Search results for: brain disorders

Authors: M. J. Pourvaghar, M. E. Bahram

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Obesity and overweight is one of the most common metabolic disorders in industrialized countries and in developing countries. One consequence of pathological obesity is cardiovascular disease and metabolic syndrome. Chemerin is an adipocyne that plays a role in the regulation of the adipocyte function and the metabolism of glucose in the liver and musculoskeletal system. Most likely, chemerin is involved in obesity-related disorders such as type 2 diabetes and cardiovascular disease. Aerobic exercises reduce the level of chemerin and cause macrophage penetration into fat cells and inflammatory factors. Several efforts have been made to clarify the cellular and molecular mechanisms of hypertrophy and muscular atrophy. Myostatin, a new member of the TGF-β family, is a transforming growth factor β that its expression negatively regulates the growth of the skeletal muscle; and the increase of this hormone has been observed in conditions of muscular atrophy. While in response to muscle overload, its levels decrease after the atrophy period, TGF-β is the most important cytokine in the development of skeletal muscle. Myostatin plays an important role in muscle control, and animal and human studies show a negative role of myostatin in the growth of skeletal muscle. Separation of myostatin from Golgi begins on the ninth day of the onset period and continues until birth at all times of muscle growth. Higher levels of myostatin are found in obese people. Resistance training for 10 weeks could reduce levels of plasma myostatin.

Keywords: chemerin, myostatin, obesity, physical activity

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Authors: Olusola Olalekan Elekofehinti, Isaac Gbadura Adanlawo, Joao Batista Teixeira Rocha

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We evaluated the potential neuroprotective effect of Phyllantus nuriri against Fe2+ and SNP induced oxidative stress in mitochondria of rats brain. Cellular viability was assessed by MTT reduction, reactive oxygen species (ROS) generation was measured using the probe 2,7-dichlorofluorescein diacetate (DCFH-DA). Glutathione content was measured using dithionitrobenzoic acid (DTNB). Fe2+ (10µM) and SNP (5µM) significantly decreased mitochondrial activity, assessed by MTT reduction assay, in a dose-dependent manner, this occurred in parallel with increased glutathione oxidation, ROS production and lipid peroxidation end-products (thiobarbituric acid reactive substances, TBARS). The co-incubation with methanolic extract of Phyllantus nuriri (10-100 µg/ml) reduced the disruption of mitochondrial activity, gluthathione oxidation, ROS production as well as the increase in TBARS levels caused by both Fe2+ and SNP in a dose dependent manner. HPLC analysis of the extract revealed the presence of gallic acid (20.54±0.01), caffeic acid (7.93±0.02), rutin (25.31±0.05), quercetin (31.28±0.03) and kaemferol (14.36±0.01). This result suggests that these phytochemicals account for the protective actions of Phyllantus nuriri against Fe2+ and SNP -induced oxidative stress. Our results show that Phyllantus nuriri consist important bioactive molecules in the search for an improved therapy against the deleterious effects of Fe2+, an intrinsic producer of reactive oxygen species (ROS), that leads to neuronal oxidative stress and neurodegeneration.

Keywords: Phyllantus niruri, neuroprotection, oxidative stress, mitochondria, synaptosome

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Authors: Evangelos Koumparoudis

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The definition of death is a deep philosophical question, and no single meaning can be ascribed to it. This essay focuses on the ontological, epistemological, and ethical aspects of death and dying in view of technological progress in information technology and biomedicine. It starts with the ad hoc 1968 Harvard committee that proposed that the criterion for the definition of death be irreversible coma and then refers to the debate over the whole brain death formula, emphasizing the integrated function of the organism and higher brain formula, taking consciousness and personality as essential human characteristics. It follows with the contribution of information technology in personalized and precision medicine and anti-aging measures aimed at life prolongation. It also touches on the possibility of the creation of human-machine hybrids and how this raises ontological and ethical issues that concern the “cyborgization” of human beings and the conception of the organism and personhood based on a post/transhumanist essence, and, furthermore, if sentient AI capable of autonomous decision-making that might even surpass human intelligence (singularity, superintelligence) deserves moral or legal personhood. Finally, there is the question as to whether death and dying should be redefined at a transcendent level, which is reinforced by already-existing technologies of “virtual after-” life and the possibility of uploading human minds. In the last section, I refer to the current (and future) applications of nanomedicine in diagnostics, therapeutics, implants, and tissue engineering as well as the aspiration to “immortality” by cryonics. The definition of death is reformulated since age and disease elimination may be realized, and the criterion of irreversibility may be challenged.

Keywords: death, posthumanism, infomedicine, nanomedicine, cryonics

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Authors: Takashi Kaburagi, Masashi Takenaka, Yosuke Kurihara, Takashi Matsumoto

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Major depressive disorder (MDD) is one of the most common mental illnesses today. It is believed to be caused by a combination of several factors, including stress. Stress can be quantitatively evaluated using the State-Trait Anxiety Inventory (STAI), one of the best indices to evaluate anxiety. Although STAI scores are widely used in applications ranging from clinical diagnosis to basic research, the scores are calculated based on a self-reported questionnaire. An objective evaluation is required because the subject may intentionally change his/her answers if multiple tests are carried out. In this article, we present a modified index called the “multi-channel Laterality Index at Rest (mc-LIR)” by recording the brain activity from a wider area of the frontal lobe using multi-channel functional near-infrared spectroscopy (fNIRS). The presented index aims to measure multiple positions near the F_pz defined by the international 10-20 system positioning. Using 24 subjects, the dependencies on the number of measuring points used to calculate the mc-LIR and its correlation coefficients with the STAI scores are reported. Furthermore, a simple linear regression was performed to estimate the STAI scores from mc-LIR. The cross-validation error is also reported. The experimental results show that using multiple positions near the Fpz will improve the correlation coefficients and estimation than those using only two positions.

Keywords: frontal lobe, functional near-infrared spectroscopy, state-trait anxiety inventory score, stress

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Authors: Zerihun Ketema Tadesse, Dabbu Suman Reddy

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Brain-Computer Interfaces (BCIs) give the possibility for disabled people to communicate and control devices. This work aims at developing steady-state visual evoked potential (SSVEP)-based BCI for patients with limb disabilities. In hospitals, devices like nurse emergency call devices, lights, and TV sets are what patients use most frequently, but these devices are operated manually or using the remote control. Thus, disabled patients are not able to operate these devices by themselves. Hence, SSVEP-based BCI system that can allow disabled patients to control nurse calling device and other devices is proposed in this work. Portable LED visual stimulator that flickers at specific frequencies of 7Hz, 8Hz, 9Hz and 10Hz were developed as part of this project. Disabled patients can stare at specific flickering LED of visual stimulator and Emotiv EPOC used to acquire EEG signal in a non-invasive way. The acquired EEG signal can be processed to generate various control signals depending upon the amplitude and duration of signal components. MATLAB software is used for signal processing and analysis and also for command generation. Arduino is used as a hardware interface device to receive and transmit command signals to the experimental setup. Therefore, this study is focused on the design and development of Steady-state visually evoked potential (SSVEP)-based BCI for limb disabled patients, which helps them to operate and control devices in the hospital room/wards.

Keywords: SSVEP-BCI, Limb Disabled Patients, LED Visual Stimulator, EEG signal, control devices, hospital room/wards

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Authors: Kyriacos Clerides, Panagiotis Herodotou, Constantina Polycarpou, Evagoras Xydas

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Background: Musculoskeletal disorders (MSDs) in the workplace is a very common problem in Europe which are caused by multiple risk factors. In recent years, wearable devices and exoskeletons for the workplace have been trying to address the various risk factors that are associated with strenuous tasks in the workplace. The logistics sector is a huge sector that includes warehousing, storage, and transportation. However, the task associated with logistics is not well-studied in terms of MSDs risk. This study was aimed at looking into the MSDs affecting workers of logistics companies. It compares the prevalence of MSDs among workers and evaluates multiple risk factors that contribute to the development of MSDs. Moreover, this study seeks to obtain user feedback on the adoption of exoskeletons in such a work environment. Materials and Methods: The study was conducted among workers in logistics companies in Nicosia, Cyprus, from July to September 2022. A set of standardized questionnaires was used for collecting different types of data. Results: A high proportion of logistics professionals reported MSDs in one or more other body regions, the lower back being the most commonly affected area. Working in the same position for long periods, working in awkward postures, and handling an excessive load, were found to be the most commonly reported job risk factor that contributed to the development of MSDs, in this study. A significant number of participants consider the back region as the most to be benefited from a wearable exoskeleton device. Half of the participants would like to have at least a 50% reduction in their daily effort. The most important characteristics for the adoption of exoskeleton devices were found to be how comfortable the device is and its weight. Conclusion: Lower back and posture were the highest risk factors among all logistics professionals assessed in this study. A larger scale study using quantitative analytical tools may give a more accurate estimate of MSDs, which would pave the way for making more precise recommendations to eliminate the risk factors and thereby prevent MSDs. A follow-up study using exoskeletons in the workplace should be done to assess whether they assist in MSD prevention.

Keywords: musculoskeletal disorders, occupational health, safety, occupational risk, logistic companies, workers, Cyprus, industrial exoskeletons, wearable devices

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Authors: Adel Khorramrouz, Monireh Ahmadi Bani, Ehsan Norouzi

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Background:-Due to the essential role of the foot in movement, foot disorders (FDs) have significant impacts on activity and quality of life. Many studies confirmed the association between FDs and demographic characteristics. On the other hand, recent advances in data collection and statistical analysis led to an increase in the volume of databases. Analysis of patient’s data through the decision tree can be used to explore the relationship between demographic characteristics and FDs. Significance of the study: This study aimed to investigate the relationship between demographic characteristics with common FDs. The second purpose is to better inform foot intervention, we classify FDs based on demographic variables. Methodologies: We analyzed 2323 subjects with pes-planus (PP), pes-cavus (PC), hallux-valgus (HV) and plantar-fasciitis (PF) who were referred to a foot therapy clinic between 2015 and 2021. Subjects had to fulfill the following inclusion criteria: (1) weight between 14 to 150 kilogram, (2) height between 30 to 220, (3) age between 3 to 100 years old, and (4) BMI between 12 to 35. Medical archives of 2323 subjects were recorded retrospectively and all the subjects examined by an experienced physician. Age and BMI were classified into five and four groups, respectively. 80% of the data were randomly selected as training data and 20% tested. We build a decision tree model to classify FDs using demographic characteristics. Findings: Results demonstrated 981 subjects from 2323 (41.9%) of people who were referred to the clinic with FDs were diagnosed as PP, 657 (28.2%) PC, 628 (27%) HV and 213 (9%) identified with PF. The results revealed that the prevalence of PP decreased in people over 18 years of age and in children over 7 years. In adults, the prevalence depends first on BMI and then on gender. About 10% of adults and 81% of children with low BMI have PP. There is no relationship between gender and PP. PC is more dependent on age and gender. In children under 7 years, the prevalence was twice in girls (10%) than boys (5%) and in adults over 18 years slightly higher in men (62% vs 57%). HV increased with age in women and decreased in men. Aging and obesity have increased the prevalence of PF. We conclude that the accuracy of our approach is sufficient for most research applications in FDs. Conclusion:-The increased prevalence of PP in children is probably due to the formation of the arch of the foot at this age. Increasing BMI by applying high pressure on the foot can increase the prevalence of this disorder in the foot. In PC, the Increasing prevalence of PC from women to men with age may be due to genetics and innate susceptibility of men to this disorder. HV is more common in adult women, which may be due to environmental reasons such as shoes, and the prevalence of PF in obese adult women may also be due to higher foot pressure and housekeeping activities.

Keywords: decision tree, demographic characteristics, foot disorders, machine learning

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Authors: John Toussaint

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Objective: Our society is suffering from an epidemic of body image dissatisfaction, and related disorders appear to be increasing globally for children. There is much to indicate that children's body image and eating attitudes are being affected negatively by socio-cultural factors such as parents, peers and media. Most studies and theories, however, have focused extensively on the daughter-mother relationship. Very few studies have investigated the role of attachment to the father as an important factor in the development of girls’ and women’s attitudes towards themselves and their bodies. Recently, data have shown that the father’s parenting style, as well as the quality of the relationship with him is crucial for the understanding of the development and persistence of body image disorders. This presentation is based on samples of participants with self-defined body image dissatisfaction, and the self-reported measures of their fathers’ parental behaviours, emotional warmth, support, or protection. Attachment theory does offer support in exploring these relationships and it is used in this presentation to assist in understanding the relationship between the father and his daughter in relation to body image and mental health. Clinical implications are also offered in respect to work with body image, eating disorders and relational therapy. Methods: As awareness of the increasing frequency of body image concerns in children grows, so too does the need for a simple, valid and reliable measure of body image. The Children's Body Image Scale (CBIS) designed in Australia, depicts seven male and females figures from which children are to choose their perceived body type and ideal body type. This was compared with a range of international body mass index (BMI) reference standards. These measures together with individual one-on-one interviews were completed by 158 children aged 7-12 years. Results: A high frequency of body image dissatisfaction was indicated in the children's responses. 55% of girls and 41% of boys said they would like to be thinner, and wished for an ideal BMI figure below the 10th percentile. This is an unhealthy and unattainable level of body fatness for the majority of children when considered in relation to the reported secular trend of their increasing average body size. Thin children were generally ranked as best and perceived as kind, happy, academically skilled, and socially successful. Fat children were perceived as unintelligent, lazy, greedy, unpopular, and unable to play physical games. Conclusions: Body image ideals and fat stereotypes are well entrenched among children. There is much to indicate that children's body image and eating attitudes are being affected negatively by sociocultural factors such as parents, peers and media. Teachers and health professionals could promote intervention programs for children involving knowledge and acceptance of genetic influences on body type; the dangerous effects of weight loss dieting; the importance of physical activity and eating healthy; and scepticism and critical analysis of mass media messages.

Keywords: body image, father attachment, mental health, eating disorders

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Authors: Mina Salamatmanesh, Elizabeth Fitzpatrick, Tim Ramsay, Josee Lagacé, Lindsey Sikora, JoAnne Whittingham

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Introduction: Hearing loss (HL) is one of the most common disorders that presents at birth and in early childhood. Universal newborn hearing screening (UNHS) has been adopted based on the assumption that with early identification of HL, children will have access to optimal amplification and intervention at younger ages, therefore, taking advantage of the brain’s maximal plasticity. One particular challenge for parents in the early years is achieving consistent hearing aid (HA) use which is critical to the child’s development and constitutes the first step in the rehabilitation process. This study examined the consistency of hearing aid use in young children based on data logging information documented during audiology sessions in the first three years after hearing aid fitting. Methodology: The first 100 children who were diagnosed with bilateral HL before 72 months of age since 2003 to 2015 in a pediatric audiology clinic and who had at least two hearing aid follow-up sessions with available data logging information were included in the study. Data from each audiology session (age of child at the session, average hours of use per day (for each ear) in the first three years after HA fitting) were collected. Clinical characteristics (degree of hearing loss, age of HA fitting) were also documented to further understanding of factors that impact HA use. Results: Preliminary analysis of the results of the first 20 children shows that all of them (100%) have at least one data logging session recorded in the clinical audiology system (Noah). Of the 20 children, 17(85%) have three data logging events recorded in the first three years after HA fitting. Based on the statistical analysis of the first 20 cases, the median hours of use in the first follow-up session after the hearing aid fitting in the right ear is 3.9 hours with an interquartile range (IQR) of 10.2h. For the left ear the median is 4.4 and the IQR is 9.7h. In the first session 47% of the children use their hearing aids ≤5 hours, 12% use them between 5 to 10 hours and 22% use them ≥10 hours a day. However, these children showed increased use by the third follow-up session with a median (IQR) of 9.1 hours for the right ear and 2.5, and of 8.2 hours for left ear (IQR) IQR is 5.6 By the third follow-up session, 14% of children used hearing aids ≤5 hours, while 38% of children used them ≥10 hours. Based on the primary results, factors like age and level of HL significantly impact the hours of use. Conclusion: The use of data logging information to assess the actual hours of HA provides an opportunity to examine the: a) challenges of families of young children with HAs, b) factors that impact use in very young children. Data logging when used collaboratively with parents, can be a powerful tool to identify problems and to encourage and assist families in maximizing their child’s hearing potential.

Keywords: hearing loss, hearing aid, data logging, hours of use

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Authors: Sule Yucelbas, Gulay Tezel, Cuneyt Yucelbas, Seral Ozsen

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In this study, it was tried to identify some heart rhythm disorders by electrocardiography (ECG) data that is taken from MIT-BIH arrhythmia database by subtracting the required features, presenting to artificial neural networks (ANN), artificial immune systems (AIS), artificial neural network based on artificial immune system (AIS-ANN) and particle swarm optimization based artificial neural network (PSO-NN) classifier systems. The main purpose of this study is to evaluate the performance of hybrid AIS-ANN and PSO-ANN classifiers with regard to the ANN and AIS. For this purpose, the normal sinus rhythm (NSR), atrial premature contraction (APC), sinus arrhythmia (SA), ventricular trigeminy (VTI), ventricular tachycardia (VTK) and atrial fibrillation (AF) data for each of the RR intervals were found. Then these data in the form of pairs (NSR-APC, NSR-SA, NSR-VTI, NSR-VTK and NSR-AF) is created by combining discrete wavelet transform which is applied to each of these two groups of data and two different data sets with 9 and 27 features were obtained from each of them after data reduction. Afterwards, the data randomly was firstly mixed within themselves, and then 4-fold cross validation method was applied to create the training and testing data. The training and testing accuracy rates and training time are compared with each other. As a result, performances of the hybrid classification systems, AIS-ANN and PSO-ANN were seen to be close to the performance of the ANN system. Also, the results of the hybrid systems were much better than AIS, too. However, ANN had much shorter period of training time than other systems. In terms of training times, ANN was followed by PSO-ANN, AIS-ANN and AIS systems respectively. Also, the features that extracted from the data affected the classification results significantly.

Keywords: AIS, ANN, ECG, hybrid classifiers, PSO

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Authors: Parvin Mirmiran, Zahra Bahadoran, Nazanin Moslehi, Fereidoun Azizi

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Background and aim: We aimed to investigate the effects of green fruits and vegetables (green FV) consumption on the 3-year changes of cardiometabolic risk factors. Methods: This longitudinal study was conducted in the framework of Tehran Lipid and Glucose Study, between 2006-2008 and 2009-2011, on 1272 adults. Dietary intake of green FV, including green cabbage, broccoli, lettuce, celery, green beans, green peas, cucumber, leafy vegetables, zucchini, green chili and bell pepper, and kiwi fruit, has been assessed by a validated semi-quantitative food frequency questionnaire at baseline and second examination. Demographics, anthropometrics and biochemical measures were evaluated at baseline and 3 years later. The associations of cardiometabolic risk changes with mean intake of green FV were estimated. Results: The mean age of men and women at baseline was 39.8±12.7 and 37.3±12.1 years, respectively. Mean intake of green FV was 152±77 g/d. More intake from green FV was accompanied to more intake of vitamin A, α and β-carotene, lutein, β-criptoxanthine, potassium, magnesium and fiber. Consumption of green FV was inversely associated with 3-year change of waist circumference (β= -0.07, P=0.01), total cholesterol (β= -0.11, P=0.01) and triglycerides (β= -0.13, P=0.01). Each 25 g/d increase in consumption of green FV decreased the incidence of hyper-triglyceridemia by 12% (OR:0.88, 95%CI:0.71-0.99) in men. In women, no significant association was observed between consumption of green FV with cardiometabolic risk factors. Conclusion: Higher consumption of green FV could have preventive effects against abdominal fat gain and lipid disorders.

Keywords: cardiometabolic risk factors, abdominal obesity, lipid disorders, fruits, vegetables

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Authors: Emílie Kučerová, Tereza Veverková, Marina Morozovová, Eva Kudová, Jitka Viktorová

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The blood-brain barrier (BBB) is a key element regulating the transport of substances between the blood and the central nervous system (CNS). The BBB protects the CNS from potentially harmful substances and maintains a suitable environment for nervous activity in the CNS, but at the same time, it represents a significant obstacle to the entry of drugs into the CNS. Pharmacoresistant epilepsy is a form of epilepsy that cannot be suppressed using two (or more) appropriately chosen antiepileptic drugs. In many cases, pharmacoresistant epilepsy is characterized by an increased concentration of efflux pumps on the luminal sides of the endothelial cells that form the BBB and an increased number of drug-metabolizing enzymes in the BBB cells, thereby preventing the effective transport of antiepileptic drugs into the CNS. Currently, a number of scientific groups are focusing on the preparation and improvement of BBB models in vitro in order to study cell interactions or transport mechanisms. However, in pathological conditions such as pharmacoresistant epilepsy, there are changes in BBB structure, and current BBB models are insufficient for related research. Our goal is to develop a suitable BBB model for pharmacoresistant epilepsy in vitro and use it to test the transfer of potential antiepileptic drugs. This model is created by co-culturing immortalized human cerebral microvascular endothelial cells, human vascular pericytes and immortalized human astrocytes. The BBB in vitro is cultivated in the form of a 2D transwell model and the integrity of the barrier is verified by measuring transendothelial electrical resistance (TEER). From the current results, a contact cell arrangement with the cultivation of endothelial cells on the upper side of the insert and the co-cultivation of astrocytes and pericytes on the lower side of the insert is selected as the most promising for BBB model cultivation. The pharmacoresistance of the BBB model is achieved by long-term cultivation of endothelial cells in an increasing concentration of selected antiepileptic drugs, which should lead to increased production of efflux pumps and drug-metabolizing enzymes. The pharmacoresistant BBB model in vitro will be further used for the screening of substances that could act both as antiepileptics and at the same time as inhibitors of efflux pumps in endothelial cells. This project was supported by the Technology Agency of the Czech Republic (TACR), Personalized Medicine: Translational research towards biomedical applications, No. TN02000109 and by the Academy of Sciences of the Czech Republic (AS CR) – grant RVO 61388963.

Keywords: antiepileptic drugs, blood-brain barrier, efflux transporters, pharmacoresistance

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Authors: Suphaket Saenthaweesuk, Nutiya Somparn, Atcharaporn Thewmore

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The present study aims to investigate the effects of Cymbopogon citratus, Stapf (CS) or lemon grass ethanol extract on antioxidant and vascular disorders parameters in rat. The CS ethanol extract was screened for its phytochemical contents and antioxidant activity in vitro. Moreover, the extract was studied in rats to evaluate its effects in vivo. Rats were orally administered with CS at 1,000 mg/kg/day for 30 days. Phytochemical screening of CS extract indicated the presence of tannins, flavonoids and phenolic compounds. The extract contained phenolic compounds 1,400.10 ± 0.47 mg of gallic acid equivalents per gram CS extract. The free radical scavenging activity assessed by DPPH assay gave IC50 of 168.77 ± 3.32µg/mL, which is relatively lower than that of BHT with IC50 of 12.34 ± 1.14 µg/mL. In the animals, the protein expression of antioxidant enzymes, γ-glutamylcysteine ligase (γ-GCL) in liver was significantly increased. This was consistent with elevation of serum catalase (CAT) and superoxide dismutase (SOD) activities. However, Protein expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule (ICAM-1) and endothelial nitric oxide synthase (eNOS) in heart and aorta were not differenced from normal control. Taken together, the present study provides evidence that CCS water extract exhibits direct antioxidant properties and can induce cytoprotective enzymes in vivo.

Keywords: antioxidant, Cymbopogon citratus Stapf, VCAM-1, γ-glutamylcysteine ligase

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Authors: Nenny Harijani, Dhandy Koesoemo Wardhana

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The aim of this study is to know the bacteriocin as antimicrobial activity produced by Lactic Acid Bacteria (LAB) as Antibacterial of Sub Clinic Mastitis on Dairy Cows. The antimicrobial is produced by LAB which isolates from cattle intestine can inhibit the growth Staphylococcus aureus, Steptocococcus agalactiae an Escherichia coli which were caused by dairy cattle subclinical mastitis. The failure of this bacteria growth was indicated by the formation of a clear zone surrounding the colonies on Brain Heart Infusion Agar plate. The bacteriocin was produced by Lactic Acid Bacteria (LAB) as antimicrobial, which could inhibit the growth of indicator bacteria Staphylococcus aureus, S.aglactiae and E.coli. This study was also developed bacteriocin to be used as a therapeutic of subclinical mastitis on dairy cows. The method used in this study was isolation, selection and identification of LAB using Mann Rogosa Sharp Medium, followed by characterization of the bacteriocin produced by LAB. The result of the study showed that bacteriocin isolated from beef cattle’s intestine could inhibit the growth Staphylococcus aureus, S. agalactiae, an Escherichia coli, which was indicated by clear zone surrounding the colonies on Brain Heart Infusion Agar plate. Characteristics of bacteriocin were heat-stable exposed to 80 0C for 30 minutes and 100 ⁰C for 15 minutes and inactivated by proteolytic enzymes such as trypsin. This approach has suggested the development of bacteriocin as a therapeutic agent for subclinical mastitis in dairy cattle.

Keywords: lactic acid bacteria, bacteriocin, staphylococcus aureus, S. agalactiae, E. coli, sub

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Authors: Dana Cassandra Winkler, Delia Leiding, Rene Bergs, Franziska Kaiser, Ramona Kirchhart, Ute Habel

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Background: Violence is a multidimensional phenomenon, affecting people of every age, socio-economic status and gender. Nevertheless, most studies primarily focus on men perpetrating women. Aim of the present study is to identify the likelihood of mental and somatic disorders and risk-taking behavior in male violence affected. In addition, the relationship between age of violence experience and the risk for health-related problems was analyzed. Method: On the basis of current evidence, a questionnaire was developed focusing on demographic background, health status, risk-taking behavior, and active and passive violence exposure. In total, 5221 males (Mean: 56,1 years, SD: 17,6) were consulted. To account for the time of violence experience in an efficient way, age clusters ‘0-12 years’, ‘13-20 years’, ‘21-35 years’, ‘36-65 years’ and ‘over 65 years’ were defined. A binary logistic regression was calculated to reveal differences in violence-affected and non-violence affected males regarding health and risk-taking factors. Males who experienced violence on a daily/ almost daily basis vs. males who reported violence occurrence once/ several times a month/ year were compared with respect to health factors and risk-taking behavior. Data of males, who indicated active and passive violence exposure, were analyzed by a chi²-analysis, to investigate a possible relation between the age of victimization and violence perpetration. Findings: Results imply that general violence experience, independent of active and passive violence exposure increases the likelihood in favor of somatic-, psychosomatic- and mental disorders as well as risk-taking behavior in males. Experiencing violence on a daily or almost daily basis in childhood and adolescence may serve as a predictor for increased health problems and risk-taking behavior. Furthermore, the violence experience and perpetration occur significantly within the same age cluster. This underlines the importance of a near-term intervention to minimize the risk, that victims become perpetrators later. Conclusion: The present study reveals predictors concerning health risk factors as well as risk-taking behavior in males with violence exposure. The results of this study may underscore the benefit of intervention and regular health care approaches in violence-affected males and underline the importance of acknowledging the overlap of violence experience and perpetration for further research.

Keywords: health disease, male, mental health, prevalence, risk-taking behavior, violence

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Authors: Dugeree Otgongerel, Kyong Jin Cho, Yu-Han Kim, Sangmee Ahn Jo

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Excessive activation of glutamate receptor is thought to be involved in retinal ganglion cell (RGC) death after ischemia- reperfusion damage. Glutamate carboxypeptidase II (GCPII) is an enzyme responsible for the synthesis of glutamate. Several studies showed that inhibition of GCPII prevents or reduces cellular damage in brain diseases. Thus, in this study, we examined the expression of GCPII in rat retina and the role of GCPII in acute high IOP ischemia-reperfusion damage of eye by using a GCPII inhibitor, 2-(phosphonomethyl) pentanedioic acid (2-PMPA). Animal model of ischemia-reperfusion was induced by raising the intraocular pressure for 60 min and followed by reperfusion for 3 days. Rats were randomly divided into four groups: either intra-vitreous injection of 2-PMPA (11 or 110 ng per eye) or PBS after ischemia-reperfusion, 2-PMPA treatment without ischemia-reperfusion and sham-operated normal control. GCPII immunoreactivity in normal rat retina was detected weakly in retinal nerve fiber layer (RNFL) and retinal ganglionic cell layer (RGL) and also inner plexiform layer (IPL) and outer plexiform layer (OPL) strongly where are co-stained with an anti-GFAP antibody, suggesting that GCPII is expressed mostly in Muller and astrocytes. Immunostaining with anti-BRN antibody showed that ischemia- reperfusion caused RGC death (31.5 %) and decreased retinal thickness in all layers of damaged retina, but the treatment of 2-PMPA twice at 0 and 48 hour after reperfusion blocked these retinal damages. GCPII level in RNFL layer was enhanced after ischemia-reperfusion but was blocked by PMPA treatment. This result was confirmed by western blot analysis showing that the level of GCPII protein after ischemia- reperfusion increased by 2.2- fold compared to control, but this increase was blocked almost completely by 110 ng PMPA treatment. Interestingly, GFAP immunoreactivity in the retina after ischemia- reperfusion followed by treatment with PMPA showed similar pattern to GCPII, increase after ischemia-reperfusion but reduction to the normal level by PMPA treatment. Our data demonstrate that increase of GCPII protein level after ischemia-reperfusion injury is likely to cause glial activation and/or retinal cell death which are mediated by glutamate, and GCPII inhibitors may be useful in treatment of retinal disorders in which glutamate excitotoxicity is pathogenic.

Keywords: glutamate carboxypepptidase II, glutamate excitotoxicity, ischemia-reperfusion, retinal ganglion cell

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Authors: Mohammadreza Ashouria, Majid Motamedzadeb

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Rapid Entire Body Assessment (REBA) and Quick Exposure Check (QEC) are two general methods to assess the risk factors of work-related musculoskeletal disorders (WMSDs). This study aimed to compare ergonomic risk assessment outputs from QEC and REBA in terms of agreement in distribution of postural loading scores based on analysis of working postures. This cross-sectional study was conducted in an engine oil company in which 40 jobs were studied. A trained occupational health practitioner observed all jobs. Job information was collected to ensure the completion of ergonomic risk assessment tools, including QEC, and REBA. The result revealed that there was a significant correlation between final scores (r=0.731) and the action levels (r =0.893) of two applied methods. Comparison between the action levels and final scores of two methods showed that there was no significant difference among working departments. Most of the studied postures acquired low and moderate risk level in QEC assessment (low risk=20%, moderate risk=50% and High risk=30%) and in REBA assessment (low risk=15%, moderate risk=60% and high risk=25%).There is a significant correlation between two methods. They have a strong correlation in identifying risky jobs and determining the potential risk for incidence of WMSDs. Therefore, there is a possibility for researchers to apply interchangeably both methods, for postural risk assessment in appropriate working environments.

Keywords: observational method, QEC, REBA, musculoskeletal disorders

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Authors: Alexander N. Savostyanov, Tatiana A. Dolgorukova, Elena A. Esipenko, Mikhail S. Zaleshin, Margherita Malanchini, Anna V. Budakova, Alexander E. Saprygin, Tatiana A. Golovko, Yulia V. Kovas

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EEG correlates of mathematical and trait anxiety level were studied in 52 healthy Russian-speakers during execution of error-recognition tasks with lexical, arithmetic and algebraic conditions. Event-related spectral perturbations were used as a measure of brain activity. The ERSP plots revealed alpha/beta desynchronizations within a 500-3000 ms interval after task onset and slow-wave synchronization within an interval of 150-350 ms. Amplitudes of these intervals reflected the accuracy of error recognition, and were differently associated with the three conditions. The correlates of anxiety were found in theta (4-8 Hz) and beta2 (16-20 Hz) frequency bands. In theta band the effects of mathematical anxiety were stronger expressed in lexical, than in arithmetic and algebraic condition. The mathematical anxiety effects in theta band were associated with differences between anterior and posterior cortical areas, whereas the effects of trait anxiety were associated with inter-hemispherical differences. In beta1 and beta2 bands effects of trait and mathematical anxiety were directed oppositely. The trait anxiety was associated with increase of amplitude of desynchronization, whereas the mathematical anxiety was associated with decrease of this amplitude. The effect of mathematical anxiety in beta2 band was insignificant for lexical condition but was the strongest in algebraic condition. EEG correlates of anxiety in theta band could be interpreted as indexes of task emotionality, whereas the reaction in beta2 band is related to tension of intellectual resources.

Keywords: EEG, brain activity, lexical and numerical error-recognition tasks, mathematical and trait anxiety

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Authors: Wafa Al Jabri

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Background: In Middle Eastern Islamic Countries (MEICs), there is a high prevalence of genetic blood disorders (GBDs), particularly sickle cell disease and thalassemia. The GBDs are considered a major public health concern, especially with the increase in affected populations along with the associated psychological, social, and financial cost of management. Despite the availability of premarital screening services (PSS) that aim to identify the asymptomatic carriers of GBDs and provide genetic counseling to couples in order toreduce the prevalence of these diseases; yet, the success rate of PSS is very low due to religious and socio-cultural concerns. Purpose: This paper aims to highlight the factors that affect the success of PSS in MEICs. Methods: A literature review of articles located in CINAHL, PubMed, SCOPUS, and MedLinewas carried out using the following terms: “premarital screening,” “success,” “effectiveness,” and “ genetic blood disorders.” Second, a hand search of the reference lists and Google searches were conducted to find studies that did not exist in the primary database searches. Only studies which are conducted in MEICs countries and published in the last five years were included. Studies that were not published in English were excluded. Results: Fourteen articles were included in the review. The results showed that PSS in most of the MEICs was successful in achieving its objective of identifying high-risk marriages; however, the service failed to meetitsultimate goal of reducing the prevalence of GBDs. Various factors seem to hinder the success of PSS, including poor public awareness, late timing of the screening, culture and social stigma, religious beliefs, availability of prenatal diagnosis and therapeutic abortion, emotional factors, and availability of genetic counseling services. However, poor public awareness, late timing of the screening, and unavailability of adequate counseling services were the most common barriers identified. Conclusion: Overcoming the identified barriers by providing effective health education programs, offering the screening test to young adults at an earlier stage, and tailoring the genetic counseling would be crucial steps to provide a framework for an effective PSS in MEICs.

Keywords: premarital screening, success, effectiveness, and genetic blood disorders

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Authors: Sushil Kumar Singh, Ashok Kumar, Ankit Ganeshpurkar, Ravi Singh, Devendra Kumar

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In spectrum of neurodegenerative diseases, Alzheimer’s disease (AD) is characterized by the presence of amyloid β plaques and neurofibrillary tangles in the brain. It results in cognitive and memory impairment due to loss of cholinergic neurons, which is considered to be one of the contributing factors. Donepezil, an acetylcholinesterase (AChE) inhibitor which also inhibits butyrylcholinesterase (BuChE) and improves the memory and brain’s cognitive functions, is the most successful and prescribed drug to treat the symptoms of AD. The present work is based on designing of the selective BuChE inhibitors using computational techniques. In this work, machine learning models were trained using classification algorithms followed by screening of diverse chemical library of compounds. The various molecular modelling and simulation techniques were used to obtain the virtual hits. The amide derivatives of 4-(phenylsulfonamido) benzoic acid were synthesized and characterized using 1H & 13C NMR, FTIR and mass spectrometry. The enzyme inhibition assays were performed on equine plasma BuChE and electric eel’s AChE by method developed by Ellman et al. Compounds 31, 34, 37, 42, 49, 52 and 54 were found to be active against equine BuChE. N-(2-chlorophenyl)-4-(phenylsulfonamido)benzamide and N-(2-bromophenyl)-4-(phenylsulfonamido)benzamide (compounds 34 and 37) displayed IC50 of 61.32 ± 7.21 and 42.64 ± 2.17 nM against equine plasma BuChE. Ortho-substituted derivatives were more active against BuChE. Further, the ortho-halogen and ortho-alkyl substituted derivatives were found to be most active among all with minimal AChE inhibition. The compounds were selective toward BuChE.

Keywords: Alzheimer disease, butyrylcholinesterase, machine learning, sulfonamides

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Authors: Nashalla Gwyn Nyinda

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The ancient system of Tibetan Medicine, known as Sowa Rigpa across the Himalayan regions, is a systematic system of healing encouraging balance primarily through diet and behavior modifications. With the rise of the popularity of Tibetan Medicine, compliance is critical to successful treatment outcomes. As patients learn more about who they are as individuals and how their elemental balances or imbalances affect disorders and mental-emotional balance, they develop faith and dedication to their healing process. Specifically, regarding diet and behavior and the basic principles of the medical system, patient compliance increases dramatically in all treatment areas when they understand why a treatment or dietary prescription guidance is effective. Successful responses to Tibetan treatment rely on a buy-in from the patient. Trust between the slower process of Traditional medicine treatments, the Tibetan physician and the patient is a cornerstone of treatment. The resulting decrease in the use of allopathic medicine and better health outcomes for acute and chronic disorders are well documented. This paper addresses essential points of the Tibetan Medicine system, dialogue between doctor and patient focused on appropriate and seasonal changing dietetics. Such fluctuating treatment approaches, based on external elemental factors, dramatically increase treatment outcomes. Specifically, this work addresses why allopathic medicine models may need more trust development between practitioner and patient.

Keywords: compliancy in treatment, diet and lifestyle medicine, nature and elements as medicine, seasonal diets, Sowa Rigpa, traditional Tibetan medicine, treatment outcomes

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Authors: Marc Toutain, Pascale Leconte, Antoine Gauthier

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Introduction: Eating Disorders (ED), such as anorexia, bulimia, and binge eating, are psychiatric illnesses that mostly affect young people. The main symptoms concern eating (restriction, excessive food intake) and weight control behaviors (laxatives, vomiting). Psychological comorbidities (depression, executive function disorders, etc.) and problematic behaviors toward physical activity (PA) are commonly associated with ED. Acquaintances on ED risk factors are still lacking, and more community sample studies are needed to improve prevention and early detection. To our knowledge, studies are needed to specifically investigate the link between ED risk level, PA, and psychological risk factors in a community sample of adolescents. The aim of this study is to assess the relation between ED risk level, exercise (type, frequency, and motivations for engaging in exercise), and psychological factors based on the Jacobi risk factors model. We suppose that a high risk of ED will be associated with the practice of high caloric cost PA, motivations oriented to weight and shape control, and psychological disturbances. Method: An online survey destined for students has been sent to several middle schools and colleges in northwest France. This survey combined several questionnaires, the Eating Attitude Test-26 assessing ED risk; the Exercise Motivation Inventory–2 assessing motivations toward PA; the Hospital Anxiety and Depression Scale assessing anxiety and depression, the Contour Drawing Rating Scale; and the Body Esteem Scale assessing body dissatisfaction, Rosenberg Self-esteem Scale assessing self-esteem, the Exercise Dependence Scale-Revised assessing PA dependence, the Multidimensional Assessment of Interoceptive Awareness assessing interoceptive awareness and the Frost Multidimensional Perfectionism Scale assessing perfectionism. Machine learning analysis will be performed in order to constitute groups with a tree-based model clustering method, extract risk profile(s) with a bootstrap method comparison, and predict ED risk with a prediction method based on a decision tree-based model. Expected results: 1044 complete records have already been collected, and the survey will be closed at the end of May 2022. Records will be analyzed with a clustering method and a bootstrap method in order to reveal risk profile(s). Furthermore, a predictive tree decision method will be done to extract an accurate predictive model of ED risk. This analysis will confirm typical main risk factors and will give more data on presumed strong risk factors such as exercise motivations and interoceptive deficit. Furthermore, it will enlighten particular risk profiles with a strong level of proof and greatly contribute to improving the early detection of ED and contribute to a better understanding of ED risk factors.

Keywords: eating disorders, risk factors, physical activity, machine learning

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Authors: Noor Ayuni Che Zakaria, Takashi Komeda, Cheng Yee Low, Kaoru Inoue, Fazah Akhtar Hanapiah

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Previous studies have shown that there are arguments regarding the reliability and validity of the Ashworth and Modified Ashworth Scale towards evaluating patients diagnosed with upper limb disorders. These evaluations depended on the raters’ experiences. This initiated us to develop an upper limb disorder part-task trainer that is able to simulate consistent upper limb disorders, such as spasticity and rigidity signs, based on the Modified Ashworth Scale to improve the variability occurring between raters and intra-raters themselves. By providing consistent signs, novice therapists would be able to increase training frequency and exposure towards various levels of signs. A total of 22 physiotherapists and occupational therapists participated in the study. The majority of the therapists agreed that with current therapy education, they still face problems with inter-raters and intra-raters variability (strongly agree 54%; n = 12/22, agree 27%; n = 6/22) in evaluating patients’ conditions. The therapists strongly agreed (72%; n = 16/22) that therapy trainees needed to increase their frequency of training; therefore believe that our initiative to develop an upper limb disorder training tool will help in improving the clinical education field (strongly agree and agree 63%; n = 14/22).

Keywords: upper limb disorder, clinical education tool, inter/intra-raters variability, spasticity, modified Ashworth scale

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Authors: Sudheer Moorkoth, Leslie Edward Lewis, Pragna Rao

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Newborn screening (NBS) is a part of routine newborn care in many countries worldwide to detect early any rare treatable conditions and inborn errors of metabolism (IEM). India has not started this program yet. In an attempt to understand the challenges in implementing a national newborn screening program in India, we initiated a pilot newborn screening project funded by the Government of Canada. Along with initiating the newborn screening at Kasturba Hospital, Manipal in South India, for screening six disorders (Congenital Hypothyroidism(CH), Congenital Adrenal Hyperplasia (CAH), Galactosemia, Biotinidase deficiency, Glucose-6-Phosphate Dehydrogenase deficiency (G-6PD) and Phenylketonurea), we also studied the awareness of various stakeholders on the newborn screening. In a period of nine months from August 2017 to March 2018 we could screen 1915 newborns (999 male and 916 female). The result showed that there were seven babies screened positive. This interim result points to an incidence rate of 1 in 270 children for these rare disorders collectively. This includes three confirmed cases of CH, two cases of G-6PD deficiency, and one case each for Galctosemia and CAH. A questionnaire based study to understand the awareness among various stakeholders revealed that there is little awareness among parents, adolescents and anganwadi workers (public health worker). The interim data points to the need for a national newborn screening programme in India. There is also an immediate need to undertake large-scale awareness programme to create knowledge on NBS among the various stakeholders.

Keywords: awareness, inborn errors of metabolism (IEM), newborn screening, rare disease

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Authors: Muhammad Bilal, Amelia Jane Llyod, Habsah Mohamad, Jia Hui Wong, Abdul Aziz Mohamed Yusoff, Jafri Malin Abdullah, Jingli Zhang

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Epilepsy is one of the major brain afflictions occurs with uncontrolled excitation of cortex; disturbed 50 million of world’s population. About 25 percent of patients subjected to adverse effects from antiepileptic drugs (AEDs) such as depression, nausea, tremors, gastrointestinal symptoms, osteoporosis, dizziness, weight change, drowsiness, fatigue are commonly observed indications; therefore, new drugs are required to cure epilepsy. GABA is principle inhibitory neurotransmitter, control excitation of the brain. Mutation or dysfunction of GABA receptor is one of the primary causes of epilepsy, which is confirmed from many acquired models of epilepsy like traumatic brain injury, kindling, and status epilepticus models of epilepsy. GABA receptor has 3 distinct types such as GABA (A), GABA (B), GABA(C).GABA (A) receptor has 20 different subunits, α1β2γ2 subunits composition of GABA (A) receptor is the most used combination of subunits for screening of compounds against epilepsy. We expressed α1β2γ2s subunits of GABA (A) Receptor in Xenopus leavis oocytes and examined the enhancement potential of 4-Hydroxybenzoic acid compound on GABA (A) receptor via two-electrode voltage clamp current recording technique. Bamboo shoots are the young, tender offspring of bamboo, which are usually harvested after a cultivating period of 2 weeks. Proteins, acids, fat, starch, carbohydrate, fatty acid, vitamin, dietary fiber, and minerals are the major constituent found systematically in bamboo shoots. These shoots reported to have anticancer, antiviral, antibacterial activity, also possess antioxidant properties due to the presence of phenolic compounds. Student t-test analysis suggested that 4- hydroxybenzoic acid positively allosteric GABA (A) receptor, increased normalized current amplitude to 1.0304±0.0464(p value 0.032) compared with vehicle. 4-Hydrobenzoic acid, a compound from Dendrocalamus Asper bamboo shoot gives new insights for future studies on bamboo shoots with motivation for extraction of more compounds to investigate their effects on human and rodents against epilepsy, insomnia, and anxiety.

Keywords: α1β2γ2S, antiepileptic, bamboo shoots, epilepsy GABA (A) receptor, two-microelectrode voltage clamp, xenopus laevis oocytes

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Authors: Himali Gunasekara, Baddika Jayaratne

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Haematological abnormalities are known to cause Ischemic Stroke or Transient Ischemic Attack (TIA). The identification of haematological correlates plays an important role in a management and secondary prevention. The objective of this study was to describe haematological correlates of stroke and their association between stroke profile. The haematological correlates screened were Lupus Anticoagulant, Dysfibroginemia, Paroxysmal nocturnal haemoglobinurea (PNH), Sickle cell disease, Systemic Lupus Erythematosis (SLE) and Myeloploriferative Neoplasms (MPN). A cross sectional descriptive study was conducted in a sample of 152 stroke patients referred to haematology department of National Hospital of Sri Lanka for thrombophilia screening. Different tests were performed to assess each hematological correlate. Diluted Russels Viper Venom Test and Kaolin clotting time were done to assess Lupus anticoagulant. Full blood count (FBC), blood picture, Sickling test and High Performance Liquid Chromatography were the tests used for detection of Sickle cell disease. Paroxysmal nocturnal haemoglobinurea was assessed by FBC, blood picture, Ham test and Flowcytometry. FBC, blood picture, Janus Kinase 2 (V617F) mutation analysis, erythropoietin level and bone marrow examination were done to look for the Myeloproliferative neoplasms. Dysfibrinogenaemia was assessed by TT, fibrinogen antigen test, clot observation and clauss test. Anti nuclear antibody test was done to look for systemic lupus erythematosis. Among study sample, 134 patients had strokes and only 18 had TIA. The recurrence of stroke/TIA was observed in 13.2% of patients. The majority of patients (94.7%) have had radiological evidence of thrombotic event. One fourth of patients had past thrombotic events while 12.5% had family history of thrombosis. Out of haematological correlates screened, Lupus anticoagulant was the commonest haematological correlate (n=16 ) and dysfibrigonaemia(n=11 ) had the next high prevalence. One patient was diagnosed with Essential thrombocythaemia and one with SLE. None of the patients were positive for screening tests done for sickle cell disease and PNH. The Haematological correlates were identified in 19% of our study sample. Among stroke profile only presence of past thrombotic history was statistically significantly associated with haematological disorders (P= 0.04). Therefore, hematological disorders appear to be an important factor in etiological work-up of stroke patients particularly in patients with past thrombotic events.

Keywords: stroke, transient ischemic attack, hematological correlates, hematological disorders

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Authors: Mariia A. Parfenenko, Ilya S. Dantsev, Sergei V. Bochenkov, Natalia V. Vinogradova, Olga S. Groznova, Victoria Yu. Voinova

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Introduction: Autism is the most common neurodevelopmental disorder. Autism is characterized by difficulties in social interaction and adherence to stereotypic behavioral patterns and frequently co-occurs with epilepsy, intellectual disabilities, connective tissue disorders, and other conditions. CHD8 codes for chromodomain-helicase-DNA-binding protein 8 - a chromatin remodeler that regulates cellular proliferation and neurodevelopment in embryogenesis. CHD8 is one of the genes most frequently involved in autism. Patients and methods: 2 unrelated male patients, P3 and P12, aged 3 and 12 years old, underwent whole genome sequencing, which determined that they both had different likely pathogenic variants, both previously undescribed in literature. Sanger sequencing later determined that P12 inherited the variant from his affected mother. Results: P3 and P12 presented with autism, a developmental delay, ataxia, sleep disorders, overgrowth, and macrocephaly, as well as other clinical features typically present in patients with causative variants in CHD8. The mother of P12 also has autistic traits, as well as ataxia, hypotonia, sleep disorders, and other symptoms. However, P3 and P12 also have different cardiac abnormalities. P3 had signs of a repolarization disorder: a flattened T wave in the III and aVF derivations and a negative T wave in the V1-V2 derivations. He also had structural valve anomalies with associated regurgitation, local contractility impairment of the left ventricular, and diastolic dysfunction of the right ventricle. Meanwhile, P12 had Wolff-Parkinson-White syndrome and underwent radiofrequency ablation at the age of 2 years. At the time of observation, P12 had mild sinus arrhythmia and an incomplete right bundle branch block, as well as arterial hypertension. Discussion: Cardiac abnormalities were not previously reported in patients with causative variants in CHD8. The underlying mechanism for the formation of those abnormalities is currently unknown. However, the two hypotheses are either a disordered interaction with CHD7 – another chromodomain remodeler known to be directly involved in the cardiophenotype of CHARGE syndrome – a rare condition characterized by coloboma, heart defects and growth abnormalities, or the disrupted functioning of CHD8 as an A-Kinase Anchoring Protein, which are known to modulate cardiac function. Conclusion: We observed 2 unrelated autistic males with likely pathogenic variants in CHD8 that presented with typical symptoms of CHD8-related neurodevelopmental disorder, as well as cardiac abnormalities. Cardiac abnormalities have, until now, been considered uncharacteristic for patients with causative variants in CHD8. Further accumulation of data, including experimental evidence of the involvement of CHD8 in heart formation, will elucidate the mechanism underlying the cardiophenotype of those patients. Acknowledgements: Molecular genetic testing of the patients was made possible by the Charity Fund for medical and social genetic aid projects «Life Genome.»

Keywords: autism spectrum disorders, chromodomain-helicase-DNA-binding protein 8, neurodevelopmental disorder, cardio phenotype

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Authors: Deepanjali Gurav, Kun Qian

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In-vitro metabolic diagnosis relies on designed materials-based analytical platforms for detection of selected metabolites in biological samples, which has a key role in disease detection and therapeutic evaluation in clinics. However, the basic challenge deals with developing a simple approach for metabolic analysis in bio-samples with high sample complexity and low molecular abundance. In this work, we report a designer plasmonic nanoshells based platform for direct detection of small metabolites in clinical samples for in-vitro metabolic diagnostics. We first synthesized a series of plasmonic core-shell particles with tunable nanoshell structures. The optimized plasmonic nanoshells as new matrices allowed fast, multiplex, sensitive, and selective LDI MS (Laser desorption/ionization mass spectrometry) detection of small metabolites in 0.5 μL of bio-fluids without enrichment or purification. Furthermore, coupling with isotopic quantification of selected metabolites, we demonstrated the use of these plasmonic nanoshells for disease detection and therapeutic evaluation in clinics. For disease detection, we identified patients with postoperative brain infection through glucose quantitation and daily monitoring by cerebrospinal fluid (CSF) analysis. For therapeutic evaluation, we investigated drug distribution in blood and CSF systems and validated the function and permeability of blood-brain/CSF-barriers, during therapeutic treatment of patients with cerebral edema for pharmacokinetic study. Our work sheds light on the design of materials for high-performance metabolic analysis and precision diagnostics in real cases.

Keywords: plasmonic nanoparticles, metabolites, fingerprinting, mass spectrometry, in-vitro diagnostics

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Authors: Muhsin Kizhisseri, Jorg Schluter, Saleh Gharie

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Atherosclerosis is the main reason of stroke, which is one of the deadliest diseases in the world. The carotid artery in the brain is the prominent location for atherosclerotic progression, which hinders the blood flow into the brain. The inclusion of computational fluid dynamics (CFD) into the diagnosis cycle to understand the hemodynamics of the patient-specific carotid artery can give insights into stroke prediction. Realistic outlet boundary conditions are an inevitable part of the numerical simulations, which is one of the major factors in determining the accuracy of the CFD results. The Windkessel model-based outlet boundary conditions can give more realistic characteristics of the distal vascular branches of the carotid artery, such as the resistance to the blood flow and compliance of the distal arterial walls. This study aims to find the most influential distal branches of the carotid artery by using the Windkessel model parameters in the outlet boundary conditions. The parametric study approach to Windkessel model parameters can include the geometrical features of the distal branches, such as radius and length. The incorporation of the variations of the geometrical features of the major distal branches such as the middle cerebral artery, anterior cerebral artery, and ophthalmic artery through the Windkessel model can aid in identifying the most influential distal branch in the carotid artery. The results from this study can help physicians and stroke neurologists to have a more detailed and accurate judgment of the patient's condition.

Keywords: stroke, carotid artery, computational fluid dynamics, patient-specific, Windkessel model, distal vascular branches

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Authors: Mona Hejazi, Ali Motie Nasrabadi

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Epilepsy is a persistent neurological disorder that affects more than 50 million people worldwide. Hence, there is a necessity to introduce an efficient prediction model for making a correct diagnosis of the epileptic seizure and accurate prediction of its type. In this study we consider how the Effective Connectivity (EC) patterns obtained from intracranial Electroencephalographic (EEG) recordings reveal information about the dynamics of the epileptic brain and can be used to predict imminent seizures, as this will enable the patients (and caregivers) to take appropriate precautions. We use this definition because we believe that effective connectivity near seizures begin to change, so we can predict seizures according to this feature. Results are reported on the standard Freiburg EEG dataset which contains data from 21 patients suffering from medically intractable focal epilepsy. Six channels of EEG from each patients are considered and effective connectivity using Directed Transfer Function (DTF) and Granger Causality (GC) methods is estimated. We concentrate on effective connectivity standard deviation over time and feature changes in five brain frequency sub-bands (Alpha, Beta, Theta, Delta, and Gamma) are compared. The performance obtained for the proposed scheme in predicting seizures is: average prediction time is 50 minutes before seizure onset, the maximum sensitivity is approximate ~80% and the false positive rate is 0.33 FP/h. DTF method is more acceptable to predict epileptic seizures and generally we can observe that the greater results are in gamma and beta sub-bands. The research of this paper is significantly helpful for clinical applications, especially for the exploitation of online portable devices.

Keywords: effective connectivity, Granger causality, directed transfer function, epilepsy seizure prediction, EEG

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