A long-period radio transient active for three decades.

Several long-period radio transients have recently been discovered, with strongly polarized coherent radio pulses appearing on timescales between tens to thousands of seconds1,2. In some cases, the radio pulses have been interpreted as coming from rotating neutron stars with extremely strong magnetic fields, known as magnetars; the origin of other, occasionally periodic and less-well-sampled radio transients is still debated3. Coherent periodic radio emission is usually explained by rotating dipolar magnetic fields and pair-production mechanisms, but such models do not easily predict radio emission from such slowly rotating neutron stars and maintain it for extended times. On the other hand, highly magnetic isolated white dwarfs would be expected to have long spin periodicities, but periodic coherent radio emission has not yet been directly detected from these sources. Here we report observations of a long-period (21 min) radio transient, which we have labelled GPM J1839-10. The pulses vary in brightness by two orders of magnitude, last between 30 and 300 s and have quasiperiodic substructure. The observations prompted a search of radio archives and we found that the source has been repeating since at least 1988. The archival data enabled constraint of the period derivative to <3.6 × 10-13 s s-1, which is at the very limit of any classical theoretical model that predicts dipolar radio emission from an isolated neutron star.

Localized thermonuclear bursts from accreting magnetic white dwarfs.

Nova explosions are caused by global thermonuclear runaways triggered in the surface layers of accreting white dwarfs1-3. It has been predicted4-6 that localized thermonuclear bursts on white dwarfs can also take place, similar to type-I X-ray bursts observed in accreting neutron stars. Unexplained rapid bursts from the binary system TV Columbae, in which mass is accreted onto a moderately strong magnetized white dwarf from a low-mass companion, have been observed on several occasions in the past 40 years7-11. During these bursts, the optical/ultraviolet luminosity increases by a factor of more than three in less than an hour and fades in around ten hours. Fast outflows have been observed in ultraviolet spectral lines7, with velocities of more than 3,500 kilometres per second, comparable to the escape velocity from the white dwarf surface. Here we report on optical bursts observed in TV Columbae and in two additional accreting systems, EI Ursae Majoris and ASASSN-19bh. The bursts have a total energy of approximately 10-6  times than those of classical nova explosions (micronovae) and bear a strong resemblance to type-I X-ray bursts12-14. We exclude accretion or stellar magnetic reconnection events as their origin and suggest thermonuclear runaway events in magnetically confined accretion columns as a viable explanation.

Social cognition in cervical dystonia: phenotype and relationship to anxiety and depression.

BACKGROUND AND PURPOSE: Anxiety and depression are common disabling comorbidities in cervical dystonia (CD) and may predispose to social withdrawal and social cognitive impairments. The relationship between social cognition and depressive/anxiety symptoms in CD is under-investigated. METHODS: Forty-six CD patients (40 women; mean age ± SD, 55.57 ± 10.84 years) were administered the following social cognition battery: Affect Naming, Prosody Face and Pair Matching subtests from the Wechsler Adult Intelligence Scale IV and Wechsler Memory Scale IV (social perception), reality-known and reality-unknown false belief reasoning tasks (theory of mind), Empathy Quotient and Social Norms Questionnaire 22 (social behaviour), alongside the Benton Facial Recognition Task (non-emotional facial discrimination). Alongside CD severity, the Hospital Anxiety and Depression Scale measured depressive/anxiety comorbid diagnostic status and severity, and the Liebowitz Social Anxiety Scale assessed social phobia. Social cognition tasks were standardized using published normative data and a cut-off of z < -1.5 for impairment. RESULTS: More than 90% of our CD patients performed normally on social perception and social behaviour tests. Performance on impaired belief reasoning (theory of mind) was impaired in 10 of 46 (21.74%); five of 46 (10.87%) were impaired on the Empathy Quotient. Better performance on the Affect Naming task was associated with comorbid anxiety (η2  = 0.09, medium-to-large effect size) and greater anxiety, depression and social phobia severity. Worse performance on the Empathy Quotient was associated with comorbid depression (η2  = 0.11, medium-to-large effect size) and greater depression severity. CD patients had significantly more difficulties with fearful face identification (P < 0.001). CONCLUSIONS: Greater social perception abilities in CD patients with more severe anxiety and depression suggest efficient modulation and self-adaptation of social cognitive skills.

External validation of a simple risk score based on the ASPRE trial algorithm for preterm pre-eclampsia considering maternal characteristics in nulliparous pregnant women: a multicentre retrospective cohort study.

OBJECTIVE: To validate the performance of a first-trimester simple risk score based on the ASPRE trial algorithm for pre-eclampsia. DESIGN: Multicentre retrospective cohort analysis. SETTING: Four Italian hospitals. POPULATION: Unselected nulliparous women at 11-13 weeks of gestation from January 2014 through to January 2018. METHODS: Model performance was evaluated based on discrimination and calibration. MAIN OUTCOME MEASURES: Delivery before 37 weeks of gestation with a diagnosis of pre-eclampsia. RESULTS: Based on 73 preterm pre-eclampsia cases and 7546 controls (including 101 cases of late pre-eclampsia), the area under the receiver operating characteristics curve was 0.659 (95% CI 0.579-0.726). The sensitivity was 32.9% (95% CI 22.1-43.7) at a false-positive rate of 8.8%. The positive likelihood ratio was 3.74 (95% CI 2.67-5.23), the positive predictive value was 3.49% (95% CI 2.12-4.86%) and the negative predictive value was 99.3% (95% CI 99.1-99.5%). The sensitivity and positive likelihood ratio were approximately 40% lower than in the original study. The calibration analysis showed a good agreement between observed and expected risks (P = 0.037). Comparison with the Fetal Medicine Foundation (FMF) algorithm yielded a difference in the area under the curve of 0.084 (P = 0.007). CONCLUSIONS: In our Italian population, the simple risk score had a lower performance than expected for the prediction of preterm pre-eclampsia in nulliparous women. The FMF algorithm applied to the same data set resulted in a better prediction. TWEETABLE ABSTRACT: Simple risk score predicts preterm pre-eclampsia in Italy.

Multivariable evaluation of maternal hemodynamic profile in pregnancy complicated by fetal growth restriction: prospective study.

OBJECTIVE: To evaluate the association between fetal growth restriction (FGR) and maternal hemodynamic parameters using multivariable analysis, adjusting for major confounding factors, such as hypertensive disorders of pregnancy (pre-eclampsia and gestational hypertension). METHODS: A prospective cohort study was conducted between January 2013 and April 2016. Two cohorts of patients were recruited, between 24 and 39 weeks of gestation, in a high-risk outpatient setting. These cohorts comprised 49 appropriate-for-gestational-age singleton fetuses and 93 that were FGR (abdominal circumference (AC) at recruitment in the second half of pregnancy ≤ 10th percentile with a previous normal AC at 20-22 weeks). Maternal echocardiography was performed at the time of enrolment and included hemodynamic parameters of systolic and diastolic function and cardiac remodeling indices. Data were analyzed using a multivariable generalized linear model to estimate the association of FGR with maternal hemodynamic parameters after adjusting for significant confounding factors. RESULTS: In the multivariable analysis, after adjustment for hypertensive disorders of pregnancy and smoking, FGR was associated with a 14% increase in maternal total vascular resistance, 16% reduction in cardiac output, 13% reduction in left ventricular mass and 11% reduction in heart rate; similar results were observed for the corresponding indexed parameters. Hypertensive disorders of pregnancy in the absence of FGR were associated with a 25% increase in total vascular resistance, 16% increase in left ventricular mass and 14% reduction in diastolic function; similar results were observed for the corresponding indexed parameters. CONCLUSION: FGR is significantly and independently associated with several maternal hemodynamic parameters, even after adjustment for major confounding factors, such as hypertensive disorders of pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Experimental investigation and modeling of diffusion dialysis for HCl recovery from waste pickling solution.

Hydrochloric acid recovery from pickling solutions was studied by employing a batch diffusion dialysis (DD) laboratory test-rig equipped with Fumasep membranes. The effect of main operating parameters such as HCl concentration (0.1-3 M) and the presence of Fe2+ (up to 150 g/l) was investigated to simulate the system operation with real industrial streams. The variation of HCl, Fe2+ and water flux was identified. When only HCl is present, a recovery efficiency of 100% was reached. In the presence of FeCl2, higher acid recovery efficiencies, up to 150%, were observed due to the so-called "salt effect", which promotes the passage of acid even against its concentration gradient. A 7% leakage of FeCl2 was detected in the most severe conditions. An original analysis on water flux in DD operation has indicated that osmotic flux prevails at low HCl concentrations, while a dominant "drag flux" in the opposite direction is observed for higher HCl concentrations. A comprehensive mathematical model was developed and validated with experimental data. The model has a time and space distributed-parameters structure allowing to effectively simulate steady-state and transient batch operations, thus providing an operative tool for the design and optimisation of DD units.

First comprehensive tool for screening pain in Parkinson's disease: the King's Parkinson's Disease Pain Questionnaire.

BACKGROUND AND PURPOSE: Pain is highly prevalent in Parkinson's disease (PD), impacting patients' ability, mood and quality of life. Detecting the presence of pain in its multiple modalities is necessary for adequate personalized management of PD. A 14-item, PD-specific, patient-based questionnaire (the King's Parkinson's Disease Pain Questionnaire, KPPQ) was designed corresponding to the rater-based KPP Scale (KPPS). The present multicentre study was aimed at testing the validity of this screening tool. METHODS: First, a comparison between the KPPQ scores of patients and matched controls was performed. Next, convergent validity, reproducibility (test-retest) and diagnostic performance of the questionnaire were analysed. RESULTS: Data from 300 patients and 150 controls are reported. PD patients declared significantly more pain symptoms than controls (3.96 ± 2.56 vs. 2.17 ± 1.39; P < 0.0001). The KPPQ convergent validity was high with KPPS total score (rS  = 0.80) but weak or moderate with other pain assessments. Test-retest reliability was satisfactory with kappa values ≥0.65 except for item 5, Dyskinetic pains (κ = 0.44), and the intraclass correlation coefficient (ICC) for the KPPQ total score was 0.98. After the scores of the KPPS were adapted for screening (0, no symptom; ≥1, symptom present), a good agreement was found between the KPPQ and the KPPS (ICC = 0.88). A strong correlation (rS  = 0.80) between the two instruments was found. The diagnostic parameters of the KPPQ were very satisfactory as a whole, with a global accuracy of 78.3%-98.3%. CONCLUSIONS: These results suggest that the KPPQ is a useful, reliable and valid screening instrument for pain in PD to advance patient-related outcomes.

Genetic variation at the Th2 immune gene IL13 is associated with IgE-mediated paediatric food allergy.

BACKGROUND: Food allergies pose a considerable world-wide public health burden with incidence as high as one in ten in 12-month-old infants. Few food allergy genetic risk variants have yet been identified. The Th2 immune gene IL13 is a highly plausible genetic candidate as it is central to the initiation of IgE class switching in B cells. OBJECTIVE: Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy. METHOD: We genotyped nine IL13 "tag" single nucleotide polymorphisms (tag SNPs) in 367 challenge-proven food allergic cases, 199 food-sensitized tolerant cases and 156 non-food allergic controls from the HealthNuts study. 12-month-old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran-Mantel-Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co-located sample of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication sample phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed. RESULTS: IL13 rs1295686 was associated with challenge-proven food allergy in the discovery sample (P=.003; OR=1.75; CI=1.20-2.53). This association was also detected in the replication sample (P=.03, OR=1.37, CI=1.03-1.82) and further supported by a meta-analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE. CONCLUSIONS AND CLINICAL RELAVANCE: We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge-proven food allergy.

Genomewide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA-DRB1.

BACKGROUND: Genetic variants for IgE-mediated peanut allergy are yet to be fully characterized and to date only one genomewide association study (GWAS) has been published. OBJECTIVE: To identify genetic variants associated with challenge-proven peanut allergy. METHODS: We carried out a GWAS comparing 73 infants with challenge-proven IgE-mediated peanut allergy against 148 non-allergic infants (all ~ 1 year old). We tested a total of 3.8 million single nucleotide polymorphisms, as well as imputed HLA alleles and amino acids. Replication was assessed by de novo genotyping in a panel of additional 117 cases and 380 controls, and in silico testing in two independent GWAS cohorts. RESULTS: We identified 21 independent associations at P ≤ 5 × 10-5 but were unable to replicate these. The most significant HLA association was the previously reported amino acid variant located at position 71, within the peptide-binding groove of HLA-DRB1 (P = 2 × 10-4 ). Our study therefore reproduced previous findings for the association between peanut allergy and HLA-DRB1 in this Australian population. CONCLUSIONS AND CLINICAL RELEVANCE: Genetic determinants for challenge-proven peanut allergy include alleles at the HLA-DRB1 locus.

The skin barrier function gene SPINK5 is associated with challenge-proven IgE-mediated food allergy in infants.

BACKGROUND: A defective skin barrier is hypothesized to be an important route of sensitization to dietary antigens and may lead to food allergy in some children. Missense mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) skin barrier gene have previously been associated with allergic conditions. OBJECTIVE: To determine whether genetic variants in and around SPINK5 are associated with IgE-mediated food allergy. METHOD: We genotyped 71 "tag" single nucleotide polymorphisms (tag-SNPs) within a region spanning ~263 kb including SPINK5 (~61 kb) in n=722 (n=367 food-allergic, n=199 food-sensitized-tolerant and n=156 non-food-allergic controls) 12-month-old infants (discovery sample) phenotyped for food allergy with the gold standard oral food challenge. Transepidermal water loss (TEWL) measures were collected at 12 months from a subset (n=150) of these individuals. SNPs were tested for association with food allergy using the Cochran-Mantel-Haenszel test adjusting for ancestry strata. Association analyses were replicated in an independent sample group derived from four paediatric cohorts, total n=533 (n=203 food-allergic, n=330 non-food-allergic), mean age 2.5 years, with food allergy defined by either clinical history of reactivity, 95% positive predictive value (PPV) or challenge, corrected for ancestry by principal components. RESULTS: SPINK5 variant rs9325071 (A⟶G) was associated with challenge-proven food allergy in the discovery sample (P=.001, OR=2.95, CI=1.49-5.83). This association was further supported by replication (P=.007, OR=1.58, CI=1.13-2.20) and by meta-analysis (P=.0004, OR=1.65). Variant rs9325071 is associated with decreased SPINK5 gene expression in the skin in publicly available genotype-tissue expression data, and we generated preliminary evidence for association of this SNP with elevated TEWL also. CONCLUSIONS: We report, for the first time, association between SPINK5 variant rs9325071 and challenge-proven IgE-mediated food allergy.

Genome-scale estimate of the metabolic turnover of E. coli from the energy balance analysis.

In this article the notion of metabolic turnover is revisited in the light of recent results of out-of-equilibrium thermodynamics. By means of Monte Carlo methods we perform an exact sampling of the enzymatic fluxes in a genome scale metabolic network of E. coli in stationary growth conditions from which we infer the metabolites turnover times. However the latter are inferred from net fluxes, and we argue that this approximation is not valid for enzymes working nearby thermodynamic equilibrium. We recalculate turnover times from total fluxes by performing an energy balance analysis of the network and recurring to the fluctuation theorem. We find in many cases values one of order of magnitude lower, implying a faster picture of intermediate metabolism.

Gilles de la Tourette syndrome - A treatable condition?

INTRODUCTION: Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder characterized by chronic motor and vocal tics. Psychiatric comorbidity is frequent but does not enter into the official classification of the syndrome. In the present article, we will focus on treatment options for tics. METHODS: We have reviewed the relevant literature on treatment of tics and GTS, especially in the period from 2011-2016 since the publication of the European Society for the Study of Tourette Syndrome (ESSTS) treatment guidelines in 2011. RESULTS: We present current and up-to-date approaches in psychotherapy, pharmacotherapy and neurosurgery for GTS with an outlook for the upcoming years. CONCLUSIONS: Although many patients and health-care professionals seem to view tics and/or GTS as difficult to treat, or believe that treatment requires severe side effects with reduction in quality of life, we wish to convey that there is cause for optimism, both with regard to available treatment modalities and future therapeutic developments.

King's Parkinson's disease pain scale, the first scale for pain in PD: An international validation.

Pain is a key unmet need and a major aspect of non-motor symptoms of Parkinson's disease (PD). No specific validated scales exist to identify and grade the various types of pain in PD. We report an international, cross-sectional, open, multicenter, one-point-in-time evaluation with retest study of the first PD-specific pain scale, the King's PD Pain Scale. Its seven domains include 14 items, each item scored by severity (0-3) multiplied by frequency (0-4), resulting in a subscore of 0 to 12, with a total possible score range from 0 to 168. One hundred seventy-eight PD patients with otherwise unexplained pain (age [mean ± SD], 64.38 ± 11.38 y [range, 29-85]; 62.92% male; duration of disease, 5.40 ± 4.93 y) and 83 nonspousal non-PD controls, matched by age (64.25 ± 11.10 y) and sex (61.45% males) were studied. No missing data were noted, and floor effect was observed in all domains. The difference between mean and median King's PD Pain Scale total score was less than 10% of the maximum observed value. Skewness was marginally high (1.48 for patients). Factor analysis showed four factors in the King's PD Pain Scale, explaining 57% of the variance (Kaiser-Mayer-Olkin, 0.73; sphericity test). Cronbach's alpha was 0.78, item-total correlation mean value 0.40, and item homogeneity 0.22. Correlation coefficients of the King's PD Pain Scale domains and total score with other pain measures were high. Correlation with the Scale for Outcomes in PD-Motor, Non-Motor Symptoms Scale total score, and quality of life measures was high. The King's PD Pain Scale seems to be a reliable and valid scale for grade rating of various types of pain in PD.

Clinical and epidemiological characteristics of infectious keratitis in Paraguay.

To describe the clinical and epidemiological characteristics of patients with severe infectious keratitis in Asunción, Paraguay between April 2009 and September 2011. All patients with the clinical diagnosis of severe keratitis (ulcer ≥2 mm in size and/or central location) were included. Empiric treatment consisted of topical antibiotics and antimycotics; in cases of advanced keratitis, fortified antibiotics were used. After microbiological analysis, treatment was changed if indicated. In total 48 patients (62.5 % males, 25 % farmers) were included in the analysis. A central ulcer was found in 81.3 % (n = 39). The median delay between onset of symptoms and time of first presentation at our institution was 7 days (range 1-30 days). Fungal keratitis was diagnosed in 64.5 % (n = 31) of patients, of which Fusarium sp. (n = 17) was the most common. Twenty-one patients (43.8 %) reported previous trauma to the eye. The globe could be preserved in all cases. While topical therapy only was sufficient in most patients, a conjunctival flap was necessary in six patients suffering from fungal keratitis. The high rate of fungal keratitis in this series is remarkable, and microbiological analysis provided valuable information for the appropriate treatment. In this setting, one has to be highly suspicious of fungal causes of infectious keratitis.

Oral immunotherapy and tolerance induction in childhood.

Prevalence rates of food allergy have increased rapidly in recent decades. Of concern, rates of increase are greatest among children under 5 yrs of age and for those food allergies that persist into adulthood such as peanut or tree nut allergy and shellfish allergy. Given these trends, the overall prevalence of food allergy will compound over time as the number of children affected by food allergy soars and a greater proportion of food-allergic children are left with persistent disease into adulthood. It is therefore vital to identify novel curative treatment approaches for food allergy. Acquisition of oral tolerance to the diverse array of ingested food antigens and intestinal microbiota is an active immunologic process that is successfully established in the majority of individuals. In subjects who develop food allergy, there is a failure or loss of oral tolerance acquisition to a limited number of food allergens. Oral immunotherapy (OIT) offers a promising approach to induce specific oral tolerance to selected food allergens and represents a potential strategy for long-term curative treatment of food allergy. This review will summarize the current understanding of oral tolerance and clinical trials of OIT for the treatment of food allergy.

Mood instability and functional recovery in bipolar disorders.

OBJECTIVE: The aim of this study was to identify psychopathological factors associated with long-term functional outcome in euthymic bipolar disorder patients and to test new measures of mood instability and symptoms intensity. METHOD: Fifty-five patients with more than 12 months of follow-up were included. In addition to traditional clinical variables, the time spent ill was documented using a modified life-charting technique based on NIHM life-charting method. New measures, Mood Instability Factor, and Mood Intensity Factor were defined and assessed. Functioning Assessment Short Test (FAST) was used to assess disability. RESULTS: The follow-up period was 3.00 ± 1.51 years. Weeks with subsyndromal depressive symptoms (ß = 0.133, t = 2.556, P = 0.014), weeks with mild manic symptoms (ß = 1.441, t = 3.10, P = 0.003), and the Mood Instability Factor (ß = 0.105, t = 3.593, P = 0.001) contributed to approximately 46% of the FAST total score variance. CONCLUSION: New methodologies including subsyndromal symptoms and mood instability parameters might contribute to understand the worse long-term functional outcome that affects a considerable percentage of BD patients even after episode remission. Concerns about therapeutic approaches are discussed.

Effect of lithium in pyramidal neurons of Cornu Ammonis in an animal model.

Bipolar disorder has been associated with a decrease in hippocampal size, and lithium appears to reverse this neuroanatomical abnormality. The objective of this work was to evaluate, at a cellular level, the size of both cell body and nucleus of pyramidal neurons located throughout the Cornu Ammonis (CA1 to CA4 regions). To perform this duty, we used 16 rats that were randomized into two groups: control and dietary lithium-treated. After one month, they were sacrificed and their brains removed for histopathological analysis. Serial photos of the entire Cornu Ammonis were taken and, after dividing them into 4 regions of interest, we measured the cell body and nucleus on each pyramidal neuron belonging to the first 5 photos of each region of interest. As a result of this histological analysis, cell body area and nuclear area were significantly larger in the experimental group in a specific area of the Cornu Ammonis that could correspond to CA2 or the transition between CA1 and CA2. These results suggest that the effect of lithium is not homogeneous throughout the hippocampus and allows directing future studies to a specific area of this structure.

Genome-scale profiling reveals a subset of genes regulated by DNA methylation that program somatic T-cell phenotypes in humans.

The aim of this study was to investigate the dynamics and relationship between DNA methylation and gene expression during early T-cell development. Mononuclear cells were collected at birth and at 12 months from 60 infants and were either activated with anti-CD3 for 24 h or cultured in media alone, and the CD4+ T-cell subset purified. DNA and RNA were co-harvested and DNA methylation was measured in 450 000 CpG sites in parallel with expression measurements taken from 25 000 genes. In unstimulated cells, we found that a subset of 1188 differentially methylated loci were associated with a change in expression in 599 genes (adjusted P value<0.01, ß-fold >0.1). These genes were enriched in reprogramming regions of the genome known to control pluripotency. In contrast, over 630 genes were induced following low-level T-cell activation, but this was not associated with any significant change in DNA methylation. We conclude that DNA methylation is dynamic during early T-cell development, and has a role in the consolidation of T-cell-specific gene expression. During the early phase of clonal expansion, DNA methylation is stable and therefore appears to be of limited importance in short-term T-cell responsiveness.

T-cell activation genes differentially expressed at birth in CD4+ T-cells from children who develop IgE food allergy.

BACKGROUND: Presymptomatic immaturity in neonatal T-cell function is a consistent antecedent of allergic disease, including reduced responsiveness to polyclonal activation. METHODS: To elucidate the underlying mechanisms, we examined for differences in T-cell gene expression in longitudinal samples collected at birth and at 1 year of age in children with (n = 30) and without IgE-mediated food allergy (n = 30). We employed a low-level soluble anti-CD3 stimulus to activate the T-cell receptor (TCR) and surveyed gene expression by DNA microarray in purified CD4(+) T-cells. Allergen-specific responses were assessed in parallel functional studies. RESULTS: At birth, the allergic group showed a reduced number of genes up regulated in response to anti-CD3 treatment on the microarray and a reduced lympho proliferative capacity, suggesting clear differences in T-cell signalling pathways. Polymerase chain reaction (PCR) validation of candidate genes confirmed significantly lower expression of a number of genes in the allergic group including RELB, NFKB2, LIF and FAS. By 12 months of age, there were marked changes in the anti-CD3 response in all infants, culminating in upregulation of cytokine genes (IL-5, IL-13, IL-17 and IL-22). Neonatal differences were no longer apparent. Instead, the allergic group, all symptomatic by this age, showed differential expression of T-cell lineage pathways including GATA-3, MAL and FcER1 in unstimulated T-cells. Allergen stimulation induced significantly higher cytokines production (IL-5, IL-13 and IFNγ) in the allergic group. CONCLUSION: Although transient, suboptimal neonatal T-cell activation pathways that signal through the NF-κB complex may affect the developmental transition of T-cell phenotypes in the periphery shortly after birth and may increase the risk of food allergy.

Social cognition in euthymic bipolar disorder: systematic review and meta-analytic approach.

OBJECTIVE: Deficits in social cognition have been reported in euthymic subjects with bipolar disorder (BD). However, some studies have failed to find differences favoring controls. As most investigations have been conducted with small samples, they have not had sufficient power to detect statistically significant differences. Furthermore, studies communicating positive results have scarcely attempted to estimate effect sizes for patient-control differences. The aim of this study was to summarize the findings of reports on social cognition in patients with euthymic BD and to combine their data to identify possible deficits and quantify their magnitude. METHOD: Systematic literature review and meta-analysis. RESULTS: Impairments of moderate magnitude (0.5 < d < 0.8) were noted across mentalizing skills, whereas small but significant effect sizes (d < 0.5) were observed for facial emotion recognition. No patient-control differences were found for decision-making. CONCLUSION: Meta-analytic findings provide evidence for emotion processing and theory of mind deficits in remitted bipolar patients. However, it is not yet clear whether these areas of impairment are related to neurocognitive dysfunctions or to medication effects. The results are discussed with regard to targets for future neuropsychological research on BDs.