycemia. SCFAs enhance insulin sensitivity or secretion, beta-cell functions, leptin release, mitochondrial functions, and intestinal gluconeogenesis in human organs, which positively affect type 2 diabetes (T2D). Research models presented that SCFAs either enhance the release of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) from L-cells (entero-endocrine) or promote the release of leptin hormone satiation in adipose tissues through G-protein receptors, i.e., GPR-41/GPR-43. Dietary fibers are the components of foods that influence AIM and produce SCFAs, which may be offering beneficial effects on T2D. This review addresses the effectiveness of SCFAs in modulating gut AIM in the fermentation of dietary fiber and their worth against T2D.

Keywords: dietary fibers, intestinal microbiota, short-chain fatty acids, fermentation, type 2 diabetes

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Authors: John K. Mensah, Mary A. Sword Sayer, Ryan L. Nadel, George Matusick, Zhaofei Fan, Lori G. Eckhardt

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Leptographium terebrantis is an opportunistic root pathogen commonly associated with loblolly pine (Pinus taeda L.) stands that are undergoing a loss of vigor in the southeastern US. In order to understand the relationship between L. terebrantis inoculum density and host physiology, an artificial inoculation study was conducted in a five-year-old naturally regenerated loblolly pine stand over a 24 week period in a completely randomized design. L. terebrantis caused sapwood occlusions that increased in severity as inoculum density increased. The occlusions significantly reduced water transport through the stem but did not interfere with fascicle-level stomatal conductance or induce moisture stress in the saplings. The resilience of stomatal conductance among pathogen-infested saplings is attributed to the growth and hydraulic function of new sapwood that developed after artificial inoculation. Results demonstrate that faster-growing families of loblolly pine may be capable of tolerating the vascular root disease when the formation of new sapwood is supported by sustained crown health.

Keywords: hydraulic conductance, inoculum density, Leptographium terebrantis, Pinus taeda, sapwood occlusion

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Authors: Shital Patil, Surendra Bhosale

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Cardiac diseases are the leading causes of mortality and morbidity in the world, from recent few decades accounting for a large number of deaths have emerged as the most life-threatening disorder globally. Machine learning and Artificial intelligence have been playing key role in predicting the heart diseases. A relevant set of feature can be very helpful in predicting the disease accurately. In this study, we proposed a comparative analysis of 4 different features selection methods and evaluated their performance with both raw (Unbalanced dataset) and sampled (Balanced) dataset. The publicly available Z-Alizadeh Sani dataset have been used for this study. Four feature selection methods: Data Analysis, minimum Redundancy maximum Relevance (mRMR), Recursive Feature Elimination (RFE), Chi-squared are used in this study. These methods are tested with 8 different classification models to get the best accuracy possible. Using balanced and unbalanced dataset, the study shows promising results in terms of various performance metrics in accurately predicting heart disease. Experimental results obtained by the proposed method with the raw data obtains maximum AUC of 100%, maximum F1 score of 94%, maximum Recall of 98%, maximum Precision of 93%. While with the balanced dataset obtained results are, maximum AUC of 100%, F1-score 95%, maximum Recall of 95%, maximum Precision of 97%.

Keywords: cardio vascular diseases, machine learning, feature selection, SMOTE

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Authors: Erika Pénzesné Kónya

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The conservation programme of various vascular plant species has been started in the Botanical garden o fEszterházy College in Eger cooperating with two national parks in the Northern mountain region and Botanical garden of Eötvös Lóránd University in Budapest. The seeds of the species were collected in the chosen habitats with the permission determined by the National Parks and the conservation specialists. Now we have different numbers of individuals from mainly endemic and relict species. We took some experiments to know how can we germinate and grow up this species succesfully up to blooming and fruiting. In the temperate zone the majority of species after ripening the seeds or corps get dormancy to avoid the inadequate period to germinate. The seeds of species need variously pre-treatment (for example pre-chill) and suitable environment (for example basic medium) to unlock the seed dormancy and germinate in large scale. This impacts are often similar to in their originally habitat. To bloom the plants need suitable types of soil, but we couldn’t grow them in the most fruitful soil of habitat. Suitable microclimate is usually more important for some relict species than the soil, that’s why should we make experiments to find the suitable essential conditions for different species and know all of fenological states of them. These experiments can start a method for growing common wild native plants as food materials.

Keywords: ex situ conservation, germination success, soil preference Hungary, regionality, native wild plants

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Authors: Hye Jin Kim, Hwa Sung Shin

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Ischemic stroke means the caused brain damage due to neurological defects, occurring occlusion of cerebral vascular resulting in thrombus or embolism. t-PA (tissue Plasminogen Activator) is the only thrombolytic agent passed the FDA (Food and Drug Administration). However, t-PA directly dissolves the thrombus (direct activity) through fibrinolysis, showing side effects such as re-occlusion. In this study, we evaluated the thrombolytic activities of the serine protease extracted from lugworms inhabiting tidal flats. The new serine protease identified as 38 kDa by SDS-PAGE was not toxic to brain endothelial cells line (hCMEC/D3). Also, the plasmin synthesis inhibition activity (indirect activity) of the new serine protease was confirmed through fibrin zymography assay and fibrin plate assay. It was higher than direct activity as compared to u-PA (urokinase Plasminogen Activator). The activities were found to be maintained at a wide range of temperature (4-70 ℃) and pH 7-10 compared to previous thrombolytic agents from the azocasein assay. In addition, the new serine protease has shown anticoagulant activity from fibrinogenolytic activity assay. In conclusion, the serine protease in lug worms inhabiting the tidal flats could be considered a promising thrombolytic candidate for the treatment of ischemic stroke.

Keywords: alkaline serine protease, bifunctional thrombolytic activity, fibrinolytic activity, ischemic stroke, lug worms

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Authors: Vikas Sharma, V. K. Dixit

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Anacyclus pyrethrum (A. pyrethrum) has been used as Vajikaran Rasayana (aphrodisiac) in traditional Indian ayurvedic medicine to treat male sexual dysfunction, including infertility. Aphrodisiac activity may be due to an increase in the production or effect of androgens, so this study sought to evaluate the androgenic and spermatogenic potential of the alkylamide-rich ethanol solution extract. Male Wistar strain rats weighing between 150 and 180 g were completely randomized divided into five groups. The ethanol solution extract of A. pyrethrum was administered to groups of rats in 50, 100, and 150 mg/kg doses for a period of 28 days, and the action was compared with control and testosterone-treated rats. Thirteen N-alkylamides were detected in the extract by using HPLC/UV/electrospray ionization mass spectrometry method. Extract administration at all the doses produced significant increase in body weight, sperm count, motility, and viability along with serum testosterone, luteinizing hormone, and follicle-stimulating hormone concentrations. Histoarchitecture of testis revealed increased spermatogenic activities. Seminal fructose content was also significantly increased after 28 days of treatment. Our results suggest that the ethanol solution extract of the roots of A. pyrethrum has androgenic potential and may improve male fertility by enhancing spermatogenesis.

Keywords: N-alkylamides, testosterone, Anacyclus pyrethrum, androgen

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Authors: Majid Shahbazi

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Subclavian artery stenosis (SAS) is a common vascular disease that can cause a range of symptoms, from arm fatigue and weakness to ischemic stroke. Revascularization procedures, such as percutaneous transluminal angioplasty and stenting, are widely used to treat SAS and improve blood flow to the affected arm. However, the optimal management of patients with SAS is still unclear, and further research is needed to evaluate the safety and efficacy of different treatment options. This study aims to investigate the characteristics of patients with SAS who underwent revascularization procedures in Latvia (Specifically RAKUS). The research part of this paper aims to describe and analyze the demographics, comorbidities, diagnostic methods, types of revascularization procedures, and antiaggregant therapy used. The goal of this study is to provide insights into the current clinical practice in Latvia and help future treatment decision-makers. To achieve this aim, a retrospective study of 76 patients with SAS who underwent revascularization procedures was performed. After statistical analysis of the data, the study provided insights into the characteristics and management of patients with SAS in Latvia, highlighting the most observed comorbidities in these patients, the preferred diagnostic methods, and the most performed procedures. These findings can inform clinical decision-making and may have implications for the management of patients with subclavian artery stenosis in Latvia.

Keywords: subclavian artery stenosis, revascularization, characteristics of patients, comorbidities, retrospective analysis

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Authors: Azza Gaber Farag, Yasser Atta Shehata, Sara Elsayed Elghazouly, Mustafa Elsayed Elshaib, Nesreen Gamal Elden Elhelbawy

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Background: Androgen receptor (AR) polymorphism in cytosine adenineguanine (CAG) repeat has an effect on the functional capacity of AR in males. However, little researches in this field are available regarding female sexual function. Aim: To investigate the possible link between polymorphism in the CAG repeat of AR gene and female sexual function in a sample of the Egyptian population. Materials and methods: 500 Egyptian married females completed a questionnaire regarding sociodemographic, reproductive, and sexual data. AR CAG repeat length was analyzed for those having female sexual dysfunctions (FSD) using real-time PCR. Results: The most sensitive domain to AR CAG repeat length was the orgasm domain that showed significant positive correlations with short allele (p=0.001), long allele (p=.015), biallellic mean (p=.000), and X weighted biallelic mean (p=.000). The satisfaction domain had significant positive correlations with the biallelic mean (p=.035), and the X weighted biallelic mean (p=. 032). However, the pain domain was of significant negative correlations with AR polymorphism of short allele (p=.002), biallelic mean (p=.013), and X weighted biallelic mean (p = . 011). Conclusions: AR polymorphism could represent a non-negligible aspect in female sexual function. The lower AR CAG repeat polymorphism was of significant impact on FSD, affecting mainly female orgasm followed by pain disorders that finally reflected On her sexual satisfaction.

Keywords: female sexual dysfunction, androgen receptor, CAG repeat polymorphism, androgen

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Authors: Mohammed Alenezy

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The function of cardiac motion can be used as an indicator of the heart abnormality by evaluating longitudinal, circumferential, and Radial Strain of the left ventricle. In this paper, the Radial Strain and SR is studied using tagged MRI (tMRI) data during the cardiac cycle on the mid-ventricle level of the left ventricle. Materials and methods: The short-axis view of the left ventricle of five healthy human (three males and two females) and four healthy male rats were imaged using tagged magnetic resonance imaging (tMRI) technique covering the whole cardiac cycle on the mid-ventricle level. Images were processed using Image J software to calculate the left ventricle wall Radial Strain and radial SR. The left ventricle Radial Strain and radial SR were calculated at the mid-ventricular level during the cardiac cycle. The peak Radial Strain for the human and rat heart was 40.7±1.44, and 46.8±0.68 respectively, and it occurs at 40% of the cardiac cycle for both human and rat heart. The peak diastolic and systolic radial SR for human heart was -1.78 s-1 ± 0.02 s-1 and 1.10±0.08 s-1 respectively, while for rat heart it was -5.16± 0.23s-1 and 4.25±0.02 s-1 respectively. Conclusion: This results show the ability of the tMRI data to characterize the cardiac motion during the cardiac cycle including diastolic and systolic phases which can be used as an indicator of the cardiac dysfunction by estimating the left ventricle Radial Strain and radial SR at different locations of the cardiac tissue. This study approves the validity of the tagged MRI data to describe accurately the cardiac radial motion.

Keywords: left ventricle, radial strain, tagged MRI, cardiac cycle

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Authors: Okyu Kwon, Dongho Kang, Byungsik Kim, Seungkwon Jung

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We propose a technique to measure the impact of loss of traffic function in a particular area to surrounding areas. The proposed method is applied to the city of Seoul, which is the capital of South Korea, with a population of about ten million. Based on the actual road network in Seoul, we construct an abstract road network between 1kmx1km grid cells. The link weight of the abstract road network is re-adjusted considering traffic volume measured at several survey points. On the modified abstract road network, we evaluate the traffic vulnerability by calculating a network measure of betweenness centrality (BC) for every single grid cells. This study analyzes traffic impacts caused by road dysfunction due to heavy rainfall in urban areas. We could see the change of the BC value in all other grid cells by calculating the BC value once again when the specific grid cell lost its traffic function, that is, when the node disappeared on the grid-based road network. The results show that it is appropriate to use the sum of the BC variation of other cells as the influence index of each lattice cell on traffic. This research was supported by a grant (2017-MOIS31-004) from Fundamental Technology Development Program for Extreme Disaster Response funded by Korean Ministry of Interior and Safety (MOIS).

Keywords: vulnerability, road network, beweenness centrality, heavy rainfall, road impact

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Authors: Sadia Munir

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Preeclampsia is the contributor to the worldwide maternal mortality of approximately 100,000 deaths a year. It complicates about 10% of all pregnancies and is the first cause of maternal admission to intensive care units. Predicting preeclampsia is a major challenge in obstetrics. More importantly, no major progress has been achieved in the treatment of preeclampsia. As placenta is the main cause of the disease, the only way to treat the disease is to extract placental and deliver the baby. In developed countries, the cost of an average case of preeclampsia is estimated at £9000. Interestingly, preeclampsia may have an impact on the health of mother or infant, beyond the pregnancy. We performed a systematic search of PubMed including the combination of terms such as preeclampsia, biomarkers, treatment, hypoxia, inflammation, oxidative stress, vascular endothelial growth factor A, activin A, inhibin A, placental growth factor, transforming growth factor β-1, Nodal, placenta, trophoblast cells, microRNAs. In this review, we have summarized current knowledge on the identification of potential biomarkers for the diagnosis of preeclampsia. Although these studies show promising data in early diagnosis of preeclampsia, the current value of these factors as biomarkers, for the precise prediction of preeclampsia, has its limitation. Therefore, future studies need to be done to support some of the very promising and interesting data to develop affordable and widely available tests for early detection and treatment of preeclampsia.

Keywords: activin, biomarkers, growth factors, miroRNA

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Authors: Chen-Sheng Chen, Tsung-Yi Huang, Pi-Chang Sun

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Chronic stroke patients often have complaints about hand dysfunction due to flexor hypertonia and extensor weakness, which makes it difficult to open their affected hand for functional grasp. Hand rehabilitation after stroke is essential for restoring functional independence. Constraint-induced movement therapy has shown to be a successful treatment for patients who have acquired certain level of wrist and finger extension. The goal of this study was to investigate the feasibility of task-oriented approach incorporating 3D-printed dynamic hand device by evaluating hand functional performance. This study manufactured a hand device using 3d printer for chronic stroke. The experimental group engaged task-oriented approach with dynamic hand device, but the control group only received task-oriented approach. Outcome measurements include palmar pinch force (PPF), lateral pinch force (LPF), grip force (GF), and Box and Blocks Test (BBT). The results of study revealed the improvement of PPF in experimental group but not in control group. Meanwhile, improvement in LPF, GF and BBT can be found in both groups. This study demonstrates that the 3D-printed dynamic hand device is an effective therapeutic assistive device to improve pinch force, grasp force, and dexterity and facilitate motivation during home program in individuals with chronic stroke.

Keywords: 3D printing, biomechanics, hand orthosis, stroke

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Authors: Shahad Alkhalifah, Jonh Wright

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Autism spectrum disorder (ASD) is a pervasive developmental disorder associated, for 42% to 88% of people with ASD, with sensory processing disorders. Sensory processing disorders (SPD) impact daily functioning, and it is, therefore, essential to be able to diagnose them accurately. Currently, however, there is no assessment tool available for the Saudi Arabia (SA) population that would cover a wider enough age range. Therefore, this study aimed to assess the psychometric properties of the Sensory Processing Measure Preschool-Home Form (SPM-P) when used in English, with a population of English-speaking Saudi participants. This was chosen due to time limitations and the urgency in providing practitioners with appropriate tools. Using a convenience sampling approach group of caregivers of typically developing (TD) children and a group of caregivers for children with ASD were recruited (N = 40 and N = 16, respectively), and completed the SPM-P Home Form. Participants were also invited to complete it again after two weeks for test-retest reliability, and respectively, nine and five agreed. Reliability analyses suggested some issues with a few items when used in the Saudi culture, and, along with interscale correlations, it highlighted concerns with the factor structure. However, it was also found that the SPM-P Home has good criterion-based validity, and it is, therefore, suggested that it can be used until a tool is developed through translation and cultural adaptation. It is also suggested that the current factor structure of SPM-P Home is reassessed using a large sample.

Keywords: autism, sensory, assessment, reliability, sensory processing dysfunction, preschool, validity

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Authors: I. Boroňová, J. Bernasovská, J. Kmec, E. Petrejčíková

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Dilated cardiomyopathy (DCM) is a severe cardiovascular disorder characterized by progressive systolic dysfunction due to cardiac chamber dilatation and inefficient myocardial contractility often leading to chronic heart failure. Recently, a genome-wide association studies (GWASs) on DCM indicate that the ZBTB17 gene rs10927875 single nucleotide polymorphism is associated with DCM. The aim of the study was to identify the distribution of ZBTB17 gene rs10927875 polymorphism in 50 Slovak patients with DCM and 80 healthy control subjects using the Custom Taqman®SNP Genotyping assays. Risk factors detected at baseline in each group included age, sex, body mass index, smoking status, diabetes and blood pressure. The mean age of patients with DCM was 52.9±6.3 years; the mean age of individuals in control group was 50.3±8.9 years. The distribution of investigated genotypes of rs10927875 polymorphism within ZBTB17 gene in the cohort of Slovak patients with DCM was as follows: CC (38.8%), CT (55.1%), TT (6.1%), in controls: CC (43.8%), CT (51.2%), TT (5.0%). The risk allele T was more common among the patients with dilated cardiomyopathy than in normal controls (33.7% versus 30.6%). The differences in genotype or allele frequencies of ZBTB17 gene rs10927875 polymorphism were not statistically significant (p=0.6908; p=0.6098). The results of this study suggest that ZBTB17 gene rs10927875 polymorphism may be a risk factor for susceptibility to DCM in Slovak patients with DCM. Studies of numerous files and additional functional investigations are needed to fully understand the roles of genetic associations.

Keywords: ZBTB17 gene, rs10927875 polymorphism, dilated cardiomyopathy, cardiovascular disorder

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Authors: Ashit Syngle, Inderjit Verma, Pawan Krishan

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Aim: Endothelial progenitor cells (EPCs) are unique populations which have reparative potential in overcoming the endothelial damage and reducing cardiovascular risk. Patients with ankylosing spondylitis (AS) have increased risk of cardiovascular morbidity and mortality. The aim of this study was to investigate the endothelial progenitor cell population in AS patients and its potential relationships with disease variables. Methods: Endothelial progenitor cells were measured in peripheral blood samples from 20 AS and 20 healthy controls by flow cytometry on the basis of CD34 and CD133 expression. Disease activity was evaluated by using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Functional ability was monitored by using Bath Ankylosing Spondylitis Functional Index (BASFI). Results: EPCs were depleted in AS patients as compared to the healthy controls (CD34+/CD133+: 0.027 ± 0.010 % vs. 0.044 ± 0.011 %, p<0.001). EPCs depletion were significantly associated with disease duration (r=-0.52, p=0.01) and BASDAI (r=-0.45, p=0.04). Conclusion: This is the first study to demonstrate endothelial progenitor cells depletion in AS patients. EPCs depletion inversely correlates with disease duration and disease activity, suggesting the pivotal role of inflammation in depletion of EPCs. EPC would possibly also serve as a therapeutic target for preventing cardiovascular disease in AS.

Keywords: ankylosing spondylitis, endothelial progenitor cells, inflammation, vascular damage

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Authors: Alia Ali, Azeem Taj, Muhammed Joher Amin, Farrukh Iqbal, Zafar Iqbal

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Background: Hypertension is commonly found in patients with Diabetic Kidney Disease (DKD). Microalbuminuria is the first clinical sign of involvement of kidneys in patients with type 2 diabetes. Uncontrolled hypertension induces a higher risk of cardiovascular events, including death, increasing proteinuria and progression to kidney disease. Objectives: To determine the correlation between microalbuminuria and hypertension and their association with other risk factors in type 2 diabetic patients. Methods: One hundred and thirteen type 2 diabetic patients were screened for microalbuminuria and raised blood pressure, attending the diabetic clinic of Shaikh Zayed Hospital, Lahore, Pakistan. The study was conducted from November 2012 to June 2013. Results: Patients were divided into two groups. Group 1, those with normoalbuminuria (n=63) and Group 2, those having microalbuminuria (n=50). Group 2 patients showed higher blood pressure values as compared to Group 1. The results were statistically significant and showed poor glycemic control as a contributing risk factor. Conclusion: The study concluded that there is high frequency of hypertension among type 2 diabetics but still much higher among those having microalbuminuria. So, early recognition of renal dysfunction through detection of microalbuminuria and to start treatment without any delay will confer future protection from end-stage renal disease as well as hypertension and its complications in type 2 diabetic patients.

Keywords: hypertension, microalbuminuria, diabetic kidney disease, type 2 Diabetes mellitus

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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: Lourdes De Fátima Ibañez Valdés, Humberto Foyaca Sibat

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Background: Cysticercosis (Ct) is a preventable and eradicable zoonotic parasitic disease secondary to an infection caused by the larva form of pig tapeworm Taenia solium (Ts), which is mainly seen in people living in developing countries. However, the number of carriers in developed countries increases gradually due to globalization and uncontrolled migration. In this study, we look for the role played by autoimmune innate microglia (Mg) in the pathogenesis of intraparenchymal/subarachnoid neurocysticercosis. (I-SNCC)/ischemic -reperfusion injury (IRI). After reviewing this issue, we formulate some hypotheses regarding to the role of Mg in this process and deliver some novel therapeutic approaches for I- SNCC/IRI. Method: We searched the medical literature comprehensively, looking for published medical subject heading (MeSH) terms like "neurocysticercosis"; "pathogenesis of neurocysticercosis"; "comorbidity in NCC"; OR "I-SNCC"; OR "IRI;" OR "NCC/IS;" OR "Treatment of I-SNCC/IRI;" OR “MPC;” OR “ischemic stroke” OR “subarachnoid neurocysticercosis” OR “racemose neurocysticercosis” Results: All selected manuscripts were peer-reviewed, and we did not find publications related to Mga/I-SNCC/IRI. Comments and concluding remarks: We hypothesized the role played by Mg on the pathogenesis of I-SNCC the role of Mg during the colloid/nodular stage of INCC and racemose NCC and an associated ischemic stroke based on the well-known benefits of Mg polarization.

Keywords: Cysticercosis, neurocysticercosis, microglia activation, apoptosis, pyroptosis, necroptosis, PANoptosis, PANoptosome, infectious vasculitis, ischemic stroke, vascular dementia, racemose neurocysticercosis, subarachnoid neurocysticercosis, extra parenchymal neurocysticercosis

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Authors: Nandini Mohan, Elayne Ahern

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Neurocognitive deficits, as well as psychosocial dysfunction, are typically observed in major depressive disorder (MDD). These deficits persist even after a significant reduction of symptoms and remission from MDD. These deficits have also been linked to greater relapse rates. The link between neurocognitive deficits, relapse, and psychosocial functioning in MDD, on the other hand, has received little attention. This review aimed to conduct an in-depth review of the literature on the association between neurocognitive deficits, relapse, and psychosocial functioning in MDD remission. We used search terms related to MDD, MDD remission, psychosocial functioning, neurocognitive impairments, and relapse to conduct a systematic review of English-language literature in PubMed, PsycArticles, PsycINFO, Medline, and Web of Science to identify relevant studies in the area from which 15 studies were identified for inclusion following an examination against inclusion/ exclusion criteria. Executive functioning, psychomotor speed, and memory were closely related to the psychosocial deficits in the phase of MDD remission. Similarly, Executive function, divided attention, and inhibition were closely related to the relapse in the phase of MDD remission. The limitations of the present review include limited and contradicting evidence that led to fewer studies being included. The implications of this review include an understanding of the difference between clinical and full-functional recovery. This evidence can be the basis for incorporating treatment measures that focus on neurocognitive and psychosocial deficits along with the affective symptoms of MDD.

Keywords: depression, MDD, remission, relapse, neurocognitive functioning, psychosocial deficits

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Authors: Sakina Fatima, Joseph-Patrick W. E. Clarke, Patricia A. Thibault, Subha Kalyaanamoorthy, Michael Levin, Aravindhan Ganesan

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Heteronuclear ribonucleoprotein (hnRNPA1 or A1) is associated with the pathology of different diseases, including neurological disorders and cancers. In particular, the aggregation and dysfunction of A1 have been identified as a critical driver for neurodegeneration (NDG) in Multiple Sclerosis (MS). Structurally, A1 includes a low-complexity domain (LCD) and two RNA-recognition motifs (RRMs), and their interdomain coordination may play a crucial role in A1 aggregation. Previous studies propose that RNA-inhibitors or nucleoside analogs that bind to RRMs can potentially prevent A1 self-association. Therefore, molecular-level understanding of the structures, dynamics, and nucleotide interactions with A1 RRMs can be useful for developing therapeutics for NDG in MS. In this work, a combination of computational modelling and biochemical experiments were employed to analyze a set of RNA-A1 RRM complexes. Initially, the atomistic models of RNA-RRM complexes were constructed by modifying known crystal structures (e.g., PDBs: 4YOE and 5MPG), and through molecular docking calculations. The complexes were optimized using molecular dynamics simulations (200-400 ns), and their binding free energies were computed. The binding affinities of the selected complexes were validated using a thermal shift assay. Further, the most important molecular interactions that contributed to the overall stability of the RNA-A1 RRM complexes were deduced. The results highlight that adenine and guanine are the most suitable nucleotides for high-affinity binding with A1. These insights will be useful in the rational design of nucleotide-analogs for targeting A1 RRMs.

Keywords: hnRNPA1, molecular docking, molecular dynamics, RNA-binding proteins

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Authors: Syed M. Shahid, Rozeena Shaikh, Syeda N. Nawab, Abid Azhar

Abstract:

Diabetes mellitus (DM) is a prevalent non-communicable disease worldwide. DM may lead to many vascular complications like hypertension, nephropathy, retinopathy, neuropathy and foot infections. Pathogenesis of diabetic nephropathy (DN) is implicated by the polymorphisms in genes encoding the specific components of renin angiotensin aldosterone system (RAAS) which include angiotensinogen (AGT), angiotensin-II receptor and angiotensin converting enzyme (ACE) genes. This study was designed to explore the possible association of AG (M268T) polymorphism in the patients of diabetes and nephropathy in Pakistan. Study subjects included 100 controls, 260 diabetic patients without renal insufficiency and 190 diabetic nephropathy patients with persistent albuminuria. Fasting blood samples were collected from all the subjects after getting institutional ethical approval and informed consent. The biochemical estimations, PCR amplification and direct sequencing for the specific region of AGT gene was carried out. A significantly high frequency of TT genotype and T allele of AGT (M268T) was observed in the patients of diabetes with nephropathy as compared to controls and diabetic patients without any known renal impairment. The TT genotype and T allele of AGT (M268T) polymorphism may be considered as a genetic risk factor for the development and progression of nephropathy in diabetes. Further cross sectional population studies would be of help to establish and confirm the observed possible association of AGT gene variations with development of nephropathy in diabetes.

Keywords: RAAS, AGT (M268T), diabetes, nephropathy

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Authors: Brahmi Brahim, Mohammad Habibur Rahman, Maarouf Saad, Cristóbal Ochoa Luna

Abstract:

A repetitive training movement is an efficient method to improve the ability and movement performance of stroke survivors and help them to recover their lost motor function and acquire new skills. The ETS-MARSE is seven degrees of freedom (DOF) exoskeleton robot developed to be worn on the lateral side of the right upper-extremity to assist and rehabilitate the patients with upper-extremity dysfunction resulting from stroke. Practically, rehabilitation activities are repetitive tasks, which make the assistive/robotic systems to suffer from repetitive/periodic uncertainties and external perturbations induced by the high-order dynamic model (seven DOF) and interaction with human muscle which impact on the tracking performance and even on the stability of the exoskeleton. To ensure the robustness and the stability of the robot, a new nonlinear backstepping control was implemented with designed tests performed by healthy subjects. In order to limit and to reject the periodic/repetitive disturbances, an iterative estimator was integrated into the control of the system. The estimator does not need the precise dynamic model of the exoskeleton. Experimental results confirm the robustness and accuracy of the controller performance to deal with the external perturbation, and the effectiveness of the iterative estimator to reject the repetitive/periodic disturbances.

Keywords: backstepping control, iterative control, Rehabilitation, ETS-MARSE

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Authors: Mariane G. Tadros, Shahira M. Ezzat, Maha M. Salama, Mohamed A. Farag

Abstract:

In this study, the in vitro anticholinesterase activity of the volatile oils of both O. basilicum and O. africanum was investigated and both samples showed significant activity. As a result, the major constituents of the two oils were isolated using several column chromatography. Linalool, 1,8-cineol and eugenol were isolated from the volatile oil of O. basilicum and camphor was isolated from the volatile oil of O. africanum. The anticholinesterase activity of the isolated compounds were also evaluated where 1,8-cineol showed the highest inhibitory activity followed by camphor. To confirm these activities, learning and memory enhancing effects were tested in mice. Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist. Anti-amnesic effects of both volatile oils and their terpenoids were investigated by the passive avoidance task in mice. We also examined their effects on brain acetylcholinesterase activity. Results showed that scopolamine-induced cognitive dysfunction was significantly attenuated by administration of the volatile oils and their terpenoids, eugenol and camphor, in the passive avoidance task and inhibited brain acetylcholinesterase activity. These results suggest that O. basilicum and O. africanum volatile oils can be good candidates for further studies on Alzheimer’s disease via their acetylcholinesterase inhibitory actions.

Keywords: Ocimum baselicum, Ocimum africanum, GC/MS analysis, anticholinesterase

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Authors: Yu-Chieh Chen, Kuei-Feng Shen, Chia-Ling Chao

Abstract:

The purpose of this report was to present the nursing experience and case of an unexpected cerebellar hemorrhagic stroke with acute hydrocephalus patient after lumbar spine surgery. The patient had been suffering from an emergent external ventricular drainage and stayed in the Surgical Intensive Care Unit from July 8, 2016, to July 22, 2016. During the period of the case, the data were collected for attendance, evaluation, observation, interview, searching medical record, etc. An integral evaluation of the patient's physiological 'psychological' social and spiritual states was also noted. The author noticed the following major nursing problems including ineffective cerebral perfusion 'physical activity dysfunction' family resource preparation for disability. The author provided nursing care to maintain normal intracranial pressure, along with a well-therapeutic relationship and applied interdisciplinary medical/nursing team to draft an individualized and appropriate nursing plan for them to face the psychosocial impact of the patient disabilities. We also actively participated in the rehabilitation treatments to improve daily activity and confidence. This was deemed necessary to empower them to a more positive attitude in the future.

Keywords: family resourace preparation inability, hemorrhagic sroke, ineffective tissue cerebral perfusion, lumbar spine surgery

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Authors: Yu-Chen Hsu, Kuang C. Lin

Abstract:

The artificial lung called extracorporeal membrane oxygenation (ECMO) is an important medical machine that supports persons whose heart and lungs dysfunction. Previously, investigation of steady deoxygenated blood flows passing through hollow fibers for oxygen transport was carried out experimentally and computationally. The present study computationally analyzes the effect of biological pulsatile flow on the oxygen transport in blood. A 2-D model with a pulsatile flow condition is employed. The power law model is used to describe the non-Newtonian flow and the Hill equation is utilized to simulate the oxygen saturation of hemoglobin. The dimensionless parameters for the physical model include Reynolds numbers (Re), Womersley parameters (α), pulsation amplitudes (A), Sherwood number (Sh) and Schmidt number (Sc). The present model with steady-state flow conditions is well validated against previous experiment and simulations. It is observed that pulsating flow amplitudes significantly influence the velocity profile, pressure of oxygen (PO2), saturation of oxygen (SO2) and the oxygen mass transfer rates (m ̇_O2). In comparison between steady-state and pulsating flows, our findings suggest that the consideration of pulsating flow in the computational model is needed when Re is raised from 2 to 10 in a typical range for flow in artificial lung.

Keywords: artificial lung, oxygen transport, non-Newtonian flows, pulsating flows

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Authors: Thomas Geninatti, Bruno Giacomo, Alessandro Grattoni

Abstract:

Nanofluidic devices have been investigated for over a decade as promising platforms for the controlled release of therapeutics. The nanochannel drug delivery system (nDS), a membrane fabricated with high precision silicon techniques, capable of zero-order release of drugs by exploiting diffusion transport at the nanoscale originated from the interactions between molecules with nanochannel surfaces, showed the flexibility of the sustained release in vitro and in vivo, over periods of time ranging from weeks to months. To improve the implantable bio nanotechnology, in order to create a system that possesses the key features for achieve the suitable release of therapeutics, the next generation of nDS has been created. Platinum electrodes are integrated by e-beam deposition onto both surfaces of the membrane allowing low voltage (<2 V) and active temporal control of drug release through modulation of electrostatic potentials at the inlet and outlet of the membrane’s fluidic channels. Hence, a tunable administration of drugs is ensured from the nanochannel drug delivery system. The membrane will be incorporated into a peek implantable capsule, which will include drug reservoir, control hardware and RF system to allow suitable therapeutic regimens in real-time. Therefore, this new nanotechnology offers tremendous potential solutions to manage chronic disease such as cancer, heart disease, circadian dysfunction, pain and stress.

Keywords: nanochannel membrane, drug delivery, tunable release, personalized administration, nanoscale transport, biomems

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Authors: B. V. Murlimanju

Abstract:

Background: Scaphoid bone is commonly fractured among all the bones of the wrist. The fracture can damage the arteries and would cause avascular necrosis of the scaphoid. In this present study, the goal was to study the topography and number of nutrient foramina in the scaphoid bones of South Indian population. Methods: We studied 46 human scaphoid bones, among them 20 were left sided and 26 belonged to the right side. The scaphoid bones were available at the department of anatomy of our institution. The scaphoid bones were macroscopically observed for the topography and number of nutrient foramina. The data was collected, tabulated and analyzed. Results: The nutrient foramina were observed in all the scaphoid bones (100%). The locations of the foramina were over the non-articular surfaces in all these scaphoids. They were distributed over the palmar and dorsal surfaces. The foramina were found proximal as well as distal to the mid waist of the scaphoid bone. Their number ranged between 9 and 54 in each scaphoid bone. The number ranged between 2-24 over the palmar surface and 7-36 over the dorsal surface. They ranged between 2-24 proximal to the waist and 3-39 distal to the waist. Conclusion: The knowledge of arterial supply, topography of nutrient foramen and their number is essential to understand the concepts of avascular necrosis of scaphoid bone. It will be enlightening to understand the non-union of the fracture of waist of the scaphoid. The morphological data is required to the operating hand surgeon. We do believe that the present study has provided additional information about the topography and number of nutrient foramina of the human scaphoid bones.

Keywords: avascular necrosis, nutrient foramen, scaphoid, vascular

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Authors: Mahdieh Jajroudi

Abstract:

Developing a pharmacokinetic model for the neuroendocrine tumors therapy agent 177Lu-DOTATATE in nude mice bearing AR42J rat pancreatic tumor to investigate and evaluate the behavior of the complex was the main purpose of this study. The utilization of compartmental analysis permits the mathematical differencing of tissues and organs to become acquainted with the concentration of activity in each fraction of interest. Biodistribution studies are onerous and troublesome to perform in humans, but such data can be obtained facilely in rodents. A physiologically based pharmacokinetic model for scaling up activity concentration in particular organs versus time was developed. The mathematical model exerts physiological parameters including organ volumes, blood flow rates, and vascular permabilities; the compartments (organs) are connected anatomically. This allows the use of scale-up techniques to forecast new complex distribution in humans' each organ. The concentration of the radiopharmaceutical in various organs was measured at different times. The temporal behavior of biodistribution of 177Lu labeled somatostatin analogues was modeled and drawn as function of time. Conclusion: The variation of pharmaceutical concentration in all organs is characterized with summation of six to nine exponential terms and it approximates our experimental data with precision better than 1%.

Keywords: biodistribution modeling, compartmental analysis, 177Lu labeled somatostatin analogues, neuroendocrine tumors

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