Search results for: peripheral arterial disease

Authors: Malik Abdul Jabbar Zen, Wiwik Misaco Yuniarti, Azisya Amalia Karimasari, Novita Priandini

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Zoonos is as an infectiontransmitted froma nimals to human sand vice versa currently having increased in the last 20 years. The experts/scientists predict that zoonosis will be a threat to the community in the future since it leads on 70% emerging infectious diseases (EID) and the high mortality of 50%-90%. The zoonosis’ spread from animal to human is caused by contaminated food known as foodborne disease. One World One Health, as the conceptual prevention toward zoonosis, requires the crossed disciplines cooperation to accelerate and streamlinethe handling ofanimal-based disease. E-Vet Smart Rapid System is an integrated innovation in the veterinary expertise application is able to facilitate the prevention, treatment, and educationagainst pandemic diseases and zoonosis. This system is constructed by Decision Support System (DSS) method provides a database of knowledge that is expected to facilitate the identification of disease rapidly, precisely, and accurately as well as to identify the deduction. The testingis conducted through a black box test case and questionnaire (N=30) by validity and reliability approach. Based on the black box test case reveals that E-Vet Rapid System is able to deliver the results in accordance with system design, and questionnaire shows that this system is valid (r > 0.361) and has a reliability (α > 0.3610).

Keywords: diagnosis, disease, expert systems, livestock, zoonosis

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Authors: Sadek A. Makhlouf, Hassan M. Nouh

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Bone hydatidosis is an infection in worldwide distribution. Although there is no evidence in literature on Bone Hydatid disease in Libya, we tried to present the first epidemiological study of this disease in Eastern Libya through retrospective study from 1995 to 2013. Our data were collected from 3 hospitals in Eastern Libya particularly the sheep-raising areas with total number of musculoskeletal infection cases of two thousand one hundred ninety-four (2,194). There were five (5) five cases of bone infection, four (4) of it have been diagnosed after more than three (3) months. Our study is comparable to other international study but this type of bone infection need further studies for effective control strategies for all dogs to avoid serious complications that might happened from the delay in diagnosing this type of disease.

Keywords: bone infection, hydatidosis, Eastern Libya, sheep-raising areas

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Authors: Faisal Almalki

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Pyran is a heterocyclic group containing oxygen that possesses a variety of pharmacological effects. Pyran is also one of the most prevalent structural subunits in natural products, such as xanthones, coumarins, flavonoids, benzopyrans, etc. Additionally demonstrating the neuroprotective properties of pyrans is the fact that this heterocycle has recently attracted the attention of scientists worldwide. Alzheimer's Disease (AD) treatment and diagnosis are two of the most critical research objectives worldwide. Increased amounts of extracellular senile plaques, intracellular neurofibrillary tangles, and a progressive shutdown of cholinergic basal forebrain neuron transmission are often related with cognitive impairment. This review highlights the various pyran scaffolds of natural and synthetic origin that are effective in the treatment of AD. For better understanding synthetic compounds are categorized as different types of pyran derivatives like chromene, flavone, xanthone, xanthene, etc. The discussion encompasses both the structure-activity correlations of these compounds as well as their activity against AD. Because of the intriguing actions that were uncovered by these pyran-based scaffolds, there is no question that they are at the forefront of the search for potential medication candidates that could treat Alzheimer's disease.

Keywords: alzheimer’s disease, pyran, coumarin, xanthone

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Authors: M. A. Sohaly, M. A. Elfouly

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Parkinson's disease (PD) is a heterogeneous movement disorder that often appears in the elderly. PD is induced by a loss of dopamine secretion. Some drugs increase the secretion of dopamine. In this paper, we will simply study the stability of PD models as a nonlinear delay differential equation. After a period of taking drugs, these act as positive feedback and increase the tremors of patients, and then, the differential equation has positive coefficients and the system is unstable under these conditions. We will present a set of suggested modifications to make the system more compatible with the biodynamic system. When giving a set of numerical examples, this research paper is concerned with the mathematical analysis, and no clinical data have been used.

Keywords: Parkinson's disease, stability, simulation, two delay differential equation

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Authors: Amin Mehrabi, Mohsen Salesi, Pourya Pasavand

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Context and objective: The purpose of this research is to study the effect of exercise time (morning/evening) on amount of Troponin T in males' plasma suffering from cardiovascular disease. Method: 15 cardiovascular patients selected as the research subjects. At 7 a.m. pretest blood samples taken from the subjects and they did the exercise protocol in presence of a doctor. Immediately after and 3 hours after that blood measurements done. A week later, the subjects did the same steps at 7 p.m. The SPSS v.20 software used to analyze data. Findings: This study proved that circadian rhythm does not have any effect on the response of myocarditis tissue to exercise and cardiovascular patients allowed to exercise in any times of a day.

Keywords: cardiovascular disease, time of exercise, troponin T (cTnT), myocarditis

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Authors: Rachna Agarwal, R. Naveen, Darpan Thakre, Rohit Shahi, Maryam Abbasi, Upendra Rathore, Latika Gupta

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Aim: Retinal changes are the window to systemic vasculature. Therefore, we explored retinal changes in patients with idiopathic inflammatory myopathies (IIM) as a surrogate for vascular health. Methods: Adult and juvenile IIM patients visiting a tertiary care centre in 2021 satisfying the International Myositis Classification Criteria were enrolled for detailed ophthalmic examination in comparison with healthy controls (HC). Patients with conditions that precluded thorough posterior chamber examination were excluded. Scale variables are expressed as median (IQR). Multivariate analysis (binary logistic regression-BLR) was conducted, adjusting for age, gender, and comorbidities besides factors significant in univariate analysis. Results: 43 patients with IIM [31 females; age 36 (23-45) years; disease duration 5.5 (2-12) months] were enrolled for participation. DM (44%) was the most common diagnosis. IIM patients exhibited frequent attenuation of retinal vessels (32.6% vs. 4.3%, p <0.001), AV nicking (14% vs. 2.2%, p=0.053), and vascular tortuosity (18.6% vs. 2.2%, p=0.012), besides decreased visual acuity (53.5% vs. 10.9%, p<0.001) and immature cataracts (34.9% vs. 2.2%, p<0.001). Attenuation of vessels [OR 10.9 (1.7-71), p=0.004] emerged as significantly different from HC after adjusting for covariates in BLR. Notably, adults with IIM were more predisposed to retinal abnormalities [21 (57%) vs. 1 (16%), p=0.068], especially attenuation of vessels [14(38%) vs. 0(0), p=0.067] than jIIM. However, no difference was found in retinal features amongst the subtypes of adult IIM, nor did they correlate with MDAAT, MDI, or HAQ-DI. Conclusion: Retinal microvasculopathy and diminution of vision occur in nearly one-third to half of the patients with IIM. Microvasculopathy occurs across subtypes of IIM, and more so in adults, calling for further investigation as a surrogate for damage assessment and potentially even systemic vascular health.

Keywords: idiopathic inflammatory myopathies, vascular health, retinal microvasculopathy, arterial attenuation

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Authors: Anjali Roy, Mirza S. Baig

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Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid rich plaque enriched with necrotic core, modified lipid accumulation, smooth muscle cells, endothelial cells, leucocytes and macrophages. Macrophage foam cells play a critical role in the occurrence and development of inflammatory atherosclerotic plaque. Foam cells are the fat-laden macrophages in the initial stage atherosclerotic lesion formation. Foam cells are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening. The mechanisms that drive atherosclerotic plaque progression remain largely unknown. Dissecting the molecular mechanism involved in process of macrophage foam cell formation will help to develop therapeutic interventions for atherosclerosis. To investigate the mechanism, we studied the role of nitric oxide synthase 1(NOS1)-mediated nitric oxide (NO) on low-density lipoprotein (LDL) uptake by bone marrow derived macrophages (BMDM). Using confocal microscopy, we found that incubation of macrophages with NOS1 inhibitor, TRIM (1-(2-Trifluoromethylphenyl) imidazole) or L-NAME (N omega-nitro-L-arginine methyl ester) prior to LDL treatment significantly reduces the LDL uptake by BMDM. Further, addition of NO donor (DEA NONOate) in NOS1 inhibitor treated macrophages recovers the LDL uptake. Our data strongly suggest that NOS1 derived NO regulates LDL uptake by macrophages and foam cell formation. Moreover, we also checked proinflammatory cytokine mRNA expression through real time PCR in BMDM treated with LDL and copper oxidized LDL (OxLDL) in presences and absences of inhibitor. Normal LDL does not evoke cytokine expression whereas OxLDL induced proinflammatory cytokine expression which significantly reduced in presences of NOS1 inhibitor. Rapid NOS-1-derived NO and its stable derivative formation act as signaling agents for inducible NOS-2 expression in endothelial cells, leading to endothelial vascular wall lining disruption and dysfunctioning. This study highlights the role of NOS1 as critical players of foam cell formation and would reveal much about the key molecular proteins involved in atherosclerosis. Thus, targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages at early stage of disease and hence dampening the atherosclerosis progression.

Keywords: atherosclerosis, NOS1, inflammation, oxidized LDL

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Authors: Fernando L. P. Santos, Luiz G. Lyra, Helenice O. Florentino, Daniela R. Cantane

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Dengue is a febrile infectious disease caused by a virus of the family Flaviridae. It is transmitted by the bite of mosquitoes, usually of the genus Aedes aegypti. It occurs in tropical and subtropical areas of the world. This disease has been a major public health problem worldwide, especially in tropical countries such as Brazil, and its incidence has increased in recent years. Dengue is a subject of intense research. Efficient forms of mosquito control must be considered. In this work, the mono-objective optimal control problem was solved for analysing the dengue disease problem. Chemical and biological controls were considered in the mathematical aspect. This model describes the dynamics of mosquitoes in water and winged phases. We applied the genetic algorithms (GA) to obtain optimal strategies for the control of dengue. Numerical simulations have been performed to verify the versatility and the applicability of this algorithm. On the basis of the present results we may recommend the GA to solve optimal control problem with a large region of feasibility.

Keywords: genetic algorithm, dengue, Aedes aegypti, biological control, chemical control

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Authors: Sultan Mahmud, Qamar Zaman, Travis Esau, Young Chang

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Strawberry powdery mildew (PM) is a serious disease that has a significant impact on strawberry production. Field scouting is still a major way to find PM disease, which is not only labor intensive but also almost impossible to monitor disease severity. To reduce the loss caused by PM disease and achieve faster automatic detection of the disease, this paper proposes an approach for detection of the disease, based on image texture and classified with support vector machines (SVMs) and k-nearest neighbors (kNNs). The methodology of the proposed study is based on image processing which is composed of five main steps including image acquisition, pre-processing, segmentation, features extraction and classification. Two strawberry fields were used in this study. Images of healthy leaves and leaves infected with PM (Sphaerotheca macularis) disease under artificial cloud lighting condition. Colour thresholding was utilized to segment all images before textural analysis. Colour co-occurrence matrix (CCM) was introduced for extraction of textural features. Forty textural features, related to a physiological parameter of leaves were extracted from CCM of National television system committee (NTSC) luminance, hue, saturation and intensity (HSI) images. The normalized feature data were utilized for training and validation, respectively, using developed classifiers. The classifiers have experimented with internal, external and cross-validations. The best classifier was selected based on their performance and accuracy. Experimental results suggested that SVMs classifier showed 98.33%, 85.33%, 87.33%, 93.33% and 95.0% of accuracy on internal, external-I, external-II, 4-fold cross and 5-fold cross-validation, respectively. Whereas, kNNs results represented 90.0%, 72.00%, 74.66%, 89.33% and 90.3% of classification accuracy, respectively. The outcome of this study demonstrated that SVMs classified PM disease with a highest overall accuracy of 91.86% and 1.1211 seconds of processing time. Therefore, overall results concluded that the proposed study can significantly support an accurate and automatic identification and recognition of strawberry PM disease with SVMs classifier.

Keywords: powdery mildew, image processing, textural analysis, color co-occurrence matrix, support vector machines, k-nearest neighbors

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Authors: Jamal Almatawah, Hamad Matar, Abdulsalam Altemeemi

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The World Health Organization (WHO) has recognized environmental noise as harmful pollution that causes adverse psychosocial and physiologic effects on human health. The motor vehicle is considered to be one of the main source of noise pollution. It is a universal phenomenon, and it has grown to the point that it has become a major concern for both the public and policymakers. The aim of this paper, therefore, is to investigate the Traffic noise levels and the contributing factors that affect its level, such as traffic volume, heavy-vehicle Speed and other metrological factors in Ishbiliyah as a sample of a residential area in Kuwait. Three types of roads were selected in Ishbiliyah expressway, major arterial and collector street. The other source of noise that interferes the traffic noise has also been considered in this study. Traffic noise level is measured and analyzed using the Bruel & Kjaer outdoor sound level meter 2250-L (2250 Light). The Count-Cam2 Video Camera has been used to collect the peak and off-peak traffic count. Ambient Weather WM-5 Handheld Weather Station is used for metrological factors such as temperature, humidity and wind speed. Also, the spot speed was obtained using the radar speed: Decatur Genesis model GHD-KPH. All the measurement has been detected at the same time (simultaneously). The results showed that the traffic noise level is over the allowable limit on all types of roads. The average equivalent noise level (LAeq) for the Expressway, Major arterial and Collector Street was 74.3 dB(A), 70.47 dB(A) and 60.84 dB(A), respectively. In addition, a Positive Correlation coefficient between the traffic noise versus traffic volume and between traffic noise versus 85th percentile speed was obtained. However, there was no significant relation and Metrological factors. Abnormal vehicle noise due to poor maintenance or user-enhanced exhaust noise was found to be one of the highest factors that affected the overall traffic noise reading.

Keywords: traffic noise, residential area, pollution, vehicle noise

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Authors: Ana Corberan-Vallet, Karen C. Florez, Ingrid C. Marino, Jose D. Bermudez

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In 2016, the Region of the Americas was declared free of measles, a viral disease that can cause severe health problems. However, since 2017, measles has reemerged in Venezuela and has subsequently reached neighboring countries. In 2018, twelve American countries reported confirmed cases of measles. Governmental and health authorities in Colombia, a country that shares the longest land boundary with Venezuela, are aware of the need for a strong response to restrict the expanse of the epidemic. In this work, we apply a Bayesian hierarchical Poisson model with an underlying cluster structure to describe disease incidence in Colombia. Concretely, the proposed methodology provides relative risk estimates at the department level and identifies clusters of disease, which facilitates the implementation of targeted public health interventions. Socio-demographic factors, such as the percentage of migrants, gross domestic product, and entry routes, are included in the model to better describe the incidence of disease. Since the model does not impose any spatial correlation at any level of the model hierarchy, it avoids the spatial confounding problem and provides a suitable framework to estimate the fixed-effect coefficients associated with spatially-structured covariates.

Keywords: Bayesian analysis, cluster identification, disease mapping, risk estimation

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Authors: Rania A. R. Soudan, Easter Joury

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Introduction: Psoriasis is a common chronic dermatologic disease. It may affect the mucous membranes. The presence of oral mucosal lesions has been a subject of controversy. The aim: To determine possible association between oral mucosal lesions and psoriasis, and to correlate the same with different types of psoriasis and severity of the disease. Materials and Methods: The oral mucosa was clinically examined in 100 randomly selected Syrian psoriatic patients presented to the Dermatological Diseases Hospital in Damascus University, Syria (February 2009 - December 2010), and in 100 matched controls. PASI index was used to evaluate the disease severity. Chi-square and Student t-test were used to compare differences between groups. Results: Oral mucosal lesions were observed in 72% of the psoriasis cases, while 46% of the control group’s subjects had oral lesions. Fissured tongue, geographic tongue, and red lesions were detected in 36%, 25%, and 7% of the examined psoriatics, respectively. These lesions were significantly more frequent in the psoriatics than in the controls. A correlation was found between furred tongue and the age of the psoriasis patients. However, an association was observed for fissured tongue, furred tongue with the severity of the disease, and for fissured tongue, white lesions, cheilitis with nail involvement. However, no correlation with the psoriasis types was recorded. Conclusion: Some oral mucosal lesions were associated with psoriasis, so these lesions may be considered as oral manifestations of this disease, and should be taken into account in new studies as possible predictors or markers of this dermatitis. Further studies are recommended to confirm these oral manifestations.

Keywords: psoriasis, tongue, mucosa, lesions

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Authors: Septiawan A. Saputro, Purnami Widyaningsih, Sutanto Sastraredja

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Measles is a disease which can spread caused by a virus and has been a priority’s Ministry of Health in Indonesia to be solved. Each infected person can be recovered and get immunity so that the spread of the disease can be constructed with susceptible infected recovered (SIR). To prevent the spread of measles transmission, the Ministry of Health holds vaccinations program. The aims of the research are to derive susceptible vaccinated infected recovered (SVIR) model, to determine the patterns of disease spread with SVIR model, and also to apply the SVIR model on the spread of measles in Indonesia. Based on the article, it can be concluded that the spread model of measles with vaccinations, that is SVIR model. It is a first-order differential equation system. The patterns of disease spread is determined by solution of the model. Based on that model Indonesia will be a measles-free nation in 2186 with the average of vaccinations scope about 88% and the average score of vaccinations failure about 4.9%. If it is simulated as Ministry of Health new programs with the average of vaccinations scope about 95% and the average score of vaccinations failure about 3%, then Indonesia will be a measles-free nation in 2184. Even with the average of vaccinations scope about 100% and no failure of vaccinations, Indonesia will be a measles-free nation in 2183. Indonesia’s target as a measles-free nation in 2020 has not been reached.

Keywords: measles, vaccination, susceptible infected recovered (SIR), susceptible vaccinated infected recovered (SVIR)

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Authors: Eyup Ozkan, Ozkan U. Nalbantoglu, Aycan Gundogdu, Mehmet Hora, A. Emre Onuk

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The human microbiome has been associated with cardiological conditions and this relationship is becoming to be defined beyond the gastrointestinal track. In this study, we investigate the alteration in circulatory microbiota in the context of Coronary Artery Disease (CAD). We received circulatory blood samples from suspected CAD patients and maintain 16S ribosomal RNA sequencing to identify each patient’s microbiome. It was found that Corynebacterium and Methanobacteria genera show statistically significant differences between healthy and CAD patients. The overall biodiversities between the groups were observed to be different revealed by machine learning classification models. We also achieve and demonstrate the performance of a diagnostic method using circulatory blood microbiome-based estimation.

Keywords: coronary artery disease, blood microbiome, machine learning, angiography, next-generation sequencing

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Authors: H. C. Chinwenyi, H. D. Ibrahim, J. O. Adekunle

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The incubation period is defined as the time from infection with a microorganism to development of symptoms. In this research, two disease models: one with incubation period and another without incubation period were studied. The study involves the use of a  mathematical model with a single incubation period. The test for the existence and stability of the disease free and the endemic equilibrium states for both models were carried out. The fourth order Runge-Kutta method was used to solve both models numerically. Finally, a computer program in MATLAB was developed to run the numerical experiments. From the results, we are able to show that the endemic equilibrium state of the model with incubation period is locally asymptotically stable whereas the endemic equilibrium state of the model without incubation period is unstable under certain conditions on the given model parameters. It was also established that the disease free equilibrium states of the model with and without incubation period are locally asymptotically stable. Furthermore, results from numerical experiments using empirical data obtained from Nigeria Centre for Disease Control (NCDC) showed that the overall population of the infected people for the model with incubation period is higher than that without incubation period. We also established from the results obtained that as the transmission rate from susceptible to infected population increases, the peak values of the infected population for the model with incubation period decrease and are always less than those for the model without incubation period.

Keywords: asymptotic stability, Hartman-Grobman stability criterion, incubation period, Routh-Hurwitz criterion, Runge-Kutta method

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Authors: Yishu Gong, Liangliang Yang, Jianyu Zhang, Zhengyu Chen, Sihong He, Xusheng Zhang, Wei Zhang

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects millions of people worldwide and is characterized by cognitive decline and behavioral changes. People living with Alzheimer’s disease often find it hard to complete routine tasks. However, there are limited objective assessments that aim to quantify the difficulty of certain tasks for AD patients compared to non-AD people. In this study, we propose to use speech emotion recognition (SER), especially the frustration level, as a potential biomarker for quantifying the difficulty patients experience when describing a picture. We build an SER model using data from the IEMOCAP dataset and apply the model to the DementiaBank data to detect the AD/non-AD group difference and perform longitudinal analysis to track the AD disease progression. Our results show that the frustration level detected from the SER model can possibly be used as a cost-effective tool for objective tracking of AD progression in addition to the Mini-Mental State Examination (MMSE) score.

Keywords: Alzheimer’s disease, speech emotion recognition, longitudinal biomarker, machine learning

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Authors: Diana C. El Assal, Fatima Monteiro, Caroline May, Peter Barbuti, Silvia Bolognin, Averina Nicolae, Hulda Haraldsdottir, Lemmer R. P. El Assal, Swagatika Sahoo, Longfei Mao, Jens Schwamborn, Rejko Kruger, Ines Thiele, Kathrin Marcus, Ronan M. T. Fleming

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Degeneration of substantia nigra pars compacta dopaminergic neurons is one of the hallmarks of Parkinson's disease. These neurons have a highly complex axonal arborisation and a high energy demand, so any reduction in ATP synthesis could lead to an imbalance between supply and demand, thereby impeding normal neuronal bioenergetic requirements. Synaptic mitochondria exhibit increased vulnerability to dysfunction in Parkinson's disease. After biogenesis in and transport from the cell body, synaptic mitochondria become highly dependent upon oxidative phosphorylation. We applied a systems biochemistry approach to identify the metabolic pathways used by neuronal mitochondria for energy generation. The mitochondrial component of an existing manual reconstruction of human metabolism was extended with manual curation of the biochemical literature and specialised using omics data from Parkinson's disease patients and controls, to generate reconstructions of synaptic and somal mitochondrial metabolism. These reconstructions were converted into stoichiometrically- and fluxconsistent constraint-based computational models. These models predict that Parkinson's disease is accompanied by an increase in the rate of glycolysis and a decrease in the rate of oxidative phosphorylation within synaptic mitochondria. This is consistent with independent experimental reports of a compensatory switching of bioenergetic pathways in the putamen of post-mortem Parkinson's disease patients. Ongoing work, in the context of the SysMedPD project is aimed at computational prediction of mitochondrial drug targets to slow the progression of neurodegeneration in the subset of Parkinson's disease patients with overt mitochondrial dysfunction.

Keywords: bioenergetics, mitochondria, Parkinson's disease, systems biochemistry

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Authors: Pedro Gomes, Lia Ferreira, Sofia Garcia, Jaime Babulal, Luís Costa, Luís Castelo, José Muras, Isabel Gonçalves, Rui Carvalho

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Introduction: Foot ulcers and their complications are an important cause of morbidity and mortality in diabetes. Objectives: The present study aims to evaluate the outcomes in terms of need for hospitalization, amputation, healing time and mortality in patients with new-onset diabetic foot ulcers in subgroups stratified by etiology. Methods: A retrospective study based on clinical assessment of patients presenting with new ulcers to a multidisciplinary diabetic foot consult during 2012. Outcomes were determined until September 2014, from hospital registers. Baseline clinical examination was done to classify ulcers as neuropathic, ischemic or neuroischemic. Results: 487 patients with new diabetic foot ulcers were observed; 36%, 15% and 49% of patients had neuropathic, ischemic and neuroischemic ulcers, respectively. For analysis, patients were classified as having predominantly neuropathic (36%) or ischemic foot (64%). The mean age was significantly higher in the group with ischemic foot (70±12 vs 63±12 years; p <0.001), as well as the duration of diabetes (18±10 vs 16 ± 10years, p <0.05). A history of previous amputation was also significantly higher in this group (24.7% vs 15.6%, p <0.05). The evolution of ischemic ulcers was significantly worse, with a greater need for hospitalization (27.2% vs 18%, p <0.05), amputation (11.5% vs 3.6% p <0.05) mainly major amputation (3% vs. 0%; p <0.001) and higher mean healing time (151 days vs 89 days, p <0.05). The mortality rate at 18 months, was also significantly higher in the ischemic foot group (7.3% vs 1.8%, p <0.05). Conclusions: All types of diabetic foot ulcers are associated with high morbidity and mortality, however, the presence of arterial disease confers a poor prognosis. Diabetic foot can be successfully treated only by the multidisciplinary team which can provide more comprehensive and integrated care.

Keywords: diabetes, foot ulcers, etiology, outcome

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Authors: A. Elmajdoub, A. El-Mahmoudy

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The present study was designed to investigate the neurotransmitters that mediate the excitatory response of the circular muscle of final branches of mesenteric artery in bovine calves. Mesentery was dissected and the iliac branches were separated and used. The final mesenteric branches of diameter 400 micrometers and less responded strongly to norepinephrine and moderately to ATP. However, the mesenteric branches of wider diameters were gradually less responsive to norepinephrine and those of diameter 700 micrometers were exclusively nonresponsive. These arteries were strongly responsive to ATP (100 µM). Norepinephrine response was sensitive to phentolamine (3 µM) and prazosin (5 µM) indicating that it is mediated by α1 receptor; while ATP response was sensitive to suramin (200 µM), PPADS (50 µM), but not to cibacron blue (100 µM) indicating that it is mediated via P2X receptor. Further confirmatory experiments were performed including application of α1 and P2X receptor specific agonists which are methoxamine and α,β-methylene ATP. Methoxamine (1 µM) showed effects similar to norepinephrine in final branches and was without effect in wider branches. α,β-methylene ATP (1 µM), exhibited more pronounced effects on both wide and narrow branches but in parallel manner to that of ATP. Agonists for α2 and P2Y receptors as clonidine (10 µM) and 2-meThio ATP (10 µM), respectively, were without effect indicating that involvement of these receptors is unlikely. The neuropeptide-Y (200 nM) did not have any effects on either the narrow or the wide rings. Conclusion: These data may imply that in the most peripheral mesenteric arteries a strong vasopressor power represented by norepinephrine and ATP integration is needed for maintaining peripheral resistance; on the other hand a mild vasopressor power mediated only by ATP is enough to maintain the vascular tone in the relatively central mesenteric branches.

Keywords: ATP, calves, mesenteric artery, norepinephrine

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Authors: Hami Ashraf, Farid Kosari

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Graft-versus-host disease (GvHD) is a common complication of allogeneic hematopoietic stem cell transplantation that can lead to significant morbidity and mortality. Histopathological examination of affected tissues is an essential tool for diagnosing and grading GvHD in animal models, which are used to study disease mechanisms and evaluate new therapies. In this systematic review, we identified and analyzed original research articles in PubMed, Scopus, Web of Science, and Google Scholar that described grading systems for GvHD in animal models based on histopathological features. We found that several grading systems have been developed, which vary in the tissues and criteria they assess, the severity scoring scales they use, and the level of detail they provide. Skin, liver, and gut are the most commonly evaluated tissues, but lung and thymus are also included in some systems. Our analysis highlights the need for standardized criteria and consistent use of grading systems to enable comparisons between studies and facilitate the translation of preclinical findings to clinical practice.

Keywords: graft-versus-host disease, GvHD, animal model, histopathology, grading system

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Authors: Ashish Kumar Agrahari, Amit Kumar

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Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal blood disorder that manifests with hemolytic anemia, thrombosis, and peripheral blood cytopenias. The disease is caused by the deficiency of two glycosylphosphatidylinositols (GPI)-anchored proteins (CD55 and CD59) in the hemopoietic stem cells. The deficiency of GPI-anchored proteins has been associated with the somatic mutations in phosphatidylinositol glycan class A (PIGA). However, the mutations that do not cause PNH is associated with the multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2). To best of our knowledge, no computational study has been performed to explore the atomistic level impact of PIGA mutations on the structure and dynamics of the protein. In the current work, we are mainly interested to get insights into the molecular mechanism of PIGA mutations. In the initial step, we screened the most pathogenic mutations from the pool of publicly available mutations. Further, to get a better understanding, pathogenic mutations were mapped to the modeled structure and subjected to 50ns molecular dynamics simulation. Our computational study suggests that four mutations are highly vulnerable to altering the structural conformation and stability of the PIGA protein, which illustrates its association with PNH and MCAHS2 phenotype.

Keywords: homology modeling, molecular dynamics simulation, missense mutations PNH, MCAHS2, PIGA

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Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

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Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

Keywords:

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Authors: P. S. Akami, H. Nahunnaro, A. Zubainatu

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Cercospora leaf spot (Cercospora sesami. Zimm) has been identified as one of the most prevalent diseases, posing serious constraints to sesame production in producing areas. Two sets of experiments were carried out. The first and second experiments were conducted in the Modibbo Adama University of Technology Yola at the Crop Production and Horticulture and Plant Science Departments, respectively. The field experiment was carried out using a Randomized Complete Block Design and was replicated three times on a plot size of 4m x 5m with four sesame varieties and three Mancob-M fungicide levels (0g, 2g and 4g) to give a total of Twelve treatments. The laboratory experiment involved the isolation of the pathogens from diseased leaves with symptoms of Cercospora leaf spot, which was identified as Cercospora sesami. Data collected were subjected to analysis of variance for a randomized complete block design using SAS (1999) statistical package. The treatment means that are significantly different were separated using the Least Significant Difference at P=0.05. The result revealed that 4g Mancob M recorded the lowest mean value for disease incidence and severity at 8WAS, which was 90.30% and 35.60%, respectively, while the control (0g) recorded the highest mean value for disease incidence and severity at 90.30% and 59.80% respectively. Ex-Sudan recorded the lowest value of 720 kg/ha, while NCRIBEN 03 recorded the highest yield of 834 kg/ha-¹. For the concentrations, 2g recorded a higher yield of 843 kg/ha-¹ followed by 0g, which recorded 765 kg/ha-¹. Conclusively, Cercospora leaf spot of sesame was found to be prevalent. E8 has a higher resistance to the disease, while NCRIBEN 03 tends to be more susceptible. It is therefore recommended that further trials should be carried out using different varieties in different locations.

Keywords: disease, evaluation, prevalence, treatment, resistance

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Authors: Duanghathai Saipinta, Tanittian Panyamongkol, Witaya Suriyasathaporn

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Animal management aims to provide a suitable environment for animals allowing maximal productivity in those animals. Prevention of disease is an important part of animal management. Foot-and-mouth disease (FMD) is a highly contagious viral disease in cattle and is an economically important animal disease worldwide. Monitoring the FMD virus in farms is useful management for the prevention of the FMD outbreak. A recent publication indicated collection samples from nasal swabs can be used for monitoring FMD in symptomatic cows. Therefore, the objectives of this study were to determine the FMD virus in asymptomatic dairy cattle using nasal swab samples during the absence of an FMD outbreak. The study was conducted from December 2020 to June 2021 using 185 asymptomatic signs of FMD dairy cattle in Chiang Mai Province, Thailand. By random cow selection, nasal mucosal swabs were used to collect samples from the selected cows and then were to evaluate the presence of FMD viruses using the real-time rt-PCR assay. In total, 4.9% of dairy cattle detected FMD virus, including 2 dairy farms in Mae-on (8 samples; 9.6%) and 1 farm in the Chai-Prakan district (1 sample; 1.2%). Interestingly, both farms in Mae-on were the outbreak of the FMD after this detection for 6 months. This indicated that the FMD virus presented in asymptomatic cattle might relate to the subsequent outbreak of FMD. The outbreak demonstrates the presence of the virus in the environment. In conclusion, monitoring of FMD can be performed by nasal swab collection. Further investigation is needed to show whether the FMD virus presented in asymptomatic FMD cattle could be the cause of the subsequent FMD outbreak or not.

Keywords: cattle, foot-and-mouth disease, nasal swab, real-time rt-PCR assay

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Authors: Nabil Omar, Farah Jibril, Oraib Amjad

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Purpose: Trabecatine is a is a potent marine-derived antineoplastic drug which binds to the minor groove of the DNA, bending DNA towards the major groove resulting in a changed conformation that interferes with several DNA transcription factors, repair pathways and cell proliferation. Trabectedin was approved by the European Medicines Agency (EMA; London, UK) for the treatment of adult patients with advanced stage soft tissue sarcomas in whom treatment with anthracyclines and ifosfamide has failed, or for those who are not candidates for these therapies. The recommended dosing regimen is 1.5 mg/m2 IV over 24 hours every 3 weeks. The purpose of this study was to comprehensively review available data on the safety and efficacy of trabectedin used as indicated for patients at a Tertiary Cancer Center at Qatar. Methods: A medication administration report generated in the electronic health record identified all patients who received trabectedin between November 1, 2015 and November 1, 2017. This retrospective chart review evaluated the indication of trabectedin use, compliance to administration protocol and the recommended monitoring parameters, number of patients improved on the drug and continued treatment, number of patients discontinued treatment due to side-effects and the reported side effects. Progress and discharged notes were utilized to report experienced side effects during trabectedin therapy. A total of 3 patients were reviewed. Results: Total of 2 out of 3 patients who received trabectedin were receiving it for non-FDA and non-EMA, approved indications; metastatic rhabdomyosarcoma and ovarian cancer stage IV with poor prognosis. And only one patient received it as indicated for leiomyosarcoma of left ureter with metastases to liver, lungs and bone. None of the patients has continued the therapy due to development of serious side effects. One patient had stopped the medication after one cycle due to disease progression and transient hepatic toxicity, the other one had disease progression and developed 12 % reduction in LVEF after 12 cycles of trabectedin, and the third patient deceased, had disease progression on trabectedin after the 10th cycle that was received through peripheral line which resulted in developing extravasation and left arm cellulitis requiring debridement. Regarding monitoring parameters, at baseline the three patients had ECHO, and Creatine Phosphokinase (CPK) but it was not monitored during treatment as recommended. Conclusion: Utilizing this medication as indicated with performing the appropriate monitoring parameters as recommended can benefit patients who are receiving it. It is important to reinforce the intravenous administration via central intravenous line, the re-assessment of left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan at 2- to 3-month intervals thereafter until therapy is discontinued, and CPK and LFTs levels prior to each administration of trabectedin.

Keywords: trabectedin, drug-use evaluation, safety, effectiveness, adverse drug reaction, monitoring

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Authors: Ali Fuad Ashour

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

Keywords: multiple sclerosis, Kuwait, exercise, demographic

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Authors: Mai M. Farid, Ximeng Yang, Tomoharu Kuboyama, Yuna Inada, Chihiro Tohda

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Intro: Trigonella foenum-graecum (Fenugreek), from Fabaceae family is a well-known plant traditionally used as food and medicine. Many pharmacological effects of Trigonella foenum- graecum seeds extract (TF extract) were evaluated such as anti-diabetic, anti-tumor and anti-dementia effects using in vivo models. Regarding the anti-dementia effects of TF extract, diabetic rats, aluminum chloride-induced amnesia rats and scopolamine-injected mice were used previously for evaluation, which are not well established as Alzheimer’s disease models. In addition, those previous studies, active constituents in TF extract for memory function were not identified. Method: This study aimed to clarify the effect of TF extract on Alzheimer’s disease model, 5XFAD mouse that overexpresses mutated APP and PS1 genes and determine the major active constituent in the brain after oral intake of TF extract. Results: Trigonelline was detected in the cerebral cortex of 5XFAD mice after 24 hours of oral administration of TF extract by LC-MS/MS. Oral administration of TF extract for 17 days improved object location memory in 5XFAD mice. Conclusion: These results suggest that TF extract and its active constituents could be an expected therapeutic candidate for Alzheimer’s disease.

Keywords: Alzheimer's disease, LC-MS/MS, memory recovery, Trigonella foenum-graecum Seeds, 5XFAD mice

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Authors: Angelis P. Barlampas

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Purpose: A 29 years old woman presented in the emergency department with psychiatric symptoms. The psychiatrist ordered a computed tomography scan as part of a general examination. Material and methods: The CT showed bilateral enlarged choroid plexus structures mimicking papillomata and situated in the trigones of the lateral ventricles. The left choroid plexus was heavily calcified, but the right one has no any obvious calcifications. Results: It is well kown that any brain mass can present with behavioral changes and even psychiatric symptomatology. Papillomata of the ventricular system have been described to cause psychotic episodes. According to literature, choroid plexus papillomas are seldom neuroepithelial intraventricular tumors, which are benign and categorized as WHO grade 1 tumors. They are more common in the pediatric population, but they can occur in the adults, too1. In addition, the distinction between choroid plexus papilloma and carcinoma is very difficult and impossible by imagine alone. It can only be implied with more advanced imaging, such as arterial spin labeling and MRI. The final diagnosis is, of course, after surgical excision. The usual location in adults is the fourth ventricle, but in children, it is the lateral ventricles. Their imaging appearance is that of a solid vascular tumor, which enhances intensely after the intravenous administration of contrast material. One out of fourth tumors presents speckled calcifications1. In our case, there are symmetrically sized masses at the trigones, and there are no calcifications in one of them, whereas the other one is grossly calcified. Also, there is no obvious hydrocephalus or any other evidence of increased intracranial pressure. General conclusions: When there is a new psychiatric patient, someone must undergo any possible examination, and of course, a brain CT study should be done to exclude any rare organic causes that may be responsible for the disease.

Keywords: phycosis, intraventricular masses, CT, brain calcifications

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Authors: Bárbara Durão, Pedro Almeida, David Ramilo, André Meneses, Rute Canejo-Teixeira

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The importance of quality of life (QoL) assessment in veterinary medicine is an integral part of patient care. This is especially true in cases of chronic diseases, such as chronic kidney disease (CKD), where the ever more advanced treatment options prolong the patient’s life. Whether this prolongment of life comes with an acceptable quality of life remains has been called into question. The aim of this study was to evaluate the relationship between CKD disease biomarkers and QoL in cats. Thirty-seven cats diagnosed with CKD and with no known concurrent illness were enrolled in an observational study. Through the course of several evaluations, renal biomarkers were assessed in blood and urine samples, and owners retrospectively described their cat’s quality of life using a validated instrument for this disease. Correlations between QoL scores (AWIS) and the biomarkers were assessed using Spearman’s rank test. Statistical significance was set at p-value < 0.05, and every serial sample was considered independent. Thirty-seven cats met the inclusion criteria, and all owners completed the questionnaire every time their pet was evaluated, giving a total of eighty-four questionnaires, and the average-weighted-impact-score was –0.5. Results showed there was a statistically significant correlation between the quality of life and most of 17 the studied biomarkers and confirmed that CKD has a negative impact on QoL in cats especially due to the management of the disease and secondary appetite disorders. To our knowledge, this is the attempt to assess the correlation between renal biomarkers and QoL in cats. Our results reveal a strong potential of this type of approach in clinical management, mainly in situations where it is not possible to measure biomarkers. Whilst health-related QoL is a reliable predictor of mortality and morbidity in humans; our findings can help improve the clinical practice in cats with CKD.

Keywords: chronic kidney disease, biomarkers, quality of life, feline

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Authors: Asrat M.Belachew, Tiago Pereira, Institute of Mathematics, Computer Sciences, Avenida Trabalhador São Carlense, 400, São Carlos, 13566-590, Brazil

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Infectious diseases are among the most prominent threats to human beings. They cause morbidity and mortality to an individual and collapse the social, economic, and political systems of the whole world collectively. Mathematical models are fundamental tools and provide a comprehensive understanding of how infectious diseases spread and designing the control strategy to mitigate infectious diseases from the host population. Modeling the spread of infectious diseases using a compartmental model of inhomogeneous populations is good in terms of complexity. However, in the real world, there is a situation that accounts for heterogeneity, such as ages, locations, and contact patterns of the population which are ignored in a homogeneous setting. In this work, we study how classical an SEIR infectious disease spreading of the compartmental model can be extended by incorporating the mobility of population between heterogeneous cities during an outbreak of infectious disease. We have formulated an SEIR multi-cities epidemic spreading model using a system of 4k ordinary differential equations to describe the disease transmission dynamics in k-cities during the day and night. We have shownthat the model is epidemiologically (i.e., variables have biological interpretation) and mathematically (i.e., a unique bounded solution exists all the time) well-posed. We constructed the next-generation matrix (NGM) for the model and calculated the basic reproduction number R0for SEIR-epidemic spreading model with cities mobility. R0of the disease depends on the spectral radius mobility operator, and it is a threshold between asymptotic stability of the disease-free equilibrium and disease persistence. Using the eigenvalue perturbation theorem, we showed that sending a fraction of the population between cities decreases the reproduction number of diseases in interconnected cities. As a result, disease transmissiondecreases in the population.

Keywords: SEIR-model, mathematical model, city mobility, epidemic spreading

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