Publications by authors named "Ronán M Conroy"

66 Publications

Systemic delivery of antagomirs during blood-brain barrier disruption is disease-modifying in experimental epilepsy.

Mol Ther 2021 Feb 18. Epub 2021 Feb 18.

Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin D02 YN77, Ireland; FutureNeuro SFI Research Centre, Royal College of Surgeons in Ireland, Dublin D02 YN77, Ireland. Electronic address:

Oligonucleotide therapies offer precision treatments for a variety of neurological diseases, including epilepsy, but their deployment is hampered by the blood-brain barrier (BBB). Previous studies showed that intracerebroventricular injection of an antisense oligonucleotide (antagomir) targeting microRNA-134 (Ant-134) reduced evoked and spontaneous seizures in animal models of epilepsy. In this study, we used assays of serum protein and tracer extravasation to determine that BBB disruption occurring after status epilepticus in mice was sufficient to permit passage of systemically injected Ant-134 into the brain parenchyma. Intraperitoneal and intravenous injection of Ant-134 reached the hippocampus and blocked seizure-induced upregulation of miR-134. A single intraperitoneal injection of Ant-134 at 2 h after status epilepticus in mice resulted in potent suppression of spontaneous recurrent seizures, reaching a 99.5% reduction during recordings at 3 months. The duration of spontaneous seizures, when they occurred, was also reduced in Ant-134-treated mice. In vivo knockdown of LIM kinase-1 (Limk-1) increased seizure frequency in Ant-134-treated mice, implicating de-repression of Limk-1 in the antagomir mechanism. These studies indicate that systemic delivery of Ant-134 reaches the brain and produces long-lasting seizure-suppressive effects after systemic injection in mice when timed with BBB disruption and may be a clinically viable approach for this and other disease-modifying microRNA therapies.
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http://dx.doi.org/10.1016/j.ymthe.2021.02.021DOI Listing
February 2021

The Irish National Adverse Event Study-2 (INAES-2): longitudinal trends in adverse event rates in the Irish healthcare system.

BMJ Qual Saf 2021 Jan 12. Epub 2021 Jan 12.

Department of Geriatric and Stroke Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.

Objectives: To quantify the prevalence and nature of adverse events in acute Irish hospitals in 2015 and to assess the impact of the National Clinical Programmes and the National Clinical Guidelines on the prevalence of adverse events by comparing these results with the previously published data from 2009.

Design And Methods: A retrospective chart review of 1605 admissions to eight Irish hospitals in 2015, using identical methods to those used in 2009.

Results: The percentage of admissions associated with one or more adverse events was unchanged (p=0.48) at 14% (95% CI=10.4% to 18.4%) in 2015 compared with 12.2% (95% CI=9.5% to 15.5%) in 2009. Similarly, the prevalence of preventable adverse events was unchanged (p=0.3) at 7.4% (95% CI=5.3% to 10.5%) in 2015 compared with 9.1% (95% CI=6.9% to 11.9%) in 2009. The incidence densities of preventable adverse events were 5.6 adverse events per 100 admissions (95% CI=3.4 to 8.0) in 2015 and 7.7 adverse events per 100 admissions (95% CI=5.8 to 9.6) in 2009 (p=0.23). However, the percentage of preventable adverse events due to hospital-associated infections decreased to 22.2% (95% CI=15.2% to 31.1%) in 2015 from 33.1% (95% CI=25.6% to 41.6%) in 2009 (p=0.01).

Conclusion: Adverse event rates remained stable between 2009 and 2015. The percentage of preventable adverse events related to hospital-associated infection decreased, which may represent a positive impact of the related national programmes and guidelines.
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http://dx.doi.org/10.1136/bmjqs-2020-011122DOI Listing
January 2021

Childhood trauma and adult mental disorder: A systematic review and meta-analysis of longitudinal cohort studies.

Acta Psychiatr Scand 2021 03 18;143(3):189-205. Epub 2021 Jan 18.

Department of Psychology, Royal College of Surgeons in Ireland, Dublin, Ireland.

Objective: To systematically review evidence for the association between trauma experienced in childhood or adolescence, and the subsequent experience of affective or psychotic mental disorders in adulthood.

Methods: Electronic databases (Scopus, Medline (for Ovid), EMBASE and PsychINFO) were searched for peer-reviewed, longitudinal cohort studies in the English language examining child or adolescent exposure to trauma, and adult-diagnosed depression, anxiety, psychotic disorder or bipolar disorder. A total of 23 manuscripts were retained.

Results: Results revealed a significant association between the following childhood exposures and adult mental disorder: bullying (victimhood, perpetration and frequency); emotional abuse; physical neglect; parental loss; and general maltreatment (unspecified and/or multiple trauma exposure). There was some evidence of a dose-response relationship with those exposed to multiple forms of maltreatment having more than three times the odds of developing a mental disorder (Odds ratio = 3.11, 95% CI = 1.36-7.14). There was no significant association found between physical or sexual abuse and adult mental disorder; however, this is likely an artefact of how these adversities were assessed.

Conclusion: There is strong evidence of an association between childhood trauma and later mental illness. This association is particularly evident for exposure to bullying, emotional abuse, maltreatment and parental loss. The evidence suggests that childhood and adolescence are an important time for risk for later mental illness, and an important period in which to focus intervention strategies.
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http://dx.doi.org/10.1111/acps.13268DOI Listing
March 2021

Depression prevalence using the HADS-D compared to SCID major depression classification: An individual participant data meta-analysis.

J Psychosom Res 2020 12 23;139:110256. Epub 2020 Sep 23.

Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, Québec, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Québec, Canada; Department of Psychiatry, McGill University, Montréal, Québec, Canada; Department of Psychology, McGill University, Montréal, Québec, Canada; Department of Medicine, McGill University, Montréal, Québec, Canada; Department of Educational and Counselling Psychology, McGill University, Montréal, Québec, Canada; Biomedical Ethics Unit, McGill University, Montréal, Québec, Canada. Electronic address:

Objectives: Validated diagnostic interviews are required to classify depression status and estimate prevalence of disorder, but screening tools are often used instead. We used individual participant data meta-analysis to compare prevalence based on standard Hospital Anxiety and Depression Scale - depression subscale (HADS-D) cutoffs of ≥8 and ≥11 versus Structured Clinical Interview for DSM (SCID) major depression and determined if an alternative HADS-D cutoff could more accurately estimate prevalence.

Methods: We searched Medline, Medline In-Process & Other Non-Indexed Citations via Ovid, PsycINFO, and Web of Science (inception-July 11, 2016) for studies comparing HADS-D scores to SCID major depression status. Pooled prevalence and pooled differences in prevalence for HADS-D cutoffs versus SCID major depression were estimated.

Results: 6005 participants (689 SCID major depression cases) from 41 primary studies were included. Pooled prevalence was 24.5% (95% Confidence Interval (CI): 20.5%, 29.0%) for HADS-D ≥8, 10.7% (95% CI: 8.3%, 13.8%) for HADS-D ≥11, and 11.6% (95% CI: 9.2%, 14.6%) for SCID major depression. HADS-D ≥11 was closest to SCID major depression prevalence, but the 95% prediction interval for the difference that could be expected for HADS-D ≥11 versus SCID in a new study was -21.1% to 19.5%.

Conclusions: HADS-D ≥8 substantially overestimates depression prevalence. Of all possible cutoff thresholds, HADS-D ≥11 was closest to the SCID, but there was substantial heterogeneity in the difference between HADS-D ≥11 and SCID-based estimates. HADS-D should not be used as a substitute for a validated diagnostic interview.
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http://dx.doi.org/10.1016/j.jpsychores.2020.110256DOI Listing
December 2020

Genetic deletion of microRNA-22 blunts the inflammatory transcriptional response to status epilepticus and exacerbates epilepsy in mice.

Mol Brain 2020 08 21;13(1):114. Epub 2020 Aug 21.

Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin, D02 YN77, Ireland.

MicroRNAs perform important roles in the post-transcriptional regulation of gene expression. Sequencing as well as functional studies using antisense oligonucleotides indicate important roles for microRNAs during the development of epilepsy through targeting transcripts involved in neuronal structure, gliosis and inflammation. MicroRNA-22 (miR-22) has been reported to protect against the development of epileptogenic brain networks through suppression of neuroinflammatory signalling. Here, we used mice with a genetic deletion of miR-22 to extend these insights. Mice lacking miR-22 displayed normal behaviour and brain structure and developed similar status epilepticus after intraamygdala kainic acid compared to wildtype animals. Continuous EEG monitoring after status epilepticus revealed, however, an accelerated and exacerbated epilepsy phenotype whereby spontaneous seizures began sooner, occurred more frequently and were of longer duration in miR-22-deficient mice. RNA sequencing analysis of the hippocampus during the period of epileptogenesis revealed a specific suppression of inflammatory signalling in the hippocampus of miR-22-deficient mice. Taken together, these findings indicate a role for miR-22 in establishing early inflammatory responses to status epilepticus. Inflammatory signalling may serve anti-epileptogenic functions and cautions the timing of anti-inflammatory interventions for the treatment of status epilepticus.
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http://dx.doi.org/10.1186/s13041-020-00653-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441563PMC
August 2020

Intestinal parasitosis, anaemia and risk factors among pre-school children in Tigray region, northern Ethiopia.

BMC Infect Dis 2020 May 27;20(1):379. Epub 2020 May 27.

Department of Medical Microbiology, College of Health Sciences, Aksum University, Tigray, Ethiopia.

Background: Intestinal parasitic infections (IPIs) and anaemia are major health problems. This study assessed the prevalence of intestinal parasitic infections, anaemia and associated factors among pre-school children in rural areas of the Tigray region, northern Ethiopia.

Methods: A community based cross-sectional study was conducted among 610 pre-school children in rural communities of Northern Ethiopia from June 2017 to August 2017. Stool specimens were examined for the presence of trophozoites, cysts, oocysts, and ova using direct, formal-ethyl acetate concentration, Kato-Katz, and Ziehl-Neelsen techniques. Haemoglobin was measured using a HemoCue spectrometer.

Results: Among the 610 participating pre-school children in the study, the prevalence of IPIs and anaemia were 58% (95% conference interval (CI): 54.1-61.9%) and 21.6% (95% CI: 18.5-25.1%), respectively. Single, double, and triple parasitic infections were seen in 249 (41, 95% CI: 37-45%), 83 (14, 95% CI: 11-17%), and 22 (3.6, 95% CI: 2.4-5.4%) children, respectively. Of the seven intestinal parasitic organisms recorded from the participants, Entamoeba histolytica/dispar was the most prevalent 220 (36.1%) followed by Giardia lamblia 128 (20.1%), and Hymenolepis nana 102 (16.7%). Mixed infections were common among G. lamblia, E. histolytica/dispar and Cryptosporidium spp. oocyst. Intestinal parasitic infection prevalence increased from 47% in children aged 6-11 months to 66% in those aged 48-59 months; the prevalence ratio (PR) associated with a one-year increase in age was 1.08 (95% CI: 1.02-1.14, p = 0.009). Age-adjusted prevalence was higher in children who had been dewormed (PR = 1.2; 95% CI: 1.00-1.4, p = 0.045), and lower in households having two or more children aged under five (PR = 0.76, 95% CI: 0.61-0.95, p = 0.015). Anaemia rose from 28% in children aged 6-11 months to 43% in those aged 12-23 months, then fell continuously with age, reaching 7% in those aged 48-59 months. Age adjusted, anaemia was more prevalent in households using proper disposal of solid waste (PR = 1.5, 95% CI: 0.1-2.10, p = 0.009) while eating raw meat (PR = 0.49, 95% CI: 0.45-0.54, p = 0.000), any maternal education (PR = 0.64 95% CI: 0.52-0.79, p = 0.000), and household water treatment (PR = 0.75, 95% CI: 0.56-1.0, p = 0.044) were associated with lower prevalence of anaemia.

Conclusions: More than half of the children were infected with intestinal parasites, while anaemia prevalence was concentrated in the 12-23 month age group. This study has identified a number of potentially modifiable risk factors to address the significant prevalence of IPIs and anaemia in these children. Improvements in sanitation, clean water, hand hygiene, maternal education could address both short and long-term consequences of these conditions in this vulnerable population.
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http://dx.doi.org/10.1186/s12879-020-05101-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251880PMC
May 2020

Probability of major depression diagnostic classification based on the SCID, CIDI and MINI diagnostic interviews controlling for Hospital Anxiety and Depression Scale - Depression subscale scores: An individual participant data meta-analysis of 73 primary studies.

Authors:
Yin Wu Brooke Levis Ying Sun Ankur Krishnan Chen He Kira E Riehm Danielle B Rice Marleine Azar Xin Wei Yan Dipika Neupane Parash Mani Bhandari Mahrukh Imran Matthew J Chiovitti Nazanin Saadat Jill T Boruff Pim Cuijpers Simon Gilbody Dean McMillan John P A Ioannidis Lorie A Kloda Scott B Patten Ian Shrier Roy C Ziegelstein Melissa Henry Zahinoor Ismail Carmen G Loiselle Nicholas D Mitchell Marcello Tonelli Samir Al-Adawi Anna Beraldi Anna P B M Braeken Natalie Büel-Drabe Adomas Bunevicius Gregory Carter Chih-Ken Chen Gary Cheung Kerrie Clover Ronán M Conroy Daniel Cukor Carlos E da Rocha E Silva Eli Dabscheck Federico M Daray Elles Douven Marina G Downing Anthony Feinstein Panagiotis P Ferentinos Felix H Fischer Alastair J Flint Maiko Fujimori Pamela Gallagher Milena Gandy Simone Goebel Luigi Grassi Martin Härter Josef Jenewein Nathalie Jetté Miguel Julião Jae-Min Kim Sung-Wan Kim Marie Kjærgaard Sebastian Köhler Wim L Loosman Bernd Löwe Rocio Martin-Santos Loreto Massardo Yutaka Matsuoka Anja Mehnert Ioannis Michopoulos Laurent Misery Ricard Navines Meaghan L O'Donnell Ahmet Öztürk Jurate Peceliuniene Luis Pintor Jennie L Ponsford Terence J Quinn Silje E Reme Katrin Reuter Alasdair G Rooney Roberto Sánchez-González Marcelo L Schwarzbold Vesile Senturk Cankorur Juwita Shaaban Louise Sharpe Michael Sharpe Sébastien Simard Susanne Singer Lesley Stafford Jon Stone Serge Sultan Antonio L Teixeira Istvan Tiringer Alyna Turner Jane Walker Mark Walterfang Liang-Jen Wang Jennifer White Dana K Wong Andrea Benedetti Brett D Thombs

J Psychosom Res 2020 02 13;129:109892. Epub 2019 Dec 13.

Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, QC, Canada; Department of Psychiatry, McGill University, Montréal, QC, Canada; Department of Psychology, McGill University, Montréal, QC, Canada; Department of Medicine, McGill University, Montréal, QC, Canada; Department of Educational and Counselling Psychology, McGill University, Montréal, QC, Canada. Electronic address:

Objective: Two previous individual participant data meta-analyses (IPDMAs) found that different diagnostic interviews classify different proportions of people as having major depression overall or by symptom levels. We compared the odds of major depression classification across diagnostic interviews among studies that administered the Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D).

Methods: Data accrued for an IPDMA on HADS-D diagnostic accuracy were analysed. We fit binomial generalized linear mixed models to compare odds of major depression classification for the Structured Clinical Interview for DSM (SCID), Composite International Diagnostic Interview (CIDI), and Mini International Neuropsychiatric Interview (MINI), controlling for HADS-D scores and participant characteristics with and without an interaction term between interview and HADS-D scores.

Results: There were 15,856 participants (1942 [12%] with major depression) from 73 studies, including 15,335 (97%) non-psychiatric medical patients, 164 (1%) partners of medical patients, and 357 (2%) healthy adults. The MINI (27 studies, 7345 participants, 1066 major depression cases) classified participants as having major depression more often than the CIDI (10 studies, 3023 participants, 269 cases) (adjusted odds ratio [aOR] = 1.70 (0.84, 3.43)) and the semi-structured SCID (36 studies, 5488 participants, 607 cases) (aOR = 1.52 (1.01, 2.30)). The odds ratio for major depression classification with the CIDI was less likely to increase as HADS-D scores increased than for the SCID (interaction aOR = 0.92 (0.88, 0.96)).

Conclusion: Compared to the SCID, the MINI may diagnose more participants as having major depression, and the CIDI may be less responsive to symptom severity.
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http://dx.doi.org/10.1016/j.jpsychores.2019.109892DOI Listing
February 2020

Weight as an assay-independent predictor of poor response to enteric aspirin in cardiovascular patients.

Platelets 2020 May 18;31(4):530-535. Epub 2019 Sep 18.

Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland , Dublin, Ireland.

Aspirin non-response is associated with poor outcome but there is no agreement between the different methods to asses it. Weight has been shown to be a predictor of poor response but only using one method. In this study, we determine the effects of weight on different assays of platelet function. The response to aspirin was determined in 138 cardiology patients using serum thromboxane, arachidonic acid-induced platelet aggregation and VerifyNow©. Twenty-five percent of patients showed an inadequate response to aspirin in at least one assay on the initial test. After ensuring patient compliance only 5% of patients were considered to be non-responders. Only 9% of non-responders were non-responsive in all three assays. When switched to plain aspirin, only 2% of patients were non-responsive. All patients responded adequately to 150 mg aspirin. The non-responders were significantly heavier than responders (78.5 kg ± 14.0 (SD); BMI: 28.4 kg/m± 4.4 v's 102.6 kg ± 20.6, = .0016; BMI: 38.3 kg/m ± 7.6, = .0015). A rule-based approach of using plain aspirin in patients over 90 kg or BMI 32 along with patient education to ensure compliance will ensure that all patients respond to their aspirin without the need for testing.
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http://dx.doi.org/10.1080/09537104.2019.1667495DOI Listing
May 2020

Prevalence and relationship between burnout and depression in our future doctors: a cross-sectional study in a cohort of preclinical and clinical medical students in Ireland.

BMJ Open 2019 05 1;9(4):e023297. Epub 2019 May 1.

Faculty of Medicine and Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.

Objectives: This cross-sectional study was designed to measure burnout and its impact on risk of depression in a medical student population, comparing the preclinical and clinical years.

Design: We conducted a survey of 269 medical school students in both preclinical and clinical years at the Royal College of Surgeons in Ireland, using the Beck Depression Inventory-Fast Screen (BDI-FS), the Maslach Burnout Inventory-Student Survey and items assessing willingness to use mental health services. Burnout scores were calibrated to probability of depression caseness and classified as low risk (<25%), intermediate (25%-50%) and high risk (>50%) of depression.

Results: There was a 39% (95% CI 33% to 45%) prevalence of depressive caseness based on a score of ≥6 on the BDI-FS. Prevalence did not vary significantly between clinical and preclinical years. The rate of burnout varied significantly between years (p=0.032), with 35% in the high-burnout category in clinical years compared with 26% in preclinical years. Those in the low burnout category had a 13% overall prevalence of depressive symptoms, those in the intermediate category had a 38% prevalence and those in the high category had a 66% prevalence of depressive symptoms. Increasing emotional exhaustion (OR for one-tertile increase in score 2.0, p=0.011) and decreasing academic efficacy (OR 2.1, p=0.007) increased the odds of being unwilling to seek help for mental health problems (11%).

Conclusion: While previous studies have reported significant levels of burnout and depression, our method of calibrating burnout against depression allows burnout scores to be interpreted in terms of their impact on mental health. The high prevalences, in line with previous research, point to an urgent need to rethink the psychological pressures of health professions education.
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http://dx.doi.org/10.1136/bmjopen-2018-023297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502268PMC
May 2019

Antagonizing Increased Levels at the Chronic Stage of Experimental TLE Reduces Spontaneous Recurrent Seizures.

J Neurosci 2019 06 23;39(26):5064-5079. Epub 2019 Apr 23.

Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, 3584 CG Utrecht, The Netherlands,

Mesial temporal lobe epilepsy (mTLE) is a chronic neurological disease characterized by recurrent seizures. The antiepileptic drugs currently available to treat mTLE are ineffective in one-third of patients and lack disease-modifying effects. miRNAs, a class of small noncoding RNAs which control gene expression at the post-transcriptional level, play a key role in the pathogenesis of mTLE and other epilepsies. Although manipulation of miRNAs at acute stages has been reported to reduce subsequent spontaneous seizures, it is uncertain whether targeting miRNAs at chronic stages of mTLE can also reduce seizures. Furthermore, the functional role and downstream targets of most epilepsy-associated miRNAs remain poorly understood. Here, we show that is selectively upregulated within neurons in epileptic brain and report that targeting using antagomirs after onset of spontaneous recurrent seizures can reduce seizure activity at the chronic stage of experimental mTLE in male mice. Further, by using an unbiased approach combining immunoprecipitation and RNA sequencing, we identify several novel neuronal targets of , including Mef2 proteins are key regulators of excitatory synapse density. Mef2a and show reciprocal expression regulation in human (of both sexes) and experimental TLE, and regulates dendritic spine number and type through Mef2. Together, our data show that is target for reducing seizure activity in chronic epilepsy, and that deregulation of in epilepsy may alter expression and thereby affect synaptic function and plasticity. miRNAs are post-transcriptional regulators of gene expression with roles in the pathogenesis of epilepsy. However, the precise mechanism of action and therapeutic potential of most epilepsy-associated miRNAs remain poorly understood. Our study reveals dramatic upregulation of the key neuronal miRNA in both experimental and human mesial temporal lobe epilepsy. Silencing in experimental temporal lobe epilepsy reduces seizure activity at the spontaneous recurrent seizure stage. These data support the exciting possibility that miRNAs can be targeted to combat seizures after spontaneous seizure activity has been established. Further, by using unbiased approaches novel neuronal targets of , including members of the Mef2 protein family, are identified that begin to explain how deregulation of may contribute to epilepsy.
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http://dx.doi.org/10.1523/JNEUROSCI.3014-18.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595945PMC
June 2019

Does stroke health promotion increase awareness of appropriate behavioural response? Impact of the face, arm, speech and time (FAST) campaign on population knowledge of stroke risk factors, warning signs and emergency response.

Eur Stroke J 2018 Jun 11;3(2):117-125. Epub 2018 Jan 11.

3Department of Epidemiology & Public Health Medicine, Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin 2, Ireland.

Introduction: Inability to identify stroke warning signs accurately is an important cause of delay in seeking medical attention, leading to potential ineligibility for acute intervention. We report on post-campaign findings (wave 2) of national surveys to estimate changes in population knowledge following a media-based Face, Arm, Speech, Time stroke awareness campaign, comparing findings to those of a pre-campaign population survey (wave 1). One thousand and ten randomly selected adults (18+) completed the Stroke Awareness Questionnaire on knowledge of warning signs, risk factors and response to stroke at wave 2 and findings were compared to wave 1 survey results. Logistic regression was used to examine the association between demographic characteristics and self-reported risk factors with knowledge of stroke and emergency response.

Results: No significant differences existed in the ability of respondents to define stroke or to identify two or more stroke risk factors between waves 1 and 2 surveys (71% and 70%, respectively). Respondents to the wave 2 survey were five times more likely (odds ratio 4.9,  < .001) than those responding at wave 1 to know at least two warning signs of stroke (67% vs. 31%, respectively), specifically those targeted by the Face, Arm, Speech, Time campaign. While significant improvement in intention to call an ambulance was noted (odds ratio 1.5,  < .001, 57% at wave 2 compared to 47% at wave 1), for almost half of respondents (43%) this would not have been their first response to stroke. Less than 5% of respondents to both surveys identified thrombolysis as an emergency treatment for stroke (3.9% at wave 2 compared to 1.8% at wave 1).

Discussion: Although significant improvements were made in several areas of stroke knowledge and intended response, awareness of acute stroke interventions was poor and intended behavioural response was suboptimal.

Conclusion: Findings from this study indicate need for targeted campaigns to improve population understanding of the reasons underlying the importance of rapid emergency response to stroke.
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http://dx.doi.org/10.1177/2396987317753453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460411PMC
June 2018

Use of a Novel Measure of Nontechnical Skills in Surgical Trainees: Is There an Association With Technical Skills Performance?

J Surg Educ 2019 Mar - Apr;76(2):519-528. Epub 2018 Oct 26.

National Surgical Training Centre, Royal College of Surgeons in Ireland, Dublin, Ireland. Electronic address:

Objective: To investigate whether scores on a psychological measure of concentration and interpersonal characteristics, The Attentional and Interpersonal Style Inventory (TAIS), are associated with performance of surgical skills.

Design: Postgraduate surgical trainees completed an operative surgical skills assessment in the simulation laboratory and the psychological measure (TAIS). The surgical skills assessment consisted of 6 tasks (3 per trainee): laceration suturing; lipoma excision; incision and closure of a laparotomy wound; bowel anastomosis; saphenofemoral junction ligation and basic laparoscopic skills. The association between operative surgical skill performance and TAIS factors was investigated.

Setting: The TAIS assessments and surgical skills assessments were conducted at the National Surgical Training Centre at the Royal College of Surgeons in Ireland (RCSI).

Participants: One hundred and two surgical trainees in years one and two (PGY 2-3 equivalent) participated in the study.

Results: Performance on 2 of the 6 tasks assessed (bowel anastomosis and lipoma excision) were positively associated with multiple TAIS factors (energy, confidence, competitiveness, extroversion, self-criticism and performing under pressure). Another factor, focus over time, was significantly associated with scores on the lipoma excision task.

Conclusions: Trainees with high levels of energy, confidence, competitiveness, extroversion, and focus over time and low levels of self-criticism demonstrated better performance on specific technical skills tasks.
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http://dx.doi.org/10.1016/j.jsurg.2018.08.012DOI Listing
September 2020

A novel statistical method for assessing effective adherence to medication and calculating optimal drug dosages.

PLoS One 2018 20;13(4):e0195663. Epub 2018 Apr 20.

Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.

Objective: We derive a novel model-based metric for effective adherence to medication, and validate it using data from the INhaler Compliance Assessment device (INCATM). This technique employs dose timing data to estimate the threshold drug concentration needed to maintain optimal health.

Methods: The parameters of the model are optimised against patient outcome data using maximum likelihood methods. The model is fitted and validated by secondary analysis of two independent datasets from two remote-monitoring studies of adherence, conducted through clinical research centres of 5 Irish hospitals. Training data came from a cohort of asthma patients (~ 47,000 samples from 218 patients). Validation data is from a cohort of 204 patients with COPD recorded between 2014 and 2016.

Results: The time above threshold measure is strongly predictive of adverse events (exacerbations) in COPD patients (Odds Ratio of exacerbation = 0.52 per SD increase in adherence, 95% Confidence Interval [0.34-0.79]). This compares well with the best known previous method, the Area Under the dose-time Curve (AUC) (Odds Ratio = 0.69, 95% Confidence Interval [0.48-0.99]). In addition, the fitted value of the dose threshold (0.56 of prescribed dosage) suggests that prescribed doses may be unnecessarily high given good adherence.

Conclusions: The resulting metric accounts for missed doses, dose-timing errors, and errors in inhaler technique, and provides enhanced predictive validity in comparison to previously used measures. In addition, the method allows us to estimate the correct dosage required to achieve the effect of the medication using the patients' own adherence data and outcomes. The adherence score does depend not on sex or other demographic factors suggesting that effective adherence is driven by individual behavioural factors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195663PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909911PMC
July 2018

Potent Anti-seizure Effects of Locked Nucleic Acid Antagomirs Targeting miR-134 in Multiple Mouse and Rat Models of Epilepsy.

Mol Ther Nucleic Acids 2017 Mar 10;6:45-56. Epub 2016 Dec 10.

Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin D02 YN77, Ireland. Electronic address:

Current anti-epileptic drugs (AEDs) act on a limited set of neuronal targets, are ineffective in a third of patients with epilepsy, and do not show disease-modifying properties. MicroRNAs are small noncoding RNAs that regulate levels of proteins by post-transcriptional control of mRNA stability and translation. MicroRNA-134 is involved in controlling neuronal microstructure and brain excitability and previous studies showed that intracerebroventricular injections of locked nucleic acid (LNA), cholesterol-tagged antagomirs targeting microRNA-134 (Ant-134) reduced evoked and spontaneous seizures in mouse models of status epilepticus. Translation of these findings would benefit from evidence of efficacy in non-status epilepticus models and validation in another species. Here, we report that electrographic seizures and convulsive behavior are strongly reduced in adult mice pre-treated with Ant-134 in the pentylenetetrazol model. Pre-treatment with Ant-134 did not affect the severity of status epilepticus induced by perforant pathway stimulation in adult rats, a toxin-free model of acquired epilepsy. Nevertheless, Ant-134 post-treatment reduced the number of rats developing spontaneous seizures by 86% in the perforant pathway stimulation model and Ant-134 delayed epileptiform activity in a rat ex vivo hippocampal slice model. The potent anticonvulsant effects of Ant-134 in multiple models may encourage pre-clinical development of this approach to epilepsy therapy.
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http://dx.doi.org/10.1016/j.omtn.2016.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363384PMC
March 2017

Effects of P2X7 receptor antagonists on hypoxia-induced neonatal seizures in mice.

Neuropharmacology 2017 04 10;116:351-363. Epub 2017 Jan 10.

Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; Irish Centre for Fetal and Neonatal Translational Research (INFANT) Cork, Ireland. Electronic address:

Neonatal seizures are a common consequence of hypoxic/ischemic encephalopathy (HIE). Phenobarbital remains the frontline treatment for neonatal seizures but is often ineffective. The P2X7 receptor (P2X7R) is a cell surface-expressed ionotropic receptor activated by high amounts of ATP which may be released during seizures or as a consequence of tissue injury. Here, we explored the role of the P2X7R in a mouse model of neonatal seizures induced by hypoxia. Exposure of postnatal day 7 (P7) mouse pups to global hypoxia (5% O for 15 min) produced electrographically-defined seizures with behavioural correlates that persisted after restitution of normoxia. Expression of the P2X7R showed age-dependent increases in the hippocampus and neocortex of developing mice and was present in human neonatal brain. P2X7R transcript and protein levels were increased 24 h after neonatal hypoxia-induced seizures in mouse pups. EEG recordings in pups determined that injection of the P2X7R antagonist A-438079 (25 mg/kg, intraperitoneal) reduced electrographic seizure number, EEG power and spiking during hypoxia. A-438079 did not reduce post-hypoxia seizures. Caspase-1 processing and molecular markers of inflammation and microglia were reduced in A438079-treated mice. Electrographic seizure-suppressive effects were also observed with a second P2X7R antagonist, JNJ-47965567, in the same model. The present study shows hypoxia-induced seizures alter expression of purinergic and neuroinflammatory signalling components and suggest potential applications but also limitations of the P2X7R as a target for the treatment of HIE and other causes of neonatal seizures.
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http://dx.doi.org/10.1016/j.neuropharm.2017.01.005DOI Listing
April 2017

Distinct behavioral and epileptic phenotype differences in 129/P mice compared to C57BL/6 mice subject to intraamygdala kainic acid-induced status epilepticus.

Epilepsy Behav 2016 11 13;64(Pt A):186-194. Epub 2016 Oct 13.

Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin, 2, Ireland. Electronic address:

Animal models of status epilepticus are important tools to understand the pathogenesis of epileptic brain injury and evaluate potential seizure-suppressive, neuroprotective, and antiepileptogenic treatments. Focal elicitation of status epilepticus by intraamygdala kainic acid in mice produces unilateral hippocampal damage and the emergence of spontaneous recurrent seizures after a short latent period. The model has been characterized in C57BL/6, BALB/c, and SJL mice where strain-specific differences were found in the extent of hippocampal damage. 129/P mice are a common background strain for genetic models and may display unique characteristics in this model. We therefore compared responses to intraamygdala kainic acid between 129/P and C57BL/6 mice. Racine scale-scored convulsive behavior during status epilepticus was substantially lower in 129/P mice compared with that in C57BL/6 mice. Analysis of surface-recorded electroencephalogram (EEG) showed differences between strains in several frequency bands; EEG total power was greater during ictal episodes while duration of seizures was slightly shorter in 129/P mice. Histological analysis revealed similar hippocampal injury between strains, with neuronal death mainly confined to the ipsilateral CA3 subfield. Expression of genes associated with gliosis and neuroinflammatory responses was also similar between strains after seizures. Video-EEG telemetry recordings showed that 129/P mice first display spontaneous seizures within a few days of status epilepticus similar to C57BL/6 mice. However, high mortality in 129/P mice prevented a quantitative comparison of the epileptic seizure phenotypes between strains. This study defined behavioral, EEG, and histopathologic features of this mouse strain in a model increasingly useful for the study of the genetic contribution to acquired epilepsy. Intraamygdala kainic acid in 129/P mice could serve as a model of nonconvulsive status epilepticus, but long-term assessments will require model adjustment to mitigate the severity of the emergent epileptic phenotype.
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http://dx.doi.org/10.1016/j.yebeh.2016.09.031DOI Listing
November 2016

Transient P2X7 Receptor Antagonism Produces Lasting Reductions in Spontaneous Seizures and Gliosis in Experimental Temporal Lobe Epilepsy.

J Neurosci 2016 06;36(22):5920-32

Department of Physiology and Medical Physics, and

Unlabelled: Neuroinflammation is thought to contribute to the pathogenesis and maintenance of temporal lobe epilepsy, but the underlying cell and molecular mechanisms are not fully understood. The P2X7 receptor is an ionotropic receptor predominantly expressed on the surface of microglia, although neuronal expression has also been reported. The receptor is activated by the release of ATP from intracellular sources that occurs during neurodegeneration, leading to microglial activation and inflammasome-mediated interleukin 1β release that contributes to neuroinflammation. Using a reporter mouse in which green fluorescent protein is induced in response to the transcription of P2rx7, we show that expression of the receptor is selectively increased in CA1 pyramidal and dentate granule neurons, as well as in microglia in mice that developed epilepsy after intra-amygdala kainic acid-induced status epilepticus. P2X7 receptor levels were increased in hippocampal subfields in the mice and in resected hippocampus from patients with pharmacoresistant temporal lobe epilepsy. Cells transcribing P2rx7 in hippocampal slices from epileptic mice displayed enhanced agonist-evoked P2X7 receptor currents, and synaptosomes from these animals showed increased P2X7 receptor levels and altered calcium responses. A 5 d treatment of epileptic mice with systemic injections of the centrally available, potent, and specific P2X7 receptor antagonist JNJ-47965567 (30 mg/kg) significantly reduced spontaneous seizures during continuous video-EEG monitoring that persisted beyond the time of drug presence in the brain. Hippocampal sections from JNJ-47965567-treated animals obtained >5 d after treatment ceased displayed strongly reduced microgliosis and astrogliosis. The present study suggests that targeting the P2X7 receptor has anticonvulsant and possibly disease-modifying effects in experimental epilepsy.

Significance Statement: Temporal lobe epilepsy is the most common and drug-resistant form of epilepsy in adults. Neuroinflammation is implicated as a pathomechanism, but the upstream mechanisms driving gliosis and how important this is for seizures remain unclear. In our study, we show that the ATP-gated P2X7 receptor is upregulated in experimental epilepsy and resected hippocampus from epilepsy patients. Targeting the receptor with a new centrally available antagonist, JNJ-47965567, suppressed epileptic seizures well beyond the time of treatment and reduced underlying gliosis in the hippocampus. The findings suggest a potential disease-modifying treatment for epilepsy based on targeting the P2X7 receptor.
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http://dx.doi.org/10.1523/JNEUROSCI.4009-15.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601816PMC
June 2016

The Irish National Adverse Events Study (INAES): the frequency and nature of adverse events in Irish hospitals-a retrospective record review study.

BMJ Qual Saf 2017 02 9;26(2):111-119. Epub 2016 Feb 9.

Department of Geriatric and Stroke Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.

Introduction: Irish healthcare has undergone extensive change recently with spending cuts and a focus on quality initiatives; however, little is known about adverse event occurrence.

Objective: To assess the frequency and nature of adverse events in Irish hospitals.

Methods: 1574 (53% women, mean age 54 years) randomly selected adult inpatient admissions from a sample of eight hospitals, stratified by region and size, across the Republic of Ireland in 2009 were reviewed using two-stage (nurse review of patient charts, followed by physician review of triggered charts) retrospective chart review with electronic data capture. Results were weighted to reflect the sampling strategy. The impact on adverse event rate of differing application of international adverse event criteria was also examined.

Results: 45% of charts were triggered. The prevalence of adverse events in admissions was 12.2% (95% CI 9.5% to 15.5%), with an incidence of 10.3 events per 100 admissions (95% CI 7.5 to 13.1). Over 70% of events were considered preventable. Two-thirds were rated as having a mild-to-moderate impact on the patient, 9.9% causing permanent impairment and 6.7% contributing to death. A mean of 6.1 added bed days was attributed to events, representing an expenditure of €5550 per event. The adverse event rate varied substantially (8.6%-17.0%) when applying different published adverse event eligibility criteria.

Conclusions: This first study of adverse events in Ireland reports similar rates to other countries. In a time of austerity, adverse events in adult inpatients were estimated to cost over €194 million. These results provide important baseline data on the adverse event burden and, alongside web-based chart review, provide an incentive and methodology to monitor future patient-safety initiatives.
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http://dx.doi.org/10.1136/bmjqs-2015-004828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5284341PMC
February 2017

Antagomirs targeting microRNA-134 increase hippocampal pyramidal neuron spine volume in vivo and protect against pilocarpine-induced status epilepticus.

Brain Struct Funct 2015 Jul 30;220(4):2387-99. Epub 2014 May 30.

Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.

Emerging data support roles for microRNA (miRNA) in the pathogenesis of various neurologic disorders including epilepsy. MicroRNA-134 (miR-134) is enriched in dendrites of hippocampal neurons, where it negatively regulates spine volume. Recent work identified upregulation of miR-134 in experimental and human epilepsy. Targeting miR-134 in vivo using antagomirs had potent anticonvulsant effects against kainic acid-induced seizures and was associated with a reduction in dendritic spine number. In the present study, we measured dendritic spine volume in mice injected with miR-134-targeting antagomirs and tested effects of the antagomirs on status epilepticus triggered by the cholinergic agonist pilocarpine. Morphometric analysis of over 6,400 dendritic spines in Lucifer yellow-injected CA3 pyramidal neurons revealed increased spine volume in mice given antagomirs compared to controls that received a scrambled sequence. Treatment of mice with miR-134 antagomirs did not alter performance in a behavioral test (novel object location). Status epilepticus induced by pilocarpine was associated with upregulation of miR-134 within the hippocampus of mice. Pretreatment of mice with miR-134 antagomirs reduced the proportion of animals that developed status epilepticus following pilocarpine and increased animal survival. In antagomir-treated mice that did develop status epilepticus, seizure onset was delayed and total seizure power was reduced. These studies provide in vivo evidence that miR-134 regulates spine volume in the hippocampus and validation of the seizure-suppressive effects of miR-134 antagomirs in a model with a different triggering mechanism, indicating broad conservation of anticonvulsant effects.
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http://dx.doi.org/10.1007/s00429-014-0798-5DOI Listing
July 2015

Mortality after surgery in Ireland.

Lancet 2013 Dec;382(9910):2063

Department of Psychology, Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin 2, Ireland.

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http://dx.doi.org/10.1016/S0140-6736(13)62685-9DOI Listing
December 2013

Does aptitude influence the rate at which proficiency is achieved for laparoscopic appendectomy?

J Am Coll Surg 2013 Dec 17;217(6):1020-7. Epub 2013 Sep 17.

National Surgical Training Centre, Royal College of Surgeons in Ireland, Dublin, Ireland. Electronic address:

Background: The attainment of technical competence for surgical procedures is fundamental to a proficiency-based surgical training program. We hypothesized that aptitude may directly affect one's ability to successfully complete the learning curve for minimally invasive procedures. The aim was to assess whether aptitude has an impact on ability to achieve proficiency in completing a simulated minimally invasive surgical procedure. The index procedure chosen was a laparoscopic appendectomy.

Study Design: Two groups of medical students with disparate aptitude were selected. Aptitude (visual-spatial, depth perception, and psychomotor ability) was measured by previously validated tests. Indicators of technical proficiency for laparoscopic appendectomy were established by trained surgeons with an individual case volume of more than 150. All subjects were tested consecutively on the ProMIS III (Haptica) until they reached predefined proficiency in this procedure. Simulator metrics, critical error scores, and Objective Structured Assessment of Technical Skills (OSATS) scores were recorded.

Results: The mean numbers of attempts to achieve proficiency in performing a laparoscopic appendectomy for group A (high aptitude) and B (low aptitude) were 6 (range 4 to 7) and 14 (range 10 to 18), respectively (p < 0.0001). Significant differences were found between the 2 groups for path length (p = 0.014), error score (p = 0.021), and OSATS score (p < 0.0001) at the initial attempt.

Conclusions: High aptitude is directly related to a rapid attainment of proficiency. These findings suggest that resource allocation for proficiency-based technical training in surgery may need to be tailored according to a trainee's natural ability.
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http://dx.doi.org/10.1016/j.jamcollsurg.2013.07.405DOI Listing
December 2013

Psychometric evaluation of the CASP-19 quality of life scale in an older Irish cohort.

Qual Life Res 2013 Nov 16;22(9):2549-59. Epub 2013 Mar 16.

Royal College of Surgeons in Ireland, Beaux Lane House, Lwr Mercer St, Dublin 2, Ireland,

Purpose: This study aims to evaluate the validity of current measurement models for the control, autonomy, self-realisation, and pleasure (CASP) measure of quality of life (QoL)-a second-order four-factor CASP-19 model and a second-order three-factor CASP-12 version-in a recent population survey. A previous large sample study did not report good fit for these measurement models. The study also aims to re-develop the model and propose a well-fitting alternative.

Methods: To evaluate the current measurement models, confirmatory factor analysis (CFA) was used. A cross-sectional sample (n = 6,823) representative of the Irish community-dwelling population aged 50 and over was obtained from the Irish Longitudinal Study of Ageing (TILDA). Model revision was based on descriptive statistics, exploratory factor analysis and examination of fit diagnostic statistics. Revised models were tested using CFA.

Results: The results of the CFA did not support the validity of the established measurement models. A reformulated 12-item, two-factor model comprising control/autonomy and self-realisation/pleasure, with residual covariances for negatively worded items, had excellent fit to the data (χ(2) 161.90, df = 44, p < 0.001; RMSEA = 0.03, 90 % CI 0.02-0.03), and a clearer conceptual rationale. The same model with one overall QoL factor had similar excellent fit.

Conclusions: We recommend the use of the single-factor model (CASP-R12) when assessing overall quality of life. The dimensions of control/autonomy and self-realisation/pleasure can be examined separately by researchers interested in those constructs. Researchers using structural equation modelling can use the well-fitting measurement model outlined here including adjustment for residual covariances.
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http://dx.doi.org/10.1007/s11136-013-0388-7DOI Listing
November 2013

Solar water disinfection (SODIS): a review from bench-top to roof-top.

J Hazard Mater 2012 Oct 7;235-236:29-46. Epub 2012 Aug 7.

Royal College of Surgeons in Ireland, Dublin 2, Ireland.

Solar water disinfection (SODIS) has been known for more than 30 years. The technique consists of placing water into transparent plastic or glass containers (normally 2L PET beverage bottles) which are then exposed to the sun. Exposure times vary from 6 to depending on the intensity of sunlight and sensitivity of the pathogens. Its germicidal effect is based on the combined effect of thermal heating of solar light and UV radiation. It has been repeatedly shown to be effective for eliminating microbial pathogens and reduce diarrhoeal morbidity including cholera. Since 1980 much research has been carried out to investigate the mechanisms of solar radiation induced cell death in water and possible enhancement technologies to make it faster and safer. Since SODIS is simple to use and inexpensive, the method has spread throughout the developing world and is in daily use in more than 50 countries in Asia, Latin America, and Africa. More than 5 million people disinfect their drinking water with the solar disinfection (SODIS) technique. This review attempts to revise all relevant knowledge about solar disinfection from microbiological issues, laboratory research, solar testing, up to and including real application studies, limitations, factors influencing adoption of the technique and health impact.
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http://dx.doi.org/10.1016/j.jhazmat.2012.07.053DOI Listing
October 2012

Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects.

Nat Med 2012 Jul;18(7):1087-94

Department of Physiology and Medical Physics and Centre for Study of Neurological Disorders, Royal College of Surgeons in Ireland, Dublin, Ireland.

Temporal lobe epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of neurological disorders. In experimental models of prolonged, injurious seizures (status epilepticus) and in human epilepsy, we found upregulation of miR-134, a brain-specific, activity-regulated miRNA that has been implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21% and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus in mice reduced the later occurrence of spontaneous seizures by over 90% and mitigated the attendant pathological features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure-suppressant and neuroprotective actions; determining whether these are anticonvulsant effects or are truly antiepileptogenic effects requires additional experimentation.
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http://dx.doi.org/10.1038/nm.2834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438344PMC
July 2012

AIB1:ERα transcriptional activity is selectively enhanced in aromatase inhibitor-resistant breast cancer cells.

Clin Cancer Res 2012 Jun 1;18(12):3305-15. Epub 2012 May 1.

Endocrine Oncology Research Group, Department of Surgery and Epidemiology, Royal College of Surgeons in Ireland, University College Dublin, Dublin, Ireland.

Purpose: The use of aromatase inhibitors (AI) in the treatment of estrogen receptor (ER)-positive, postmenopausal breast cancer has proven efficacy. However, inappropriate activation of ER target genes has been implicated in the development of resistant tumors. The ER coactivator protein AIB1 has previously been associated with initiation of breast cancer and resistance to endocrine therapy.

Experimental Design: Here, we investigated the role of AIB1 in the deregulation of ER target genes occurring as a consequence of AI resistance using tissue microarrays of patients with breast cancer and cell line models of resistance to the AI letrozole.

Results: Expression of AIB1 associated with disease recurrence (P = 0.025) and reduced disease-free survival time (P = 0.0471) in patients treated with an AI as first-line therapy. In a cell line model of resistance to letrozole (LetR), we found ERα/AIB1 promoter recruitment and subsequent expression of the classic ER target genes pS2 and Myc to be constitutively upregulated in the presence of both androstenedione and letrozole. In contrast, the recruitment of the ERα/AIB1 transcriptional complex to the nonclassic ER target cyclin D1 and its subsequent expression remained sensitive to steroid treatment and could be inhibited by treatment with letrozole. Molecular studies revealed that this may be due in part to direct steroid regulation of c-jun-NH(2)-kinase (JNK), signaling to Jun and Fos at the cyclin D1 promoter.

Conclusion: This study establishes a role for AIB1 in AI-resistant breast cancer and describes a new mechanism of ERα/AIB1 gene regulation which could contribute to the development of an aggressive tumor phenotype.
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http://dx.doi.org/10.1158/1078-0432.CCR-11-3300DOI Listing
June 2012

From prevention to nursing home care: a comprehensive national audit of stroke care.

Cerebrovasc Dis 2011 8;32(4):385-92. Epub 2011 Oct 8.

School of Physiotherapy, Royal College of Surgeons in Ireland, Dublin, Ireland.

Background: Many countries are developing national audits of stroke care. However, these typically focus on stroke care from acute event to hospital discharge rather than the full spectrum from prevention to long-term care. We report on a comprehensive national audit of stroke care in the community and hospitals in the Republic of Ireland. The findings provide insights into the wider needs of people with stroke and their families, a basis for developing stroke-appropriate health strategies, and a global model for the evaluation of stroke services.

Methods: Six national surveys were completed: general practitioners (prevention and primary care), hospital organisational and clinical audit of 2,570 consecutive stroke admissions (acute and hospital care), allied health professionals and public health nurses (discharge to community care), nursing homes (needs of patients discharged to long-term care), and patient and carers (post-hospital phase of rehabilitation and ongoing care).

Results: The audit identified substantial deficits in a number of areas including primary prevention, emergency assessment/investigation and treatment in hospital, discharge planning, rehabilitation and ongoing secondary prevention, and communication with patients and families. There was a lack of coordination and communication between the acute and community services, with a dearth of therapy services in both home and nursing home settings.

Conclusion: This multi-faceted national stroke audit facilitated multiple perspectives on the continuum of stroke prevention and care. An overall synthesis of surveys supports the development of a multidisciplinary perspective in planning the development of comprehensive stroke services at the national level, and may assist in regional and global development of stroke strategies.
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http://dx.doi.org/10.1159/000330640DOI Listing
March 2012

Randomized intervention study of solar disinfection of drinking water in the prevention of dysentery in Kenyan children aged under 5 years.

Environ Sci Technol 2011 Nov 5;45(21):9315-23. Epub 2011 Oct 5.

Natural Resources and the Environment, CSIR, P.O. Box 395, Pretoria, South Africa.

We report the results of a randomized controlled intervention study (September 2007 to March 2009) investigating the effect of solar disinfection (SODIS) of drinking water on the incidence of dysentery, nondysentery diarrhea, and anthropometric measurements of height and weight among children of age 6 months to 5 years living in peri-urban and rural communities in Nakuru, Kenya. We compared 555 children in 404 households using SODIS with 534 children in 361 households with no intervention. Dysentery was recorded using a pictorial diary. Incidence rate ratios (IRR) for both number of days and episodes of dysentery and nondysentery diarrhea were significantly (P < 0.001) reduced by use of solar disinfection: dysentery days IRR = 0.56 (95% CI 0.40 to 0.79); dysentery episodes IRR = 0.55 (95% CI 0.42 to 0.73); nondysentery days IRR = 0.70 (95% CI 0.59 to 0.84); nondysentery episodes IRR = 0.73 (95% CI 0.63 to 0.84). Anthropometry measurements of weight and height showed median height-for-age was significantly increased in those on SODIS, corresponding to an average of 0.8 cm over a 1-year period over the group as a whole (95% CI 0.7 to 1.6 cm, P = 0.031). Median weight-for-age was higher in those on SODIS, corresponding to a 0.23 kg difference in weight over the same period; however, the confidence interval spanned zero and the effect fell short of statistical significance (95% CI -0.02 to 0.47 kg, P = 0.068). SODIS and control households did not differ in the microbial quality of their untreated household water over the follow-up period (P = 0.119), but E. coli concentrations in SODIS bottles were significantly lower than those in storage containers over all follow-up visits (P < 0.001). This is the first trial to show evidence of the effect of SODIS on childhood anthropometry, compared with children in the control group and should alleviate concerns expressed by some commentators that the lower rates of dysentery associated with SODIS are the product of biased reporting rather than reflective of genuinely decreased incidence.
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http://dx.doi.org/10.1021/es2018835DOI Listing
November 2011