Identification of STOML2 as a putative novel asthma risk gene associated with IL6R.

BACKGROUND: Functional variants in the interleukin-6 receptor gene (IL6R) are associated with asthma risk. We hypothesized that genes co-expressed with IL6R might also be regulated by genetic polymorphisms that are associated with asthma risk. The aim of this study was to identify such genes. METHODS: To identify genes whose expression was correlated with that of IL6R, we analyzed gene expression levels generated for 373 human lymphoblastoid cell lines by the Geuvadis consortium and for 38 hematopoietic cell types by the Differentiation Map Portal (DMAP) project. Genes correlated with IL6R were then screened for nearby single nucleotide polymorphisms (SNPs) that were significantly associated with both variation in gene expression levels (eSNPs) and asthma risk. RESULTS: We identified 90 genes with expression levels correlated with those of IL6R and that also had a nearby eSNP associated with disease risk in a published asthma GWAS (N = 20 776). For 16 (18%) genes, the association between the eSNP and asthma risk replicated with the same direction of effect in a further independent published asthma GWAS (N = 27 378). Among the top replicated associations (FDR < 0.05) were eSNPs for four known (IL18R1, IL18RAP, BCL6, and STAT6) and one putative novel asthma risk gene, stomatin-like protein 2 (STOML2). The expression of STOML2 was negatively correlated with IL6R, while eSNPs that increased the expression of STOML2 were associated with an increased asthma risk. CONCLUSION: The expression of STOML2, a gene that plays a key role in mitochondrial function and T-cell activation, is associated with both IL-6 signaling and asthma risk.

Temporal lobe epilepsy and affective disorders: the role of the subgenual anterior cingulate cortex.

OBJECTIVE: Reduced deactivation within the default mode network (DMN) is common in individuals with primary affective disorders relative to healthy volunteers (HVs). It is unknown whether similar network abnormalities are present in temporal lobe epilepsy (TLE) patients with a history of affective psychopathology. METHODS: 17 TLE patients with a lifetime affective diagnosis, 31 TLE patients with no formal psychiatric history and 30 HVs were included. We used a visuo-spatial 'n-back' paradigm to compare working memory (WM) network activation between these groups. Post hoc analyses included voxel-based morphometry and diffusion tensor imaging. The Beck Depression Inventory-Fast Screen and Beck Anxiety Inventory were completed on the day of scanning. FINDINGS: Each group activated the fronto-parietal WM networks and deactivated the typical DMN in response to increasing task demands. Group comparison revealed that TLE patients with lifetime affective morbidity showed significantly greater deactivation in subgenual anterior cingulate cortex (sACC) than either the TLE-only or the HVs (p<0.001). This effect persisted after covarying for current psychotropic medication and severity of current depressive/anxiety symptoms (all p<0.001). Correlational analysis revealed that this finding was not driven by differences in task performance. There were no significant differences in grey matter volume or structural connectivity between the TLE groups. CONCLUSIONS: Our results provide novel evidence suggesting that affective psychopathology in TLE has a neurobiological correlate, and in this context the sACC performs differently compared with network activity in primary affective disorders.

Neural correlates of working memory in Temporal Lobe Epilepsy--an fMRI study.

It has traditionally been held that the hippocampus is not part of the neural substrate of working memory (WM), and that WM is preserved in Temporal Lobe Epilepsy (TLE). Recent imaging and neuropsychological data suggest this view may need revision. The aim of this study was to investigate the neural correlates of WM in TLE using functional MRI (fMRI). We used a visuo-spatial 'n-back' paradigm to compare WM network activity in 38 unilateral hippocampal sclerosis (HS) patients (19 left) and 15 healthy controls. WM performance was impaired in both left and right HS groups compared to controls. The TLE groups showed reduced right superior parietal lobe activity during single- and multiple-item WM. No significant hippocampal activation was found during the active task in any group, but the hippocampi progressively deactivated as the task demand increased. This effect was bilateral for controls, whereas the TLE patients showed progressive unilateral deactivation only contralateral to the side of the hippocampal sclerosis and seizure focus. Progressive deactivation of the posterior medial temporal lobe was associated with better performance in all groups. Our results suggest that WM is impaired in unilateral HS and the underlying neural correlates of WM are disrupted. Our findings suggest that hippocampal activity is progressively suppressed as the WM load increases, with maintenance of good performance. Implications for understanding the role of the hippocampus in WM are discussed.

Genome-wide association study to identify genetic determinants of severe asthma.

BACKGROUND: The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. OBJECTIVE: To identify common genetic variants affecting susceptibility to severe asthma. METHODS: A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. RESULTS: An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10((-8)) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10((-8)) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. CONCLUSIONS: The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.

Pharmacogenetics of ß2 adrenergic receptor gene polymorphisms, long-acting ß-agonists and asthma.

Adrenergic ß2 receptor (ADRß2) agonists are widely used in asthma. Approximately 10% of patients have severe, poorly controlled disease despite extensive use of ADRß2 agonists. Variations in responses to ADRß2 agonists can, in part, be attributed to genetic variation, with 49 different polymorphisms having been identified for the ADRß2 gene. Although clear associations exist between ADRß2 gene polymorphisms, such as +46G>A, and patient response, the importance of these polymorphisms remains controversial. Patient selection, the number of polymorphisms analysed, differences in the type/dose of ADRß2 agonist, use of inhaled corticosteroids and population sizes have all varied. Most studies were limited to mild or moderate asthmatics using ADRß2 agonists sparingly. It is difficult to extrapolate from these studies to individual patients who have severe asthma, use a variety of ADRß2 agonists and do so frequently. The extent to which ADRß2 gene polymorphisms are relevant to asthma management needs further review, both clinically and at the molecular level. In vitro studies have helped to define the functional changes induced by specific ADRß2 gene polymorphisms, including 3'-untranslated region poly-C repeat. The resulting ADRß2 gene haplotypes (rather than genotypes), the interactions among ADRß2 gene haplotypes and variations in the chemistry of different agonists deserve more detailed assessment. Responses to ADRß2 agonists depend on effective downstream signalling following ADRß2 activation and also on receptor regulation. Studies on other regulators of ADRß2 receptor signalling and trafficking may be equally important in understanding the functional role of ADRß2 gene polymorphisms. The role of ADRß2 gene polymorphisms in the pathogenesis and management of severe asthma cannot be clearly defined until more specific and targeted research studies are performed.

Prostaglandin E2 and cysteinyl leukotriene concentrations in sputum: association with asthma severity and eosinophilic inflammation.

BACKGROUND: Inflammation of the airways in asthma is associated with the production of cysteinyl leukotrienes (cysLT), prostaglandin (PG)E(2), 8-isoprostane, nitric oxide and other mediators. However, the relationship between asthma severity or eosinophilic inflammation and the concentrations of mediators in sputum is unclear. OBJECTIVE: To assess sputum PGE(2), cysLT, 8-isoprostane and nitrate concentrations, as well as urinary leukotriene (LT)E(4) and 9alpha,11beta-prostaglandin (PG)F(2) concentrations, in patients with differing severities of asthma and eosinophilic or non-eosinophilic airway inflammation. METHODS: Inflammatory cells in sputum were assessed in 12 patients with mild, 14 with moderate and 12 with severe persistent asthma, as well as in 13 control subjects. Asthmatic patients were categorized into those with eosinophilic or non-eosinophilic airway inflammation. Sputum PGE(2), cysLT and 8-isoprostane, and urinary LTE(4) were extracted on immunoaffinity sorbents, and the concentrations of all mediators were measured using enzyme immunoassays. Sputum nitrate concentrations were measured on a chemiluminescence analyzer. RESULTS: Sputum PGE(2) concentrations were higher in both moderate (1710 pg/mL) and severe asthmatic (1590 pg/mL) compared with control subjects (827 pg/mL) (P<0.05). CysLT concentrations were higher in moderate asthmatic compared with control or severe asthmatic subjects (P<0.05). Sputum PGE(2) concentrations were lower in patients with eosinophilic (1180 pg/mL) compared with non-eosinophilic airway inflammation (2520 pg/mL) (P=0.02). In contrast, sputum cysLT and urinary LTE(4) concentrations were higher in those with eosinophilic airway inflammation (P<0.05). Forced expiratory volume in 1 s was inversely correlated with sputum eosinophils in all asthmatic patients (r(s)=-0.5, P=0.002). There were no significant differences in sputum 8-isoprostane or nitrate concentrations. CONCLUSIONS: Increased airway concentrations of PGE(2) are consistent with the hypothesis that PGE(2) has a bronchoprotective and anti-inflammatory role in patients with more severe asthma. A reduced PGE(2) to cysLT ratio in the airways may adversely affect lung function and contribute to persistence of symptoms and airway remodelling in patients with eosinophilic airway inflammation.

Use of balloon catheter tamponade for massive postpartum haemorrhage.

Haemorrhage is one of the leading global causes of maternal mortality. The Rüsch balloon has been used in the treatment of postpartum haemorrhage (PPH) after failure of medical management. It is often effective in tamponading uterine bleeding, thus providing an alternative to hysterectomy. We describe a series of 22 cases in which we used the Rüsch balloon to control massive obstetric haemorrhage after failure to control haemorrhage by medical means. In our study, 13 out of 22 patients (59.1%) required no further interventions after balloon tamponade. Seven patients (31.8%) required hysterectomy to control the bleeding. We include a review of the current literature on balloon tamponade for PPH, including analysis of six relevant case series. This demonstrates a variety of methods based on tamponade to terminate uterine haemorrhage. Our study highlights the benefit of balloon tamponade for massive PPH and the importance of its involvement in labour ward protocols.

Alpha-thrombin induces release of platelet-derived growth factor-like molecule(s) by cultured human endothelial cells.

Cultured endothelial cells secrete a platelet-derived growth factor-like molecule (PDGFc). We examined the effects of purified human alpha-thrombin on the production of PDGFc in cultures of human umbilical vein endothelial cells (HUVE) using a specific radioreceptor assay for PDGF. Addition of physiologically relevant concentrations of alpha-thrombin (0.1 to 10 U/ml) induced a time- and dose-dependent increase in the release of PDGFc into the culture medium. Significant stimulation of PDGFc release was observed as early as 1.5 h after addition of alpha-thrombin (10 U/ml) with a 4.9 +/- 1.1 fold increase at 24 h (mean +/- SEM of nine experiments, P less than 0.01). alpha-Thrombin treatment of HUVE did not affect cell viability as assessed by trypan blue dye exclusion. The receptor binding of PDGFc secreted by HUVE in response to alpha-thrombin was inhibited by monospecific antibody to purified human PDGF indicating that the molecule(s) is closely related to PDGF. alpha-Thrombin inactivated with diisopropylfluorophosphate was without stimulatory effect. Lysis of HUVE by repeated cycles of freeze/thaw released minimal PDGFc (less than 0.3 ng per 10(6) cells) compared to levels of PDGFc released into supernatant medium in response to alpha-thrombin (greater than 5.0 ng per 10(6) cells after a 24-h incubation with 10 U/ml alpha-thrombin). Moreover, incubation of freeze/thaw lysates of HUVE with alpha-thrombin failed to release PDGFc. Over a 3-h time course, however, alpha-thrombin-induced secretion of PDGFc was not prevented by cycloheximide. We conclude that alpha-thrombin induces secretion of PDGFc from HUVE by a nonlytic mechanism requiring the serine esterase activity of the enzyme. Although this effect does not initially require de novo protein synthesis, it does require cell-mediated conversion of PDGFc from an inactive to an active form.

Cell salvage at caesarean section: the need for an evidence-based approach.

Haemorrhage, a leading cause of maternal morbidity and mortality, is frequently associated with caesarean section. Allogeneic blood is an increasingly rare and scare resource. Intraoperative Cell Salvage (IOCS) offers the possibility of improving outcome and reducing allogeneic blood transfusion in cases of haemorrhage at caesarean section. The available literature on the use of IOCS in obstetrics demonstrates that there is limited evidence to support or refute the use of IOCS at caesarean section. However, this procedure has been introduced into obstetric practice. Before opinions about its use become solidified, there is a window of opportunity to launch a large multicentre randomised controlled trial to address the current equipoise.

Plasma phospholipase A2 activity in patients with asthma: association with body mass index and cholesterol concentration.

BACKGROUND: Secretory phospholipases A2 (sPLA2) have functions relevant to asthmatic inflammation, including eicosanoid synthesis and effects on dendritic cells and T cells. The aim of this study was to measure sPLA2 activity in patients with stable and acute asthma and to assess potential associations with body mass index (BMI), and plasma cholesterol and vitamin C concentrations. METHODS: Plasma sPLA2 activity and concentrations of cholesterol and vitamin C were measured in 23 control subjects and 61 subjects with stable asthma (42 mild to moderate, 19 severe). In addition, sPLA2 activity was measured in 36 patients experiencing acute asthma and in 22 of these patients after recovery from the acute attack. RESULTS: sPLA2 activity was not significantly greater in severe (499.9 U; 95% confidence interval (CI) 439.4 to 560.4) compared with mild to moderate asthmatic subjects (464.8; 95% CI 425.3 to 504.3) or control subjects (445.7; 95% CI 392.1 to 499.4), although it was higher in patients with acute asthma (581.6; 95% CI 541.2 to 622.0; p<0.001). Male gender, high plasma cholesterol, increased BMI and atopy were associated with increased sPLA2 activity, while plasma vitamin C was inversely correlated with sPLA2 activity in patients with stable asthma and in control subjects. There were significant interactions between gender and plasma cholesterol and between gender and vitamin C in relation to sPLA2 activity. CONCLUSIONS: Plasma sPLA2 may provide a biological link between asthma, inflammation, increased BMI, lipid metabolism and antioxidants. Interactions among these factors may be pertinent to the pathophysiology and increasing prevalence of both asthma and obesity.

Cyclooxygenase-2 gene polymorphisms in an Australian population: association of the -1195G > A promoter polymorphism with mild asthma.

BACKGROUND: Cyclooxygenase (COX)-2 is an inducible enzyme responsible for catalysing the formation of prostaglandins (PGs) in settings of inflammation. Single nucleotide polymorphisms (SNPs) of the COX-2 gene may influence gene transcription and PG production in the asthmatic airway. OBJECTIVE: To evaluate the frequencies of COX-2 SNPs in an Australian Caucasian population, and determine potential associations between common COX-2 promoter SNPs and asthma, asthma severity and aspirin-intolerant asthma (AIA). METHODS: The frequencies of 25 COX-2 SNPs were determined in a random population (n=176). The SNPs with a minor allele frequency of >10% were then studied in asthmatic (n=663), non-asthmatic controls (n=513) and AIA subjects (n=58). Genotype, allele and haplotype associations were assessed. Functional assessment of SNPs was performed by transfection into HeLa cells measured using the luciferase dual-reporter assay system. RESULTS: Eighteen COX-2 SNPs were not detected, five were rare and two promoter SNPs, -1195G>A (rs689465), and -1290A>G (rs689466), were further studied. The A allele of the -1195 SNP was present at a significantly higher frequency among all asthmatic subjects (P=0.012). Over 60% of the asthmatic individuals were -1195A homozygotes compared with 54.6% of the control subjects (odds ratio, 1.35; 95% CI, 1.06-1.72, P=0.03). After classifying for severity, the mild asthmatics represented 64.6% of -1195AA individuals, the highest of all the asthma groups compared with 54.6% of the control subjects (odds ratio, 1.5; 95% CI, 1.12-2.02, P=0.02). The -1290A/-1195G/-765G haplotype was associated with a reduced incidence of asthma (odds ratio, 0.76; 95% CI, 0.61-0.95, P=0.017). CONCLUSION: The -1195G>A polymorphism appears to be associated with asthma, and in particular with mild asthma.

Preoperative fMRI predicts memory decline following anterior temporal lobe resection.

BACKGROUND: Anterior temporal lobe resection (ATLR) benefits many patients with refractory temporal lobe epilepsy (TLE) but may be complicated by material specific memory impairments, typically of verbal memory following left ATLR, and non-verbal memory following right ATLR. Preoperative memory functional MRI (fMRI) may help in the prediction of these deficits. OBJECTIVE: To assess the value of preoperative fMRI in the prediction of material specific memory deficits following both left- and right-sided ATLR. METHODS: We report 15 patients with unilateral TLE undergoing ATLR; eight underwent dominant hemisphere ATLR and seven non-dominant ATLR. Patients performed an fMRI memory paradigm which examined the encoding of words, pictures and faces. RESULTS: Individual patients with relatively greater ipsilateral compared with contralateral medial temporal lobe activation had greater memory decline following ATLR. This was the case for both verbal memory decline following dominant ATLR and for non-verbal memory decline following non-dominant ATLR. For verbal memory decline, activation within the dominant hippocampus was predictive of postoperative memory change whereas activation in the non-dominant hippocampus was not. CONCLUSION: These findings suggest that preoperative memory fMRI may be a useful non-invasive predictor of postoperative memory change following ATLR and provide support for the functional adequacy theory of hippocampal function. They also suggest that fMRI may provide additional information, over that provided by neuropsychology, for use in the prediction of postoperative memory decline.

Imaging language pathways predicts postoperative naming deficits.

Naming difficulties are a well recognised, but difficult to predict, complication of anterior temporal lobe resection (ATLR) for refractory epilepsy. We used MR tractography preoperatively to demonstrate the structural connectivity of language areas in patients undergoing dominant hemisphere ATLR. Greater lateralisation of tracts to the dominant hemisphere was associated with greater decline in naming function. We suggest that this method has the potential to predict language deficits in patients undergoing ATLR.

Does the mode of delivery predispose women to anal incontinence in the first year postpartum? A comparative systematic review.

OBJECTIVES: To assess if mode of delivery is associated with increased symptoms of anal incontinence following childbirth. DESIGN: Systematic review of all relevant studies in English. DATA SOURCES: Medline, Embase, Cochrane Library, bibliographies of retrieved primary articles and consultation with experts. STUDY SELECTION AND DATA EXTRACTION: Data were extracted on study characteristics, quality and results. Exposure to risk factors was compared between women with and without anal incontinence. Categorical data in 2 x 2 contingency tables were used to generate odds ratios. RESULTS: Eighteen studies met the inclusion criteria with 12,237 participants. Women having any type of vaginal delivery compared with a caesarean section have an increased risk of developing symptoms of solid, liquid or flatus anal incontinence. The risk varies with the mode of delivery ranging from a doubled risk with a forceps delivery (OR 2.01, 95% CI 1.47-2.74, P < 0.0001) to a third increased risk for a spontaneous vaginal delivery (OR 1.32, 95% CI 1.04-1.68, P = 0.02). Instrumental deliveries also resulted in more symptoms of anal incontinence when compared with spontaneous vaginal delivery (OR 1.47, 95% CI 1.22-1.78). This was statistically significant for forceps deliveries alone (OR 1.5, 95% CI 1.19-1.89, P = 0.0006) but not for ventouse deliveries (OR 1.31, 95% CI 0.97-1.77, P = 0.08). When symptoms of solid and liquid anal incontinence alone were assessed, these trends persisted but were no longer statistically significant. CONCLUSION: Symptoms of anal incontinence in the first year postpartum are associated with mode of delivery.

Early intraperitoneal transfusion and adjuvant maternal immunoglobulin therapy in the treatment of severe red cell alloimmunization prior to fetal intravascular transfusion.

This descriptive case study documents the treatment of a cohort of 6 women with pregnancies complicated by red cell alloimmunization who in previous pregnancies had objective evidence of severe fetal anemia prior to 20 weeks of gestation, with accompanying high perinatal loss (66% mortality). In the pregnancies described, 5 singletons and 1 dichorionic, diamniotic twin pregnancy underwent alternate week, serial intraperitoneal transfusions between 16 and 21 weeks, until a gestation when classical fetal intravascular transfusions could be commenced. In addition, 4 women consented to have additional, adjuvant maternal intravenous gammaglobulin (IVIG) therapy (0.8 g/kg per week). At the first fetal blood sampling at a median gestational age of 22 weeks (95% CI 21.2-23.4 weeks) the median hemoglobin concentration was 10.1 g% (95% CI 7.4-13.4 g%). In only 2 cases were the fetal hemoglobin levels at fetal blood sampling between -2 SD and -5 SD for gestational age; in 1 case this was associated with fetal mortality. This cohort indicates that such treatment may prevent severe fetal anemia from developing prior to 20 weeks and, in this cohort, indicated an improved survival of pregnancies (86% survival (6/7)), as compared to the previous history. The only perinatal mortality occurred in a growth-restricted fetus whose mother had a chronic opiate addiction. The fetus died prior to 20 weeks. Of the pregnancies that progressed beyond 20 weeks and commenced classical fetal intravascular transfusions, the survival was 100%.

Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions.

House dust mite (HDM) allergens are important factors in the increasing prevalence of asthma. The lung epithelium forms a barrier that allergens must cross before they can cause sensitization. However, the mechanisms involved are unknown. Here we show that the cysteine proteinase allergen Der p 1 from fecal pellets of the HDM Dermatophagoides pteronyssinus causes disruption of intercellular tight junctions (TJs), which are the principal components of the epithelial paracellular permeability barrier. In confluent airway epithelial cells, Der p 1 led to cleavage of the TJ adhesion protein occludin. Cleavage was attenuated by antipain, but not by inhibitors of serine, aspartic, or matrix metalloproteinases. Putative Der p 1 cleavage sites were found in peptides from an extracellular domain of occludin and in the TJ adhesion protein claudin-1. TJ breakdown nonspecifically increased epithelial permeability, allowing Der p 1 to cross the epithelial barrier. Thus, transepithelial movement of Der p 1 to dendritic antigen-presenting cells via the paracellular pathway may be promoted by the allergen's own proteolytic activity. These results suggest that opening of TJs by environmental proteinases may be the initial step in the development of asthma to a variety of allergens.

Readmission and survival following hospitalization for chronic obstructive pulmonary disease: long-term trends.

BACKGROUND: Exacerbations requiring hospital admission for chronic obstructive pulmonary disease (COPD) contribute to a decline in health status and are costly to the community. Long-term trends in admissions and associated outcomes are difficult to establish because of frequent readmissions, high case fatality and potential diagnostic transfer between COPD and asthma. The Western Australian Data Linkage System provides a unique opportunity to examine admissions for patients with COPD over the long term. METHOD: Nineteen years of hospital morbidity data, based on International Classification of Diseases-9 criteria were extracted from the Western Australian Data Linkage System (1980-1998) and merged with mortality records to examine trends in hospital admissions for COPD. RESULTS: The rate of hospital admissions for COPD has declined overall and the rate of first presentation declined in men and remained constant in women. The risk of readmission increased throughout the period (P < 0.0001) and more than half of all admissions were followed by readmission within a year. Median survival following first admission was 6 years (men 5 years; women 8 years). Age, sex and International Classification of Diseases subcategory each showed an independent effect on the risk of mortality (P < 0.0001). The poorest survival was in patients subcategorized as emphysema. For patients with multiple admissions, the likelihood of cross-over between COPD and asthma was high and increased with the total number of admissions. CONCLUSION: The rate of admission for COPD has declined in Western Australia; however, the resource burden will continue to increase because of the ageing population. This has policy implications for the development of acute care treatment programmes for COPD.

Optimizing memory function in temporal lobe epilepsy.

PURPOSE: The study aimed to assess whether engagement in a memory training programme and performing internet brain training exercises improve memory function in people with temporal lobe epilepsy (TLE). METHODS: Seventy-seven people with TLE, complaining of memory difficulties, completed the study. Participants ranged in age from 19 to 67 years and 40 had left TLE. Participants were randomised to one of four conditions; Group 1: traditional memory training, Group 2: Lumosity, an on-line cognitive training programme, Group 3: traditional memory training and Lumosity, and Group 4: no training. Memory efficiency and mood were assessed at baseline and three months later. RESULTS: Group analyses indicated improved verbal recall after training (p<0.001) and improved subjective ratings (p<0.007). More participants reported a lessening of the memory burden (p<0.007) after training; differences were significant between Groups 1 and 3 compared to Group 4. Lumosity use was not associated with changes in the memory outcome measures but there was a relationship with depression ratings and the number of memory games played (p<0.01). Conventional memory training, IQ, and post-surgical status were associated with positive memory outcomes. CONCLUSIONS: The study indicates traditional memory rehabilitation techniques can help reduce the burden of memory impairment in TLE. There was no evidence that Lumosity the on-line cognitive training programme had specific advantages. Positive change was not universal and larger studies will be required to explore factors associated with successful outcomes.

Glutathione peroxidase activity and mRNA expression in eosinophils and neutrophils of asthmatic and non-asthmatic subjects.

Asthma has been reported to be associated with a reduction in the activity of glutathione peroxidase (GSH-Px), an important antioxidant enzyme. However, the expression of GSH-Px enzyme activity has not previously been investigated in human eosinophils, which are important inflammatory cells involved in asthma. Reverse transcriptase-polymerase chain reaction and Southern blotting demonstrated that eosinophils express GSH-Px mRNA and the relative expression of GSH-Px was greater in eosinophils than in neutrophils for both asthmatic and non-asthmatic subjects. The presence of GSH-Px protein in eosinophil and neutrophil lysates was confirmed by size exclusion chromatography and by Western blotting. GSH-Px enzyme activity as measured by a spectrophotometric assay was greater in eosinophil (48.4+/-1.6 micromol NADPH oxidized x min(-1) x g(-1) protein) than in neutrophil lysates (18.1+/-0.4, n = 24, P < 0.0001). GSH-Px activities of eosinophils and neutrophils from asthmatic subjects did not differ from those of non-asthmatic subjects. Eosinophil GSH-Px activity was correlated with peripheral blood eosinophil count only in asthmatic subjects (rs = 0.59, n = 12, P = 0.04). Increased GSH-Px expression in eosinophils compared with neutrophils of asthmatic patients may provide antioxidant protection against the greater amounts of reactive oxygen species generated by these cells and may enhance the survival of eosinophils at sites of inflammation in asthma.

Cognitive outcomes of temporal lobe epilepsy surgery in older patients.

PURPOSE: To examine the cognitive risks of temporal lobe surgery in patients aged 50 years and older. METHODS: We analysed data from 55 patients who underwent temporal lobe surgery (26 left-sided:29 right sided) from 1988 to 2012 at our centre. Pre-surgical and one year post-operative memory and naming capacity were compared to data obtained from two younger cohorts; 185 aged 18-30 and 220 aged 31-49. RESULTS: Pre-operative memory impairments were most marked for the oldest cohort and were associated with a longer duration of epilepsy. Naming capacity improved with age and better performance was associated with a later age at epilepsy onset. Post-operative declines were largest in older patients, achieving statistical significance for verbal memory, naming and subjective ratings. Left temporal lobe resections carried the greatest risk of memory and naming decline. Cognitive outcomes were unrelated to seizure outcome, VIQ or mood. CONCLUSION: Our findings indicate the cognitive risks of TLE surgery are greater for older patients. Cognitive outcomes need to be considered when assessing the efficacy of epilepsy surgery in older cohorts and pre-operative performance levels need to be taken into account.