Search results for: cardiovascular disorders

Authors: Faezah Shekh Abdullah, Mohd. Azizuddin Mohd. Yussof, Komathy Thiagarajan, Hasnoorina Husin, Noor Azreena Abd Aziz

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Polycystic ovary syndrome has been associated with multiple disorders such as endocrine disorder, metabolic syndrome, infertility, and endometrial cancer. Women with polycystic ovary syndrome (PCOS) are anticipated to develop three times more chances for endometrial cancer than women without PCOS. This study, therefore, was conducted to determine the association between polycystic ovary syndrome and endometrial cancer and to determine the cervical cytology features of PCOS. Patients attending the Subfertility Clinic of the National Population and Family Development Board were recruited and examined physically by medical practitioners. They were categorized into two groups; i) the PCOS group if they met Rotterdam Criteria 2004 and ii) the control group if they did not meet Rotterdam Criteria 2004. Cervical sampling was done on all patients via the Liquid-Based Cytology (LBC) method in the pre-and post-subfertility treatment. A total of 167 patients participated in the study, of which 79 belonged to the PCOS group and 88 to the control group. The findings showed no cervical and endometrial cancer cases in both groups. The Liquid-Based Cytology results in the PCOS group displayed more cases with cellular changes, i.e., benign inflammation, atrophic smear and Candida sp. infection. To conclude, no association was found between polycystic ovary syndrome and endometrial cancer. A more holistic study with a higher number of participants can further determine the association between endometrial cancer and PCOS. Furthermore, a longer duration between LBC pre- and post-subfertility treatment should be implied to observe changes in the cervical cells.

Keywords: endometrial cancer, liquid-based cytology, PCOS, polycystic ovary syndrome

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Authors: Sudhir Kumar, V. R. Sinha

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Water in oil topical microemulsions of 5-FU were developed and optimized using face centered central composite design. Topical w/o microemulsion of 5-FU were prepared using sorbitan monooleate (Span 80), polysorbate 80 (Tween 80), with different oils such as oleic acid (OA), triacetin (TA), and isopropyl myristate (IPM). The ternary phase diagrams designated the microemulsion region and face centered central composite design helped in determining the effects of selected variables viz. type of oil, smix ratio and water concentration on responses like drug content, globule size and viscosity of microemulsions. The CCD design exhibited that the factors have statistically significant effects (p<0.01) on the selected responses. The actual responses showed excellent agreement with the predicted values as suggested by the CCD with lower residual standard error. Similarly, the optimized values were found within the range as predicted by the model. Furthermore, other characteristics of microemulsions like pH, conductivity were investigated. For the optimized microemulsion batch, ex-vivo skin flux, skin irritation and retention studies were performed and compared with marketed 5-FU formulation. In ex vivo skin permeation studies, higher skin retention of drug and minimal flux was achieved for optimized microemulsion batch then the marketed cream. Results confirmed the actual responses to be in agreement with predicted ones with least residual standard errors. Controlled release of drug was achieved for the optimized batch with higher skin retention of 5-FU, which can further be utilized for the treatment of many dermatological disorders.

Keywords: 5-FU, central composite design, microemulsion, ternanry phase diagram

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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: Ramiro Quintanilla-Licea, Isvar K. Angeles-Hernandez, Javier Vargas-Villarreal

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Amebiasis caused by Entamoeba histolytica, associated with high morbidity and mortality, is currently a significant public health problem worldwide, especially in developing countries. In the world, around 50 million people develop this illness, and up to 100,000 deaths occur annually. Due to the side-effects and the resistance that pathogenic protozoa show against common antiparasitic drugs (e.g., metronidazole), growing attention has been paid to plants used in traditional medicine around the world to find new antiprotozoal agents. In this study is reported about the isolation and structure elucidation of antiamoebic compounds occurring in Lippia graveolens Kunth (Mexican oregano). The work-up of the methanol extract of L. graveolens afforded the known flavonoids pinocembrin (1), sakuranetin (2), cirsimaritin (3) and naringenin (4) by bioguided isolation using several chromatographic techniques. Structural elucidation of the isolated compounds was based on spectroscopic/spectrometric analyses (IR; 1H- and 13C-NMR; MS) and comparison with literature data. These compounds showed significant antiprotozoal activity against Entamoeba histolytica trophozoites using in vitro tests (positive control metronidazole IC50 0.205 µg/mL). The antiprotozoal activity of pinocembrin and naringenin (IC50 of 29.51 µg/mL and 28.85 µg/mL, respectively) was higher compared with sakuranetin (44.47 µg/mL) and with cirsimaritin (150.00 µg/mL), revealing that a 5,7-dihydroxylated A ring is essential for antiprotozoal activity. These research funds may validate the use of this plant in the traditional Mexican medicine for the treatment of some digestive disorders and can help to integrate the use of extracts of L. graveolens in the conventional and complementary medicine for the treatment of parasitic diseases.

Keywords: amoebiasis, antiprotozoal agents, bioguided isolation, infectious diseases

Procedia PDF Downloads 189

Authors: Angelis P. Barlampas

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The purpose of this study is to inform the reader, about the various applications of artificial intelligence (AI), in cardiac imaging. AI grows fast and its role is crucial in medical specialties, which use large amounts of digital data, that are very difficult or even impossible to be managed by human beings and especially doctors.Artificial intelligence (AI) refers to the ability of computers to mimic human cognitive function, performing tasks such as learning, problem-solving, and autonomous decision making based on digital data. Whereas AI describes the concept of using computers to mimic human cognitive tasks, machine learning (ML) describes the category of algorithms that enable most current applications described as AI. Some of the current applications of AI in cardiac imaging are the follows: Ultrasound: Automated segmentation of cardiac chambers across five common views and consequently quantify chamber volumes/mass, ascertain ejection fraction and determine longitudinal strain through speckle tracking. Determine the severity of mitral regurgitation (accuracy > 99% for every degree of severity). Identify myocardial infarction. Distinguish between Athlete’s heart and hypertrophic cardiomyopathy, as well as restrictive cardiomyopathy and constrictive pericarditis. Predict all-cause mortality. CT Reduce radiation doses. Calculate the calcium score. Diagnose coronary artery disease (CAD). Predict all-cause 5-year mortality. Predict major cardiovascular events in patients with suspected CAD. MRI Segment of cardiac structures and infarct tissue. Calculate cardiac mass and function parameters. Distinguish between patients with myocardial infarction and control subjects. It could potentially reduce costs since it would preclude the need for gadolinium-enhanced CMR. Predict 4-year survival in patients with pulmonary hypertension. Nuclear Imaging Classify normal and abnormal myocardium in CAD. Detect locations with abnormal myocardium. Predict cardiac death. ML was comparable to or better than two experienced readers in predicting the need for revascularization. AI emerge as a helpful tool in cardiac imaging and for the doctors who can not manage the overall increasing demand, in examinations such as ultrasound, computed tomography, MRI, or nuclear imaging studies.

Keywords: artificial intelligence, cardiac imaging, ultrasound, MRI, CT, nuclear medicine

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Authors: Patcharapa Thaweekul, Paskorn Sritipsukho

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Background: During the training period of the 6-year medical curriculum, medical students seem to have many risk behaviors of developing obesity. This study aims to demonstrate the prevalence and risk behavior of obesity and related metabolic disorders among the final-year medical students of Thammasat University as well as the change in nutritional status during studying program. Methods: 123 participants were asked to complete the self-report questionnaires. Weight, height, waist circumference and blood pressure were obtained. Blood samples were drawn for total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides and plasma glucose. Body weight and height of the medical students in the first year were obtained from the medical report at the entry. Results: The prevalence of overweight and obesity at the entry to medical school was 22.0% and increased to 30.1% in the final year. Two obese students (5.4%) was diagnosed as metabolic syndrome. During 6-year curriculum, the BMI gained in male medical students were more significant as compared to female students (1.76±1.74 and 0.43±1.82 kg/m2, respectively; p <.001). The current BMI is significantly correlated with the BMI at entry. Serum LDL-C in the overweight/obese students was significantly higher as compared to the normal weight and underweight group. Sleep deprivation was a significantly frequent behavior in the overweight/obese students. Conclusion: Medical students, as having high-risk behaviors, should be assessed for the nutritional status and metabolic parameters. Medical schools should promote the healthy behaviors to increase the healthy eating and exercise habits and reduced the risk behaviors among them.

Keywords: medical students, metabolic syndrome, obesity, risk behaviors

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Authors: Azadeh Rouhandeh, Chris Joslin, Zhen Qu, Yuu Ono

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The centre of rotation of the hip joint is needed for an accurate simulation of the joint performance in many applications such as pre-operative planning simulation, human gait analysis, and hip joint disorders. In human movement analysis, the hip joint center can be estimated using a functional method based on the relative motion of the femur to pelvis measured using reflective markers attached to the skin surface. The principal source of errors in estimation of hip joint centre location using functional methods is soft tissue artefacts due to the relative motion between the markers and bone. One of the main objectives in human movement analysis is the assessment of soft tissue artefact as the accuracy of functional methods depends upon it. Various studies have described the movement of soft tissue artefact invasively, such as intra-cortical pins, external fixators, percutaneous skeletal trackers, and Roentgen photogrammetry. The goal of this study is to present a non-invasive method to assess the displacements of the markers relative to the underlying bone using optical motion capture data and tissue thickness from ultrasound measurements during flexion, extension, and abduction (all with knee extended) of the hip joint. Results show that the artefact skin marker displacements are non-linear and larger in areas closer to the hip joint. Also marker displacements are dependent on the movement type and relatively larger in abduction movement. The quantification of soft tissue artefacts can be used as a basis for a correction procedure for hip joint kinematics.

Keywords: hip joint center, motion capture, soft tissue artefact, ultrasound depth measurement

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Authors: Farideh Doostan, Sahar Mohseni Taklloo, Mohammad Nosrati

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Chronic diseases are non-communicable and largely preventable by lifestyle changes including healthy diet consumption. They are the most common cause of death in the world and projected to increase by 15% globally between 2010 and 2020.The hazardous effects of behavioral and dietary risk factors on chronic disease have been established in prospective cohort studies and randomized trials. Because of some changes occur in college students’ lifestyle, assessment of dietary risk factors is important in these populations. Objective: This research was the first study that conducted to evaluate dietary intakes of Kermanian college students with WHO/FAO nutritional objectives. Material and Methods: In this descriptive cross-sectional study, 229 healthy college students of health faculty in Kerman University of Medical Sciences that do not intake any medical drugs were recruited using multistage sampling in 2013.Usual dietary intake was collected using a valid Food Frequency Questionnaire (FFQ) and diet quality was calculated based on WHO nutrient goals. To analysis of data between two groups, independent sample t. test and man whitney were applied. Results: Two hundred and twenty-nine college students; 151 females (65.9%) and 78 males (34.1%), the mean age of 21.9 years were studied. The mean of the Body Mass Index (Kg/m2) and Waist Circumference (cm) in males were 22.34 ±3.52 and 80.76±11.16 and in females were 21.19±2.62 and 73.67±7.65 respectively. Mean of daily cholesterol intake in males was significantly more than females (305±101 VS 268±98; P=0.008) and more than WHO/FAO recommendation (less than 300 mg/day). The mean of daily sodium intake in men and women were 10.4±1 and 10.9±5.3 respectively. These amounts were more than WHO/FAO recommendation (less than 2g/day). In addition, women were consumed fruit and vegetables more than men (839±336 VS 638±281; p ‹ 0.001) and these amounts were more than WHO/FAO recommendation (more than 400g/day) in both groups. Other intake indices were in the range of WHO/FAO recommendations, So that Percent of calories intake from total fat, saturated fatty acids, polyunsaturated fatty acids and added sugar were in compliance with WHO/FAO recommendations. Conclusion: Cholesterol intake in men and sodium intake in all participants were more than WHO/FAO recommendation. These dietary components are the most important causes of cardiovascular disease (one of the main causes of death in our population). These results indicated that proper nutritional education and interventions are needed in this population.

Keywords: college students, food intake, WHO /FAO nutrient intake goals, Kerman

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Authors: C. Chaillou

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The dominant theoretical approaches in Criminology are interested in the phenomenon of delinquency from the question of the management of the risks incurred by the population. Thus, this research advocate prevention of this phenomenon by a tracking of early disorders in children. Treatments offered to rely on medical research (genetics and biology are cited as a reference) and assuming a high naturalization of delinquent behaviour. Programs that are offered also reduce to a recovery of the deviant behaviour, and rely readily on behavioral guidelines, with an educational grant. Public policy then rely on these programs to prevent unwanted behaviour within a given population and to reduce the risk for the company. This is the case in France, with national institutes making (juvenile) violence a public health problem. We consider that other approaches, issues of sociology, are more relevant to the treatment of offenders. These approaches are moving, not on its prevention, but from its inputs and its outputs. Several modalities of entries and exits of delinquency can find and analyze in terms of process. We assume that there is a dynamic inherent in the individual and it is important to take into account the environment of the offender. These different types of processes can illuminate from the derived work of the Psychoanalytical psychopathology and lead to more effective treatment of delinquent acts. Psychoanalytic concepts have enabled us to offer a new look means to treat delinquency, placing several types of relationship with the other and relating to the clinical structure and the uniqueness of the case, we have been able to enter subjective and unconscious logics at work in delinquent acts. This research has facilitated the reduction of these types of subjective responses and proposed others, opening to a reintegration of offenders in a social link them being more favourable and in a longer term.

Keywords: delinquency, insertion, social link, unconscious

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Authors: Shweta Verma

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Background: Epilepsy is a chronic non-communicable central nervous system (CNS) disorder which affects a large population of all ages. Different classes of drugs are used for the treatment of this neurological disorder, but due to augmented drug resistance and side effects, these drugs become incompetent. Therefore, we design the synthesis of ten new derivatives of Phenytoin. The moiety of Phenytoin was hybridized with different phenols by using three step approach. The synthesized molecules were then investigated for different physicochemical parameters, such as Log P values using diverse software programs and to predict the potential to cross the blood-brain barrier. Objective: The Phenytoin derivatives were designed, synthesized, and characterized to meet the structural necessities indispensable for antiepileptic activity. Method: Firstly, the chloroacetylation of the 5,5-diphenyl hydantoin was carried out, and then various substituted phenols were added to it. The synthesized compounds were characterized and evaluated for antianxiety activity by elevated plus maze method and antiepileptic activity by using subcutaneous pentylenetetrazole (scPTZ) and maximal electroshock (MES) models and neurotoxicity. Result: The number of derivatives of 5,5-diphenyl hydantoin was developed and optimized. The number of parameters was optimized which reveal that the compound containing chloro group such as C3 and C6 showed imperative potential when compared with the standard drug Diazepam. Other compounds containing nitro and methyl group were also found to possess activity. Conclusion: It was summarized that the new compounds of 5,5-diphenyl hydantoin derivatives were synthesized. The results of the data show that the compound containing chloro group is more potent for CNS activity. The new compounds have the probability of being optimized further to engender new scaffolds to treat various CNS disorders.

Keywords: phenytoin, parameters, CNS activity, blood-brain barrier, Log P, CNS active

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Authors: Sara Zelman, Courtney Meyer, Hiren Patel, Lisa Philpotts, Sue Lahey, Thomas Burke

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Background: As the global burden of disease shifts from infectious diseases to noncommunicable diseases, there is growing urgency to provide treatment for time-sensitive illnesses, such as ST-Elevation Myocardial Infarctions (STEMIs). The standard of care for STEMIs in developed countries is Percutaneous Coronary Intervention (PCI). However, this is inaccessible in resource-limited settings. Before the discovery of PCI, Streptokinase (STK) and other thrombolytic drugs were first-line treatments for STEMIs. STK has been recognized as a cost-effective and safe treatment for STEMIs; however, in settings which lack access to PCI, it has not become the established second-line therapy. A systematic literature review was conducted to geographically map the use of STK for STEMIs in resource-limited settings. Methods: Our literature review group searched the databases Cinhal, Embase, Ovid, Pubmed, Web of Science, and WHO’s Index Medicus. The search terms included ‘thrombolytics’ AND ‘myocardial infarction’ AND ‘resource-limited’ and were restricted to human studies and papers written in English. A considerable number of studies came from Latin America; however, these studies were not written in English and were excluded. The initial search yielded 3,487 articles, which was reduced to 3,196 papers after titles were screened. Three medical professionals then screened abstracts, from which 291 articles were selected for full-text review and 94 papers were chosen for final inclusion. These articles were then analyzed and mapped geographically. Results: This systematic literature review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with 18 of 94 studies taking place in India. Furthermore, 13 studies occurred in Pakistan, followed by Iran (6), Sri Lanka (5), Brazil (4), China (4), and South Africa (4). Conclusion: Our systematic review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with the highest utilization occurring in India. This demonstrates that even though STK has high utility for STEMI treatment in resource-limited settings, it still has not become the standard of care. Future research should investigate the barriers preventing the establishment of STK use as second-line treatment after PCI.

Keywords: cardiovascular disease, global health, resource-limited setting, ST-Elevation Myocardial Infarction, Streptokinase

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Authors: Tünde Tifordiána Simonyi, Tímea Harmath-Tánczos

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The primary aim of the current research is to present the significance of a multicultural perspective in clinical neuropsychology and to present the test battery of the Multicultural Neuropsychological Scale (MUNS). The method includes the MUNS screening tool that involves stimuli common to most cultures in the world. The test battery measures general cognitive functioning focusing on five cognitive domains (memory, executive function, language, visual construction, and attention) tested with seven subtests that can be utilized within a wide age range (15-89), and lower and higher education participants. It is a scale that is sensitive to mild cognitive impairments. Our study presents the first results with the Hungarian translation of MUNS on a healthy sample. The education range was 4-25 years of schooling. The Hungarian sample was recruited by snowball sampling. Within the investigated population (N=151) the age curve follows an inverted U-shaped curve regarding cognitive performance with a high load on memory. Age, reading fluency, and years of education significantly influenced test scores. The sample was tested twice within a 14-49 days interval to determine test-retest reliability, which is satisfactory. Besides the findings of the study and the introduction of the test battery, the article also highlights its potential benefits for both research and clinical neuropsychological practice. The importance of adapting, validating and standardizing the test in other languages besides the Hungarian language context is also stressed. This test battery could serve as a helpful tool in mapping general cognitive functions in psychiatric and neurological disorders regardless of the cultural background of the patients.

Keywords: general cognitive functioning, multicultural, MUNS, neuropsychological test battery

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Authors: Ammar Alobaidy, Lamees Alsawafi, Malak Almawali, Balqees Alabri, Hajer Alhamrashdi

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Background: There is scarce data in the literature concerning the use of Arabic version neuron psychological cognitive tests in the geriatric age group of the Omani population. Objectives: Our aim is to obtain norms for normal elderly Omanis assessed by The Consortium to Establish a Registry for Alzheimer's disease (CERAD) neuro psychological battery and to compare these norms with other studies in the literature. Methods: 84 attendants and visitors of in-patients at Sultan Qaboos University Hospital, elder than 55 years, were interviewed. All participants were assessed by Dementia Rating Scale & Geriatric Depression Scale to ensure the integrity of their activities of daily living and the absence of depression, respectively. The performance of all participants in the CERAD battery was rated by a single rater to optimize the inter-rater reliability. Results: The cut-point for average performance in CERAD battery is dependent on the age, sex, and level of education and cannot be set as a single cut-point for all elderly Omanis. Conclusion: This study has shown the effect of age, sex, and level of education on the cognitive performance of normal elderly Omanis. The normative data obtained from this study can be utilized to differentiate between the cognitive decline of normal aging and the cognitive impairment due to various neuro cognitive disorders in the elderly Omanis, and probably culturally similar Arabic speaking communities.

Keywords: CERAD, neuropsychological battery, normal aging, elderly Omanis

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Authors: B. Bergström, A. Ladd, A. Jones, L. Rosso, P. Michael

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Attitudes toward treatment manuals serve as a meaningful predictor of general attitudes toward evidence-based practice. Despite demonstrating high effectiveness in treating many mental disorders, manualized treatments have been underutilized by practitioners. Thus, one can assess the state of the field regarding the adoption of evidence-based practices by surveying practitioner attitudes towards manualized treatments. This study is an adapted replication that assesses psychology graduate student attitudes towards manualized treatments, as a general marker for attitudes towards evidence-based practice. Training programs provide future clinicians with the foundation for critical skills in clinical practice. Research demonstrates that post-graduate continuing education has little to no effect on clinical practice; thus, graduate programs serve as the primary, and often final platform for all future practice. However, there are little empirical data identifying the attitudes and training of graduate students in utilizing manualized treatments. The empirical analysis of this study indicates an increase in positive attitudes among graduate student attitudes towards manualized treatments (within the United States), when compared to past surveys of professional psychologists. Findings from this study may inform graduate programs of barriers for students in developing positive attitudes toward manualized treatments and evidence-based practice. This study also serves as a preliminary predictor of the state-of-the field, in regards to professional psychologists attitudes towards evidence-based practice, if attitudes remain stable. This study indicates that the attitudes toward utilizing evidence-based practices, such as treatment manuals, has become more positive since year 2000.

Keywords: exposure therapy, evidence based practice, manualized treatments, student attitudes

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Authors: J. Nyenhuis, J. Drelich

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This research study was designed to determine if food crops could be bio-fortified with micro-nutrients by growing sprouts on mineral fortified fiber mats. Diets high in processed foods have been found to lack essential micro-nutrients for optimum human development and overall health. Some micro-nutrients such as copper (Cu) have been found to enhance the inflammatory response through its oxidative functions, thereby having a role in cardiovascular disease (CVD), metabolic syndrome (MetS), diabetes and related complications. Recycled cellulose fibers and clay saturated with micro-nutrient ions can be converted to a novel mineral-metal hybrid material in which the fiber mat becomes a carrier of essential micro-nutrients. The reduction of ionic to metallic copper was accomplished using hydrogen at temperatures ranging from 400o to 600oC. Copper particles with diameters ranging from ~1 to 400-500 nm reside on the recycled fibers that make up the mats. Seeds purchased from a commercial, organic supplier were germinated on the specially engineered cellulose fiber mats that incorporated w10 wt% clay fillers saturated with either copper particles or ionic copper. After the appearance of the first leaves, the sprouts were dehydrated and analyzed for Cu content. Nutrient analysis showed 1.5 to 1.6 increase in Cu of the sprouts grown on the fiber mats with copper particles, and 2.3 to 2.5 increase on mats with ionic copper as compared to the control samples. The antibacterial properties of materials saturated with copper ions at room temperature and at temperatures up to 400°C have been verified with halo method tests against Escherichia Coli in previous studies. E. coli is a known pathogenic risk in sprout production. Copper exhibits excellent antibacterial properties when tested on S. aureus, a pathogenic gram-positive bacterium. This has also been confirmed for the fiber-copper hybrid material in this study. This study illustrates the potential for the use of engineered mats as a viable way to increase the micro-nutrient composition of locally-grown food crops and the need for additional research to determine the uptake, nutritional implications and risks of micro-nutrient bio-fortification.

Keywords: bio-fortification, copper nutrient analysis, micro-nutrient uptake, sprouts and mineral-fortified mats

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Authors: Sayyed-javad Ziaolhagh, Ali-Reza Saadatifar

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Introduction: Athletes frequently perform anabolic steroid resistance exercise, but the effects of medical doses and abuse along with resistance exercise on structural damage to the Pancreases and also jujube extract are unknown. The aim of this study was to investigate the effects of resistance training on body weight and hip fractures induced by boldenone injection in male rats. Materials and methods: In this experimental study, 30 male Wistar rats aged 8-12 weeks (weight 202±9.34 g) were randomly divided into five groups: control, boldenone, extract of iujuba+boldenone, boldenone+resistance training and boldenone+resistance training +extract of jujuba. The resistance training program included climbing the ladder for 8 weeks, 3 days a week, 1 session training in a day and each session consisted of the 3 sets and 5 repetitions. Injection was conducted in depth in the hamstring once a week on an appointed day. After anesthesia, autopsy was performed, and the cardiac tissue was isolated. Results: Results showed that boldenone caused tissue damage, congestion, and nuclei unclear and diffuse. In the group "resistance + Boldenone," The Pancreases tissue showed a high degree of hyperemia, and the muscle cells were somewhat abnormal. In boldenone + jujube, the appearance of the tissue was normal, and the rejuvenating effect was visible. Conclusion: Boldenone appears to cause structural damage to the Pancreases tissue. Strength training with Jujube Extract can reduce part of the pancreatic system disorders (necrosis and inflammation) caused by anabolic steroid use.

Keywords: boldenone, Jujube extract, pancreases tissue, resistance training

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Authors: Mitra Shokrollahi, Mia Stanic, Anisha Hundal, Janet N. Y. Chan, Defne Urman, Chris A. Jordan, Anne Hakem, Roderic Espin, Jun Hao, Rehna Krishnan, Philipp G. Maass, Brendan C. Dickson, Manoor P. Hande, Miquel A. Pujana, Razqallah Hakem, Karim Mekhail

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Current models suggest that DNA double-strand breaks (DSBs) can move to the nuclear periphery for repair. It is unclear to what extent human DSBs display such repositioning. Here we show that the human nuclear envelope localizes to DSBs in a manner depending on DNA damage response (DDR) kinases and cytoplasmic microtubules acetylated by α-tubulin acetyltransferase-1 (ATAT1). These factors collaborate with the linker of nucleoskeleton and cytoskeleton complex (LINC), nuclear pore complex (NPC) protein NUP153, the nuclear lamina and kinesins KIF5B and KIF13B to generate DSB-capturing nuclear envelope tubules (dsbNETs). dsbNETs are partly supported by nuclear actin filaments and the circadian factor PER1 and reversed by kinesin KIFC3. Although dsbNETs promote repair and survival, they are also co-opted during poly (ADP-ribose) polymerase (PARP) inhibition to restrain BRCA1-deficient breast cancer cells and are hyper-induced in cells expressing the aging-linked lamin A mutant progerin. In summary, our results advance understanding of nuclear structure-function relationships, uncover a nuclear-cytoplasmic DDR and identify dsbNETs as critical factors in genome organization and stability.

Keywords: DNA damage response, genome stability, nuclear envelope, cancer, age-related disorders

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Authors: Andrei Pomana, Graham Brewer

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Autism is a lifelong developmental disorder that affects verbal and non-verbal communication, behaviour and sensory processing. As a result, people on the autism spectrum have a difficult time when confronted with environments that have high levels of sensory stimulation. This is often compounded by the inability to properly communicate their wants and needs to caregivers. The capacity for people with autism to integrate depends on their ability to at least tolerate highly stimulating public environments for short periods of time. The overall challenges that people on the spectrum and their caregivers face need to be established in order to properly create and assess methods to mitigate the effects of high stimulus public spaces. The paper aims to identify the challenges that people on the autism spectrum and their caregivers face in typical public environments. Nine experienced autism therapists have participated in a semi-structured interview regarding the challenges that people with autism and their caregivers face in public environments. The qualitative data shows that the unpredictability of events and the high sensory stimulation present in public environments, especially auditory, are the two biggest contributors to the difficulties that people on the spectrum face. If the stimuli are not removed in a short period of time, uncontrollable behaviours or 'meltdowns' can occur, which leave the person incapacitated and unable to respond to any outside input. Possible solutions to increase integration in public spaces for people with autism revolve around removing unwanted sensory stimulus, creating personalized barriers for certain stimuli, equipping people with autism with better tools to communicate their needs or to orient themselves to a safe location and providing a predictable pattern of events that would prepare individuals for tasks ahead of time.

Keywords: autism, built environment, meltdown, public environment, sensory processing disorders

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Authors: Ubaka Chukwuemeka Michael, Ukwe Chinwe Victoria

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Background: The use of antipsychotic monotherapy remains the standard for schizophrenic disorders so also a prescription switch from older typical to newer atypical classes of antipsychotics on the basis of better efficacy and tolerability. However, surveys on the quality of antipsychotic drug use and substitution in developing countries are very scarce. This study was intended to evaluate quality and factors that drive the prescription and substitution of antipsychotic drugs among schizophrenic patients visiting a regional psychiatric hospital. Methods: Case files of patients visiting a federal government funded Neuropsychiatric Hospital between July 2012 and July 2014 were systematically retrieved. Patient demographic characteristics, clinical details and drug management data were collected and subjected to descriptive and inferential data analysis to determine quality and predictors of utilization. Results: Of the 600 case files used, there were more male patients (55.3%) with an overall mean age of 33.7±14.4 years. Typical antipsychotic agents accounted for over 85% of prescriptions, with majority of the patients receiving more than 2 drugs in at least a visit (80.9%). Fluphenazine (25.2%) and Haloperidol (18.8%) were mostly given as antipsychotics for treatment initiation while Olazenpine (23.0%) and Benzhexol (18.3%) were the most currently prescribed antipsychotics. Nearly half (42%, 252/600) of these patients were switched from one class to another, with 34.5% (207/600) of them switched from typical to atypical drug classes. No demographic or clinical factors influenced drug substitutions but a younger age and being married influenced being prescribed a polypharmacy regimen (more than 2 drugs) and an injectable antipsychotic agent. Conclusion: The prevalence of antipsychotic polypharmacy and use of typical agents among these patients was high. However, only age and marital status affected the quality of antipsychotic prescriptions among these patients.

Keywords: antipsychotics, drug substitution, pharmacoepidemiology, polypharmacy

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Authors: Angeliki Vassila, Dimitrios Kalogeropoulos, Rania Rawashdeh, Nigel Hall, Najiha Rahman, Mark Fabian, Suresh Thulasidharan, Hossain Parwez

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Introduction: Necrotising scleritis is a severe form of scleritis and poses a significant threat to vision. It can manifest in various systemic autoimmune disorders, systemic vasculitis, or as a consequence of microbial infections. The objective of this study is to present a case of necrotizing scleritis associated with scleroderma, which was further complicated by a secondary Staphylococcus epidermidis infection. Methods: This is a retrospective analysis that examines the medical records of a patient who was hospitalised in the Eye Unit at University Hospital Southampton. Results: A 78-year-old woman presented at the eye casualty department of our unit with a two-week history of progressively worsening pain in her left eye. She received a diagnosis of necrotising scleritis and was admitted to the hospital for further treatment. It was decided to commence a three-day course of intravenous methylprednisolone followed by a tapering regimen of oral steroids. Additionally, a conjunctival swab was taken, and two days later, it revealed the presence of S. epidermidis, indicating a potential secondary infection. Given this finding, she was also prescribed topical (Ofloxacin 0.3% - four times daily) and oral (Ciprofloxacin 750mg – twice daily) antibiotics. The inflammation and symptoms gradually improved, leading to the patient being scheduled for a scleral graft and applying an amniotic membrane to cover the area of scleral thinning. Conclusions: Rheumatoid arthritis and granulomatosis with polyangiitis are the most commonly identifiable systemic diseases associated with necrotising scleritis. Although association with scleroderma is extremely rare, early identification and treatment are necessary to prevent scleritis-related complications.

Keywords: scleritis, necrotizing scleritis, scleroderma, autoimmune disease

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Authors: B. Sadek, N. Khan, D. Łażewska, K. Kieć-Kononowicz

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The effects of the non-imidazole histamine H3 receptor (H3R) antagonist DL77 in passive avoidance paradigm (PAP) and novel object recognition (NOR) task in MK801-induced cognitive deficits associated with schizophrenia (CDS) in adult male rats, and applying donepezil (DOZ) as a reference drug were investigated. The results show that acute systemic administration of DL77 (2.5, 5, and 10 mg/kg, i.p.) significantly improved MK801-induced (0.1 mg/kg, i.p.) memory deficits in PAP. The ameliorating activity of DL77 (5 mg/kg, i.p.) in MK801-induced deficits was partly reversed when rats were pretreated with the centrally-acting H2R antagonist zolantidine (ZOL, 10 mg/kg, i.p.) or with the antimuscarinic antagonist scopolamine (SCO, 0.1 mg/kg, i.p.), but not with the CNS penetrant H1R antagonist pyrilamine (PYR, 10 mg/kg, i.p.). Moreover, the memory enhancing effect of DL77 (5 mg/kg, i.p.) in MK801-induced memory deficits in PAP was strongly reversed when rats were pretreated with a combination of ZOL (10 mg/kg, i.p.) and SCO (1.0 mg/kg, i.p.). Furthermore, the significant ameliorative effect of DL77 (5 mg/kg, i.p.) on MK801-induced long-term memory (LTM) impairment in NOR test was comparable to the DOZ-provided memory-enhancing effect, and was abrogated when animals were pretreated with the histamine H3R agonist R-(α)-methylhistamine (RAMH, 10 mg/kg, i.p.). However, DL77(5 mg/kg, i.p.) failed to provide procognitive effect on MK801-induced short-term memory (STM) impairment in NOR test. In addition, DL77 (5 mg/kg) did not alter anxiety levels and locomotor activity of animals naive to elevated-plus maze (EPM), demonstrating that improved performances with DL77 (5 mg/kg) in PAP or NOR are unrelated to changes in emotional responding or spontaneous locomotor activity. These results provide evidence for the potential of H3Rs for the treatment of neurodegenerative disorders related to impaired memory function, e.g. CDS.

Keywords: histamine H3 receptor, antagonist, learning, memory impairment, passive avoidance paradigm, novel object recognition

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Authors: José Nogueira

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This research aims to analyze the impact of autism spectrum disorders (ASD) in families with children and youth (0-25 years) with ASD in Portugal. The impact will be evaluated on a multidimensional perspective, following the work on the concept of quality life from WHOQOL Group (UN). The study includes quantitative and qualitative methodology. It correlates statistical sources and other information with the data obtained through a survey of a sample of about 100 families with children/youth with ASD (October and November 2013). The results indicate a strong impact of autism on the quality of life for families in all study dimensions. The research shows a negative impact on quality of life for families in material and financial conditions, physical and emotional well-being, career progression, feelings of injustice, social participation and self-perception of happiness. The quality of life remained in the relationship with the family and the spouse, interpersonal relationships and beliefs about himself. The ASD improved the quality of life aspects such as interest, knowledge and exercise of rights on disability, autonomy to make decisions and be able to deal with stress. Other dimensions are contemplated: a detailed characterization of the child/young with ASD and all family members (household composition, relationship status, academic qualifications, occupation, income, and leisure) the impact of diagnosis in the family wellbeing, medical and therapeutic processes, school inclusion, public support, social participation, and the adequacy and implementation of legislation. The study evaluates also the strengths and weaknesses of the Portuguese public rehabilitation system and demonstrates how a good law-in-theory may not solve the problems of families in practice due to the allocation of insufficient public resources, both financial and human resources.

Keywords: autism, families, quality of life, autism spectrum disorder

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Authors: Katalin Gocze, Gabriella Kiss, Zsuzsanna Gurdan, Krisztian Kvell, Attila Trabert

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Introduction: On a worldwide scale running has become an increasingly popular leisure time activity during the past decade. Since the participation rate of women has risen significantly the aim of our study was to analyze the mental status, sleeping habits and the prevalence of depression among female runners. Methods: Cross-sectional analysis included the use of validated and globally used surveys for the comprehensive evaluation of insomnia (AIS), depression (BDI), exercise dependence (EDS) and exercise addiction (EAI). Recreational and amateur female runners participating at half-marathon events in Hungary were asked to take part in our pilot study. Results: Participants mean age was 42.03±9.03 years. The prevalence of imsomnia was 18.87%. 60.34% has worries regarding their weight and 43.1% think that they have an actual weight problem. 77.6% stated that their body weight has an influence on their mood. 2.7% displayed borderline clinical depression, the prevalence of mild mood disorders was 10.81%. 17.2% had previously problems with disordered eating. Participants had a mean total EDS score of 46.94±15.55 and a mean total of 13.49±3.80 on EAI. Component scores were the highest for tolerance (a need for increased amounts of exercise to achieve the desired effect or a diminished effect occurs with continued use of the same amount of exercise). Conclusion: Even tough running can help improve mental health, tackle depression and overcome adversity, athletes are at risk of experiencing psychological difficulties which have an impact on their physical perfomance as well. Further research can help initiate targeted educational and screening programs to ensure that female athletes find a path to emotional well-being.

Keywords: depression, eating disorder, exercise addiction, exercise dependence, insomnia, running

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Authors: Syrus Zimaze, George Nsimbe, Valley Mugwanya, Matiya Lule, Edgar Watson, Patrick Gwayambadde

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Physical inactivity is a growing global epidemic, also recognised as a major public health challenge. Globally, there are alarming rates of children reported with cardiovascular disease and obesity with limited interventions. In Sub Saharan Africa, there is limited information about involvement in physical activity especially among children aged 6 to 18 years. The aim of this study was to explore factors associated with involvement in physical activity among children in Uganda. Methods: We included all parents with children aged 6 to 18 years training with Excel Soccer Academy between January 2017 and June 2018. Physical activity definition was time spent participating in routine soccer training at the academy for more than 30 days. Each child's attendance was recorded, and parents provided demographic and social economic data. Data on predictors of physical activity involvement were collected using a standardized questionnaire. Descriptive statistics and frequency were used. Binary logistic regression was used at the multi variable level adjusting for education, residence, transport means and access to information technology. Results: Overall 356 parents were interviewed; Boys 318 (89.3%) engaged more in physical activity than girls. The median age for children was 13 years (IQR:6-18) and 42 years (IQR:37-49) among parents. The median time spent at the Excel soccer academy was 13.4 months (IQR: 4.6-35.7) Majority of the children attended formal education, p < 0.001). Factors associated with involvement in physical activity included: owning a permanent house compared to a rented house (odds ratio [OR] :2.84: 95% CI: 2.09-3.86, p < 0.0001), owning a car compared to using public transport (OR: 5.64 CI: 4.80-6.63, p < 0.0001), a parent having received formal education compared to non-formal education (OR: 2.93 CI: 2.47-3.46, p < 0.0001) and daily access to information technology (OR:0.40 CI:0.25-0.66, p < 0.001). Parent’s age and gender were not associated to involvement in physical activity. Conclusions: Socioeconomic factors were positively associated with involvement in physical activity with boys participating more than girls in soccer activities. More interventions are required geared towards increasing girl’s participation in physical activity and those targeting children from less privilege homes.

Keywords: physical activity, Sub-Saharan Africa, social economic factors, children

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Authors: Rahaf Alasiri, Tarek Alghamdi, Abdullah Zarkan

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Background: Due to measures such as school closure, social distancing, and virtual teaching during the pandemic, primary school children's psychological well-being is greatly affected. These measures have short and long-term consequences on the children's well-being and mental health. Identifying these consequences is important. Aim: This study aimed to evaluate mood and behavior changes in children who attended school virtually. Subjects and methods: This is a cross-sectional study conducted among children and their parents who visited the outpatient clinic. A self-administered questionnaire was given to the parents of children aged between 6 to 14 years. The questionnaire includes socio-demographic characteristics, Conor's modifies scale to assess the attention deficit hyperactivity disorder (ADHD) of children, and the parental stress scale (PSS) to assess the stress symptoms of the parents. Results: Of the 66 surveyed children, 60.6% were aged between 10 to 14 years old, with the female being dominant (77.3%). The most common medical condition was asthma (7.6%), and nearly two-thirds (63.6%) indicated good health conditions during the pandemic. There was a significant inverse correlation observed between ADHD score and PSS score (r=-0.387). No significant differences are in ADHD and PSS scores in relation to the socio-demographic characteristics of the children, including age, gender, and having an associated medical condition (p>0.05). Conclusion: During the pandemic, children who attended virtual classes did not seem to affect even with restrictions. Most children indicated good health conditions during the pandemic. However, it is surprising to know that in spite of children’s high spirits during the pandemic, their parents were seen to have an increased level of stress. Strategies to address parents’ psychological disorders during the pandemic are warranted.

Keywords: children's mood, COVID-19, ADHD, parental stress

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Authors: Anne Giles

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Trauma is generally defined as an experience, or multiple experiences, overwhelming a person's ability to cope. Over time, many people recover from the neurobiological, physical, and emotional effects of trauma on their own. For some people, however, troubling symptoms develop over time that can result in distress and disability. This cluster of symptoms is classified as Post-traumatic Stress Disorder (PTSD). People who meet the criteria for PTSD and other trauma-related disorder diagnoses often hold a set of understandable but unfounded beliefs about traumatic events that cause undue suffering. Becoming aware of unhelpful beliefs—termed "cognitive distortions"—and challenging them is the realm of Cognitive Behavior Therapy (CBT). A form of CBT found by researchers to be especially effective for PTSD is Cognitive Processing Therapy (CPT). Through the compassionate use of CPT, people identify, examine, challenge, and relinquish unhelpful beliefs, thereby reducing symptoms and suffering. Widely-held cultural beliefs can interfere with the progress of recovery from trauma-related disorders. Although highly revered, largely unquestioned, and often stabilizing, cultural beliefs can be founded in simplistic, dichotomous thinking, i.e., things are all right, or all wrong, all good, or all bad. The reality, however, is nuanced and complex. After studying examples of cultural beliefs from China and the United States and how these might interfere with trauma recovery, trauma counselors can help clients derive criteria for preserving helpful beliefs, discover, examine, and jettison unhelpful beliefs, reduce trauma symptoms, and live their lives more freely and fully.

Keywords: cognitive processing therapy (CPT), cultural beliefs, post-traumatic stress disorder (PTSD), trauma recovery

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Authors: Sachin K. Samuchiwal, Barbara Balestrieri, Amanda Paskavitz, Hannah Raff, Joshua A. Boyce

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IL-33, a recently discovered member of the IL-1 cytokine family, binds to the TLR/IL1R super family receptor ST2 and induces type 2 immune responses. IL-33 is constitutively expressed in structural cells at barrier sites such as skin, lung, and intestine, and also inducibly expressed by hematopoietic cells including macrophages. Stimulation of macrophages by Lipopolysaccharide (LPS) can induce de novo IL-33 expression, and also causes the production of prostaglandin-E2 (PGE2) via cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1 (mPGES-1). Because PGE2 can regulate macrophage functions through both autocrine and paracrine mechanisms, the potential interplay of endogenous PGE2 on IL-33 production was explored. Bone-marrow derived murine macrophages (bmMF) that lack either mPGES-1 or EP2 receptor expression were stimulated with LPS in the absence or presence of exogenous PGE2 along with pharmacological agonists and antagonists. The study results demonstrate that endogenous PGE2 markedly enhances LPS-induced IL-33 production by bmMFs via EP2 receptors. Moreover, exogenous PGE2 can amplify LPS-induced IL-33 expression dominantly by EP2 and partly by EP4 receptors by a pathway involving cAMP and exchange protein activated by cAMP (EPAC), but not protein kinase A (PKA). Though both IL-33 production and PGE2 generation in response to LPS require activation of both p38 MAPK and NF-κB, PGE2 did not influence this activation. In conclusion, it is demonstrated that endogenous PGE2 signaling through EP2 and EP4 receptors is a prerequisite for LPS-induced IL-33 production in bmMFs and the underlying cAMP mediated pathway involves EPAC. Since IL-33 is a critical pro-inflammatory cytokine in various pathological disorders, this PGE2-EP2/EP4-cAMP mediated pathway can be exploited to intervene in IL-33 driven pathologies.

Keywords: bone marrow macrophages, EPAC, IL-33, PGE2

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Authors: Dileep G., Akash Singh, Dalchand Ahirwar, Arkadeep Ghosh, Ashutosh Purohit, Gaurav Guleria, Kshatriya Om Prashant, Pushkar Patel, Saksham Kumar, Vanshaj Nathani, Vikas Dangi, Shubhajit Roy Chowdhury, Varun Dutt

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Transcranial direct current stimulation (tDCS) has shown promise as a novel approach to enhance cognitive performance and provide therapeutic benefits for various brain disorders. However, the exact underlying brain mechanisms are not fully understood. We conducted a study to examine the brain's functional changes when subjected to simultaneous tDCS and music (Indian classical raga). During the study, participants in the experimental group underwent a 20-minute session of tDCS at two mA while listening to music (raga) for a duration of seven days. In contrast, the control group received a sham stimulation for two minutes at two mA over the same seven-day period. The objective was to examine whether repetitive tDCS could lead to the formation of additional functional connections between the medial prefrontal cortex (the stimulated area) and the auditory cortex in comparison to a sham stimulation group. In this study, 26 participants (5 female) underwent pre- and post-intervention scans, where changes were compared after one week of either tDCS or sham stimulation in conjunction with music. The study revealed significant effects of tDCS on functional connectivity between the stimulated area and the auditory cortex. The combination of tDCS applied over the mPFC and music resulted in newly formed connections. Based on our findings, it can be inferred that applying anodal tDCS over the mPFC enhances functional connectivity between the stimulated area and the auditory cortex when compared to the effects observed with sham stimulation.

Keywords: fNIRS, tDCS, neuroplasticity, music

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Authors: Joanna Maj

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Body machine interfaces (BMIs) afford users a non-invasive way coordinate movement. Vibrotactile stimulation has been incorporated into BMIs to allow feedback in real-time and guide movement control to benefit patients with cognitive deficits, such as stroke survivors. To advance research in this area, we examined vibrational discrimination thresholds at four body locations to determine suitable application sites for future multi-channel BMIs using vibration cues to guide movement planning and control. Twelve healthy adults had a pair of small vibrators (tactors) affixed to the skin at each location: forearm, shoulders, torso, and knee. A "standard" stimulus (186 Hz; 750 ms) and "probe" stimuli (11 levels ranging from 100 Hz to 235 Hz; 750 ms) were delivered. Probe and test stimulus pairs could occur sequentially or simultaneously (timing). Participants verbally indicated which stimulus felt more intense. Stimulus order was counterbalanced across tactors and body locations. Probabilities that probe stimuli felt more intense than the standard stimulus were computed and fit with a cumulative Gaussian function; the discrimination threshold was defined as one standard deviation of the underlying distribution. Threshold magnitudes depended on stimulus timing and location. Discrimination thresholds were better for stimuli applied sequentially vs. simultaneously at the torso as well as the knee. Thresholds were small (better) and relatively insensitive to timing differences for vibrations applied at the shoulder. BMI applications requiring multiple channels of simultaneous vibrotactile stimulation should therefore consider the shoulder as a deployment site for a vibrotactile BMI interface.

Keywords: electromyography, electromyogram, neuromuscular disorders, biomedical instrumentation, controls engineering

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Authors: Ahmed M. Kabel, Maaly A. Abd Elmaaboud

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Scleroderma is one of the connective tissue disorders characterized by skin and systemic fibrosis. Its pathogenesis involves multiple interrelated processes of autoimmunity, vasculopathy, inflammation, and oxidative stress. This study was a trial to explore the possible ameliorative effects of sodium valproate on an experimental model of skin fibrosis induced by bleomycin. Forty male BALB/c mice were divided into four equal groups as follows: control group; bleomycin group; bleomycin + sodium valproate group, and sodium valproate group. Mice were assessed for their body weight every four days throughout the whole study. Skin tissues were used to evaluate the oxidative stress parameters, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin 15, and mammalian target of rapamycin (mTOR). Skin fibrosis was evaluated by measuring dermal thickness and staining the skin tissues with Masson trichrome stain. Also, the skin tissues were immunostained with alpha smooth muscle actin (α-SMA). Administration of sodium valproate to bleomycin-treated mice resulted in the restoration of the body weight with a significant decrease in the dermal thickness, amelioration of oxidative stress, suppression of TGF-β1 and mTOR expression, and significant reduction of the percentage of α-SMA immunostaining and the proinflammatory cytokine levels compared to mice treated with bleomycin alone. In conclusion, sodium valproate has an antifibrotic effect on skin fibrosis which may represent a beneficial therapeutic modality for the management of scleroderma.

Keywords: scleroderma, bleomycin, sodium valproate, skin fibrosis

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