P300 in obsessive–compulsive disorder: Source localization and the effects of treatment

Converging evidence suggests that frontostriatal abnormalities underlie OCD symptoms. The event-related potential P300 is generated along a widely distributed network involving several of the areas implicated in OCD. P300 abnormalities reported in patients with OCD suggest increased activity in these areas. The aim of the present study was to investigate this assumption in unmedicated patients with OCD, and to assess the effects of OCD treatment on P300 brain activity patterns. Seventy-one unmedicated patients with a DSM-IV diagnosis of OCD and 71 age- and gender-matched healthy control subjects participated in the study. The P300 was obtained through 32-channel EEG during an auditory oddball paradigm. Forty-three patients underwent a second EEG assessment after treatment with sertraline and behavioural therapy. Low-resolution electromagnetic tomography (LORETA) was used to localize the sources of brain electrical activity. Results: Increased P300-related activity was observed predominantly in the left orbitofrontal cortex, but also in left prefrontal, parietal and temporal areas, in patients compared to controls at baseline. After treatment, reduction of left middle frontal cortex hyperactivity was observed in patients. Conclusions: Findings of increased activity in frontoparietal areas in patients are consistent with several previous studies. Importantly, OCD treatment led to reduction of hyperactivity in the left middle frontal cortex, an area associated with context processing and uncertainty that might be important for the emergence of OCD symptoms. Thus, the present study is the first to show an association between P300 abnormalities and activity in brain regions postulated to be involved in the pathophysiology of OCD.     

Serologic markers of persistent Chlamydia pneumonia infection and long-term prognosis after successful coronary stenting

Background

Previous studies have shown an incremental role of inflammation in late prognosis following coronary stenting (CS). In particular, high preprocedural levels of plasma C-reactive protein (CRP) have been related to increased hazard of late ischemic complications. Persistent Chlamydia pneumoniae (Cp) infection, detected by positive IgA anti-Cp titers, may be associated with this inflammatory process and portend a high risk of late adverse prognosis after CS.

Methods

A total of 483 consecutive patients with either stable or unstable coronary syndromes were followed-up for 1 year after successful CS. The composite of cardiac death, myocardial infarction, rehospitalization for rest-unstable angina, and exertional angina, whichever occurred first, was the clinical end point. Additionally, the rate of in-stent restenosis and progression of coronary artery disease during this period were evaluated. Anti-Cp titers and plasma CRP levels were measured before the procedure.

Results

Positive immunoglobulin A (IgA), but not positive immunoglobulin G (IgG), titers were significantly associated with high plasma CRP levels in patients with unstable coronary syndromes (P = .005), but not in those with stable angina (P = .7). Moreover, positive IgA titers were significantly related to increased risk of both the composite clinical end point (P = .04) and progression of coronary artery disease (P < .001) in patients with unstable coronary syndromes but not in those with stable angina. Neither positive IgA nor positive IgG titers were associated with the rate of in-stent restenosis.

Conclusions

Persistent Cp infection may drive an inflammatory response in the coronary vasculature and portends an adverse late outcome after CS in patients with unstable coronary syndromes.     

Education and age affect skill acquisition and retention in lay rescuers after a European Resuscitation Council CPR/AED course

Objectives

To examine whether education and age affect skill acquisition and retention in lay rescuers after a European Resuscitation Council (ERC) CPR/AED course.

Background

Because of the importance of bystander CPR/AED skills in the setting of cardiac arrest, acquisition and retention of resuscitation skills has gained a great amount of interest.

Methods

The ERC CPR/AED course format for written and practical evaluation was used. Eighty lay people were trained and evaluated at the end of the course, as well as at one, three, and six months.

Results

Retention of CPR/AED skills improved over time, recording the lowest practical scores at one month after initial training and the lowest written scores at initial training. In practical evaluation scores, when examined longitudinally, age presented a significant adverse effect and higher background education presented a non-significant positive effect. Moreover, regarding written evaluation scores, when examined longitudinally, education presented a significant positive effect while age did not significantly correlate with written scores.

Conclusions

Education and age affected retention of CPR/AED skills in lay rescuers. Also, our results suggest that the ERC CPR/AED course format may be poorly designed to discriminate between participants with different levels of practical and written resuscitation skills and merit a thorough investigation in future studies.     

Coronary artery disease predisposing haplogroup I of the Y chromosome,aggression and sex steroids – Genetic association analysis

Objective

Amongst middle-aged men, haplogroup I is associated with ≈50% higher risk of coronary artery disease than other paternal lineages of Y chromosome. We hypothesised that carriers of haplogroup I had higher levels of aggression and estrogens and/or lower levels of androgens early in life and thus might be more prone to cardiovascular disease than men with other lineages of Y chromosome.

Methods

We reconstructed phylogenetic tree of the Y chromosome in >1000 young apparently healthy white men from the general population. Each Y chromosome was classified into one of 13 most common European lineages. Androgens (DHEA-S, androstenedione, total testosterone) and their metabolites (total estradiol, estrone) were measured by radioimmunoassays. Information on five dimensions of aggression (total, physical, verbal, anger and hostility) was collected using Buss and Perry questionnaire.

Results

Approximately 17% men inherited haplogroup I from their fathers. Carriers of haplogroup I showed lower scores of verbal aggression than men with other haplogroups (β = −0.72, SE = 0.29, P = 0.012) and when further compared to carriers of most common R1a lineage and other haplogroups (β = −1.03, SE = 0.34, P = 0.003). However, these associations did not survive a correction for multiple testing. Sex steroids did not show even nominal level of association with haplogroup I.

Conclusion

Our data show no overall association between haplogroup I and sex-related phenotypes in young white men. These results also suggest that the previously identified association between haplogroup I and coronary artery disease is not likely mediated by unfavourable profile of sex steroids or heightened aggression early in life.     

Preferential production of IgG1, IL-4 and IL-10 in MuSK-immunized mice

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness associated with acetylcholine receptor (AChR), muscle-specific receptor kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4)-antibodies. MuSK-antibodies are predominantly of the non-complement fixing IgG4 isotype. The MuSK associated experimental autoimmune myasthenia gravis (EAMG) model was established in mice to investigate immunoglobulin (Ig) and cytokine responses related with MuSK immunity. C57BL/6 (B6) mice immunized with 30 μg of recombinant human MuSK in incomplete or complete Freund's adjuvant (CFA) showed significant EAMG susceptibility (> 80% incidence). Although mice immunized with 10 μg of MuSK had lower EAMG incidence (14.3%), serum MuSK-antibody levels were comparable to mice immunized with 30 μg MuSK. While MuSK immunization stimulated production of all antibody isotypes, non-complement fixing IgG1 was the dominant anti-MuSK Ig isotype in both sera and neuromuscular junctions. Moreover, MuSK immunized IgG1 knockout mice showed very low serum MuSK-antibody levels. Sera and MuSK-stimulated lymph node cell supernatants of MuSK immunized mice showed significantly higher levels of IL-4 and IL-10 (but not IFN-γ and IL-12), than those of CFA immunized mice. Our results suggest that through activation of Th2-type cells, anti-MuSK immunity promotes production of IL-4, which in turn activates anti-MuSK IgG1, the mouse analog of human IgG4. These findings might provide clues for the pathogenesis of other IgG4-related diseases as well as development of disease specific treatment methods (e.g. specific IgG4 inhibitors) for MuSK-related MG.     

Experimental Investigation of the TRM-to-Masonry Bond after Exposure to Elevated Temperatures: Cementitious and Alkali-Activated Matrices of Various Densities

Limited research has focused on the effect of high temperatures on the textile-reinforced mortar (TRM)-to-masonry bond. In this study, masonry prisms that were furnished with double-layered TRM strips were tested under shear bond conditions after their exposure to 200 °C and 400 °C for 1 h using the single-lap/single-prism setup. A total of four TRM systems were applied sharing the same type of textile –a dry AR glass fiber one– and different matrices: two cementitious matrices, namely a normal-weight (TRCNM) and a lightweight (TRCLM) one, and two counterpart alkali-activated matrices (TRAANM and TRAALM) based on metakaolin and fly ash. Specimens’ exposure to elevated temperatures did not alter their failure mode which was due to the sleeve fibers’ rupture along with core fibers’ slippage from the mortar. The residual bond capacity of the TRM systems decreases almost linearly with increasing exposure temperature. The alkali-activated textile reinforced mortars outperformed their cement-based counterparts in terms of bond strength at every temperature. All systems retained close to 50% of their original shear bond strength after heating at 400 °C. Per the type of binder, lightweight matrices resulted in either comparable (cement-based systems) or better (alkali-activated systems) heat protection at the TRM/masonry interface.     

Time experience in patients with schizophrenia and affective disorders

BackgroundThe experience of time, or the temporal order of external and internal events, is essential for humans. In psychiatric disorders such as depression and schizophrenia, impairment of time processing has been discussed for a long time.AimsIn this explorative pilot study, therefore, the subjective time feeling as well as objective time perception were determined in patients with depression and schizophrenia, along with possible neurobiological correlates.MethodsDepressed (n = 34; 32.4 ± 9.8 years; 21 men) and schizophrenic patients (n = 31; 35.1 ± 10.7 years; 22 men) and healthy subjects (n = 33; 32.8 ± 14.3 years; 16 men) were tested using time feeling questionnaires, time perception tasks and critical flicker-fusion frequency (CFF) and loudness dependence of auditory evoked potentials (LDAEP) to determine serotonergic neurotransmission.ResultsThere were significant differences between the three groups regarding time feeling and also in time perception tasks (estimation of given time duration) and CFF (the “DOWN” condition). Regarding the LDAEP, patients with schizophrenia showed a significant negative correlation to time experience in terms of a pathologically increased serotonergic neurotransmission with disturbed time feeling.ConclusionsImpairment of time experience seems to play an important role in depression and schizophrenia, both subjectively and objectively, and novel neurobiological correlates have been uncovered. It is suggested, therefore, that alteration of experience of time should be increasingly included in the current psychopathological findings.