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Search Results: 1 - 10 of 4710 matches for " Catherine Moorwood "
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Drug Discovery for Duchenne Muscular Dystrophy via Utrophin Promoter Activation Screening
Catherine Moorwood, Olga Lozynska, Neha Suri, Andrew D. Napper, Scott L. Diamond, Tejvir S. Khurana
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0026169
Abstract: Background Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by mutations in dystrophin, a muscle cytoskeletal protein. Utrophin is a homologue of dystrophin that can functionally compensate for its absence when expressed at increased levels in the myofibre, as shown by studies in dystrophin-deficient mice. Utrophin upregulation is therefore a promising therapeutic approach for DMD. The use of a small, drug-like molecule to achieve utrophin upregulation offers obvious advantages in terms of delivery and bioavailability. Furthermore, much of the time and expense involved in the development of a new drug can be eliminated by screening molecules that are already approved for clinical use. Methodology/Principal Findings We developed and validated a cell-based, high-throughput screening assay for utrophin promoter activation, and used it to screen the Prestwick Chemical Library of marketed drugs and natural compounds. Initial screening produced 20 hit molecules, 14 of which exhibited dose-dependent activation of the utrophin promoter and were confirmed as hits. Independent validation demonstrated that one of these compounds, nabumetone, is able to upregulate endogenous utrophin mRNA and protein, in C2C12 muscle cells. Conclusions/Significance We have developed a cell-based, high-throughput screening utrophin promoter assay. Using this assay, we identified and validated a utrophin promoter-activating drug, nabumetone, for which pharmacokinetics and safety in humans are already well described, and which represents a lead compound for utrophin upregulation as a therapy for DMD.
Translational Regulation of Utrophin by miRNAs
Utpal Basu, Olga Lozynska, Catherine Moorwood, Gopal Patel, Steve D. Wilton, Tejvir S. Khurana
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0029376
Abstract: Background Utrophin is the autosomal homolog of dystrophin, the product of the Duchenne Muscular Dystrophy (DMD) locus. Its regulation is of therapeutic interest as its overexpression can compensate for dystrophin's absence in animal models of DMD. The tissue distribution and transcriptional regulation of utrophin have been characterized extensively, and more recently translational control mechanisms that may underlie its complex expression patterns have begun to be identified. Methodology/Principal Findings Using a variety of bioinformatic, molecular and cell biology techniques, we show that the muscle isoform utrophin-A is predominantly suppressed at the translational level in C2C12 myoblasts. The extent of translational inhibition is estimated to be ~99% in C2C12 cells and is mediated by both the 5′- and 3′-UTRs of the utrophin-A mRNA. In this study we identify five miRNAs (let-7c, miR-150, miR-196b, miR-296-5p, miR-133b) that mediate the repression, and confirm repression by the previously identified miR-206. We demonstrate that this translational repression can be overcome by blocking the actions of miRNAs, resulting in an increased level of utrophin protein in C2C12 cells. Conclusions/Significance The present study has identified key inhibitory mechanisms featuring miRNAs that regulate utrophin expression, and demonstrated that these mechanisms can be targeted to increase endogenous utrophin expression in cultured muscle cells. We suggest that miRNA-mediated inhibitory mechanisms could be targeted by methods similar to those described here as a novel strategy to increase utrophin expression as a therapy for DMD.
The Relationship between Energy Literacy and Environmental Sustainability  [PDF]
Catherine Dwyer
Low Carbon Economy (LCE) , 2011, DOI: 10.4236/lce.2011.23016
Abstract: Sustainability, first identified as a characteristic of eco-systems, is the capacity to maintain a process indefinitely. Environmental sustainability receives significant public and government attention, triggered by concerns about climate change, decreasing energy supplies, and increasing food costs. Colleges and universities receive positive notice for their greening efforts, and the academy is expected to be a leader in efforts to improve sustainability. Therefore coursework and curricula must be developed to train students about sustainable resource consumption processes. This paper describes curricula materials related to energy literacy, defined as conceptual fluency with the economic and social components of energy use. These materials were developed and piloted over a three year period, and were tested with a pre- and post-course survey administered with questions based on the New Environmental Paradigm (NEP) and Environmentally Responsible Behavior (ERB). The findings of this study suggest that discussion of sustainability with disaster themes triggers anxiety that interferes with the development of ERB. In contrast, materials emphasizing the pragmatic necessity and benefits derived from sustainable practices relate to improvements in ERB. This suggests sustainability curricula should mitigate anxiety aroused by the topic, and instead emphasize pragmatic motivations for changing energy consumption patterns.
Film Subtitles as a Successful Vocabulary Learning Tool  [PDF]
Catherine Kanellopoulou
Open Journal of Modern Linguistics (OJML) , 2019, DOI: 10.4236/ojml.2019.92014
Abstract: Films are a valuable source of authentic language material, but what makes them superior to other types of authentic materials is the existence of a full storyline which leads to the increased engagement of the viewer. Despite the fact that teachers intuitively know this particular activity which may enhance language learning there is little research that has sought to thoroughly examine its potential impact on vocabulary acquisition and retention. While most studies conclude that the type of subtitling is an important factor influencing vocabulary learning; defining which particular type of subtitling is most effective seems difficult to determine and results in this area are somewhat inconclusive. Further research is, therefore, necessary to determine which type of subtitling would lead to optimum results in vocabulary acquisition and retention.
Sustainable Happiness and Well-Being: Future Directions for Positive Psychology  [PDF]
Catherine O’Brien
Psychology (PSYCH) , 2012, DOI: 10.4236/psych.2012.312A177
Abstract:

Positive psychology has influenced many disciplines in a very short span of time. This paper argues that positive psychology will realize its most significant and far reaching impact when it is applied to sustainability efforts, locally, nationally and internationally. Such application may accelerate shifts in attitudes, policies, practice and behavior. Specifically, opportunities for integrating positive psychology with sustainability education are discussed including work in the area of sustainable happiness, Education for Sustainable Development (ESD) and positive education. Sustainable happiness underscores the interrelationship between human flourishing and ecological resilience. Thus sustainable happiness and well-being are integral to building sustainable futures, and positive psychology could be increasingly influential in leading research and education that heralds a new era of understanding and political will to embrace sustainability.

Epilepsy versus non-epileptic attack disorder: A diagnostic and therapeutic challenge  [PDF]
Catherine Smith, Jason Ramtahal
Case Reports in Clinical Medicine (CRCM) , 2013, DOI: 10.4236/crcm.2013.21001
Abstract:

Epilepsy and non-epileptic attack disorder (NEAD) share a vast number of clinical features, however the aetiology and management are very different. Video-EEG is the gold standard diagnostic tool and relies on the occurrence of seizure activity during assessment to make a diagnosis. Added complexity arises from the co-existence of epilepsy and NEAD, occurring in a significant proportion of patients. Comprehensive assessment and investigation is therefore required to prevent gross mistreatment in this diagnostically difficult subgroup. We present a case of NEAD with co-existing epilepsy and the challenges that this may present in clinical practice.

Reduced Fasting Protocol for Endoscopic Percutaneous Gastrostomy in Intubated Patients  [PDF]
Catherine Ho, John Culhane
International Journal of Clinical Medicine (IJCM) , 2013, DOI: 10.4236/ijcm.2013.48066
Abstract:

Background: Previous studies have shown that ICU patients receive only a fraction of their calculated nutritional goals, and that cumulative caloric deficit in the ICU has been correlated with poor outcome. One reason for this underfeeding is the frequent interruption of enteral nutrition. Many ICU patients receive enteral feeding formula via a nasogastric (NG) tube. Feeding is typically held for several hours prior to procedures due to the theoretical risk of aspiration. An alternative is to continue feeding up until the procedure begins, then stop the feeding and place the NG to suction. This evacuates the contents of the stomach and minimizes the risk of aspiration, while reducing the interruption of feeding that can result in malnutrition. Methods: This study is a review of prospectively gathered data including 55 sequential patients who underwent bedside percutaneous endoscopic gastrostomy (PEG) placement in a mixed ICU under a reduced fasting protocol. This was compared with a historical cohort of 33 critically ill trauma patients who fasted for at least 8 hours prior to the procedure. Under the reduced fasting protocol, enteral feeding via NG was continued up until the time of the procedure. The NG was then placed to suction, and sedation was given. The NG was left in place until the esophagus was cannulated, then it was removed. The PEG was placed in standard fashion, and feeding was resumed via the PEG immediately following the procedure. Results: We have documented no peri-procedural vomiting or aspiration. New diagnosis of pneumonia within 3

English and Malay Text Messages and What They Say about Texts and Cultures  [PDF]
Ernisa Marzuki, Catherine Walter
Open Journal of Modern Linguistics (OJML) , 2013, DOI: 10.4236/ojml.2013.34037
Abstract: This study of the pragmatics of cross-cultural text messages throws light on the evolution of new hybrid forms of literacy and on the complex ways that culture is expressed and mediated in second language/ second culture contexts. An investigation was carried out into the pragmatics of apology in first-language (L1) and second-language (L2) short messaging service text messages of adult Malay speakers who are proficient users of English, living and studying in an English-speaking university environment; and into L1 English users’ text apologies in the same context. Research questions included whether these proficient L2 English users would perform differently from L1 English users in this high-stakes speech act, and from their own L1 Malay use; and whether apologies in what has been called a hybrid medium would differ from those previously studied in writing, in speech and in other electronic media. Twenty-six native speakers of English and 26 native speakers of Malay responded via text messages to discourse completion tests (DCTs) in L1; the DCTs represented either high or low levels of offence calling for apologies. The Malay native speakers also responded to apology situations in L2 English. Data were coded using an adapted version of Cohen and Olshtain’s (1981) coding scheme. Analysis of the messages sent by participants revealed clear signs of a hybrid type of text that is differently conceptualised by the two communities. It also showed that the Malay users’ second language literacy was shaped in a complex way that sometimes accommodated the second language/second culture and sometimes retained first language/first culture values.
Case Report: Propriospinal Myoclonus  [PDF]
Catherine Smith, Jason Ramtahal
Case Reports in Clinical Medicine (CRCM) , 2014, DOI: 10.4236/crcm.2014.36081
Abstract:

This report presents a case of propriospinal myoclonus (PSM) in a previously fit and well female patient who presented with truncal jerking movements when relaxed. Propriospinal myoclonus is a rare condition, of which 80% of the aetiology is idiopathic. It is characterised by involuntary jerking movements of the trunk due to spreading activity via intrinsic propriospinal pathways along the spinal cord. Polymyography is mandatory in the diagnosis of priopriospinal myoclonus however in discerning the differential diagnoses it is inferior to magnetic resonance diffusion tensor imaging. The management of propriospinal myoclonus is dependent on aetiology. Clonazepam has been shown to be effective in the treatment of idiopathic PSM for symptomatic relief.

Optimal Adiposity Measurement and Risk Stratification in Established Ischaemic Stroke  [PDF]
Olive Lennon, Catherine Blake
World Journal of Cardiovascular Diseases (WJCD) , 2014, DOI: 10.4236/wjcd.2014.413077
Abstract: Background: Prevention strategies post-stroke should target risk factor reduction which includes consideration of weight, diet and lipoprotein profiles. Limited data informs the optimal adiposity measurement post-stroke to target those at highest recurrent risk. This study aims to identify adiposity measurement/s post-stroke that best predict cardiovascular and co-morbid risk. Subjects and Methods: 142 stroke patients (100 males, 42 females; mean age 63 years) participated. Adiposity and metabolic profiles included BMI, waist circumference, waist to height ratio (WHR), triglyceride levels and hypertriglyceridemic waist. The predictive ability of these measures with indices of cardiovascular risk (Cardiovascular Risk Score) and co-morbidity (Charlson’s co-morbidity index) were examined. Results: In hierarchical multiple regression models, age and gender controlled, waist (p = 0.002), triglyceride levels (p = 0.006), BMI and WHR (p = 0.014), uniquely and significantly contributed to the variance in cardiovascular risk, in their models. Only one combination of measures (waist and triglyceride levels) improved the predictive ability of waist in cardiovascular risk stratification (p = 0.001). In men, waist (p = 0.013) and in women triglyceride levels (p = 0.012) performed as the best predictors of cardiovascular risk respectively. No combination of measures was superior to triglyceride levels in women or waist circumference measures in men in predicting cardiovascular risk. With Charlson’s co-morbidity index as the dependent variable, triglyceride levels significantly contributed to variance of the model with age and gender influences controlled (p = 0.047). No combination of measures improved the predictive ability of triglyceride levels for co-morbidity. Conclusion: Waist circumference and triglyceride levels should form a minimum dataset for adiposity when considering cardiovascular and comorbid risk post-stroke.
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