Trait cheerfulness modulates BOLD response in lateral cortical but not limbic brain areas—A pilot fMRI study

Having a good “sense of humor” is an important personality characteristic that significantly influences social communication and may represent an important coping strategy. To take things “with humor” does not only represent a state characteristic but also a personality trait that can reliably be assessed with questionnaires like the “state–trait–cheerfulness–inventory” (STCI) by Ruch [Ruch et al., Assessing the “humorous temperament”: construction of the facet and standard trait forms of the state–trait–cheerfulness–inventory—STCI, Humor 9 (1996) 303–339]. Substantial inter-individual differences among study subjects are a key feature of almost all functional magnetic resonance imaging studies on higher cognitive functions. Usually, they are considered as “statistical noise” and are not recommended for the data analysis, although they can have a high intra-individual stability. However, a number of recent fMRI studies found robust correlations between inter-individual differences in BOLD response and personality traits such as extraversion. The aim of this pilot exploratory study was to localise regions where the BOLD response was predicted by “humor personality” scores. 10 healthy male subjects viewed funny or non-funny versions of Gary Larson cartoons while BOLD response was measured with functional magnetic resonance imaging (fMRI). Data were collected from the whole brain (28 slices, slice thickness 4 mm, 1 mm gap, TR = 3 s). SPM 99 software was used. A simple regression analysis with the sub-score cheerfulness from the STCI was applied. Higher cheerfulness in the STCI predicted brain activation in the right inferior parietal lobule (Tal X, Y, Z: 45, −77, 29), but not in limbic and prefrontal brain areas. We conclude that neural correlates of cheerfulness are correlated with BOLD response in lateral cortical rather than limbic brain areas. Likely the activated region is important for a readiness or tendency to be amused, whereas the regions previously shown to be activated in humor appreciation studies are related to the understanding of the joke and the emotional reaction.     

Adolescent primiparas: changes in obstetrical risk between 1983-1987 and 1999-2005.

AIMS: Teenage pregnancies have always been considered at increased risk for obstetric complications. Deliveries in adolescent primiparas in the 5-year time periods 1983-1987 and 1999-2005 were compared against each other, the general population and against primiparas aged 20-29 years in order to reveal trends and differences in obstetric outcome. METHODS: A total of 186 primiparas delivering at an age of 17 or less between October 1999 and October 2005 were compared with 353 adolescent primiparas delivered between 1983 and 1987. Type of delivery and complications such as low birthweight, pre-eclampsia, breech presentation and third stage complications were studied. RESULTS: The percentage of adolescents in the overall obstetric population decreased. The cesarean section rate remained the same in the adolescents while increasing in the general population. Rates of low birthweight and operative vaginal delivery increased in the adolescent group and overall. Third stage complications (abnormally adherent or incomplete placentas) decreased in both groups. There were no intrauterine fetal deaths in adolescent pregnancies in either time period. Other obstetric variables were unchanged in the adolescent as well as in the general population between 1999 and 2005. When comparing the adolescents' outcome with the outcome of the 20-29-year-old primiparas between 1999 and 2005, it was noted that the rates of abstracted obstetric variables were higher in the population of the 20-29-year-olds. CONCLUSIONS: The obstetric outcome of adolescent pregnancies has remained favorable over the last 18 years. We do not consider adolescence as an obstetrical risk. We suggest that adolescent pregnancy is more a public health issue than a clinical problem.     

Proper folding of the antifungal protein PAF is required for optimal activity

The Penicillium chrysogenumantifungal protein PAF is secreted into the supernatant after elimination of a preprosequence. PAF is actively internalized into the hyphae of sensitive molds and provokes growth retardation as well as changes in morphology. Thus far, no information is available on the exact mode of action of PAF, nor on the function of its prosequence in protein activity. Therefore, we sought to investigate the effects of secreted PAF as well as of intracellularly retained pro-PAF and mature PAF on the sensitive ascomycete Aspergillus nidulans, and transformed this model organism by expression vectors containing 5'-sequentially truncated paf-coding sequences under the control of the inducible P. chrysogenum-derived xylanase promoter. Indirect immunofluorescence staining revealed the localization of recombinant PAF predominantly in the hyphal tips of the transformant Xylpaf1 which expressed prepro-PAF, whereas the protein was found to be distributed intracellularly within all segments of hyphae of the transformants Xylpaf2 and Xylpaf3 which expressed pro-PAF and mature PAF, respectively. Growth retardation of Xylpaf1 and Xylpaf3 hyphae was detected by proliferation assays and by light microscopy analysis. Using transmission electron microscopy of ultrathin hyphal sections a marked alteration of the mitochondrial ultrastructure in Xylpaf1 was observed and an elevated amount of carbonylated proteins pointed to severe oxidative stress in this strain. The effects induced by secreted recombinant PAF resembled those evoked by native PAF. The results give evidence that properly folded PAF is a prerequisite for its activity.     

123I]-FP-CIT-SPECT demonstrates dopaminergic deficit in orthostatic tremor

There is increasing evidence of a potential role of the dopaminergic system in orthostatic tremor (OT): Association with parkinsonism and treatment effects of L-dopa and dopamine agonists have been reported. Eleven patients with isolated OT had single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123)I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) as dopamine transporter tracer. Results were compared with 12 age-matched normal controls and 12 patients with Parkinson's disease (PD). A marked reduction in striatal tracer binding was found in OT compared to normal controls (p < 0.001). Tracer uptake was significantly higher and more symmetrical than in PD, and caudate and putamen were equally affected. L-dopa challenges, performed in seven patients, showed a small but non-significant improvement on EMG and a small but significant improvement in clinical parameters on blinded video rating. Two-month open-label L-dopa treatment (600 mg/day) led to a small improvement in two of five patients but no significant overall change. Olfactory function on University of Pennsylvania Smell Identification Test was normal. Our finding of a marked tracer uptake reduction on dopamine transporter SPECT supports a role of the dopaminergic system in OT. Lack of evidence of a clinically relevant therapeutic response to L-dopa suggests that other mechanisms must also be involved in the pathogenesis.     

Bacterial metabolite interference with maturation of human monocyte-derived dendritic cells

Dendritic cells (DC), the most potent APC, are central to antimicrobial immunity. Because of evolutionary pressure, it is reasonable that pathogens have evolved strategies to also subvert this host-defense mechanism. In the present study, we describe a novel way of bacterial interference with DC maturation. The bacterial metabolite n-butyrate, which occurs physiologically in high concentrations in the gastrointestinal tract and has well-known anti-inflammatory effects, is able to prevent LPS-induced maturation of DC resulting in a reduced capability to stimulate T cells. In particular, n-butyrate prevents homotypic DC clustering, inhibits IL-12 while sparing IL-10 production, and at the molecular level, blocks NF-kappa B translocation. These results demonstrate efficient targeting of DC function by a bacterial metabolite, which might explain the particular type of immune responsiveness in the presence of this bacterial agent as exemplified in the gastrointestinal tract.     

Gelotophobia in Israel: on the assessment of the fear of being laughed at

Gelotophobia is defined as the fear of being laughed at. Empirical studies revealed that it is a valid and useful concept which deserves further attention. Furthermore, gelotophobia is of relevance among nonclinical groups, and it should be best conceptualized as an individual differences phenomenon that ranges on a dimension from low to high fear of being laughed at. The present study presents the first empirical data on the fear of being laughed at in Israel (N = 220). It describes the adaptation of an instrument for the subjective assessment of gelotophobia to Hebrew. The translation yielded good psychometric properties in terms of high reliability . The Hebrew-GELOPH is best described with a one-dimensional factor solution. Items referring especially to the avoidance of places where one has made an embarrassing impression yielded higher endorsements. Gelotophobia was more prevalent among younger participants, females, and participants who were not in a relationship. Approximately 6% exceeded a cut-off score indicating at least a slight expression of gelotophobic symptoms. Results are discussed with respect to further application of the questionnaire in research and practice. If confirmed by additional studies it will have a significant implication on the understanding of gelotophobia in relation to social phobia and related phobias.     

Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease

Therapies that raise levels of HDL, which is thought to exert atheroprotective effects via effects on endothelium, are being examined for the treatment or prevention of coronary artery disease (CAD). However, the endothelial effects of HDL are highly heterogeneous, and the impact of HDL of patients with CAD on the activation of endothelial eNOS and eNOS-dependent pathways is unknown. Here we have demonstrated that, in contrast to HDL from healthy subjects, HDL from patients with stable CAD or an acute coronary syndrome (HDLCAD) does not have endothelial antiinflammatory effects and does not stimulate endothelial repair because it fails to induce endothelial NO production. Mechanistically, this was because HDLCAD activated endothelial lectin-like oxidized LDL receptor 1 (LOX-1), triggering endothelial PKCβII activation, which in turn inhibited eNOS-activating pathways and eNOS-dependent NO production. We then identified reduced HDL-associated paraoxonase 1 (PON1) activity as one molecular mechanism leading to the generation of HDL with endothelial PKCβII-activating properties, at least in part due to increased formation of malondialdehyde in HDL. Taken together, our data indicate that in patients with CAD, HDL gains endothelial LOX-1- and thereby PKCβII-activating properties due to reduced HDL-associated PON1 activity, and that this leads to inhibition of eNOS-activation and the subsequent loss of the endothelial antiinflammatory and endothelial repair-stimulating effects of HDL.