DSpace Academic/Research Unit: School of Medicine

Obesity and Employment in Ireland: Moving Beyond BMI

2012-07-09T11:21:51Z

Title: Obesity and Employment in Ireland: Moving Beyond BMI Author: MOSCA, IRENE Abstract: I use data from the first wave of the Irish Longitudinal Study on Ageing (TILDA) to investigate the impact of obesity on the labour market status of older Irish individuals. I employ an anthropometric indicator of body composition (waist circumference) along with body mass index. I include a wide array of subjective and objective health indicators in the empirical model. I find that obese women are less likely to be at work. However, both the magnitude and statistical significance of this correlation are sensitive to the definition of obesity. Factors other than socioeconomic characteristics and health are also found to play a role in explaining why obese older women are less likely to be employed. Much weaker evidence is found for men. Description: PUBLISHED

Synergistic Effect between Maternal Infection and Adolescent Cannabinoid Exposure on Serotonin 5HT1A Receptor Binding in the Hippocampus: Testing the Two Hit Hypothesis for the Development of Schizophrenia

2012-07-09T09:13:38Z

Title: Synergistic Effect between Maternal Infection and Adolescent Cannabinoid Exposure on Serotonin 5HT1A Receptor Binding in the Hippocampus: Testing the Two Hit Hypothesis for the Development of Schizophrenia Author: DALTON, VICTORIA Abstract: Infections during pregnancy and adolescent cannabis use have both been identified as environmental risk factors for schizophrenia. We combined these factors in an animal model and looked at their effects, alone and in combination, on serotonin 5HT1A receptor binding (5HT1AR) binding longitudinally from late adolescence to adulthood. Pregnant rats were exposed to the viral mimic poly I:C on embryonic day 15. Adolescent offspring received daily injections of the cannabinoid HU210 for 14 days starting on postnatal day (PND) 35. Hippocampal and cortical 5HT1AR binding was quantified autoradiographically using [3H]8-OH-DPAT, in late adolescent (PND 55), young adult (PND 65) and adult (PND 90) rats. Descendants of poly I:C treated rats showed significant increases of 15–18% in 5HT1AR in the hippocampus (CA1) compared to controls at all developmental ages. Offspring of poly I:C treated rats exposed to HU210 during adolescence exhibited even greater elevations in 5HT1AR (with increases of 44, 29, and 39% at PNDs 55, 65, and 90). No effect of HU210 alone was observed. Our results suggest a synergistic effect of prenatal infection and adolescent cannabinoid exposure on the integrity of the serotoninergic system in the hippocampus that may provide the neurochemical substrate for abnormal hippocampal-related functions relevant to schizophrenia. Description: PUBLISHED

DUNDRUM-D: Developmental Understanding of Drug Misuse & Dependence (Short version)

2012-07-05T03:21:06Z

Title: DUNDRUM-D: Developmental Understanding of Drug Misuse & Dependence (Short version) Author: KENNEDY, HARRY Abstract: This is the short version of the Developmental Understanding of Drug Misuse and Dependence DUNDRUM-D. DUNDRUM-D is an instrument which has grown out of the series of prison psychiatric morbidity studies carried out by the National Forensic Mental Health Service in the population of the Irish Prison Service. The DUNDRUM-D is distinguished from other screening and diagnostic instruments by the developmental perspective it takes on life time careers of substance use, misuse and dependence. We recognise that those with substance misuse problems commonly begin using intoxicants such as solvents very early, typically before the age of 12 and progress through other substances as they get older and are able to access more expensive intoxicants. Some will have patterns of binge use, others are continuously intoxicated. Some will use only one or two substances of choice; others will use many different types of drug almost indiscriminately. It is not uncommon for a person to make the transition from dependence on one drug to substitution for another, followed some time later by further changes in type of intoxicant or pattern of use. All such patterns shift and change over time, and recovery is always possible. Indeed spontaneous recovery is the most common outcome for most substance misuse problems. The purpose of this form of instrument is to record these patterns as an exercise in contemplation for those who are not yet at the contemplative stage or recovery. While questions are asked about harmful use and abuse, these are deliberately reserved until towards the end of the interview. We believe the regular use of this instrument is also a way of learning from one's patients/clients. The substances used, the language, patterns and practices of use all change constantly and rapidly from month to month and from city to city. We have found that this instrument can be used in its short form as a screening tool e.g. with the SADS-L or with the CAARMS. In forensic mental health practice, it is 'substance abuse' as defined in the DSM system that is the best guide to harmful use. The form of the instrument lends itself to the assessment of other problem behaviours such as gambling, binging and purging food, and repetitive self-harm to relieve tension (e.g. cutting). The DUNDRUM-D can be used by any professionally qualified clinician. Description: PUBLISHED

DUNDRUM-D: Developmental Understanding of Drug Misuse & Dependence

2012-07-27T10:58:03Z

Title: DUNDRUM-D: Developmental Understanding of Drug Misuse & Dependence Author: KENNEDY, HARRY Abstract: Developmental Understanding of Drug Misuse and Dependence DUNDRUM-D This instrument has grown out of the series of prison psychiatric morbidity studies carried out by the National Forensic Mental Health Service in the population of the Irish Prison Service. The DUNDRUM-D is distinguished from other screening and diagnostic instruments by the developmental perspective it takes on life time careers of substance use, misuse and dependence. We recognise that those with substance misuse problems commonly begin using intoxicants such as solvents very early, typically before the age of 12 and progress through other substances as they get older and are able to access more expensive intoxicants. Some will have patterns of binge use, others are continuously intoxicated. Some will use only one or two substances of choice; others will use many different types of drug almost indiscriminately. It is not uncommon for a person to make the transition from dependence on one drug to substitution for another, followed some time later by further changes in type of intoxicant or pattern of use. All such patterns shift and change over time, and recovery is always possible. Indeed spontaneous recovery is the most common outcome for most substance misuse problems. The purpose of this form of instrument is to record these patterns as an exercise in contemplation for those who are not yet at the contemplative stage or recovery. While questions are asked about harmful use and abuse, these are deliberately reserved until towards the end of the interview. We believe the regular use of this instrument is also a way of learning from one's patients/clients. The substances used, the language, patterns and practices of use all change constantly and rapidly from month to month and from city to city. We have found that this instrument can be used in its short form as a screening tool e.g. with the SADS-L or with the CAARMS. In forensic mental health practice, it is 'substance abuse' as defined in the DSM system that is the best guide to harmful use. The form of the instrument lends itself to the assessment of other problem behaviours such as gambling, binging and purging food, and repetitive self-harm to relieve tension (e.g. cutting). The DUNDRUM-D can be used by any professionally qualified clinician. Description: PUBLISHED

Age-related changes in the hippocampus (loss of synaptophysin and glial-synaptic interaction) are modified by systemic treatment with an NCAM-derived peptide, FGL

2012-06-27T14:41:58Z

Title: Age-related changes in the hippocampus (loss of synaptophysin and glial-synaptic interaction) are modified by systemic treatment with an NCAM-derived peptide, FGL Author: LYNCH, MARINA ANNETTA Abstract: Altered synaptic morphology, progressive loss of synapses and glial (astrocyte and microglial) cell activation are considered as characteristic hallmarks of ageing. Recent evidence suggests that there is a concomitant age-related decrease in expression of the presynaptic protein, synaptophysin, and the neuronal glycoprotein CD200, which, by interacting with its receptor, plays a role in maintaining microglia in a quiescent state. These age-related changes may be indicative of reduced neuroglial support of synapses. FG Loop (FGL) peptide synthesised from the second fibronectin type III module of neural cell adhesion molecule (NCAM), has previously been shown to attenuate age-related glial cell activation, and to ‘restore’ cognitive function in aged rats. The mechanisms by which FGL exerts these neuroprotective effects remain unclear, but could involve regulation of CD200, modifying glial-synaptic interactions (affecting neuroglial ‘support’ at synapses), or impacting directly on synaptic function. Light and electron microscopic (EM) analyses were undertaken to investigate whether systemic treatment with FGL (i) alters CD200, synaptophysin (presynaptic) and PSD95 (postsynaptic) immunohistochemical expression levels, (ii) affects synaptic number, or (iii) exerts any effects on glial-synaptic interactions within young (4 month-old) and aged (22 month-old) rat hippocampus. Treatment with FGL attenuated the age-related loss of synaptophysin immunoreactivity (-ir) within CA3 and hilus (with no major effect on PSD-95-ir), and of CD200-ir specifically in the CA3 region. Ultrastructural morphometric analyses showed that FGL treatment (i) prevented age-related loss in astrocyte-synaptic contacts, (ii) reduced microglia-synaptic contacts in the CA3 stratum radiatum, but (iii) had no effect on the mean number of synapses in this region. These data suggest that FGL mediates its neuroprotective effects by regulating glial-synaptic interaction. Description: IN_PRESS

CD200 fusion protein decreases microglial activation in the hippocampus of aged rats

2012-06-27T14:01:58Z

Title: CD200 fusion protein decreases microglial activation in the hippocampus of aged rats Author: LYNCH, MARINA ANNETTA; COX, FRANCES FIONNUALA Abstract: The glycoprotein, CD200, is primarily expressed on neurons and its cognate receptor CD200R is expressed principally on cells of the myeloid lineage, including microglia. The interaction of CD200 with its receptor plays a significant role in maintaining microglia in a quiescent state and therefore a decrease in CD200 expression in brain is associated with evidence of microglial activation. Conversely, activation of CD200R, for example using a CD200 fusion protein (CD200Fc), should result in a decrease in microglial activation. Here we assessed the effect of delivery of CD200Fc intrahippocampally on microglial activation and on long-term potentiation (LTP) in perforant path-granule cell synapses in young and aged rats. We hypothesized that the age-related changes in microglial activation would be attenuated by CD200Fc resulting in an improved ability of aged rats to sustain LTP. The data indicate that expression of markers of microglial activation including major histocompatibility complex Class II (MHCII) and CD40 mRNA, as well as MHCII immunoreactivity, were increased in hippocampus of aged, compared with young, rats and that these changes were associated with a deficit in LTP; these changes were attenuated in hippocampal tissue prepared from aged rats which received CD200Fc. Microglial activation and a deficit in LTP have also been reported in lipopolysaccharide (LPS)-treated rats and, here, we report that these changes were also attenuated in CD200Fc-treated animals. Thus the negative impact of microglial activation on the ability of aged and LPS-treated rats to sustain LTP is ameliorated when CD200R is activated by CD200Fc. Description: IN_PRESS

Antimicrobial management and appropriateness of treatment of urinary tract infection in general practice in Ireland.

2012-06-27T13:49:17Z

Title: Antimicrobial management and appropriateness of treatment of urinary tract infection in general practice in Ireland. Author: BENNETT, KATHLEEN Abstract: BACKGROUND: Urinary tract infections (UTIs) are the second most common bacterial infections in general practice and a frequent indication for prescription of antimicrobials. Increasing concern about the association between the use of antimicrobials and acquired antimicrobial resistance has highlighted the need for rational pharmacotherapy of common infections in general practice. METHODS: Management of urinary tract infections in general practice was studied prospectively over 8 weeks. Patients presenting with suspected UTI submitted a urine sample and were enrolled with an opt-out methodology. Data were collected on demographic variables, previous antimicrobial use and urine samples. Appropriateness of different treatment scenarios was assessed by comparing treatment with the laboratory report of the urine sample. RESULTS: A total of 22 practices participated in the study and included 866 patients. Bacteriuria was established for 21% of the patients, pyuria without bacteriuria for 9% and 70% showed no laboratory evidence of UTI. An antimicrobial agent was prescribed to 56% (481) of the patients, of whom 33% had an isolate, 11% with pyuria only and 56% without laboratory evidence of UTI. When taking all patients into account, 14% patients had an isolate identified and were prescribed an antimicrobial to which the isolate was susceptible. The agents most commonly prescribed for UTI were co-amoxyclav (33%), trimethoprim (26%) and fluoroquinolones (17%). Variation between practices in antimicrobial prescribing as well as in their preference for certain antimicrobials, was observed. Treatment as prescribed by the GP was interpreted as appropriate for 55% of the patients. Three different treatment scenarios were simulated, i.e. if all patients who received an antimicrobial were treated with nitrofurantoin, trimethoprim or ciprofloxacin only. Treatment as prescribed by the GP was no more effective than treatment with nitrofurantoin for all patients given an antimicrobial or treatment with ciprofloxacin in all patients. Prescribing cost was lower for nitrofurantoin. Empirical treatment of all patients with trimethoprim only was less effective due to the higher resistance levels. CONCLUSIONS: There appears to be considerable scope to reduce the frequency and increase the quality of antimicrobial prescribing for patients with suspected UTI. Description: PUBLISHED

Dietary fat, abdominal obesity and smoking modulate the relationship between plasma complement component 3 concentrations and metabolic syndrome risk

2013-03-14T09:08:15Z

Title: Dietary fat, abdominal obesity and smoking modulate the relationship between plasma complement component 3 concentrations and metabolic syndrome risk Author: MC MANUS, ROSS Abstract: Objective: Chronic inflammation plays a role in the pathogenesis of metabolic syndrome (MetS) and cardiovascular disease (CVD). Complement component 3 (C3) is a novel cardiometabolic risk factor. Whether dietary fat intake modulates MetS risk conferred by elevated C3 concentrations is unknown. Our objective is to investigate the relationship between C3 concentrations and risk of the MetS and its phenotypes, and to further examine whether dietary fat intake modulates these relationships. Methods: Biochemical, dietary and lifestyle measurements were determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754). Results: Elevated C3 concentrations (> median) were associated with increased risk of impaired insulin sensitivity [OR 1.78, CI 1.34-2.36, P < 0.0001], insulin resistance [OR 1.73, CI 1.31-2.89, P = 0.0001], abdominal obesity [OR 2.15, CI 1.43-3.24, P = 0.0002] and low HDL cholesterol [OR 1.40, CI 1.05-1.86, P = 0.02] compared to low C3 concentrations. Increased MetS risk conferred by elevated C3 concentrations [OR 3.11, 95% CI 2.52-3.82, P < 0.0001] was further accentuated among high dietary fat consumers [OR 4.80, 95% CI 2.77-8.33, P < 0.0001] (particularly of saturated [OR 4.05, 95% CI 2.33-7.05, P < 0.0001] and monounsaturated fat [OR 4.48, 95% CI 2.62-7.56, P < 0.0001]), and smokers [OR 3.83, 95% CI 2.12-6.94, P < 0.0001], however this effect was abolished in abdominally lean individuals [OR 1.46, 95% CI 0.69-3.14, P = 0.33]. Conclusions: Dietary fat (intake and composition), abdominal obesity and smoking modulate the relationship between elevated plasma C3 concentrations and MetS risk. Description: PUBLISHED

Mitochondrial mutagenesis correlates with the local inflammatory environment in arthritis

2012-06-27T11:28:06Z

Title: Mitochondrial mutagenesis correlates with the local inflammatory environment in arthritis Author: O'SULLIVAN, JACINTHA Abstract: Background: To examine the association between mitochondrial mutagenesis and the proinflammatory microenvironment in patients with inflammatory arthritis. Methods: Fifty patients with inflammatory arthritis underwent arthroscopy and synovial tissue biopsies, synovial fluid and clinical assessment were obtained. Fifteen patients pre/post-TNFi therapy were also recruited. Normal synovial biopsies were obtained from 10 subjects undergoing interventional arthroscopy. Macroscopic synovitis/vascularity was measured by visual analogue scale. Cell-specific markers CD3 (T cells) and CD68 (macrophages) were quantified by immunohistology. TNFα, IL-6, IFNγ and IL-1β were measured in synovial fluids by MSD multiplex assays. Synovial tissue mitochondrial mutagenesis was quantified using a mitochondrial random mutation capture assay (RMCA). The direct effect of TNFα on oxidative stress and mitochondrial function was assessed in primary cultures of rheumatoid arthritis synovial fibroblast cells (RASFCs). Mitochondrial mutagenesis, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and mitochondrial mass (MM) were quantified using the RMCA and specific cell fluorescent probes. Results: A significant increase in mtDNA mutation frequency was demonstrated in inflamed synovial tissue compared with control (p<0.05), an effect that was independent of age. mtDNA mutations positively correlated with macroscopic synovitis (r=0.52, p<0.016), vascularity (r=0.54, p<0.01) and with synovial fluid cytokine levels of TNFα (r=0.74, p<0.024) and IFNγ (r=0.72, p<0.039). mtDNA mutation frequency post-TNFi therapy was significantly lower in patients with a DAS<3.2 (p<0.05) and associated with clinical and microscopic measures of disease (p<0.05). In vitro TNFα significantly induced mtDNA mutations, ROS, MM and MMP in RASFCs (all p<0.05). Conclusion: High mitochondrial mutations are strongly associated with synovial inflammation showing a direct link between mitochondrial mutations and key proinflammatory pathways. Description: IN_PRESS

The Alert Programme for Self Regulation - an evaluation of a group based intervention for children attending a child and adolescent mental health clinic

2012-06-27T09:48:14Z

Title: The Alert Programme for Self Regulation - an evaluation of a group based intervention for children attending a child and adolescent mental health clinic Author: CREMIN, KATIE Description: PUBLISHED