Engineering and optimisation of mini-dystrophin constructs for Duchenne muscular dystrophy gene therapy

PhD ThesisMuscular dystrophies (MDs) are inherited disorders characterised by muscle weakness and atrophy. One of the most severe forms is Duchenne muscular dystrophy (DMD) which together with the milder allelic form Becker muscular dystrophy (BMD) are known as the dystrophinopathies and result from defects in the X-linked gene encoding dystrophin. Dystrophin is a structural protein of the muscle that connects the internal cytoskeleton of muscle fibres to the extracellular matrix. DMD is also amongst the most common forms of muscular dystrophy, affecting ~1 in 4000 live male birth and manifests as rapidly progressive muscle degeneration leading to loss of ambulation and death in the second or third decade from respiratory or cardiac failure. Currently, there is no cure for this devastating disease. Clinical management of symptoms and complications is limited to stabilising the condition, slowing deterioration over time and palliative care. Since discovery of the DMD gene in 1986, researchers have dedicated substantial effort into vector technologies, facilitating the use of gene therapy to reintroduce a functional copy of the dystrophin gene into muscle fibres, a potential approach to treat DMD patients. However, this approach poses additional challenges relative to many gene therapy approaches since the full-length dystrophin cDNA is ~14 kb, exceeding the packaging capacity of most viral vectors. A number of large internal in-frame dystrophin deletions have been identified in patients that produce a relatively mild phenotype with later age of onset and a slower rate of disease progression than classical DMD. This observation has inspired the construction of internally truncated, but largely functional versions of dystrophin suitable for gene transfer using viral vectors. So far the most widely used miniaturised dystrophin transgenes have been tested in AAV-mediated gene delivery which has identified several limitations indicating the use of more favourable transgenes that have smaller deletions, yet carrying more functional parts of dystrophin. In this study human mini-dystrophin constructs of 4.3-7.7 kb in size were designed that retain key functional elements of dystrophin molecule and their relative functionality investigated in mdx mice. The ultimate aim of this study is the characterisation and optimisation of these mini-dystrophin constructs for gene delivery studies via viral vectors as a therapeutic tool for treatment of Duchenne muscular dystrophy

ESP Courses and Identity Formation: The Case of Introvert Students

Identity formation is one of the main concerns of today’s education and can have a vital role in ESP learners’ future professional success. This study investigated whether the employment of interactive practices in ESP courses had any impact on the identity formation of introvert students. Initially, 200 undergraduate students majoring in Computer Sciences, Accounting, and Physical Education answered the introversion/extraversion section of the Myers-Briggs Type Indicator (MBTI) and Cheek and Briggs’ Aspects of Identity Questionnaire (AIQ-IV). Based on their performance on MBTI, 90 learners with the extravert, introvert, and non-discriminating personality traits were selected from six classes and formed the three Extravert, Introvert, and Control (n1=n2=n3=30) groups. The students had taken a Specialized English course in the second semester of their BA program. The classes lasted 14 sessions. During the treatment, the researchers employed different activities for teaching ESP. After the instruction, the participants took the AIQ-IV. The results of ANCOVA indicated that the Introvert group gained significantly higher scores on the identity questionnaire than the Extravert and Control groups. The results of paired samples t-tests showed that while introverts had improved considerably in all components of the identity questionnaire, the Extravert and Control groups did not show any changes. The findings indicated that in interactive classroom environments, introvert learners had more inclination than the extravert and mixed introvert and extravert learners toward a shift in identity. The study has implications for ESP teachers, practitioners, and educators

A Model for the Relationship between Work Attitudes and Beliefs of Knowledge Workers with Their Turnover Intention

Growing of science and technology and extending of knowledge-based organizations, the development and maintenance of high-performance knowledge workers with high-potential will be very critical institutionally and nationally. This study aimed to explore the predictability of knowledge workers’ intention to stay through their work attitudes and beliefs including believe in reliability of managers, job satisfaction and organizational commitment in the context of the academic community of Iran. Standard questionnaires were used to measure the variables. In order to gather data, stratified random sampling of faculty members in colleges and higher education institutions in South Khorasan, was accomplished. The results obtained in method of path analysis with AMOS software show that believe of knowledge workers in reliability of managers and organizational commitment can anticipate intend to stay. Among them, trust in management has the strongest indirect effect on the intention to stay. Also, job satisfaction through organizational commitment can predict the intention to stay of knowledge workers

Exploring the components of professional ethics for residents of Iranian universities of medical sciences

Background: Professional ethics answers the ethical issues of various professions and has specific principles for it. The purpose of this study was to identify the Components of professional ethics for residents of Iranian universities of medical sciences.Methods: This qualitative study was conducted in Aja University of Medical Sciences. Semi-structured tools were used to collect data. The participants in this study were ethics experts in medical sciences who were selected by purposive sampling. Interviews with 19 experts led to data saturation. Data were analyzed using content analysis by Inductive approach. The Lincoln and Cuba criteria were used to evaluate the study data. Results: Based on the findings, 3 main themes including Organizational Ethics, Social Ethics, and Individual Ethics, and 12 sub-themes were obtained, as the components of professional ethics for residents of Iranian universities of medical sciences.Conclusion: It is recommended that educational officials in university, while paying more attention to professional ethics in the curriculum of residents, may use the results of this study in the development of professional ethics training programs for residents of medical sciences

Economic importance and GIS mapping of medicinal plants in Iran: A Case study of Darkesh

Iran with a wide diversity of wild medicinal plants (8,000 Medicinal plants) is increasingly becoming a valuable source of household income for many rural people. We showed that economic potential of the wild medicinal plant and their contribution to the local people’s livelihoods. This study identified the economic importance of medicinal plants and evaluated with Geographical Information System (GIS) tool to develop spatial maps covering medicinal plants prevalent in Darkesh area, Northern Khorasan, Iran. Then provide the coordinates of the identified area as your results. 10 medicinal plants belonging to 4 families were collected and its geographical distribution is illustrated in the GIS map. More than 50 species were collected and 10 species being the most frequently collected in this area. Most plants were collected in the form of whole plant. It was estimated that at least 18.000 USD are being annually traded in study area, the 10 species most frequently collected contributing most of the retail value. Results from this study indicate that the collection of certain medicinal plants could be increased livelihood for edge community of natural resources. Also, the geographical location of medicinal plants facilitates easy access of medicinal plant's natural habitat and would help to find out potential of medicinal plants in the study area.Keywords: Medicinal plants, Geographical distribution, GIS Mapping, Darkesh, Ira

Accidental Chronic Poisoning with Methotrexate; Report of Two Cases

Methotrexate has been used widely in dermatology, oncology and rheumatology fields. However, methotrexate-induced mucocutaneous lesions may occur in rare cases. In this case presentation, we report two cases of accidental poisoning with methotrexate. They had accidentally used methotrexate instead of digoxin. This case report emphasizes that early diagnosis and appropriate management is critical in order to improve outcome. 

Arch width changes in patients with Class II division 1 malocclusion treated with maxillary first premolar extraction and non-extraction method

Background: The aim of this study was to determine arch width changes during maxillary first premolars extraction and non-extraction treatment in patients with Class II division 1 malocclusion. Material and Methods: Dental casts of 91 Class II division 1 patients (36 males and 55 females) were evaluated. The minimum age of the subjects at the beginning of treatment was above 16 years. 48 patients were treated with extraction of the maxillary first premolars and 43 patients were treated without extraction. Pre- and post-treatment maxillary and mandibular inter-canine and inter-molar arch widths were measured. Results: At the end of treatment, maxillary and mandibular inter-canine widths of both groups increased significantly. The maxillary inter-molar width decreased in the extraction group and increased in the non-extraction group. The mandibular inter-molar width increased significantly in both groups. No significant differences were observed between males and females. Conclusions: The results of this study indicated that there was a tendency for an increase in arch width during both the extraction and non-extraction treatment except maxillary inter-molar width in the extraction cases

Comparison of Insulin Expression Levels in White Blood Cells of infants with and without Family History of Type II Diabetes

Background: Type II diabetes is known as one of the most important, prevalent, and expensive diseases of mankind. Late diagnosis and subsequent delayed initiation of treatment or surveillance of patients create a variety of problems for affected individuals. This has raised increasing concerns for public health authorities throughout the world. In the current study, we aimed to find a new approach for early identification of high-risk individuals at initial months of their life. This allows us to take preventive measures as early as possible.Materials and Methods: In our study, 102 infants - from one to six months - were selected and placed in two case and control groups. The case group contained 52 babies with at least one of their parents identified as a type II diabetic patient. The control group comprised 50 babies with no family history of type II diabetes in paternal and maternal first-degree relatives. Afterwards, the expression level of insulin gene was analyzed in white blood cells of both groups. Information related to infants - referred to outpatient and inpatient wards of three main pediatric hospitals placed in Tehran - and their parents were collected through questionnaires within a two-year period. The study inclusion criteria for infants were confirmed type II diabetes in at least one of their parents, the absence of any metabolic disorder, and the absence of any disturbing vital signs. After drawing 2 ml of babies’ peripheral blood, total RNA of white blood cells (WBC) was extracted, and used for cDNA synthesis. Real-Time PCR was then applied to quantitatively evaluate the expression levels of insulin gene. The results of Real-Time PCR were statistically analyzed by non-parametric tests of Mann-Whitney and Kruskal-Wallis.Results: The expression of insulin gene was observed in white blood cells of all samples. However, there was a significant difference in expression levels between case and control groups (p<0.05). There was a statistically significant difference in mean levels of gene expression among babies with diabetic mother, and healthy groups (RQ=0.5, P-value=0.002), but this value wasn’t significant for babies with diabetic father (RQ=0.78, P>0.05).Conclusion: Numerous genes contribute to the development of diabetes and novel disease-causing genes are increasingly being discovered. Identification of disease-prone individuals through examining merely one underlying gene is complicated and challenging. Interestingly, all of these abnormally functioning genes finally manifest themselves in the altered expression levels of insulin gene. The expression status of insulin gene in WBCs could be suggested as a useful approach for identification of individuals at high risk for developing diabetes. This paves the way for taking appropriate measures at infancy period in order to prevent the disease as well as inhibit its various side effects in the following years of patient’s life

COMPARISON OF VARIOUS MEASUREMENT TECHNIQUES FOR CHARACTERIZING THE HYDRODYNAMICS OF GAS-SOLID FLUIDIZED BEDS

There are various techniques to characterize the hydrodynamic of fluidized beds. Nowadays, sensor development is widely used to determine the hydrodynamic state of a fluidized bed to improve control and safety of the operation of such reactors. The objective of this study was to compare the advantages and disadvantages of the intrusive and novel non-intrusive techniques. The measurement techniques investigated in this work were vibration of the bed, acoustic emission and pressure. Extensive measurements were carried out at different superficial gas velocities with different particle sizes. Vibration and acoustic emissions were recorded at 25 KHz for 30 s using accelerometer and microphone, respectively. Pressure fluctuation signals were also collected at a sampling frequency of 400 Hz. These measurements were used for investigating the changes in the flow structure, specifically the flow regime transitions. The recorded signals were processed using wavelet analysis and statistical tools. It was shown that the variation of standard deviation, skewness and kurtosis of vibration signals against superficial gas velocity of the bed obey the same trend for different techniques. Results indicated that analyzing the vibration and acoustic signals can be considered as effective non intrusive techniques to characterize the hydrodynamics of gas-solid fluidized beds and in some cases they show better prediction of the hydrodynamic parameters

A comparative study of the effectiveness of nonattendance and workshop education of primary school teachers on their knowledge, attitude and function towards ADHD students in Isfahan in 2010

Abstract BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is the most common childhood behavioral disorder causing hyperactivity, attention deficit and education decline among students. The teachers may not have enough knowledge about this disorder and are in a real need in this field. Teachers' education is one of the ways to get knowledge about this disorder. Nowadays, finding a way like a short term nonattendance education method is highly in demand. Therefore, the aim of the study was to compare effectiveness of nonattendance and workshop education of primary school teachers on their knowledge, attitude, and function towards ADHD students