Search results for: clinical pathway
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4301

Search results for: clinical pathway

2021 Effect of Risperidone and Haloperidol on Clinical Picture and Some Biochemical Parameters of Schizophrenic Libyan Patients

Authors: Mabruka S. Elashheb, Adullah Ali Bakush

Abstract:

Schizophrenia is referred to as a disorder, not a disease, because there has not been any clear, reliable, and specific etiological factor. Even if schizophrenia is not a very frequent disease, it is among the most burdensome and costly illnesses worldwide. Prevention of relapse is a major goal of maintenance treatment in patients with psychotic disorders. We performed a comparison of a newer, atypical antipsychotic drug, Risperidone, and an older, conventional neuroleptic drug, Haloperidol, in terms of the effect on the usual kidney and liver functions and negative and positive symptoms in patients with schizophrenia and schizoaffective disorder after three and five weeks of their treatments. It is apparent from the comparative data of Haloperidol and Risperidone treatments in schizophrenic patients that Resperidone had superior improvement of negative and positive symptoms of patients, no harmful effect on liver and kidney functions and greater efficacy and faster recovery from schizophrenic symptoms in patients. On the basis of our findings of the present study, we concluded that treatment with Risperidone is superior to Haloperidol in reducing the risk of relapse among outpatients with schizophrenic disorders.

Keywords: schizophrenia, Haloperidol, Risperidone, positive and negative symptom

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2020 Phases of Marital Conflict among Married Kuwaiti Women

Authors: Hend Almaseb

Abstract:

Gottman proposed a model of marital conflict with three phases: Agenda-Building, Arguing, and Negotiation. Among a sample of 520 married Kuwaiti women, this study examined the relationship between these phases and the following demographic variables: Level of education, Family income, Health, Occupation, and Tribal affiliation. In addition, the study 1) investigated the marital conflict phases the participants reported having experienced or are currently experiencing and 2) identified the variables that predict one of these conflict phases. The results showed a significant relationship between the following: 1) the Agenda-Building phase and Health; 2) the Arguing phase and Family income, Occupation, and Tribal Affiliation; and 3) the Negotiation phase and Level of education. In addition, a linear regression shows a substantial correlation between the two predictor variables (Level of education and Health problems) and the Agenda Building and Negotiation phases and 5) another substantial correlation between Family income and Arguing.

Keywords: clinical social work, Kuwait, marital conflict, women

Procedia PDF Downloads 164
2019 Dizziness in the Emergency: A 1 Year Prospective Study

Authors: Nouini Adrâa

Abstract:

Background: The management of dizziness and vertigo can be challenging in the emergency department (ED). It is important to rapidly diagnose vertebrobasilar stroke (VBS), as therapeutic options such as thrombolysis and anticoagulation require prompt decisions. Objective: This study aims to assess the rate of misdiagnosis in patients with dizziness caused by VBS in the ED. Methods and Results: The cohort was comprised of 82 patients with a mean age of 55 years; 51% were women and 49% were men. Among dizzy patients, 15% had VBS. We used Cohen’s kappa test to quantify the agreement between two raters – namely, emergency physicians and neurologists – regarding the causes of dizziness in the ED. The agreement between emergency physicians and neurologists is low for the final diagnosis of central vertigo disorders and moderate for the final diagnosis of VBS. The sensitivity of ED clinal examination for benign conditions such as BPPV was low at 56%. The positive predictive value of the ED clinical examination for VBS was also low at 50%. Conclusion: There is a substantial rate of misdiagnosis in patients with dizziness caused by VBS in the ED. To reduce the number of missing diagnoses of VBS in the future, there is a need to train emergency physicians in neuro vestibular examinations, including the HINTS examination for acute vestibular syndrome (AVS) and the Dix-Hallpike (DH) maneuver for episodic vestibular syndrome. Using video head impulse tests could help reduce the rate of misdiagnosis of VBS in the ED.

Keywords: dizziness, vertigo, vestibular disease, emergency

Procedia PDF Downloads 56
2018 Investigating Sediment-Bound Chemical Transport in an Eastern Mediterranean Perennial Stream to Identify Priority Pollution Sources on a Catchment Scale

Authors: Felicia Orah Rein Moshe

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Soil erosion has become a priority global concern, impairing water quality and degrading ecosystem services. In Mediterranean climates, following a long dry period, the onset of rain occurs when agricultural soils are often bare and most vulnerable to erosion. Early storms transport sediments and sediment-bound pollutants into streams, along with dissolved chemicals. This results in loss of valuable topsoil, water quality degradation, and potentially expensive dredged-material disposal costs. Information on the provenance of fine sediment and priority sources of adsorbed pollutants represents a critical need for developing effective control strategies aimed at source reduction. Modifying sediment traps designed for marine systems, this study tested a cost-effective method to collect suspended sediments on a catchment scale to characterize stream water quality during first-flush storm events in a flashy Eastern Mediterranean coastal perennial stream. This study investigated the Kishon Basin, deploying sediment traps in 23 locations, including 4 in the mainstream and one downstream in each of 19 tributaries, enabling the characterization of sediment as a vehicle for transporting chemicals. Further, it enabled direct comparison of sediment-bound pollutants transported during the first-flush winter storms of 2020 from each of 19 tributaries, allowing subsequent ecotoxicity ranking. Sediment samples were successfully captured in 22 locations. Pesticides, pharmaceuticals, nutrients, and metal concentrations were quantified, identifying a total of 50 pesticides, 15 pharmaceuticals, and 22 metals, with 16 pesticides and 3 pharmaceuticals found in all 23 locations, demonstrating the importance of this transport pathway. Heavy metals were detected in only one tributary, identifying an important watershed pollution source with immediate potential influence on long-term dredging costs. Simultaneous sediment sampling at first flush storms enabled clear identification of priority tributaries and their chemical contributions, advancing a new national watershed monitoring approach, facilitating strategic plan development based on source reduction, and advancing the goal of improving the farm-stream interface, conserving soil resources, and protecting water quality.

Keywords: adsorbed pollution, dredged material, heavy metals, suspended sediment, water quality monitoring

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2017 Robot-Assisted Learning for Communication-Care in Autism Intervention

Authors: Syamimi Shamsuddin, Hanafiah Yussof, Fazah Akhtar Hanapiah, Salina Mohamed, Nur Farah Farhan Jamil, Farhana Wan Yunus

Abstract:

Robot-based intervention for children with autism is an evolving research niche in human-robot interaction (HRI). Recent studies in this area mostly covered the role of robots in the clinical and experimental setting. Our previous work had shown that interaction with a robot pose no adverse effects on the children. Also, the presence of the robot, together with specific modules of interaction was associated with less autistic behavior. Extending this impact on school-going children, interactions that are in-tune with special education lessons are needed. This methodological paper focuses on how a robot can be incorporated in a current learning environment for autistic children. Six interaction scenarios had been designed based on the existing syllabus to teach communication skills, using the Applied Behavior Analysis (ABA) technique as the framework. Development of the robotic experience in class also covers the required set-up involving participation from teachers. The actual research conduct involving autistic children, teachers and robot shall take place in the next phase.

Keywords: autism spectrum disorder, ASD, humanoid robot, communication skills, robot-assisted learning

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2016 A Study on Urine Flow Characteristics in Ureter with Fluid-Structure Interaction

Authors: Myoung Je Song

Abstract:

Ureteral stent insertion is being used as one of the clinical interventional treatments due to stenosis and/or obstruction in the ureter. For the development of the ureteral stents, we have to know the flow patterns with and without peristalsis in the ureter. The purpose of this study is to understand the flow characteristics and movement of the ureter for the ureter model according to the presence or absence of peristalsis and to use it as fundamental information to design the optimal ureteral stent. In this study, CFD (Computational Fluid Dynamics) and FSI (Fluid-Structure Interaction) approaches were applied and compared the flow characteristics in the ureter. The distribution of streamlines was different in the near ureteropelvic junction. As a result of analyzing the area change of the ureter, the area change was large at the frontal and posterior ends, and the frontal and posterior aspects of the area change were reversed. There was no significant difference in the flow rate at the ureter outlet, and the movement of the ureter was larger when peristalsis was considered. Finally, as an introductory stage for the development of ureteral stents, basic information about the ureters according to the presence or absence of peristalsis is acquired.

Keywords: computational fluid dynamics, fluid-structure interaction, peristalsis, urine flow

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2015 Clonal Evaluation of Malignant Mesothelioma

Authors: Sabahattin Comertpay, Sandra Pastorino, Rosanna Mezzapelle, Mika Tanji, Oriana Strianese, Andrea Napolitano, Tracey Weigel, Joseph Friedberg, Paul Sugarbaker, Thomas Krausz, Ena Wang, Amy Powers, Giovanni Gaudino, Harvey I. Pass, Fatmagul Ozcelik, Barbara L. Parsons, Haining Yang, Michele Carbone

Abstract:

Tumors are thought to be monoclonal in origin. This paradigm arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas. The clonal origin of malignant mesothelioma (MM), a deadly cancer resistant to the current therapies, has not been investigated. Examination of the pleura from patients with MM shows often the presence of multiple pleural nodules, raising the question of whether they represent independent or metastatic growth processes. To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 14 sporadic and 2 familial Malignant Mesotheliomas (MM). Of 16 specimens studied, 15 were informative and 14/15 revealed two electrophoretically distinct methylated HUMARA alleles, indicating a polyclonal origin for these tumors. This discovery has important clinical implications, because an accurate assessment of tumor clonality is key to the design of novel molecular strategies for the treatment of MM.

Keywords: malignant mesothelioma, clonal origin, HUMARA, sarcomas

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2014 Chemicals to Remove and Prevent Biofilm

Authors: Cynthia K. Burzell

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Aequor's Founder, a Marine and Medical Microbiologist, discovered novel, non-toxic chemicals in the ocean that uniquely remove biofilm in minutes and prevent its formation for days. These chemicals and over 70 synthesized analogs that Aequor developed can replace thousands of toxic biocides used in consumer and industrial products and, as new drug candidates, kill biofilm-forming bacteria and fungi Superbugs -the antimicrobial-resistant (AMR) pathogens for which there is no cure. Cynthia Burzell, PhD., is a Marine and Medical Microbiologist studying natural mechanisms that inhibit biofilm formation on surfaces in contact with water. In 2002, she discovered a new genus and several new species of marine microbes that produce small molecules that remove biofilm in minutes and prevent its formation for days. The molecules include new antimicrobials that can replace thousands of toxic biocides used in consumer and industrial products and can be developed into new drug candidates to kill the biofilm-forming bacteria and fungi -- including the antimicrobial-resistant (AMR) Superbugs for which there is no cure. Today, Aequor has over 70 chemicals that are divided into categories: (1) Novel natural chemicals. Lonza validated that the primary natural chemical removed biofilm in minutes and stated: "Nothing else known can do this at non-toxic doses." (2) Specialty chemicals. 25 of these structural analogs are already approved under the U.S. Environmental Protection Agency (EPA)'s Toxic Substances Control Act, certified as "green" and available for immediate sale. These have been validated for the following agro-industrial verticals: (a) Surface cleaners: The U.S. Department of Agriculture validated that low concentrations of Aequor's formulations provide deep cleaning of inert, nano and organic surfaces and materials; (b) Water treatments: NASA validated that one dose of Aequor's treatment in the International Space Station's water reuse/recycling system lasted 15 months without replenishment. DOE validated that our treatments lower energy consumption by over 10% in buildings and industrial processes. Future validations include pilot projects with the EPA to test efficacy in hospital plumbing systems. (c) Algae cultivation and yeast fermentation: The U.S. Department of Energy (DOE) validated that Aequor's treatment boosted biomass of renewable feedstocks by 40% in half the time -- increasing the profitability of biofuels and biobased co-products. DOE also validated increased yields and crop protection of algae under cultivation in open ponds. A private oil and gas company validated decontamination of oilfield water. (3) New structural analogs. These kill Gram-negative and Gram-positive bacteria and fungi alone, in combinations with each other, and in combination with low doses of existing, ineffective antibiotics (including Penicillin), "potentiating" them to kill AMR pathogens at doses too low to trigger resistance. Both the U.S. National Institutes for Health (NIH) and Department of Defense (DOD) has executed contracts with Aequor to provide the pre-clinical trials needed for these new drug candidates to enter the regulatory approval pipelines. Aequor seeks partners/licensees to commercialize its specialty chemicals and support to evaluate the optimal methods to scale-up of several new structural analogs via activity-guided fractionation and/or biosynthesis in order to initiate the NIH and DOD pre-clinical trials.

Keywords: biofilm, potentiation, prevention, removal

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2013 A Study of Emergency Nurses' Knowledge and Attitudes regarding Pain

Authors: Liqun Zou, Ling Wang, Xiaoli Chen

Abstract:

Objective: Through the questionnaire about emergency nurses’ knowledge and attitudes regarding pain management to understand whether they are well mastered and practiced the related knowledge about pain management, providing a reference for continuous improvement of the quality of nursing care in acute pain and for improving the effect of management on emergency pain patients. Method: The Chinese version questionnaire about KASRP (knowledge and attitudes survey regarding pain) was handed out to 132 emergency nurses to do a study about the knowledge and attitude of pain management. Meanwhile, SPSS17.0 was used to do a descriptive analysis and variance analysis on collected data. Results: The emergency nurses’ correct answer rate about KASRP questionnaire is from 25% to 65% and the average correct rate is (44.65 + 7.85)%. In addition, there are 10 to 26 items being given the right answer. Therefore, the average correct items are (17.86 ± 3.14). Moreover, there is no statistical significant on the differences about the correct rate for different age, gender and work experience to answer; however, the difference of the correct rate in different education background and the professional title is significant. Conclusion: There is a remarkable lack of knowledge and attitude towards pain management in emergency nurses, whose basic knowledge of pain is sufficient. Besides, there is a deviation between the knowledge of pain management and clinical practice, which needs to be improved.

Keywords: emergency nurse, pain, KASRP questionnaire, pain management

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2012 Comparative Analysis of Simulation-Based and Mixed-Integer Linear Programming Approaches for Optimizing Building Modernization Pathways Towards Decarbonization

Authors: Nico Fuchs, Fabian Wüllhorst, Laura Maier, Dirk Müller

Abstract:

The decarbonization of building stocks necessitates the modernization of existing buildings. Key measures for this include reducing energy demands through insulation of the building envelope, replacing heat generators, and installing solar systems. Given limited financial resources, it is impractical to modernize all buildings in a portfolio simultaneously; instead, prioritization of buildings and modernization measures for a given planning horizon is essential. Optimization models for modernization pathways can assist portfolio managers in this prioritization. However, modeling and solving these large-scale optimization problems, often represented as mixed-integer problems (MIP), necessitates simplifying the operation of building energy systems particularly with respect to system dynamics and transient behavior. This raises the question of which level of simplification remains sufficient to accurately account for realistic costs and emissions of building energy systems, ensuring a fair comparison of different modernization measures. This study addresses this issue by comparing a two-stage simulation-based optimization approach with a single-stage mathematical optimization in a mixed-integer linear programming (MILP) formulation. The simulation-based approach serves as a benchmark for realistic energy system operation but requires a restriction of the solution space to discrete choices of modernization measures, such as the sizing of heating systems. After calculating the operation of different energy systems in terms of the resulting final energy demands in simulation models on a first stage, the results serve as input for a second stage MILP optimization, where the design of each building in the portfolio is optimized. In contrast to the simulation-based approach, the MILP-based approach can capture a broader variety of modernization measures due to the efficiency of MILP solvers but necessitates simplifying the building energy system operation. Both approaches are employed to determine the cost-optimal design and dimensioning of several buildings in a portfolio to meet climate targets within limited yearly budgets, resulting in a modernization pathway for the entire portfolio. The comparison reveals that the MILP formulation successfully captures design decisions of building energy systems, such as the selection of heating systems and the modernization of building envelopes. However, the results regarding the optimal dimensioning of heating technologies differ from the results of the two-stage simulation-based approach, as the MILP model tends to overestimate operational efficiency, highlighting the limitations of the MILP approach.

Keywords: building energy system optimization, model accuracy in optimization, modernization pathways, building stock decarbonization

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2011 The Impact of E-Learning on Medication Administration of Nursing Students

Authors: Z. Karakus, Z. Ozer

Abstract:

Nurses are responsible for the care and treatment of individuals, as well as health maintenance and education. Medication administration is an important part of health promotion. The administration of a medicine is a common but important clinical procedure for nurses because of its complex structure. Therefore, medication errors are inevitable for nurses or nursing students. Medication errors can cause ineffective treatment, patient’s prolonged hospital stay, disablement, or death. Additionally, medication errors affect the global economy adversely by increasing health costs. Hence, preventing or decreasing of medication errors is a critical and essential issue in nursing. Nurse educators are in pursuit of new teaching methods to teach students significance of medication application. In the light of technological developments of this age, e-learning has started to be accepted as an important teaching method. E-learning is the use of electronic media and information and communication technologies in education. It has advantages such as flexibility of time and place, lower costs, faster delivery, and lower environmental impact. Students can make their own schedule and decide the learning method. This study is conducted to determine the impact of e-learning on medication administration of nursing students.

Keywords: e-learning, medication administration, nursing, nursing students

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2010 Perceived Social Support, Resilience and Relapse Risk in Recovered Addicts

Authors: Islah Ud Din, Amna Bibi

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The current study was carried out to examine the perceived social support, resilience and relapse risk in recovered addicts. A purposive sampling technique was used to collect data from recovered addicts. A multidimensional scale of perceived social support by was used to measure the perceived social support. The brief Resilience Scale (BRS) was used to assess resilience. The Stimulant Relapse Risk Scale (SRRS) was used to examine the relapse risk. Resilience and Perceived social support have substantial positive correlations, whereas relapse risk and perceived social support have significant negative associations. Relapse risk and resilience have a strong inverse connection. Regression analysis was used to check the mediating effect of resilience between perceived social support and relapse risk. The findings revealed that perceived social support negatively predicted relapse risk. Results showed that Resilience plays a role as partial mediation between perceived social support and relapse risk. This Research will allow us to explore and understand the relapse risk factor and the role of perceived social support and resilience in recovered addicts. The study's findings have immediate consequences in the prevention of relapse. The study will play a significant part in drug rehabilitation centers, clinical settings and further research.

Keywords: perceived social support, resilience, relapse risk, recovered addicts, drugs addiction

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2009 The Findings EEG-LORETA about Epilepsy

Authors: Leila Maleki, Ahmad Esmali Kooraneh, Hossein Taghi Derakhshi

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Neural activity in the human brain starts from the early stages of prenatal development. This activity or signals generated by the brain are electrical in nature and represent not only the brain function but also the status of the whole body. At the present moment, three methods can record functional and physiological changes within the brain with high temporal resolution of neuronal interactions at the network level: the electroencephalogram (EEG), the magnet oencephalogram (MEG), and functional magnetic resonance imaging (fMRI); each of these has advantages and shortcomings. EEG recording with a large number of electrodes is now feasible in clinical practice. Multichannel EEG recorded from the scalp surface provides a very valuable but indirect information about the source distribution. However, deep electrode measurements yield more reliable information about the source locations، Intracranial recordings and scalp EEG are used with the source imaging techniques to determine the locations and strengths of the epileptic activity. As a source localization method, Low Resolution Electro-Magnetic Tomography (LORETA) is solved for the realistic geometry based on both forward methods, the Boundary Element Method (BEM) and the Finite Difference Method (FDM). In this paper, we review The findings EEG- LORETA about epilepsy.

Keywords: epilepsy, EEG, EEG-LORETA

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2008 Synthesis and Pharmaco-Potential Evaluation of Quinoline Hybrids

Authors: Paul Awolade, Parvesh Singh

Abstract:

The global threat of pathogenic resistance to available therapeutic agents has become a menace to clinical practice, public health and man’s existence inconsequential. This has therefore led to an exigency in the development of new molecular scaffolds with profound activity profiles. In this vein, a versatile synthetic tool for accessing new molecules by incorporating two or more pharmacophores into a single entity with the unique ability to be recognized by multiple receptors hence leading to an improved bioactivity, known as molecular hybridization, has been explored with tremendous success. Accordingly, aware of the similarity in pharmacological activity spectrum of quinoline and 1,2,3-triazole pharmacophores such as; anti-Alzheimer, anticancer, anti-HIV, antimalarial and antimicrobial to mention but a few, the present study sets out to synthesize hybrids of quinoline and 1,2,3-triazole. The hybrids were accessed via click chemistry using copper catalysed azide-alkyne 1,3-dipolar cycloaddition reaction. All synthesized compounds were evaluated for their pharmaco-potential in an antimicrobial assay out of which the 3-OH derivative emerged as the most active with MIC value of 4 μg/mL against Cryptococcus neoformans; a value superior to standard Fluconazole and comparable to Amphotericin B. Structures of synthesized hybrids were elucidated using appropriate spectroscopic techniques (1H, 13C and 2D NMR, FT-IR and HRMS).

Keywords: bioisostere, click chemistry, molecular hybridization, quinoline, 1, 2, 3-triazole

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2007 School-Related Variables and Adolescents Substance Use

Authors: Nicolas Meylan, Eric Tardif

Abstract:

Many studies have highlighted the links between substance use and school difficulties. However, most of these studies address only the consumption in terms of frequency without considering the different types of behavior (use, abuse, dependence). Moreover, little is known about the associations between substance use and variables such as school engagement and school burnout recently described as a positive state of mind and an exhaustion syndrome related to school, respectively. Through this study, we wish to describe and compare school-related variables in adolescents with different type of substance use. Our study focuses on 402 Swiss adolescents, aged between 14 and 19 years old. They responded collectively and anonymously to a set of scales assessing substance use and several school variables (social support, stress, burnout, engagement and school climate). First, results on frequency and severity of substance use are relatively close to those observed in other studies. Second, it also appears that certain dimensions of stress, burnout, engagement and school climate are associated with the frequency of alcohol and cannabis consumption. Finally, adolescents’ substance abusers show particularly high scores of burnout, cynicism and stress related to workload, which can be understand as self-medication behavior. Additional analyzes are underway to clarify these associations. Results are discussed in terms of implications for research and clinical practice in academic burnout.

Keywords: school burnout, school engagement, adolescence, substance use, self-medication

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2006 Development & Standardization of a Literacy Free Cognitive Rehabilitation Program for Patients Post Traumatic Brain Injury

Authors: Sakshi Chopra, Ashima Nehra, Sumit Sinha, Harsimarpreet Kaur, Ravindra Mohan Pandey

Abstract:

Background: Cognitive rehabilitation aims to retrain brain injured individuals with cognitive deficits to restore or compensate lost functions. As illiterates or people with low literacy levels represent a significant proportion of the world, specific rehabilitation modules for such populations are indispensable. Literacy is significantly associated with all neuropsychological measures and retraining programs widely use written or spoken techniques which essentially require the patient to read or write. So, the aim of the study was to develop and standardize a literacy free neuropsychological rehabilitation program for improving cognitive functioning in patients with mild and moderate Traumatic Brain Injury (TBI). Several studies have pointed out to the impairments seen in memory, executive functioning, and attention and concentration post-TBI, so the rehabilitation program focussed on these domains. Visual item memorization, stick constructions, symbol cancellations, and colouring techniques were used to construct the retraining program. Methodology: The development of the program consisted of planning, preparing, analyzing, and revising the different modules. The construction focussed on areas of retraining immediate and delayed visual memory, planning ability, focused and divided attention, concentration, and response inhibition (to control irritability and aggression). A total of 98 home based retraining modules were prepared in the 4 domains (42 for memory, 42 for executive functioning, 7 for attention and concentration, and 7 for response inhibition). The standardization was done on 20 healthy controls to review, select and edit items. For each module, the time, errors made and errors per second were noted down, to establish the difficulty level of each module and were arranged in increasing level of difficulty over a period of 6 weeks. The retraining tasks were then administered on 11 brain injured individuals (5 after Mild TBI and 6 after Moderate TBI). These patients were referred from the Trauma Centre to Clinical Neuropsychology OPD, All India Institute of Medical Sciences, New Delhi, India. Results: The time was taken, errors made and errors per second were analysed for all domains. Education levels were divided into illiterates, up to 10 years, 10 years to graduation and graduation and above. Mean and standard deviations were calculated. Between group and within group analysis was done using the t-test. The performance of 20 healthy controls was analyzed and only a significant difference was observed on the time taken for the attention tasks and all other domains had non-significant differences in performance between different education levels. Comparing the errors, time taken between patient and control group, there was a significant difference in all the domains at the 0.01 level except the errors made on executive functioning, indicating that the tool can successfully differentiate between healthy controls and patient groups. Conclusions: Apart from the time taken for symbol cancellations, the entire cognitive rehabilitation program is literacy free. As it taps the major areas of impairment post-TBI, it could be a useful tool to rehabilitate the patient population with low literacy levels across the world. The next step is already underway to test its efficacy in improving cognitive functioning in a randomized clinical controlled trial.

Keywords: cognitive rehabilitation, illiterates, India, traumatic brain injury

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2005 Evaluation of the Role of Circulating Long Non-Coding RNA H19 as a Promising Biomarker in Plasma of Patients with Gastric Cancer

Authors: Doaa Hashad, Amany Elbanna, Abeer Ibrahim, Gihan Khedr

Abstract:

Background: H19 is one of the long non coding RNAs (LncRNA) that is related to the progression of many diseases including cancers. This work was carried out to study the level of the long non-coding RNA; H119, in plasma of patients with gastric cancer (GC) and to assess its significance in their clinical management. Methods: A total of sixty-two participants were enrolled in the present study. The first group included thirty-two GC patients, while the second group was formed of thirty age and sex matched healthy volunteers serving as a control group. Plasma samples were used to assess H19 gene expression using real time quantitative PCR technique. Results: H19 expression was up-regulated in GC patients with positive correlation to TNM cancer stages. Conclusions: Up-regulation of H19 is closely associated with gastric cancer and correlates well with tumor staging. Convenient, efficient quantification of H19 in plasma using real time PCR technique implements its role as a potential noninvasive prognostic biomarker in gastric cancer, that predicts patient’s outcome and most importantly as a novel target in gastric cancer treatment with better performance achieved on using both CEA and H19 simultaneously.

Keywords: biomarker, gastric, cancer, LncRNA

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2004 Hanta Virus Infection in a Child and Sequelae

Authors: Vijay Samuel, Tina Thekkekkara, Shoma Ganguly

Abstract:

There is no reported Hanta Seoul virus infection in children in the UK so far, making it quite challenging for clinicians in diagnosing, predicting and prognosticating the outcome of the infection to patients and parents. We report a case of a ten-year-old girl who presented with pyrexia associated with headache, photophobia and abdominal pain. The family had recently acquired two pet rats six weeks ago. She appeared flushed with peri-oral pallor, coated the strawberry tongue, inflamed tonsils and bilateral cervical lymphadenopathy. Her liver and splenic edges were palpable. Investigations showed that she was thrombocytopenic with deranged renal and liver functions. An ultrasound abdomen demonstrated a mildly enlarged spleen, peripancreatic lymph node and an acalculous cholecystitis. In view of her clinical presentation, a diagnosis of leptospirosis was considered and she was commenced on intravenous benzylpenicillin. The following day she became oliguric, developed significant proteinuria and her renal function deteriorated. Following conservative management, her urine output gradually improved along with her renal function, proteinuria and thrombocytopaenia. Serology for leptospirosis and various other viruses were negative. Following discussion with the Rare and Imported Pathogens Laboratory at Porton hanta virus serology was requested and found to be strongly positive for Seoul hanta virus. Following discharge she developed palpitations, fatigue, severe headache and cognitive difficulties including memory loss and difficulties in spelling, reading and mathematics. Extensive investigations including ECG, MRI brain and CSF studies were performed and revealed no significant abnormalities. Since 2012, there have been six cases of acute kidney injury due to Hantavirus infection in the UK. Two cases were from the Humber region and were exposure to wild rats and the other four were exposed to specially bred pet fancy rats. Hanta virus infections can cause mild flu like symptoms but two clinical syndromes are associated with severe disease including haemorrhagic fever with renal syndrome, which may be associated with thrombocytopenia and Hantavirus cardiopulmonary syndrome. Neuropsychological impairments reported following hantavirus pulmonary syndrome and following Puumala virus infection have been reported. Minor white matter lesions were found in about half of the patients investigated with MRI brain. Seoul virus has a global distribution owing to the dispersal of its carrier host rats, through global trade. Several ports in the region could explain the possible establishment of Seoul virus in local populations of rats in the Yorkshire and Humber region. The risk of infection for occupationally exposed groups is 1-3% compared to 32.9% for specialist pet rat owners. The report highlight’s the importance of routinely asking about pets in the family. We hope to raise awareness of the emergence of hantavirus infection in the UK, particularly in the Yorkshire and Humber region. Clinicians should consider hantavirus infection as a potential cause of febrile illness causing renal impairment in children. Awareness of the possible neuro-cognitive sequele would help the clinicians offer appropriate information and support to children and their families. Contacting Rare and Imported Pathogens Laboratory at Porton is a useful resource for clinicians in UK when they consider unusual infections.

Keywords: Seoul hantavirus in child Porton, UK Acute kidney injury

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2003 A Case of Severe Iatrogenic Cushing’s Syndrome Followed by Adrenal Crisis, Multifocal Pneumonia, Sepsis, Pulmonary Embolism and Prolonged Adrenal Insufficiency

Authors: Jelena Maletkovic

Abstract:

Background: Endogenous Cushing’s syndrome is a rare disease, but iatrogenic or drug related Cushing syndrome from glucocorticoid products is commonly seen in clinical practice. With high dose and long term use of glucocorticoids, patients can develop isolated hypothalamic-pituitary-adrenal (HPA) suppression, or HPA axis suppression can be accompanied by overt iatrogenic Cushing’s syndrome. This is a rare case where severe Cushing’s syndrome developed from an unknown medication and was followed by severe and prolonged adrenal insufficiency and multiple potentially fatal complications. Case: This is a 37-year-old woman who is presented to Emergency Room (ER) with shortness of breath and chest pain. Four months prior to this presentation the patient was a generally healthy woman who was looking for improvement in her appearance and visited local Rejuvenation Clinic. After initial consultation with a nurse, she was contacted by a physician over the phone and was advised to start taking multiple injectable medications that will arrive by mail. Medications without any labels on bottles were delivered and the patient started daily intramuscular injections. Over the next two months, she noticed rounding of her face and swelling around her eyes. She gained 20 pounds, mostly abdominal fat and became extremely fatigued. Her muscles on legs were visibly decreasing in size and she felt significant muscle weakness. Unexplained bruising occurred. She started growing hair on face and developed secondary amenorrhea. New severe back pain started. She developed depression and headaches. Finally, over a few days, a number of red-purple stretch marks that were sensitive and painful appeared over her abdomen, upper part of arms and legs. She then became suspicious that these dramatic symptoms are caused by injectable medication and she discontinued injections. Over the next few days she presented to ER with low blood pressure and oxygen saturation of 75%. Studies revealed extensive pneumonia as well as multiple pulmonary emboli. Her white blood count was elevated with 32 000 and she also had acute kidney failure on admission. She was treated for sepsis and was also given stress dose steroids. Steroids were tapered over 48 hours and discontinued. After being discharged to home, on her first visit to endocrinology clinic she had undetectable ACTH of < 2pg/mL and undetectable 8am cortisol of < 0.2mcg/dL. She did not respond to an intramuscular injection of cosyntropin 250mcg and her repeated cortisol after 60 minutes was only 1mcg/dL. The patient was diagnosed with adrenal insufficiency and was started on hydrocortisone 20mg+10mg. It took close to 2 years of slow tapering for recovery of this patient’s HPA axis and resolve all the sequelae from Cushing’s syndrome. Conclusion: Misuse and abuse of glucocorticoids have been present almost since these medications were discovered. This is a rare case where not only severe Cushing’s syndrome in full clinical picture developed but also the patient suffered multiple potentially fatal complications and prolonged adrenal insufficiency. Visits to herbal, rejuvenation, esthetic, and similar clinics are becoming more and more popular and physicians need to be aware of possible non-benign nature of medications that their patients may be using.

Keywords: iatrogenic, Cushing's syndrome, adrenal crisis, steroid abuse

Procedia PDF Downloads 168
2002 Effects of Oral Resveratrol Supplementation on Inflammation and Quality of Life in Patients with Ulcerative Colitis

Authors: M. Samsami, A. Hekmatdoost, N. Ebrahimi Daryani, P. Rezanejad Asl

Abstract:

Ulcerative colitis (UC) is an inflammatory bowel disease in which immune and inflammatory factors are thought to be effective in this disease. Resveratrol is an antioxidant and anti-inflammatory compound. This study determined the effects of resveratrol compound on inflammatory factors in patients with ulcerative colitis. This study was a double-blind randomized clinical trial conducted on 50 patients with UC. Subjects received one capsule daily for 6 wk of either resveratrol (500 mg) or a placebo. Inflammatory factors, anthropometric measures, and IBDQ-9 (Inflammatory Bowel Disease Questionnaire-9) scores were assessed at baseline and at the end of the study. STATA12 software was used for data analysis. No significant differences were found in the background variables between the two groups at baseline. The results indicated that resveratrol supplementation for 6 week significantly decreased plasma levels of TNF-a and hs-CRP and the activity of NF-κB over the placebo group (p<0.001). Significant differences remained after adjustment for vitamin C (p<0.0001). The IBDQ-9 scores increased significantly in the resveratrol group over the placebo group (p<0.001). The findings of this study showed that resveratrol supplementation can be useful in patients with ulcerative colitis.

Keywords: IBD, inflammation, resveratrol, ulcerative colitis

Procedia PDF Downloads 411
2001 COVID-19’s Effect on Pre-Existing Hearing Loss

Authors: Jonathan A. Mikhail, Arsenio Paez

Abstract:

It is not uncommon for a viral infection to cause hearing loss. Many viral infections are associated with sudden-onset, often unilateral, idiopathic sensorineural hearing loss. We conducted an exploratory study with thirty patients with pre-existing hearing loss between 50 and 64 to evaluate if COVID-19 was associated with exacerbated hearing loss. We hypothesized that hearing loss would be exacerbated by COVID-19 infection in patients with pre-existing hearing loss. A statistically significant paired T-test between pure tone averages (PTAs) at the patient’s original diagnosis and a current, updated audiometric assessment indicated a regression in hearing (p-value < .001) sensitivity following the contraction of COVID-19. Speech reception thresholds (SRTs) and word recognition scores (WRSs) were also considered, as well as the participants' gender. SRTs between each ear exhibited a statistically significant change (p-value of .002 and p-value < .001). WRSs did not show statistically significant differences (p-value of .290 and p-value of .098). A non-statistically significant Two-Way ANOVA was performed to evaluate gender’s potential role in exacerbated hearing loss and proved to be statistically insignificant (p-value of .214). This study discusses practical implications for clinical and educational pursuits in understanding COVID-19's effect on the auditory system and the need to evaluate the deadly virus further.

Keywords: audiology, COVID-19, sensorineural hearing loss, otology, auditory research

Procedia PDF Downloads 79
2000 Acute Intraperitoneal Toxicity of Sesbania grandiflora (Katuray) Methanolic Flower Extract in Swiss Albino Mice

Authors: Levylee Bautista, Dawn Grace Santos, Aishwarya Veluchamy, Jesusa Santos, Ghafoor Haque, Jr. I, Rodolfo Rafael

Abstract:

Sesbania grandiflora is widely used in traditional medicine to treat a wide range of ailments. Assessment of its toxic properties is hence crucial when considering public health protection because exposure to plant extracts may pose adverse effects on consumers. This study aimed to investigate the acute intraperitoneal toxicity of S. grandiflora flower methanolic extract (SGFME) in Swiss albino mice. Four different concentrations (11.25, 22.5, 40, and 90 mg/kg) of SGFME were administered intraperitoneally and immediate behavioral and clinical signs were observed. All concentrations of SGFME-treated mice exhibited gasping and faster respiratory rate, writhing, reddening and fanning of the ears, paralysis of the hind leg, and mortality. Such reactions may be attributed to the histamine and saponin content of S. grandiflora. Results of this study suggests that intraperitoneal administration of SGFME produced significant adverse effect in mice, therefore, caution should be exercised in using it as herbal remedy since there is little control over its quality.

Keywords: acute toxicity test, histamine, medicinal plants, Sesbania grandiflora

Procedia PDF Downloads 168
1999 Predictive Factors of Prognosis in Acute Stroke Patients Receiving Traditional Chinese Medicine Therapy: A Retrospective Study

Authors: Shaoyi Lu

Abstract:

Background: Traditional Chinese medicine has been used to treat stroke, which is a major cause of morbidity and mortality. There is, however, no clear agreement about the optimal timing, population, efficacy, and predictive prognosis factors of traditional Chinese medicine supplemental therapy. Method: In this study, we used a retrospective analysis with data collection from stroke patients in Stroke Registry In Chang Gung Healthcare System (SRICHS). Stroke patients who received traditional Chinese medicine consultation in neurology ward of Keelung Chang Gung Memorial Hospital from Jan 2010 to Dec 2014 were enrolled. Clinical profiles including the neurologic deficit, activities of daily living and other basic characteristics were analyzed. Through propensity score matching, we compared the NIHSS and Barthel index before and after the hospitalization, and applied with subgroup analysis, and adjusted by multivariate regression method. Results: Totally 115 stroke patients were enrolled with experiment group in 23 and control group in 92. The most important factor for prognosis prediction were the scores of National Institutes of Health Stroke Scale and Barthel index right before the hospitalization. Traditional Chinese medicine intervention had no statistically significant influence on the neurological deficit of acute stroke patients, and mild negative influence on daily activity performance of acute hemorrhagic stroke patient. Conclusion: Efficacy of traditional Chinese medicine as a supplemental therapy for acute stroke patients was controversial. The reason for this phenomenon might be complex and require more research to comprehend. Key words: traditional Chinese medicine, acupuncture, Stroke, NIH stroke scale, Barthel index, predictive factor. Method: In this study, we used a retrospective analysis with data collection from stroke patients in Stroke Registry In Chang Gung Healthcare System (SRICHS). Stroke patients who received traditional Chinese medicine consultation in neurology ward of Keelung Chang Gung Memorial Hospital from Jan 2010 to Dec 2014 were enrolled. Clinical profiles including the neurologic deficit, activities of daily living and other basic characteristics were analyzed. Through propensity score matching, we compared the NIHSS and Barthel index before and after the hospitalization, and applied with subgroup analysis, and adjusted by multivariate regression method. Results: Totally 115 stroke patients were enrolled with experiment group in 23 and control group in 92. The most important factor for prognosis prediction were the scores of National Institutes of Health Stroke Scale and Barthel index right before the hospitalization. Traditional Chinese medicine intervention had no statistically significant influence on the neurological deficit of acute stroke patients, and mild negative influence on daily activity performance of acute hemorrhagic stroke patient. Conclusion: Efficacy of traditional Chinese medicine as a supplemental therapy for acute stroke patients was controversial. The reason for this phenomenon might be complex and require more research to comprehend.

Keywords: traditional Chinese medicine, complementary and alternative medicine, stroke, acupuncture

Procedia PDF Downloads 360
1998 Beijerinckia indica Extracellular Extract Mediated Green Synthesis of Silver Nanoparticles with Antioxidant and Antibacterial Activities against Clinical Pathogens

Authors: Gopalu Karunakaran, Matheswaran Jagathambal, Nguyen Van Minh, Evgeny Kolesnikov, Denis Kuznetsov

Abstract:

This work investigated the use of Beijerinckia indica extracellular extract for the synthesis of silver nanoparticles using AgNO3. The formation of nanoparticles was confirmed by different methods, such as UV-Vis absorption spectroscopy, XRD, FTIR, EDX, and TEM analysis. The formation of silver nanoparticles (AgNPs) was confirmed by the change in color from light yellow to dark brown. The absorbance peak obtained at 430 nm confirmed the presence of silver nanoparticles. The XRD analysis showed the cubic crystalline phase of the synthesized nanoparticles. FTIR revealed the presence of groups that acts as stabilizing and reducing agents for silver nanoparticles formation. The synthesized silver nanoparticles were generally found to be spherical in shape with size ranging from 5 to 20 nm, as evident by TEM analysis. These nanoparticles were found to inhibit pathogenic bacterial strains. This work proved that the bacterial extract is a potential eco-friendly candidate for the synthesis of silver nanoparticles with promising antibacterial and antioxidant properties. 

Keywords: antioxidant activity, antimicrobial activity, Beijerinckia indica, characterisation, extracellular extracts, silver nanoparticles

Procedia PDF Downloads 340
1997 Red Blood Cells Deformability: A Chaotic Process

Authors: Ana M. Korol, Bibiana Riquelme, Osvaldo A. Rosso

Abstract:

Since erythrocyte deformability analysis is mostly qualitative, the development of quantitative nonlinear methods is crucial for restricting subjectivity in the study of cell behaviour. An electro-optic mechanic system called erythrodeformeter has been developed and constructed in our laboratory in order to evaluate the erythrocytes' viscoelasticity. A numerical method formulated on the basis of fractal approximation for ordinary (OBM) and fractionary Brownian motion (FBM), as well as wavelet transform analysis, are proposed to distinguish chaos from noise based on the assumption that diffractometric data involves both deterministic and stochastic components, so it could be modelled as a system of bounded correlated random walk. Here we report studies on 25 donors: 4 alpha thalassaemic patients, 11 beta thalassaemic patients, and 10 healthy controls non-alcoholic and non-smoker individuals. The Correlation Coefficient, a nonlinear parameter, showed evidence of the changes in the erythrocyte deformability; the Wavelet Entropy could quantify those differences which are detected by the light diffraction patterns. Such quantifiers allow a good deal of promise and the possibility of a better understanding of the rheological erythrocytes aspects and also could help in clinical diagnosis.

Keywords: red blood cells, deformability, nonlinear dynamics, chaos theory, wavelet trannsform

Procedia PDF Downloads 59
1996 Electroactive Ferrocenyl Dendrimers as Transducers for Fabrication of Label-Free Electrochemical Immunosensor

Authors: Sudeshna Chandra, Christian Gäbler, Christian Schliebe, Heinrich Lang

Abstract:

Highly branched dendrimers provide structural homogeneity, controlled composition, comparable size to biomolecules, internal porosity and multiple functional groups for conjugating reactions. Electro-active dendrimers containing multiple redox units have generated great interest in their use as electrode modifiers for development of biosensors. The electron transfer between the redox-active dendrimers and the biomolecules play a key role in developing a biosensor. Ferrocenes have multiple and electrochemically equivalent redox units that can act as electron “pool” in a system. The ferrocenyl-terminated polyamidoamine dendrimer is capable of transferring multiple numbers of electrons under the same applied potential. Therefore, they can be used for dual purposes: one in building a film over the electrode for immunosensors and the other for immobilizing biomolecules for sensing. Electrochemical immunosensor, thus developed, exhibit fast and sensitive analysis, inexpensive and involve no prior sample pre-treatment. Electrochemical amperometric immunosensors are even more promising because they can achieve a very low detection limit with high sensitivity. Detection of the cancer biomarkers at an early stage can provide crucial information for foundational research of life science, clinical diagnosis and prevention of disease. Elevated concentration of biomarkers in body fluid is an early indication of some type of cancerous disease and among all the biomarkers, IgG is the most common and extensively used clinical cancer biomarkers. We present an IgG (=immunoglobulin) electrochemical immunosensor using a newly synthesized redox-active ferrocenyl dendrimer of generation 2 (G2Fc) as glassy carbon electrode material for immobilizing the antibody. The electrochemical performance of the modified electrodes was assessed in both aqueous and non-aqueous media using varying scan rates to elucidate the reaction mechanism. The potential shift was found to be higher in an aqueous electrolyte due to presence of more H-bond which reduced the electrostatic attraction within the amido groups of the dendrimers. The cyclic voltammetric studies of the G2Fc-modified GCE in 0.1 M PBS solution of pH 7.2 showed a pair of well-defined redox peaks. The peak current decreased significantly with the immobilization of the anti-goat IgG. After the immunosensor is blocked with BSA, a further decrease in the peak current was observed due to the attachment of the protein BSA to the immunosensor. A significant decrease in the current signal of the BSA/anti-IgG/G2Fc/GCE was observed upon immobilizing IgG which may be due to the formation of immune-conjugates that blocks the tunneling of mass and electron transfer. The current signal was found to be directly related to the amount of IgG captured on the electrode surface. With increase in the concentration of IgG, there is a formation of an increasing amount of immune-conjugates that decreased the peak current. The incubation time and concentration of the antibody was optimized for better analytical performance of the immunosensor. The developed amperometric immunosensor is sensitive to IgG concentration as low as 2 ng/mL. Tailoring of redox-active dendrimers provides enhanced electroactivity to the system and enlarges the sensor surface for binding the antibodies. It may be assumed that both electron transfer and diffusion contribute to the signal transformation between the dendrimers and the antibody.

Keywords: ferrocenyl dendrimers, electrochemical immunosensors, immunoglobulin, amperometry

Procedia PDF Downloads 337
1995 Anthraquinone Labelled DNA for Direct Detection and Discrimination of Closely Related DNA Targets

Authors: Sarah A. Goodchild, Rachel Gao, Philip N. Bartlett

Abstract:

A novel detection approach using immobilized DNA probes labeled with Anthraquinone (AQ) as an electrochemically active reporter moiety has been successfully developed as a new, simple, reliable method for the detection of DNA. This method represents a step forward in DNA detection as it can discriminate between multiple nucleotide polymorphisms within target DNA strands without the need for any additional reagents, reporters or processes such as melting of DNA strands. The detection approach utilizes single-stranded DNA probes immobilized on gold surfaces labeled at the distal terminus with AQ. The effective immobilization has been monitored using techniques such as AC impedance and Raman spectroscopy. Simple voltammetry techniques (Differential Pulse Voltammetry, Cyclic Voltammetry) are then used to monitor the reduction potential of the AQ before and after the addition of complementary strand of target DNA. A reliable relationship between the shift in reduction potential and the number of base pair mismatch has been established and can be used to discriminate between DNA from highly related pathogenic organisms of clinical importance. This indicates that this approach may have great potential to be exploited within biosensor kits for detection and diagnosis of pathogenic organisms in Point of Care devices.

Keywords: Anthraquinone, discrimination, DNA detection, electrochemical biosensor

Procedia PDF Downloads 393
1994 Development of a Real-Time Brain-Computer Interface for Interactive Robot Therapy: An Exploration of EEG and EMG Features during Hypnosis

Authors: Maryam Alimardani, Kazuo Hiraki

Abstract:

This study presents a framework for development of a new generation of therapy robots that can interact with users by monitoring their physiological and mental states. Here, we focused on one of the controversial methods of therapy, hypnotherapy. Hypnosis has shown to be useful in treatment of many clinical conditions. But, even for healthy people, it can be used as an effective technique for relaxation or enhancement of memory and concentration. Our aim is to develop a robot that collects information about user’s mental and physical states using electroencephalogram (EEG) and electromyography (EMG) signals and performs costeffective hypnosis at the comfort of user’s house. The presented framework consists of three main steps: (1) Find the EEG-correlates of mind state before, during, and after hypnosis and establish a cognitive model for state changes, (2) Develop a system that can track the changes in EEG and EMG activities in real time and determines if the user is ready for suggestion, and (3) Implement our system in a humanoid robot that will talk and conduct hypnosis on users based on their mental states. This paper presents a pilot study in regard to the first stage, detection of EEG and EMG features during hypnosis.

Keywords: hypnosis, EEG, robotherapy, brain-computer interface (BCI)

Procedia PDF Downloads 256
1993 Development of Peptide Inhibitors against Dengue Virus Infection by in Silico Design

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

Abstract:

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

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

Procedia PDF Downloads 357
1992 Evaluation of the Cytotoxicity and Cellular Uptake of a Cyclodextrin-Based Drug Delivery System for Cancer Therapy

Authors: Caroline Mendes, Mary McNamara, Orla Howe

Abstract:

Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

Procedia PDF Downloads 310