Search results for: disease severity

Authors: Fitim Sadiku, Mjellma Rexhepi, Kreshnik Grezda, Jonijana Sadiku Tigani, Merita Qorolli, Blerta Rexhepi-Kelmendi, Zelie Sadiku, Laura Cakolli

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Background: According to the European Alliance of Associations for Rheumatology (EULAR), biologics should be considered alongside traditional treatments in Ankylosing Spondylitis (AS) patients with persistently high disease activity that directly affects functional capacity. Unfortunately, Kosovo’s health system only offers continuous treatment with etanercept (ETN), and most of the patients with AS are referred to be treated with this biological substance. Objectives: This study aims to explore the relationship between comorbidity, disease activity, and functional capacity in AS patients undergoing ETN treatment in Kosovo. Methods: In this cross-sectional study, we included patients diagnosed with AS who were being treated with ETN 50mg per week for at least 6 months at the Rheumatology Clinic of the University Clinical Center of Kosovo. Patients under 18, pregnant women, and patients with spinal fractures were excluded. This study was approved by the Ethics Committee of the Faculty of Medicine, University of Prishtina and a consent form was signed by patients for participating in the study. We collected data (September-December 2023) about socio-demographics and disease history. Moreover, the presence of comorbidities was measured by the Comorbidity Charlson Index; the disease activity was measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS), and the functional capacity was measured by the Bath Ankylosing Spondylitis Functional Index (BASFI). Results: A total of 31 out of the 39 patients with AS receiving etanercept were included aged 18 to above 65 years (M= 40 years, SD= 14.39), and 87% were male. Diagnose delay was, on average, 7 years from the first symptoms (min-max= 0-24), while the disease duration on average was 7.5 years (min-max= 1- 50). Treatment duration with etanercept was from 0.5 to 6 years. The results indicate a significant positive correlation between comorbidity and BASFI (r= .615, p= .01) and disease activity. Additionally, a significant positive correlation exists between disease activity and BASFI (r= .507, p= .004). Regression analysis highlights the significance of both comorbidity and disease activity as predictors of patients’ functional capacity F (1, 29) = 10.047, p= .05 and F(1, 29) = 17.678, p= .01. No notable gender differences were observed. The study found no significant variations in comorbidity, disease activity, and functional capacity concerning the duration of ETN treatment. Conclusion: We found that in Kosovo, it takes at least 7 years for individuals to be diagnosed with AS from the first-time symptoms are experienced. This study showed that there is a positive correlation between comorbidity and functional capacity, disease activity and functional capacity in patients with AS undergoing etanercept treatment. Furthermore, results showed that comorbidity and disease activity are predictors of the functional status of the patients with AS receiving ETN. Gender and treatment duration with etanercept did not show any significant variations in these patients.

Keywords: ankylosing spondilitis, etanercept, physical wellbeing, comorbidities

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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: Guo Yu, Haoming Ma, Peiru Zhou

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BACKGROUND: In addition to hyperglycemia, hypoglycemia, and glycemic variability, a decrease in the time in the targeted blood glucose range (TIR) may be associated with an increased risk of death for critically ill patients. However, the relationship between the TIR and mortality may be influenced by the presence of diabetes and glycemic variability. METHODS: A total of 998 diabetic and non-diabetic patients with severe diseases in the ICU were selected for this retrospective analysis. The TIR is defined as the percentage of time spent in the target blood glucose range of 3.9–10.0 mmol/L within 24 hours. The relationship between TIR and in-hospital in diabetic and non-diabetic patients was analyzed. The effect of glycemic variability was also analyzed. RESULTS: The binary logistic regression model showed that there was a significant association between the TIR as a continuous variable and the in-hospital death of severely ill non-diabetic patients (OR=0.991, P=0.015). As a classification variable, TIR≥70% was significantly associated with in-hospital death (OR=0.581, P=0.003). Specifically, TIR≥70% was a protective factor for the in-hospital death of severely ill non-diabetic patients. The TIR of severely ill diabetic patients was not significantly associated with in-hospital death; however, glycemic variability was significantly and independently associated with in-hospital death (OR=1.042, P=0.027). Binary logistic regression analysis of comprehensive indices showed that for non-diabetic patients, the C3 index (low TIR & high CV) was a risk factor for increased mortality (OR=1.642, P<0.001). In addition, for diabetic patients, the C3 index was an independent risk factor for death (OR=1.994, P=0.008), and the C4 index (low TIR & low CV) was independently associated with increased survival. CONCLUSIONS: The TIR of non-diabetic patients during ICU hospitalization was associated with in-hospital death even after adjusting for disease severity and glycemic variability. There was no significant association between the TIR and mortality of diabetic patients. However, for both diabetic and non-diabetic critically ill patients, the combined effect of high TIR and low CV was significantly associated with ICU mortality. Diabetic patients seem to have higher blood glucose fluctuations and can tolerate a large TIR range. Both diabetic and non-diabetic critically ill patients should maintain blood glucose levels within the target range to reduce mortality.

Keywords: severe disease, diabetes, blood glucose control, time in targeted blood glucose range, glycemic variability, mortality

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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: 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: Ramkumar R., Gaurav Shinde, Pratik Shroff, Sachin Kumar Jain, Nagesh Walke

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Advancements in electric vehicles have significantly reduced the powertrain noise and moving components of vehicles. As a result, in-cab noises have become more noticeable to passengers inside the car. To ensure a comfortable ride for drivers and other passengers, it has become crucial to eliminate undesirable component noises during the development phase. Standard practices are followed to identify the severity of noises based on subjective ratings, but it can be a tedious process to identify the severity of each development sample and make changes to reduce it. Additionally, the severity rating can vary from jury to jury, making it challenging to arrive at a definitive conclusion. To address this, an automotive component was identified to evaluate squeak and rattle noise issue. Physical tests were carried out for random and sine excitation profiles. Aim was to subjectively assess the noise using jury rating method and objectively evaluate the same by measuring the noise. Suitable jury evaluation method was selected for the said activity, and recorded sounds were replayed for jury rating. Objective data sound quality metrics viz., loudness, sharpness, roughness, fluctuation strength and overall Sound Pressure Level (SPL) were measured. Based on this, correlation co-efficients was established to identify the most relevant sound quality metrics that are contributing to particular identified noise issue. Regression analysis was then performed to establish the correlation between subjective and objective data. Mathematical model was prepared using artificial intelligence and machine learning algorithm. The developed model was able to predict the subjective rating with good accuracy.

Keywords: BSR, noise, correlation, regression

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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: Ali Soroush, Mehdi Mirzaei Alavijeh, Touraj Ahmadi Jouybari, Fazel Zinat-Motlagh, Abbas Aghaei, Mari Ataee

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Diabetes is a disease with long cardiovascular, renal, ophthalmic and neural complications. It is prevalent all around the world including Iran, and its prevalence is increasing. The aim of this study was to determine the factors related to self-care behavior based on health belief model among sample of Iranian diabetic patients. This cross-sectional study was conducted among 301 type 2 diabetic patients in Gachsaran, Iran. Data collection was based on an interview and the data were analyzed by SPSS version 20 using ANOVA, t-tests, Pearson correlation, and linear regression statistical tests at 95% significant level. Linear regression analyses showed the health belief model variables accounted for 29% of the variation in self-care behavior; and perceived severity and perceived self-efficacy are more influential predictors on self-care behavior among diabetic patients.

Keywords: diabetes, patients, self-care behaviors, health belief model

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Authors: Suliman Khan, Rabeea Siddique, Mengzhou Xue

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Background: Patients with neurological disorders often display altered circadian rhythms. The disrupted circadian rhythms through chronic jetlag or shiftwork are thought to increase the risk and severity of human disease, including cancer, psychiatric, and related brain diseases. In this study, we investigated the impact of shiftwork or chronic jetlag (CJL) like conditions on mice’s brains. Transcriptome profiling based on RNA sequencing revealed that genes associated with serious neurological disorders were differentially expressed in the nucleus accumbens (NAc) and prefrontal cortex (PFC). According to the qPCR analysis, several key regulatory genes associated with neurological disorders were significantly altered in the NAc, PFC, hypothalamus, hippocampus, and striatum. Serotonin levels and the expression levels of serotonin transporters and receptors were significantly altered in mice treated with CJL. Overall, these results indicate that CJL may increase the risk of neurological disorders by disrupting the key regulatory genes, biological functions, serotonin, and corticosterone. These molecular linkages can further be studied to investigate the mechanism underlying CJL or shiftwork-mediated neurological disorders in order to develop treatment strategies.

Keywords: chronic jetlag, molecular profiles, brain disorders, circadian rhythms

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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: Soledad Carinelli, Iñigo Fernández, José Luis González-Mora, Pedro A. Salazar-Carballo

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Mastitis is the most relevant inflammatory disease in cattle, affecting the animal health and causing important economic losses on dairy farms. This disease takes place in the mammary gland or udder when some opportunistic microorganisms, such as Staphylococcus aureus, Streptococcus agalactiae, Corynebacterium bovis, etc., invade the teat canal. According to the severity of the inflammation, mastitis can be classified as sub-clinical, clinical and chronic. Standard methods for mastitis detection include counts of somatic cells, cell culture, electrical conductivity of the milk, and California test (evaluation of “gel-like” matrix consistency after cell lysed with detergents). However, these assays present some limitations for accurate detection of subclinical mastitis. Currently, haptoglobin, an acute phase protein, has been proposed as novel and effective biomarker for mastitis detection. In this work, an electrochemical biosensor based on polydopamine-modified magnetic nanoparticles (MNPs@pDA) for haptoglobin detection is reported. Thus, MNPs@pDA has been synthesized by our group and functionalized with hemoglobin due to its high affinity to haptoglobin protein. The protein was labeled with specific antibodies modified with alkaline phosphatase enzyme for its electrochemical detection using an electroactive substrate (1-naphthyl phosphate) by differential pulse voltammetry. After the optimization of assay parameters, the haptoglobin determination was evaluated in milk. The strategy presented in this work shows a wide range of detection, achieving a limit of detection of 43 ng/mL. The accuracy of the strategy was determined by recovery assays, being of 84 and 94.5% for two Hp levels around the cut off value. Milk real samples were tested and the prediction capacity of the electrochemical biosensor was compared with a Haptoglobin commercial ELISA kit. The performance of the assay has demonstrated this strategy is an excellent and real alternative as screen method for sub-clinical bovine mastitis detection.

Keywords: bovine mastitis, haptoglobin, electrochemistry, magnetic nanoparticles, polydopamine

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Authors: A. Gazdzinska, P. Jagielski, E. Kaniewska, S. P. Gazdzinski, M. Wylezol

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Background: In the multi-factor etiology of obesity, an increasing degree of importance is attributed to behavioral factors. Lifestyle and health-oriented behaviors heavily influence the treatment of multiple diseases, including obesity. However, only a few studies evaluated health-related behaviors exhibited by patients qualified for bariatric surgery. None of them was performed in Polish population. Aim: Assessment of health behaviors of obese patients according to the degree of mood disorders. Method: The study involved 93 patients (66 females) who were qualified for bariatric surgery in the Department of Surgery of the Military Institute of Aviation Medicine in Warsaw. Diagnostic instrument was the Juczynski’s Inventory of Health Behavior (HBI), which evaluates health behavior in four categories, i.e. proper nutrition habits (PNH), preventive behavior (PH), health practices (HP) and positive mental attitude (PMA). The average HBI falls in the range between 24 and 120 points, for each category of health behaviors fall between 1 and 5 (higher score means higher severity declared healthy behaviors). The depressive symptoms in patients were assessed with Beck Depression Inventory (BDI). All analyses were conducted using STATISTICA 12. Results: The average age was 44.2 ± 11.5 years, mean BMI was 44.3 ± 10.5 kg/m2 and 46.8 ± 7.6 kg/m2, in females and males respectively. According to BDI, 32% patients had mild level of depression, 10% moderate and 14% severe depression. BDI scores were not different between females and males. Low results with regard to the health behaviors declared were obtained by 35.5 % of patients, medium by 44.0%, while high ones by only 20.5%. On average, patients gained 3.28 points in PNH, 3.37 points in PH, 3.29 points in HP, while 3.42 in the PMA category, showing average intensity of these behaviors. These health behaviors were practiced significantly more often by women (p = 0.04). The average HBI was 80.2; with average score of 81.5 for females and 76.6 for males, respectively (p = 0.03). Women were better in the PNH category (p = 0.02). A positive correlation was found between age and all categories of health behaviors, in particular PNH (R = 0.38; p = 0.001), PH (R = 0.26; p = 0.01), HP (R = 0.27; p = 0.01) and PMA (R = 0.24; p = 0.02), independent of gender. The severity of depression had a significant impact only on the behaviors associated with proper eating habits, which saw a negative correlation between BDI scores and the PNH (R = -0.21; p = 0.04). Conclusions: Majority of morbidly obese patients qualified for bariatric surgery obtained low to average scores in health behavior questionnaire. However, these results are similar in comparison with the Polish adult population. In accordance to these results, it seems that healthy behaviors, among them eating behaviors, do not appear to be a cause of obesity epidemic or they might be acquired when the disease is already underway. Female gender and age had a positive effect, and depression had a negative effect on the level of health behaviors among patients qualified for bariatric surgery.

Keywords: depression, habits, health behaviours, obesity

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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: Gholam Reza Mirzaei

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This research aimed to investigate the effectiveness of acceptance and commitment therapy (ACT) in reducing corona disease anxiety in the staff working at Shahid Beheshti Hospital of Shiraz. The current research was a quasi-experimental study having pre-test and post-test with two experimental and control groups. The statistical population of the research included all the staff of Shahid Beheshti Hospital of Shiraz in 2021. From among the statistical population, 30 participants (N =15 in the experimental group and N =15 in the control group) were selected by available sampling. The materials used in the study comprised the Cognitive Emotion Regulation Questionnaire (CERQ) and Corona Disease Anxiety Scale (CDAS). Following data collection, the participants’ scores were analyzed using SPSS 20 at both descriptive (mean and standard deviation) and inferential (analysis of covariance) levels. The results of the analysis of covariance (ANCOVA) showed that acceptance and commitment therapy (ACT) is effective in reducing Corona disease anxiety (mental and physical symptoms) in the staff working at Shahid Beheshti Hospital of Shiraz. The effectiveness of acceptance and commitment therapy (ACT) on reducing mental symptoms was 25.5% and on physical symptoms was 13.8%. The mean scores of the experimental group in the sub-scales of Corona disease anxiety (mental and physical symptoms) in the post-test were lower than the mean scores of the control group.

Keywords: acceptance and commitment therapy, corona disease anxiety, hospital staff, Shiraz

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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: H. Kalboussi, A. Aloui, W. Boughattas, M. Maoua, A. Brahem, S. Chatti, O. El Maalel, F. Debbabi, N. Mrizak, Y. Ben Youssef, A. Khlif, I. Bougmiza

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Background: In recent decades, the incidence of children's hematological malignancies has been increasing worldwide including Tunisia. Their severity is reflected in the importance of the medical, social and economic impact. This increase remains fully unexplained, and the involvement of genetic, environmental and occupational factors is strongly suspected. Materials and Methods: Our study is a cross-sectional survey of the type case-control conducted in the University Hospital of Farhat Hached of Sousse during the period ranging between 1 July 2011 and 30 June 2012,and which included children with acute leukemia compared to children unharmed by neoplastic disease . Cases and controls were matched by age and gender. Our objective was to: - Describe the socio-occupational characteristics of the parents of children with acute leukemia. - Identify potential occupational factors implicated in the genesis of acute leukemia. Result: The number of acute leukemia cases in the Hematology Service and day hospital of the University Hospital of Farhat Hached during the study period was 66 cases divided into in 40 boys and 26 girls with a sex ratio of 1.53. Our cases and controls were matched by age and gender. The risk of incidence of leukemia in children from smoking fathers was higher (p = 0.02, OR = 2.24, IC = [1.11 - 4.52]). The risk of incidence of leukemia in children from alcoholic fathers was higher with p = 0,009, OR = 3.9; CI = [1.33 - 11.39]. After adjusting different variables, the difference persisted significantly with pa = 0.03 and ORa = 3.5; ICa = [1.09 -11.6]. 25.7 % of cases had a family history of blood disease and neoplasia, whereas no control presented that. The difference was statistically significant (p = 0.006), OR = 1.46, IC = [1.38 - 1.56]. The parental occupational exposures associated to the occurrence of acute leukemia in children were: - Pesticides with a statistically significant difference (p = 0.03), OR = 2.94, IC = [1.06 - 8.13]. This difference persisted after adjustment with different variables pa = 0.01, ORa 3.75; ICa = [1.27 - 11.03]. - Cement without a statistically non-significant difference (p = 0.2). This difference has become significant after adjustment with the different variables pa = 0.03; ORa = 2.67; ICa = [1.06 - 6.7]. Conclusion: Parental exposure to occupational risk factors may play a role in the pathogenesis of acute leukemia in children.

Keywords: hematological malignancies, children, parents, occupational exposure

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Authors: Osama Moustafa Zayed

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Aim of the work: To evaluate the effectiveness of venous glucose, levels of serum lactate and base deficit in polytraumatized patients as simple parameters to predict the mortality in these patients. Compared to the predictive value of Trauma and injury severity (TRISS) and Acute Physiology And Chronic Health Evaluation IV (APACHE IV). Introduction: Trauma is a serious global health problem, accounting for approximately one in 10 deaths worldwide. Trauma accounts for 5 million deaths per year. Prediction of mortality in trauma patients is an important part of trauma care. Several trauma scores have been devised to predict injury severity and risk of mortality. The trauma and injury severity score (TRISS) was most common used. Regardless of the accuracy of trauma scores, is based on an anatomical description of every injury and cannot be assigned to the patients until a full diagnostic procedure has been performed. So we hypothesized that alterations in admission glucose, lactate levels and base deficit would be an early and easy rapid predictor of mortality. Patient and Method: a comparative cross-sectional study. 282 Polytraumatized patients attended to the Emergency Department(ED) of the Suez Canal university Hospital constituted. The period from 1/1/2012 to 1/4/2013 was included. Results: We found that the best cut off value of TRISS probability of survival score for prediction of mortality among poly-traumatized patients is = 90, with 77% sensitivity and 89% specificity using area under the ROC curve (0.89) at (95%CI). APACHE IV demonstrated 67% sensitivity and 95% specificity at 95% CI at cut off point 99. The best cutoff value of Random Blood Sugar (RBS) for prediction of mortality was>140 mg/dl, with 89%, sensitivity, 49% specificity. The best cut off value of base deficit for prediction of mortality was less than -5.6 with 64% sensitivity, 93% specificity. The best cutoff point of lactate for prediction of mortality was > 2.6 mmol/L with 92%, sensitivity, 42% specificity. Conclusion: According to our results from all evaluated predictors of mortality (laboratory and scores) and mortality based on the estimated cutoff values using ROC curves analysis, the highest risk of mortality was found using a cutoff value of 90 in TRISS score while with laboratory parameters the highest risk of mortality was with serum lactate > 2.6 . Although that all of the three parameter are accurate in predicting mortality in poly-traumatized patients and near with each other, as in serum lactate the area under the curve 0.82, in BD 0.79 and 0.77 in RBS.

Keywords: APACHE IV, emergency department, polytraumatized patients, serum lactate

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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: Maja Pandža, Sanjin Lovrić, Iva Čolak, Josipa Mandarić, Miro Klarić

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This study explores the role of symptoms related to mood disorders salience on different types of defense mechanisms (mature, neurotic, immature) predominance. Total of 177 both clinical and non-clinical participants in Mostar, Bosnia & Herzegovina, completed a battery of questionnaires associated with defense mechanisms and self-reported depression and anxiety symptoms. The sample was additionally divided into four groups, given the level of symptoms experienced: 1. minimal, 2. mild, 3. moderate, 4. severe depression/anxiety. Participants with minimal anxiety and depression symptoms use mature defense mechanisms more often than other three groups. Immature mechanisms are most commonly used by the group with severe depression/anxiety levels in comparison with other groups. These differences are discussed on the dynamic level of analysis to have a better understanding of the relationship between defense mechanisms' maturity and degree of mood disorders' symptom severity. Also, results given could serve as an implication for the psychotherapeutic treatment plans.

Keywords: anxiety/depression symptoms, clinical/non-clinical sample, defense mechanism maturity, dynamic approach

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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: 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: Fatima Meirkhankyzy Shaizadina, Alua Oralovna Omarova, Praskovya Mikhailovna Britskaya, Nessipkul Oryntayevna Alysheva

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In recent years in the Republic of Kazakhstan there have been registered outbreaks of measles among the population. The objective of work was the analysis of outbreak of measles in 2014 among the population of North-Kazakhstan region of the Republic of Kazakhstan. For the analysis of the measles outbreak descriptive and analytical research, techniques were used and threshold levels of morbidity were calculated. The increase of incidence was noted from March to July. The peak was registered in May and made 9.0 per 100000 population. High rates were registered in April – 5.7 per 100000 population, and in June and July they made 5.7 and 3.1 respectively. Duration of the period of increase made 5 months. The analysis of monthly incidence of measles revealed spring and summer seasonality. Across the territory it was established that 69.2% of cases were registered in the city, 29.1% in rural areas and 1.7% of cases were brought in from other regions of Kazakhstan. The registered cases and threshold values of measles during the outbreak revealed that from 12 to 24 week, and also during the 40th week the cases exceeding the threshold levels are registered. Thus, for example, for the analyzed 1 week the number of the revealed patients made 4, which exceeds the calculated threshold value (3) by 33.3%. The data exceeding the threshold values confirm the emergence of a disease outbreak or the beginning of epidemic rise in morbidity. Epidemic rise in incidence of the population of North-Kazakhstan region was observed throughout 2014. The risk group includes 0-4 year-old children, who made 22.7%, 15-19 year-olds – 25.6%, 20-24 year-olds – 20.9%. The analysis of measles cases registration by gender revealed that women are registered 1.1 times more often than men. The ratio of women to men made 1:0.87. In social and professional groups often ill are unorganized children – 23.3% and students – 19.8%. Studying clinical manifestations of measles in the hospitalized patients, the typical beginning of a disease with expressed intoxication symptoms – weakness, sickliness was established. In individual cases expressed intoxication symptoms, hemorrhagic and dyspeptic syndromes, complications in the form of overlay of a secondary bacterial infection, which defined high severity of the illness, were registered both in adults and in children. The average duration of stay of patients in the hospital made 6.9 days. The average duration of time between date of getting the disease and date of delivery of health care made 3.6 days. Thus, the analysis of monthly incidence of measles revealed spring and summer seasonality, the peak of which was registered in May. Urban dwellers are ill more often (69.2%), while in rural areas people are ill more rarely (29.1%). Throughout 2014 an epidemic rise in incidence of the population of North-Kazakhstan region was observed. Risk group includes: children under 4 – 22.7%, 15-19 year-olds – 25.6%, 20-24 year-olds – 20.9%. The ratio of women and men made 1:0.87. The typical beginning of a disease in all hospitalized with the expressed intoxication symptoms – weakness, sickliness was established.

Keywords: epidemiological analysis, measles, morbidity, outbreak

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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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Authors: Camille Plant, Katherine McGill, Pek Ang

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Oncology patients face a host of unique challenges, which are physical, psychological and philosophical in nature. This preliminary study aimed to explore the psychiatric morbidity of oncology patients in an outpatient setting at a major public hospital in Australia. The study found that 33 patients were referred to a Psychiatrist by a Clinical Psychologist or treating Oncologist. These patients attended an outpatient Psychiatry appointment at the Calvary Mater Hospital, Newcastle, over a 7 month period (June 2017-January 2018). Of these, 45% went on to have a follow-up appointment. The Clinical Global Impressions Scale (CGI) was used to gather symptom severity scores at baseline and at follow-up. The CGI is a clinician determined instrument that provides an assessment of global functioning. It is comprised of two companion one-item measures: the CGI-Severity (CGI-S) rates mental illness severity, and the CGI-Improvement (CGI-I) rates change in condition or improvement from initiation of treatment. Patients referred to a Psychiatrist were observed to be on average in the Markedly ill approaching Severely ill range (CGI-S average of 5.5). However, those patients who attended a follow-up appointment were on average only Moderately Ill at baseline (CGI-S average of 3.9). Despite these follow patients not being severely mentally ill initially, the contact was helpful, as their CGI-S scores improved on average to the Mildly Ill range (CGI-S average of 2.8). A Mixed ANOVA revealed that there was a significant improvement in mental illness severity post-follow-up appointment (Greenhouse-Geisser .000). There was a near even proportion of males and females attending appointments (58% female), and slightly more females attended a follow-up (60% female). Males were on average more mentally ill at baseline compared to females at baseline (male average M=3.86, female average M=3.56), and males had a greater reduction in mental illness severity on average compared to females (male average M=2.71, female average 3.00). This was approaching significance (.073) and would be important to explore with a larger sample size. Change in clinical condition for follow-up patients was also recorded. It was found that more than half of patients (53%) were observed to experience Minimal improvement in attending at least one follow-up appointment. There was no change for 27% of patients, and there were no patients who were worse at follow up. As this was a preliminary study with small sample size, future research conducted could explore whether there are any significant gender differences, such as whether males experience the significantly greater reduction in symptoms of mental illness compared to females, as well as any effects of cancer stage or type on psychiatric outcomes. Future research could also investigate outcomes for those patients who concurrently access a Clinical Psychologist alongside the Psychiatrist. A limitation of the study is that the outcome measure is a brief item rating completed by the clinician.

Keywords: clinical global impressions scale, psychiatry, morbidity, oncology, outcomes, psychiatry

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Authors: Tarnai Tena, Strinić Dean

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Chronic non-communicable diseases are today the leading cause of mortality, morbidity and mortality disability at the world level and in Croatia. Among them are the most represented precisely cardiovascular diseases (CVD), so today we are talking about their global card epidemic. From 2018 to 2021, cardiovascular diseases are the leading cause of death for both women and men in the Dubrovnik- Neretva County. With regard to the COVID-19 pandemic, which has taken over, without forgetting how much these patients are additionally affected, we are still talking about the primary cause of sickness and death in the population of this county and region. In this record, we present collected data processed according to gender and disease classification. We also bring a kind of overview because, for years, we have been following how the population of one of the origins of the Mediterranean diet has been struggling with cardiovascular diseases.

Keywords: cardiovascular disease, burden, COVID-19, epidemiology, ishemic heart disease, cardiovascular medicine

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Authors: Hadi O. Tohme

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This study is a review on the effectiveness of new physiotherapy techniques with external sensory stimulus compared to standard physiotherapy in the daily activities of patients with Parkinson's disease. Twenty studies from 1996 to 2015 were analyzed and discussed in this review, using the rehabilitation strategy with external sensory stimulus evaluating walking, freezing episodes, balance, transfers, and daily activities of parkinsonian patients. The study highlights the effectiveness of the variety of rehabilitation with cueing strategy used in the treatment of Parkinson's disease. Based on the literature review completed, there is a need for more specific trials with better treatment strategies to support the most appropriate choice of physiotherapy intervention using external sensory stimulus to the type and frequency of this stimulus. In addition, no trials examined the long-term benefits of the physiotherapy intervention with the external sensory stimulus. In order to determine if, or how long the improvements due to the external sensory stimulus physiotherapy intervention can last, long-term follow-up should be performed.

Keywords: cueing strategy, external sensory stimulus, parkinson disease, rehabilitation for parkinson, sensory attention focused exercises, sensory strategy reeducation

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Authors: Aussara Panya, Nunghathai Sawasdee, Mutita Junking, Chatchawan Srisawat, Kiattawee Choowongkomon, Pa-Thai Yenchitsomanus

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Dengue virus (DENV) infection is a global public health problem with approximately 100 million infected cases a year. Presently, there is no approved vaccine or effective drug available; therefore, the development of anti-DENV drug is urgently needed. The clinical reports revealing the positive association between the disease severity and viral titer has been reported previously suggesting that the anti-DENV drug therapy can possibly ameliorate the disease severity. Although several anti-DENV agents showed inhibitory activities against DENV infection, to date none of them accomplishes clinical use in the patients. The surface envelope (E) protein of DENV is critical for the viral entry step, which includes attachment and membrane fusion; thus, the blocking of envelope protein is an attractive strategy for anti-DENV drug development. To search the safe anti-DENV agent, this study aimed to search for novel peptide inhibitors to counter DENV infection through the targeting of E protein using a structure-based in silico design. Two selected strategies has been used including to identify the peptide inhibitor which interfere the membrane fusion process whereby the hydrophobic pocket on the E protein was the target, the destabilization of virion structure organization through the disruption of the interaction between the envelope and membrane proteins, respectively. The molecular docking technique has been used in the first strategy to search for the peptide inhibitors that specifically bind to the hydrophobic pocket. The second strategy, the peptide inhibitor has been designed to mimic the ectodomain portion of membrane protein to disrupt the protein-protein interaction. The designed peptides were tested for the effects on cell viability to measure the toxic to peptide to the cells and their inhibitory assay to inhibit the DENV infection in Vero cells. Furthermore, their antiviral effects on viral replication, intracellular protein level and viral production have been observed by using the qPCR, cell-based flavivirus immunodetection and immunofluorescence assay. None of tested peptides showed the significant effect on cell viability. The small peptide inhibitors achieved from molecular docking, Glu-Phe (EF), effectively inhibited DENV infection in cell culture system. Its most potential effect was observed for DENV2 with a half maximal inhibition concentration (IC50) of 96 μM, but it partially inhibited other serotypes. Treatment of EF at 200 µM on infected cells also significantly reduced the viral genome and protein to 83.47% and 84.15%, respectively, corresponding to the reduction of infected cell numbers. An additional approach was carried out by using peptide mimicking membrane (M) protein, namely MLH40. Treatment of MLH40 caused the reduction of foci formation in four individual DENV serotype (DENV1-4) with IC50 of 24-31 μM. Further characterization suggested that the MLH40 specifically blocked viral attachment to host membrane, and treatment with 100 μM could diminish 80% of viral attachment. In summary, targeting the hydrophobic pocket and M-binding site on the E protein by using the peptide inhibitors could inhibit DENV infection. The results provide proof of-concept for the development of antiviral therapeutic peptide inhibitors to counter DENV infection through the use of a structure-based design targeting conserved viral protein.

Keywords: dengue virus, dengue virus infection, drug design, peptide inhibitor

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