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Concannon C.G.,Royal College of Surgeons in Ireland | Tuffy L.P.,Royal College of Surgeons in Ireland | Weisova P.,Royal College of Surgeons in Ireland | Bonner H.P.,Royal College of Surgeons in Ireland | And 6 more authors.
Journal of Cell Biology | Year: 2010

Excitotoxicity after glutamate receptor overactivation induces disturbances in cellular ion gradients, resulting in necrosis or apoptosis. Excitotoxic necrosis is triggered by rapid, irreversible ATP depletion, whereas the ability to recover cellular bioenergetics is suggested to be necessary for the activation of excitotoxic apoptosis. In this study, we demonstrate that even a transient decrease in cellular bioenergetics and an associated activation of adenosine monophosphate-activated protein kinase (AMPK) is necessary for the activation of excitotoxic apoptosis. We show that the Bcl-2 homology domain 3 (BH3)-only protein Bim, a proapoptotic Bcl-2 family member, is activated in multiple excitotoxicity paradigms, mediates excitotoxic apoptosis, and inhibits delayed Ca2+ deregulation, mitochondrial depolarization, and apoptosisinducing factor translocation. We demonstrate that bim activation required the activation of AMPK and that prolonged AMPK activation is sufficient to induce bim gene expression and to trigger a bim-dependent cell death. Collectively, our data demonstrate that AMPK activation and the BH3-only protein Bim couple transient energy depletion to stress-induced neuronal apoptosis. © 2010 Cancannon et al.


News Article | September 8, 2016
Site: www.chromatographytechniques.com

Chemists from Trinity College Dublin, in collaboration with RCSI, have devised a revolutionary new scanning technique that produces extremely high-res 3-D images of bones—without exposing patients to X-ray radiation. The chemists attach luminescent compounds to tiny gold structures to form biologically safe 'nanoagents' that are attracted to calcium-rich surfaces, which appear when bones crack - even at a micro level. These nanoagents target and highlight the cracks formed in bones, allowing researchers to produce a complete 3-D image of the damaged regions. The technique will have major implications for the health sector as it can be used to diagnose bone strength and provide a detailed blueprint of the extent and precise positioning of any weakness or injury. Additionally, this knowledge should help prevent the need for bone implants in many cases, and act as an early-warning system for people at a high risk of degenerative bone diseases, such as osteoporosis. The research, led by the Trinity College Dublin team of Thorri Gunnlaugsson, professor of chemistry, and Esther Surender, postdoctoral researcher, has just been published in the journal Chem, a sister journal to Cell, which is published by Cell Press. "This work is the outcome of many years of successful collaboration between chemists from Trinity and medical and engineering experts from RCSI. We have demonstrated that we can achieve a three-dimensional map of bone damage, showing the so-called microcracks, using non-invasive luminescence imaging. The nanoagent we have developed allows us to visualise the nature and the extent of the damage in a manner that wasn't previously possible. This is a major step forward in our endeavour to develop targeted contrast agents for bone diagnostics for use in clinical applications," said Gunnlaugsson. The work was funded by Science Foundation Ireland and by the Irish Research Council, and benefited from collaboration with scientists at RCSI (Royal College of Surgeons in Ireland), led by Clive Lee, professor of anatomy. "Everyday activity loads our bones and causes microcracks to develop. These are normally repaired by a remodeling process, but, when microcracks develop faster, they can exceed the repair rate and so accumulate and weaken our bones. This occurs in athletes and leads to stress fractures. In elderly people with osteoporosis, microcracks accumulate because repair is compromised and lead to fragility fractures, most commonly in the hip, wrist and spine. Current X ray techniques can tell us about the quantity of bone present but they do not give much information about bone quality," said Lee. "By using our new nanoagent to label microcracks and detecting them with magnetic resonance imaging (MRI), we hope to measure both bone quantity and quality and identify those at greatest risk of fracture and institute appropriate therapy. Diagnosing weak bones before they break should therefore reduce the need for operations and implants - prevention is better than cure," he added. In addition to the unprecedented resolution of this imaging technique, another major step forward lies in it not exposing X-rays to patients. X-rays emit radiation and have, in some cases, been associated with an increased risk of cancer. The red emitting gold-based nanoagents used in this alternative technique are biologically safe - gold has been used safely by medics in a variety of ways in the body for some time. "These nanoagents have great potential for clinical application. Firstly, by using gold nanoparticles, we were able to lower the overall concentration of the agent that would have to be administered within the body, which is ideal from a clinical perspective. Secondly, by using what is called 'two-photon excitation' we were able to image bone structure using long wavelength excitation, which is not harmful or damaging to biological tissues," said Surender. "These nanoagents are similar to the contrast agents that are currently being utilized for MRI within the clinic, and hence have the potential to provide a novel means of medical bone diagnosis in the future. Specifically, by replacing the Europium with its sister ion Gadolinium, we can tune into the MRI activity of these nanoagents for future use alongside X-ray and computed tomography (CT) scans."


News Article | September 8, 2016
Site: phys.org

The chemists attach luminescent compounds to tiny gold structures to form biologically safe 'nanoagents' that are attracted to calcium-rich surfaces, which appear when bones crack - even at a micro level. These nanoagents target and highlight the cracks formed in bones, allowing researchers to produce a complete 3D image of the damaged regions. The technique will have major implications for the health sector as it can be used to diagnose bone strength and provide a detailed blueprint of the extent and precise positioning of any weakness or injury. Additionally, this knowledge should help prevent the need for bone implants in many cases, and act as an early-warning system for people at a high risk of degenerative bone diseases, such as osteoporosis. The research, led by the Trinity College Dublin team of Professor of Chemistry, Thorri Gunnlaugsson, and Postdoctoral Researcher, Esther Surender, has just been published in the leading journal Chem, a sister journal to Cell, which is published by Cell Press. Professor Gunnlaugsson said: "This work is the outcome of many years of successful collaboration between chemists from Trinity and medical and engineering experts from RCSI. We have demonstrated that we can achieve a three-dimensional map of bone damage, showing the so-called microcracks, using non-invasive luminescence imaging. The nanoagent we have developed allows us to visualise the nature and the extent of the damage in a manner that wasn't previously possible. This is a major step forward in our endeavour to develop targeted contrast agents for bone diagnostics for use in clinical applications." The work was funded by Science Foundation Ireland and by the Irish Research Council, and benefited from collaboration with scientists at RCSI (Royal College of Surgeons in Ireland), led by Professor of Anatomy, Clive Lee. Professor Lee said: "Everyday activity loads our bones and causes microcracks to develop. These are normally repaired by a remodelling process, but, when microcracks develop faster, they can exceed the repair rate and so accumulate and weaken our bones. This occurs in athletes and leads to stress fractures. In elderly people with osteoporosis, microcracks accumulate because repair is compromised and lead to fragility fractures, most commonly in the hip, wrist and spine. Current X ray techniques can tell us about the quantity of bone present but they do not give much information about bone quality." He continued: "By using our new nanoagent to label microcracks and detecting them with magnetic resonance imaging (MRI), we hope to measure both bone quantity and quality and identify those at greatest risk of fracture and institute appropriate therapy. Diagnosing weak bones before they break should therefore reduce the need for operations and implants - prevention is better than cure." In addition to the unprecedented resolution of this imaging technique, another major step forward lies in it not exposing X-rays to patients. X-rays emit radiation and have, in some cases, been associated with an increased risk of cancer. The red emitting gold-based nanoagents used in this alternative technique are biologically safe - gold has been used safely by medics in a variety of ways in the body for some time. Dr Esther Surender, Trinity, said: "These nanoagents have great potential for clinical application. Firstly, by using gold nanoparticles, we were able to lower the overall concentration of the agent that would have to be administered within the body, which is ideal from a clinical perspective. Secondly, by using what is called 'two-photon excitation' we were able to image bone structure using long wavelength excitation, which is not harmful or damaging to biological tissues." She added: "These nanoagents are similar to the contrast agents that are currently being utilised for MRI within the clinic, and hence have the potential to provide a novel means of medical bone diagnosis in the future. Specifically, by replacing the Europium with its sister ion Gadolinium, we can tune into the MRI activity of these nanoagents for future use alongside X-ray and computed tomography (CT) scans." Professor Gunnlaugsson and his research team are based in the Trinity Biomedical Sciences Institute (TBSI), which recently celebrated its 5-Year anniversary. Professor Gunnlaugsson presented his research at a symposium to mark the occasion, along with many other world-leaders in chemistry, immunology, bioengineering and cancer biology.


News Article | September 9, 2016
Site: www.rdmag.com

Chemists from Trinity College Dublin, in collaboration with RCSI, have devised a revolutionary new scanning technique that produces extremely high-res 3D images of bones -- without exposing patients to X-ray radiation. The chemists attach luminescent compounds to tiny gold structures to form biologically safe 'nanoagents' that are attracted to calcium-rich surfaces, which appear when bones crack - even at a micro level. These nanoagents target and highlight the cracks formed in bones, allowing researchers to produce a complete 3D image of the damaged regions. The technique will have major implications for the health sector as it can be used to diagnose bone strength and provide a detailed blueprint of the extent and precise positioning of any weakness or injury. Additionally, this knowledge should help prevent the need for bone implants in many cases, and act as an early-warning system for people at a high risk of degenerative bone diseases, such as osteoporosis. The research, led by the Trinity College Dublin team of Professor of Chemistry, Thorri Gunnlaugsson, and Postdoctoral Researcher, Esther Surender, has just been published in the leading journal Chem, a sister journal to Cell, which is published by CellPress. Professor Gunnlaugsson said: "This work is the outcome of many years of successful collaboration between chemists from Trinity and medical and engineering experts from RCSI. We have demonstrated that we can achieve a three-dimensional map of bone damage, showing the so-called microcracks, using non-invasive luminescence imaging. The nanoagent we have developed allows us to visualise the nature and the extent of the damage in a manner that wasn't previously possible. This is a major step forward in our endeavour to develop targeted contrast agents for bone diagnostics for use in clinical applications." The work was funded by Science Foundation Ireland and by the Irish Research Council, and benefited from collaboration with scientists at RCSI (Royal College of Surgeons in Ireland), led by Professor of Anatomy, Clive Lee. Professor Lee said: "Everyday activity loads our bones and causes microcracks to develop. These are normally repaired by a remodelling process, but, when microcracks develop faster, they can exceed the repair rate and so accumulate and weaken our bones. This occurs in athletes and leads to stress fractures. In elderly people with osteoporosis, microcracks accumulate because repair is compromised and lead to fragility fractures, most commonly in the hip, wrist and spine. Current X ray techniques can tell us about the quantity of bone present but they do not give much information about bone quality." He continued: "By using our new nanoagent to label microcracks and detecting them with magnetic resonance imaging (MRI), we hope to measure both bone quantity and quality and identify those at greatest risk of fracture and institute appropriate therapy. Diagnosing weak bones before they break should therefore reduce the need for operations and implants - prevention is better than cure." In addition to the unprecedented resolution of this imaging technique, another major step forward lies in it not exposing X-rays to patients. X-rays emit radiation and have, in some cases, been associated with an increased risk of cancer. The red emitting gold-based nanoagents used in this alternative technique are biologically safe - gold has been used safely by medics in a variety of ways in the body for some time. Dr Esther Surender, Trinity, said: "These nanoagents have great potential for clinical application. Firstly, by using gold nanoparticles, we were able to lower the overall concentration of the agent that would have to be administered within the body, which is ideal from a clinical perspective. Secondly, by using what is called 'two-photon excitation' we were able to image bone structure using long wavelength excitation, which is not harmful or damaging to biological tissues." She added: "These nanoagents are similar to the contrast agents that are currently being utilised for MRI within the clinic, and hence have the potential to provide a novel means of medical bone diagnosis in the future. Specifically, by replacing the Europium with its sister ion Gadolinium, we can tune into the MRI activity of these nanoagents for future use alongside X-ray and computed tomography (CT) scans." Professor Gunnlaugsson and his research team are based in the Trinity Biomedical Sciences Institute (TBSI), which recently celebrated its 5-Year anniversary. Professor Gunnlaugsson presented his research at a symposium to mark the occasion, along with many other world-leaders in chemistry, immunology, bioengineering and cancer biology.


Malone A.,Beaumont Hospital | Malone A.,Royal College of Surgeons in Ireland | Meldrum D.,Royal College of Surgeons in Ireland | Gleeson J.,RCSI | Bolger C.,Beaumont Hospital
Journal of Electromyography and Kinesiology | Year: 2011

The aims of this study were to validate a computerised method to detect muscle activity from surface electromyography (SEMG) signals in gait in patients with cervical spondylotic myelopathy (CSM), and to evaluate the test-retest reliability of the activation times designated by this method. SEMG signals were recorded from rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and medial gastrocnemius (MG), during gait in 12 participants with CSM on two separate test days. Four computerised activity detection methods, based on the Teager-Kaiser Energy Operator (TKEO), were applied to a subset of signals and compared to visual interpretation of muscle activation. The most accurate method was then applied to all signals for evaluation of test-retest reliability. A detection method based on a combined slope and amplitude threshold showed the highest agreement (87.5%) with visual interpretation. With respect to reliability, the standard error of measurement (SEM) of the timing of RF, TA and MG between test days was 5.5% stride duration or less, while the SEM of BF was 9.4%. The timing parameters of RF, TA and MG designated by this method were considered sufficiently reliable for use in clinical practice, however the reliability of BF was questionable. © 2011 Elsevier Ltd.


Kelleher E.,RCSI | Brugha R.,RCSI
Irish Medical Journal | Year: 2013

Well-trained and motivated medical staff are essential to a functioning health system. However, Ireland is struggling in this regard. As has been highlighted in numerous studies and reports over the years, Irish non-consultant hospital doctors (NCHDs) are demoralised and dissatisfied with working conditions in Ireland and are leaving in increasing numbers1-5. The other side of the coin is Ireland s growing reliance on overseas-trained doctors6, despite the successful scaling-up of numbers of EU (and therefore Irish) entrants to medical schools7.


Woznica A.,University of Silesia | Nowak A.,University of Silesia | Karczewski J.,University of Silesia | Klis C.,Institute for Ecology of Industrial Area | Bernas T.,RCSI
Chemosphere | Year: 2010

We describe an automatic biodetector for continuous monitoring of water toxicity (ABTOW). Construction of the ABTOW is based on natural ability of the biofilm formation to immobilize consortia of nitrifying bacteria (the sensing element) on the open cellular polyurethane foam as the support. Change of rates of oxygen consumption is used as an indicator of biocatalytic activity (nitrification) of the bacteria in response to xenobiotics. Owing to this design the ABTOW features stability long-term use, is inexpensive and simple in operation. The dynamics of ABTOW response is studied in details for phenol and cyanide as model toxins. These data indicate that the sensitivity was 3.5μM for phenol and 0.19μM for cyanide, respectively. The magnitudes of toxic effect were proportional to concentration whereas kinetics of the response is an indicator for the mechanism of toxicity. Similar methodology is applied to quantify toxicity of a range of heavy metals, herbicides and oxidative chain inhibitors. One may conclude that the presented biodetector provides a good sensitivity for continuous on-line monitoring of toxicity in water. © 2010 Elsevier Ltd.


Nally D.M.,University of Limerick | Kelly E.G.,RCSI | Clarke M.,RCSI | Ridgway P.,Trinity College Dublin
British Journal of Nutrition | Year: 2014

In patients with severe acute pancreatitis (AP), enteral nutrition is delivered by nasojejunal (NJ) tube to minimise pancreatic stimulation. Nasogastric (NG) feeding represents an alternative route. The primary objective of this systematic review and meta-analysis was to evaluate the efficacy of NG feeding. Secondary objectives were to compare the NG and NJ routes and assess the side effects of the former. The primary endpoint was exclusive NG feeding with delivery of 75 % of nutritional targets. Additional outcomes included change to total parenteral nutrition (TPN), increased pain or disease severity, vomiting, diarrhoea, delivery rate reduction and tube displacement. Among the retrieved studies, six were found to be eligible for the qualitative review and four for the meta-analysis. NG nutrition was received by 147 patients; exclusive NG feeding was achieved in 90 % (133/147). Of the 147 patients, 129 (87 %) received 75 % of the target energy. In studies where all subjects received exclusive NG nutrition, 82 % (seventy-four of the ninety patients) received >75 % of the intended energy. Compared with NJ nutrition, there was no significant difference in the delivery of 75 % of nutritional targets (pooled risk ratio (RR) 1.02; 95 % CI 0.75, 1.38.) or no increased risk of change to TPN (pooled RR 1.05; 95 % CI 0.45, 2.48), diarrhoea (pooled RR 1.28; 95 % CI 0.62, 2.66), exacerbation of pain (pooled RR 1.10; 95 % CI 0.47, 2.61) or tube displacement (pooled RR 0.44; 95 % CI 0.11, 1.73). Vomiting and diarrhoea were the most common side effects of NG feeding (13.3 and 12.9 %, respectively). With respect to the delivery of nutrition, 11.2 % of the patients required delivery rate reduction and 3.4 % dislodged the tube. Other side effects included elevated levels of aspirates (9.1 %), abdominal distension (1.5 %), pain exacerbation (7.5 %) and increased disease severity (1.6 %). In conclusion, NG feeding is efficacious in 90 % of patients. Further research is required to optimise the delivery of NG nutrition and examine 'gut-rousing' approaches to nutrition in patients with severe AP. Copyright © 2014 The Authors.


Delany C.,RCSI
Irish medical journal | Year: 2011

In 2008, planned folic acid fortification for the prevention of Neural Tube Defects (NTD) was postponed. Concurrently, the economic recession may have affected dietary folic acid intake, placing increased emphasis on supplement use. This study examined folic acid supplement use in 2009. A cross-sectional survey of 300 ante-natal women was undertaken to assess folic acid knowledge and use. Associations between demographic, obstetric variables and folic acid knowledge and use were examined. A majority, 284/297 (96%), had heard of folic acid, and 178/297 (60%) knew that it could prevent NTD. Most, 270/297 (91%) had taken it during their pregnancy, but only 107/297 (36%) had used it periconceptionally. Being older, married, planned pregnancy and better socioeconomic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from economic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from earlier years. Continuous promotion efforts are necessary. Close monitoring of folic acid intake and NTD rates is essential, particularly in the absence of fortification.


Kelleher E.,RCSI
Irish medical journal | Year: 2013

A standard application form for the ethical review of health-related research studies has recently been adopted by many Irish medical research ethics committees. In order to assess the impact of the new form, we reviewed all comments made by the Beaumont Hospital Ethics Committee during two six-month periods, immediately prior to adoption of the new form (2010), and soon afterwards (2011). Neither volume nor comment type differed significantly between the two observation periods. Participant documentation (information leaflets and consent forms) accounted for the largest proportion of comments (2010; 44%, 2011; 37%). Other common areas prompting queries were study administration (7%), design (12%) and procedures (13%), participant selection and recruitmen (8%), and lastly data protection (9%). Because of these findings, the standard operating procedures of the committee have been revised--use of provided template participant documentation is strongly encouraged, and a "Recurring Review Themes" checklist is highlighted to all applicants.

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