Search results for: diastolic dysfunction

Authors: Kuladip Jana, Bhaswati Banerjee, Parimal C. Sen

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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems along with carcinogenesis in skin, prostate, ovary, lung and mammary glands. Our study was focused on elucidating the molecular mechanism of B(a)P induced male reproductive toxicity and its prevention with phytochemical like resveratrol. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of Wistar rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased Reactive Oxygen Species (ROS), altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38 mitogen activated protein kinase (p38MAPK), cytosolic translocation of cytochrome-c, upregulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of poly ADP ribose polymerase (PARP) and down regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like steroidogenic acute regulatory protein (StAR), cytochrome P450 IIA1 (CYPIIA1), 3β hydroxy steroid dehydrogenase (3β HSD), 17β hydroxy steroid dehydrogenase (17β HSD) showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis. Next we investigated the role of resveratrol on B(a)P induced male reproductive toxicity. Our study highlighted that resveratrol co-treatment with B(a)P maintained testicular redox potential, increased serum testosterone level and prevented steroidogenic dysfunction with enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3β HSD,17β HSD) relative to treatment with B(a)P only. Resveratrol suppressed B(a)P-induced testicular activation of p38 MAPK, ATF2, iNOS and ROS production; cytosolic translocation of Cytochome c and Caspase 3 activation thereby prevented oxidative stress of testis and inhibited apoptosis. Resveratrol co-treatment also decreased B(a)P-induced AhR protein level, its nuclear translocation and subsequent CYP1A1 promoter activation, thereby decreased protein and mRNA levels of testicular cytochrome P4501A1 (CYP1A1) and prevented BPDE-DNA adduct formation. Our findings cumulatively suggest that resveratrol prevents activation of B(a)P by modulating the transcriptional regulation of CYP1A1 and acting as an antioxidant thus prevents B(a)P-induced oxidative stress and testicular apoptosis.

Keywords: benzo(a)pyrene, resveratrol, testis, apoptosis, cytochrome P450 1A1 (CYP1A1), aryl hydrocarbon receptor (AhR), p38 MAPK/ATF2/iNOS

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Authors: Sanaa Mekdad, Leenah Alsayed

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Pharmacists play an important role in the CDTM in the care of patients with heart failure (HF). CDTM allows specialized, dedicated clinical pharmacists in a formal agreement in collaborative practice with physicians. Thus, the aim of this study is to investigate the role of cardiology clinical pharmacists in CDTM in decreasing hospitalization and cost. We studied patients with left ventricular systolic dysfunction in a cluster-randomized selection in a tertiary care center. We allocated 296 patients to pharmacist intervention from 1480 patients. Results: With an acceptance rate of 86%, we documented 696 interventions carried out by clinical pharmacists in cardiology. The average intervention was 2.4 patients, and the admission after interventions decreased from 0.79 to. 0.24 (p value = 0.001). Conclusions: In HF CDTM, clinical pharmacists play a crucial role in enhancing medication management, patient education, and lifestyle modification of patients with chronic heart failure. These efforts improve patients' outcomes and lower costs by reducing hospitalization and other associated expenses.

Keywords: cardiology, medication management, heart failure, outpatient therapy, pharmacist-based services, chronic heart failure, heart failure recommendations, CDTM, Middle East, pharmacist-based services, quality of life, pharmacist

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Authors: Iulia Crisan

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Objective: The present study investigates the cross-cultural validity of three North-American performance validity indicators (PVTs) by comparing base rates of failure (BRF) in Romanian and Canadian disability applicants. Methods: Three PVTs (Test of Memory Malingering Trial 1 [TOMM-1], Rey Fifteen Item Test free recall [Rey-15 FR], and Rey FR+Recognition [Rey COMB]) were administered to a heterogeneous Romanian clinical sample (N Ro =54) and a similar Canadian sample (N Can = 52). Patients were referred for assessment to determine the severity of their cognitive deficits. Results: We compared the BRF in both samples at various cutoffs. BRF on TOMM-1 at ≤ 43 was similar (Ro = 33.3% vs. Can = 40.4%); at ≤40, Ro = 22.2% vs. Can = 25.0%. Likewise, comparable BRF were observed on Rey-15 FR at ≤ 8 (Ro = 7.4% vs. Can = 11.5%) and ≤ 11 (Ro = 27.8% vs. Can = 23.1%). However, the Romanian sample produced significantly higher failure rates on the Rey COMB at variable cutoffs (p <.05), possibly because Romanian patients were significantly older than the Canadian sample. Conclusion: Our findings offer proof of concept for the cross-cultural validity of the TOMM and Rey-15 FR. At the same time, they serve as a reminder that the generalizability of PVT cutoffs to different populations should not be assumed but verified empirically. Employing the TOMM as a criterion measure for newly developed PVTs is discussed.

Keywords: performance validity indicators, cross-cultural validity, failure base rates, clinical samples, cognitive dysfunction, TOMM-1, Rey-15, Rey COMB

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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, we found that ANXA1 could improve mitochondrial function to mitigate DN progression. However, the underlying mechanism is not fully clear yet. Here, we identified 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) by combining it with thioredoxin. Moreover, specific overexpression of UCP1 in the 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 an alternative 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: Zahraa Albasry, Hadeel D. Najim, Anmar Al-Taie

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Background: Hypertension is considered as one of the most important causes of cardiovascular complications and one of the leading causes of worldwide mortality. Identifying the potential risk factors associated with this medical health problem plays an important role in minimizing its incidence and related complications. The objective of this study is to explore the prevalence of receptor sensitivity regarding assess and understand the perception of specific predictive confounding factors on the prevalence of hypertension (HT) among a sample of Iraqi population in Baghdad, Iraq. Materials and Methods: A randomized cross sectional study was carried out on 100 adult subjects during their visit to the outpatient clinic at a certain sector of Baghdad Province, Iraq. Demographic, clinical and health records alongside specific screening and laboratory tests of the participants were collected and analyzed to detect the potential of confounding factors on the prevalence of HT. Results: 63% of the study participants suffered from HT, most of them were female patients (P < 0.005). Patients aged between 41-50 years old significantly suffered from HT than other age groups (63.5%, P < 0.001). 88.9% of the participants were obese (P < 0.001) and 47.6% had diabetes with HT. Positive family history and sedentary lifestyle were significantly higher among all hypertensive groups (P < 0.05). High salt and fatty food intake was significantly found among patients suffered from isolated systolic hypertension (ISHT) (P < 0.05). A significant positive correlation between packed cell volume (PCV) and systolic blood pressure (SBP) (r = 0.353, P = 0.048) found among normotensive participants. Among hypertensive patients, a positive significant correlation found between triglycerides (TG) and both SBP (r = 0.484, P = 0.031) and diastolic blood pressure (DBP) (r = 0.463, P = 0.040), while low density lipoprotein-cholesterol (LDL-c) showed a positive significant correlation with DBP (r = 0.443, P = 0.021). Conclusion: The prevalence of HT among Iraqi populations is of major concern. Further consideration is required to detect the impact of potential risk factors and to minimize blood pressure (BP) elevation and reduce the risk of other cardiovascular complications later in life.

Keywords: Correlation, Hypertension, Iraq, Risk factors

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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: 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: 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: 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: N. W. I. A. Jayawardana, W. A. T. A. Jayalath, W. M. T. Madhujith, U. Ralapanawa, R. S. Jayasekera, S. A. S. B. Alagiyawanna, A. M. K. R. Bandara, N. S. Kalupahana

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There is mounting evidence to the effect that dietary and lifestyle changes affect the incidence of non-communicable diseases (NCDs). This study was conducted to investigate the association of diet, physical activity, smoking, alcohol consumption and duration of sleep with overweight, obesity, hypertension and diabetes in a cohort of males from the Central Province of Sri Lanka. A total of 2694 individuals aged between 17 – 68 years (Mean = 31) were included in the study. Body Mass Index cutoff values for Asians were used to categorize the participants as normal, overweight and obese. The dietary data were collected using a food frequency questionnaire [FFQ] and data on the level of physical activity, smoking, alcohol consumption and sleeping hours were obtained using a self-administered validated questionnaire. Systolic and diastolic blood pressure, random blood glucose levels were measured to determine the incidence of hypertension and diabetes. Among the individuals, the prevalence of overweight and obesity were 34% and 16.4% respectively. Approximately 37% of the participants suffered from hypertension. Overweight and obesity were associated with older age men (P<0.0001), frequency of smoking (P=0.0434), alcohol consumption level (P=0.0287) and the quantity of lipid intake (P=0.0081). Consumption of fish (P=0.6983) and salty snacks (P=0.8327), sleeping hours (P=0.6847) and the level of physical activity were not significantly (P=0.3301) associated with the incidence of overweight and obesity. Based on the fitted model, only age was significantly associated with hypertension (P < 0.001). Further, age (P < 0.0001), sleeping hours (P=0.0953) and consumption of fatty foods (P=0.0930) were significantly associated with diabetes. Age was associated with higher odds of pre diabetes (OR:1.089;95% CI:1.053,1.127) and diabetes (OR:1.077;95% CI:1.055,1.1) whereas 7-8 hrs. of sleep per day was associated with lesser odds of diabetes (OR:0.403;95% CI:0.184,0.884). High prevalence of overweight, obesity and hypertension in working-age males is a threatening sign for this area. As this population ages in the future and urbanization continues, the prevalence of above risk factors will likely to escalate.

Keywords: age, males, non-communicable diseases, obesity

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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

Procedia PDF Downloads 267

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

Procedia PDF Downloads 230

Authors: Sujayeva V. A., Karpova I. S., Koslataya O. V., Kolyadko M. G., Russkikh I. I., Vankovich E. A.

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Objective: The goal of this study is to develop a method for the prevention of the progression of heart failure (HF) in patients with post-infarction cardiosclerosis who have suffered coronavirus infection. Methods: 135 patients with post-infarction cardiosclerosis were divided into 2 groups: Group I - patients who had suffered COVID-19 - 85 people, and Group II - patients who had not suffered COVID-19 - 50 people. Patients of group I, depending on the level of N-terminal fragment of natriuretic peptide (NTproBNP), were divided into 2 subgroups - subgroup A - with HF - 40 people, subgroup B - without HF - 45 people. All patients underwent a clinical examination, echocardiography, electrocardiotopography in 60 leads, computed angiography of the coronary arteries, heart magnetic resonance imaging, NTproBNP. Results: In the post-Covid period, in patients with post-infarction cardiosclerosis, remodeling of the left ventricle and right parts of the heart, deterioration of the systolic-diastolic function of both ventricles, increased pressure in the pulmonary artery, progression of coronary artery atherosclerosis, and an increase in the size of myocardial fibrosis were revealed. The consequence of these changes was the progression of heart failure. The developed method of medical prevention made it possible to improve the clinical course of coronary artery disease and prevent the progression of chronic heart failure in patients with post-infarction cardiosclerosis. Conclusions: In patients with post-infarction cardiosclerosis who initially had HF, after 1 year, according to laboratory and instrumental data, a slight decrease in its severity was revealed. In patients with post-infarction cardiosclerosis who did not have HF before COVID-19, HF developed 1 year after the coronavirus disease, which may be due to the identified process of myocardial fibrosis, which dictates the need to prevent the development of HF in patients with post-infarction cardiosclerosis, even those who did not initially have HF. The proposed method of medical prevention made it possible to improve the clinical course of coronary artery disease in patients with post-infarction cardiosclerosis after COVID-19, both in persons with and without HF, when included in the study. A method of medical prevention in people with post-infarction cardiosclerosis after COVID-19 infection, including spironolactone, loop diuretics, empagliflozin, sacubitril/valsartan, helped prevent the progression of HF.

Keywords: elderly, myocardial infarction, COVID-19, prevention

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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: 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: Boris Bajer, Andrea Havranova, Miroslav Vlcek, Richard Imrich, Adela Penesova

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Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes, and also prevent cardiovascular diseases, as it showed many studies (the Finnish Diabetes Prevention Study, Diabetes Prevention Program (DPP), . the China Da Qing Diabetes Prevention Study, etc.) Therefore the aim of our study was to compare the effect of intensified lifestyle intervention on cardiometabolic parameters. Methods: It is an ongoing randomized interventional clinical study (NCT02325804) focused on the reduction of body weight/fat. Intervention: hypocaloric diet (30% restriction of calories) and physical activity 150 minutes/week. Before and after 8 weeks of intervention all patients underwent complete medical examination (measurement of physical fitness, resting metabolic rate (RMR), body composition analysis, oral glucose tolerance test, parameters of lipid metabolism, and other cardiometabolic risk factors. Results: So far 39 patients finished the intervention. The average reduction of body weight was 6,8 + 4,9 kg (0-15 kg; p=0,0006), accompanied with significant reduction of body fat percentage (p ≤ 0,0001), amount of fat mass (p=0,03), waist circumference (p=0.02). Amount of lean mass and RMR remained unchanged. Heart rate (p=0,02), systolic and diastolic blood pressure was reduced (p=0,01 p=0,02 resp.) as well as insulin sensitivity was improved. Lipid parameters also changed - cholesterol, LDL decreased (p=0,05, p=0,04 resp.), while triglycerides showed tendency to decrease (p=0,055). Liver function improved, alanine aminotrasnferase (ALT) were reduced (p=0,01). Physical fitness significantly improved (as measure VO2 max (p=0,02). Conclusion: Results of our study are in line with previous results about the beneficial effect of intensive lifestyle changes on the reduction of cardiometabolic risk factors and improvement of liver function. Supported by grants APVV 15-0228; VEGA 2/0161/16

Keywords: obesity, weight loss, diet lipids, blood pressure, liver enzymes

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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: Amel Bouaziz, Seddik Khennouf, Mussa Abu Zarga, Shtayway Abdalla, Saliha Djidel, Assia Bentahar, Saliha Dahamna, Smain Amira

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The present study aimed to evaluate the hypotensive and the in vitro antioxidant activities of Crataegus azarolus L. (Rosaceae), a plant widely used as natural remedy for hypertension in folk medicine. The antioxidant potential of methanolic extract (ME)and its three fractions of Chloroform (CHE), ethyl acetate (EAE)and water (AqE) have been investigated using several assays, including the DPPH scavenging, ABTS scavenging, hydroxyl radical scavenging. Inhibition of lipid peroxidation was performed by the β-carotene bleaching assay, ferric thiocyanate method and thiobarburic acid method. Total phenolic and total flavonoid contents of the extracts were estimated using Folin-Chiocalteu reagent and AlCl3, respectively. EAE extract showed the highest polyphenolic and flavonoids contents (396,04±1.20 mg GAE/g of dry extract and 32,73 ± 0.03mg QE/g of dry extract) respectively. Similarly, this extract possessed the highest scavenging activity for DPPH radical (IC 50 = 0,006±0,0001mg /ml), ABTS radical (IC50=0.0035±0,0007 mg/ml) and hydroxyl radical(IC 50=0,283± 0.01 mg/ml). In addition, the EAE exhibited the highest antioxidant activity in the inhibition of linoleic acid/ß-carotene coupled oxidation (89,21%), lipid peroxidation in the ferric thiocyanate(FTC) method (90.13%), and thio-barbituric acid (TBA) method (74.23%). Intravenous administration of Me and EAE decreased mean arterial blood pressure, systolic and diastolic blood pressure in anesthetized rats dose-dependently, at the dose range of 0.4 to 12 mg/kg. The mean arterial blood pressure dropped by 27.58 and 39.37% for ME and EAE, respectively. In conclusion, The present study supported the significant potential to use C. azarolus by-products as a source of natural antioxidants and provides scientific justification for its traditional uses as cardio-protective and anti-hypertensive remedy.

Keywords: Crataegus azarolus, polyphenols, flavonoids, hypertension, antioxidant activity, free radicals, peroxidation

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

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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

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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: Noor F. Ilias, Mazlifah Omar, Hashbullah Ismail

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Exercise training has been shown to improve functional capacity and is recommended as a therapy for management of blood pressure. Our purpose was to establish whether different exercise capacity produces different effect size for Cardiorespiratory Fitness (CRF), systolic (SBP) and diastolic (DBP) blood pressure in patients with hypertension. Exercise characteristic is required in order to have optimal benefit from the training, but optimal exercise capacity is still unwarranted. A MEDLINE search (1985 to 2015) was conducted for exercise based rehabilitation trials in hypertensive patients. Thirty-seven studies met the selection criteria. Of these, 31 (83.7%) were aerobic exercise and 6 (16.3%) aerobic with additional resistance exercise, providing a total of 1318 exercise subjects and 819 control, the total of subjects was 2137. We calculated exercise volume and energy expenditure through the description of exercise characteristics. 4 studies (18.2%) were 451kcal - 900 kcal, 12 (54.5%) were 900 kcal – 1350 kcal and 6 (27.3%) >1351kcal per week. Peak oxygen consumption (peak VO2) increased by mean difference of 1.44 ml/kg/min (95% confidence interval [CI]: 1.08 to 1.79 ml/kg/min; p = 0.00001) with weighted mean 21.2% for aerobic exercise compare to aerobic with additional resistance exercise 4.50 ml/kg/min (95% confidence interval [CI]: 3.57 to 5.42 ml/kg/min; p = 0.00001) with weighted mean 14.5%. SBP was clinically reduce for both aerobic and aerobic with resistance training by mean difference of -4.66 mmHg (95% confidence interval [CI]: -5.68 to -3.63 mmHg; p = 0.00001) weighted mean 6% reduction and -5.06 mmHg (95% confidence interval [CI]: -7.32 to -2.8 mmHg; p = 0.0001) weighted mean 5% reduction respectively. Result for DBP was clinically reduce for aerobic by mean difference of -1.62 mmHg (95% confidence interval [CI]: -2.09 to -1.15 mmHg; p = 0.00001) weighted mean 4% reduction and aerobic with resistance training reduce by mean difference of -3.26 mmHg (95% confidence interval [CI]: -4.87 to -1.65 mmHg; p = 0.0001) weighted mean 6% reduction. Optimum exercise capacity for 451 kcal – 900 kcal showed greater improvement in peak VO2 and SBP by 2.76 ml/kg/min (95% confidence interval [CI]: 1.47 to 4.05 ml/kg/min; p = 0.0001) with weighted mean 40.6% and -16.66 mmHg (95% confidence interval [CI]: -21.72 to -11.60 mmHg; p = 0.00001) weighted mean 9.8% respectively. Our data demonstrated that aerobic exercise with total volume of 451 kcal – 900 kcal/ week energy expenditure may elicit greater changes in cardiorespiratory fitness and blood pressure in hypertensive patients. Higher exercise capacity weekly does not seem better result in management hypertensive patients.

Keywords: blood Pressure, exercise, hypertension, peak VO2

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Authors: Peter W. Woodruff, Georgios Ponirakis, Reem Ibrahim, Amani Ahmed, Hoda Gad, Ioannis N. Petropoulos, Adnan Khan, Ahmed Elsotouhy, Surjith Vattoth, Mahmoud K. M. Alshawwaf, Mohamed Adil Shah Khoodoruth, Marwan Ramadan, Anjushri Bhagat, James Currie, Ziyad Mahfoud, Hanadi Al Hamad, Ahmed Own, Peter Haddad, Majid Alabdulla, Rayaz A. Malik

Abstract:

Introduction:- We aimed to test the hypothesis that, using corneal confocal microscopy (a non-invasive method for assessing corneal nerve fibre integrity), patients with schizophrenia would show neuronal abnormalities compared with healthy participants. Schizophrenia is a neurodevelopmental and progressive neurodegenerative disease, for which there are no validated biomarkers. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging biomarker that can be used to detect neuronal abnormalities in neuropsychiatric syndromes. Methods:- Patients with schizophrenia (DSM-V criteria) without other causes of peripheral neuropathy and healthy controls underwent CCM, vibration perception threshold (VPT) and sudomotor function testing. The diagnostic accuracy of CCM in distinguishing patients from controls was assessed using the area under the curve (AUC) of the Receiver Operating Characterstics (ROC) curve. Findings:- Participants with schizophrenia (n=17) and controls (n=38) with comparable age (35.7±8.5 vs 35.6±12.2, P=0.96) were recruited. Patients with schizophrenia had significantly higher body weight (93.9±25.5 vs 77.1±10.1, P=0.02), lower Low Density Lipoproteins (2.6±1.0 vs 3.4±0.7, P=0.02), but comparable systolic and diastolic blood pressure, HbA1c, total cholesterol, triglycerides and High Density Lipoproteins were comparable with control participants. Patients with schizophrenia had significantly lower corneal nerve fiber density (CNFD, fibers/mm2) (23.5±7.8 vs 35.6±6.5, p<0.0001), branch density (CNBD, branches/mm2) (34.4±26.9 vs 98.1±30.6, p<0.0001), and fiber length (CNFL, mm/mm2) (14.3±4.7 vs 24.2±3.9, p<0.0001) but no difference in VPT (6.1±3.1 vs 4.5±2.8, p=0.12) and electrochemical skin conductance (61.0±24.0 vs 68.9±12.3, p=0.23) compared with controls. The diagnostic accuracy of CNFD, CNBD and CNFL to distinguish patients with schizophrenia from healthy controls were, according to the AUC, (95% CI): 87.0% (76.8-98.2), 93.2% (84.2-102.3), 93.2% (84.4-102.1), respectively. Conclusion:- In conclusion, CCM can be used to help identify neuronal changes and has a high diagnostic accuracy to distinguish subjects with schizophrenia from healthy controls.

Keywords:

Procedia PDF Downloads 275

Authors: Zhuohan Li, Jing Yang, Yaoyuan Cui

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The gut-brain axis (GBA), a communication network between gut microbiota and the brain, benefits for investigation of brain diseases. Currently, organ chips are considered one of the potential tools for GBA research. However, most of the available GBA chips have limitations in replicating the three-dimensional (3D) growth environment of cells and lack the required cell types for barrier function. In the present study, a microfluidic chip was developed for GBA interaction. Blood-brain barrier (BBB) module was prepared with HBMEC, HBVP, U87 cells and decellularized matrix (dECM). Intestinal epithelial barrier (IEB) was prepared with Caco-2 and vascular endothelial cells and dECM. GBA microfluidic device was integrated with IEB and BBB modules using 3D printing interconnecting microchannel scaffolds. BBB and IEB interaction on this GBA chip were evaluated with lipopolysaccharide (LPS) exposure. The present GBA chip achieved multicellular three-dimensional cultivation. Compared with the co-culture cell model in the transwell, fluorescein was absorbed more slowly by 5.16-fold (IEB module) and 4.69-fold (BBB module) on the GBA chip. Accumulation of Rhodamine 123 and Hoechst33342 was dramatically decreased. The efflux function of transporters on IEB and BBB was significantly increased on the GBA chip. After lipopolysaccharide (LPS) disrupted the IEB, and then BBB dysfunction was further observed, which confirmed the interaction between IEB and BBB modules. These results demonstrated that this GBA chip may offer a promising tool for gut-brain interaction study.

Keywords: decellularized matrix, gut-brain axis, organ-on-chip, three-dimensional printing.

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Authors: Sarah Elsayed Mohammed, Lamiaa Ahmed Ahmed, Mahmoud Mohammed Khattab

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Aim: The aim of the present study was to investigate whether combined nicorandil and bone marrow-derived mesenchymal stem cells (BMDMSC) treatment could offer an additional benefit in ameliorating isoproterenol (ISO)-induced heart failure in rats. Methods: ISO (85 and 170 mg/kg/day) was injected subcutaneously for 2 successive days, respectively. By day 3, electrocardiographic changes were recorded and serum was separated for determination of CK-MB level for confirmation of myocardial damage. Nicorandil (3 mg/kg/day) was then given orally with or without a single i.v. BMDMSC administration. Electrocardiography and echocardiography were recorded 2 weeks after beginning of treatment. Rats were then sacrificed and ventricles were isolated for estimation of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) contents, caspase-3 activity as well as inducible nitric oxide synthase (iNOS) and connexin-43 protein expressions. Moreover, histological analysis of myocardial fibrosis was performed and cryosections were done for estimation of homing of BMDMSC. Results: ISO induced a significant increase in ventricles/body weight ratio, left ventricular end diastolic (LVEDD) and systolic dimensions (LVESD), ST segment and QRS duration. Moreover, myocardial fibrosis as well as VEGF, TNF-α and TGF-β contents were significantly increased. On the other hand, connexin-43 protein expression was significantly decreased, while caspase-3 and iNOS protein expressions were significantly increased. Combined therapy provided additional improvement compared to cell treatment alone towards reducing cardiac hypertrophy, fibrosis and inflammation. Furthermore, combined therapy induced significant increase in angiogenesis and BMDMSC homing and prevented ISO induced changes in iNOS, connexin-43 and caspase-3 protein expressions. Conclusion: Combined nicorandil/BMDMSC treatment was superior to BMDMSC alone towards preventing ISO-induced heart failure in rats.

Keywords: fibrosis, isoproterenol, mesenchymal stem cells, nicorandil

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

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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: Faiz N. K. Yusufi, Aquil Ahmed, Jamal Ahmad

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Diabetes in India is growing at an alarming rate and the complications caused by it need to be controlled. Coronary heart disease (CHD) is one of the complications that will be discussed for prediction in this study. India has the second most number of diabetes patients in the world. To the best of our knowledge, there is no CHD risk score for Indian type 2 diabetes patients. Any form of CHD has been taken as the event of interest. A sample of 750 was determined and randomly collected from the Rajiv Gandhi Centre for Diabetes and Endocrinology, J.N.M.C., A.M.U., Aligarh, India. Collected variables include patients data such as sex, age, height, weight, body mass index (BMI), blood sugar fasting (BSF), post prandial sugar (PP), glycosylated haemoglobin (HbA1c), diastolic blood pressure (DBP), systolic blood pressure (SBP), smoking, alcohol habits, total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), physical activity, duration of diabetes, diet control, history of antihypertensive drug treatment, family history of diabetes, waist circumference, hip circumference, medications, central obesity and history of CHD. Predictive risk scores of CHD events are designed by cox proportional hazard regression. Model calibration and discrimination is assessed from Hosmer Lemeshow and area under receiver operating characteristic (ROC) curve. Overfitting and underfitting of the model is checked by applying regularization techniques and best method is selected between ridge, lasso and elastic net regression. Youden’s index is used to choose the optimal cut off point from the scores. Five year probability of CHD is predicted by both survival function and Markov chain two state model and the better technique is concluded. The risk scores for CHD developed can be calculated by doctors and patients for self-control of diabetes. Furthermore, the five-year probabilities can be implemented as well to forecast and maintain the condition of patients.

Keywords: coronary heart disease, cox proportional hazard regression, ROC curve, type 2 diabetes Mellitus

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Authors: Yu-Chen Hsu, Kuang C. Lin

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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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