An electrophysiological endophenotype of hypomanic and hyperthymic personality

BACKGROUND: Hyperthymic Temperament (HYT) and a closely related trait, Hypomanic Personality (HYP), have both been related to bipolar affective disorder (BAD). Intensity dependence of auditory evoked potentials (IAEP) is a suggested inverse indicator of serotonergic neurotransmission and has been found to be elevated in BAD. Therefore the present study explored for the first time whether subclinical variance of HYT/HYP is also associated with IAEP in a healthy sample. As several traits from biological personality research are correlated with HYT/HYP and also with BAD, the specificity of results against these traits was further analyzed by calculating multiple regression analyses. METHODS: Evoked potentials were recorded from a sample (N=87) homogenous for confounding variables influencing IAEP. For this reason, only 19 to 27-year-old non-smoker psychiatrically healthy male students were included. RESULTS: Significant correlations were found between IAEP and both HYP and HYT. Including Sensation or Novelty Seeking and Extraversion in Regression Analyses did not weaken the associations of HYP with IAEP much, but did affect those of HYT. However, these competing biological personality traits were hardly able to predict IAEP themselves. Impulsivity, though, was able to reduce the predictive power of HYP and HYT and to explain unique IAEP-variance. This was even more the case for Behavioral-Activation-System-Sensitivity (BAS) subscale Fun Seeking clearly dominating all regression analyses. LIMITATIONS: Homogeneity of sample. CONCLUSIONS: The impact of BAS is in agreement with the assumption that heightened BAS-sensitivity is an underlying biological cause for HYP/HYT and for BAD. Future studies on BAD should include BAS and Impulsivity besides HYP/HYT to further explore uniqueness of the latter and to develop questionnaires based on those items of a hyperthymic-hypomanic-impulsive-funseeking item pool, which possess the most external validity.     

Atherogenic mononuclear cell recruitment is facilitated by oxidized lipoprotein-induced endothelial junctional adhesion molecule-A redistribution

Background

Junctional adhesion molecule (JAM-) A is a transmembrane protein expressed in many cell types and maintains junctional integrity in endothelial cells. Upon inflammatory stimulation, JAM-A relocates to the apical surface and might thereby facilitate the recruitment of leukocytes.

Objective

Although inflammatory JAM-A redistribution is an established process, further effort is required to understand its exact role in the transmigration of mononuclear cells, particularly under atherogenic conditions.

Methods

By the use of RNA interference and genetic deletion, the role of JAM-A in the transmigration of T cells and monocytes through aortic endothelial cells was investigated. JAM-A–localization and subsequent mononuclear cell rolling, adhesion and transmigration were explored during endothelial inflammation, induced by oxidized LDL or cytokines.

Results

RNA interference or genetic deletion of JAM-A in aortic endothelial cells resulted in a decreased transmigration of mononuclear cells. Treatment of the endothelial cells with oxLDL resulted in an increase of both permeability and apical JAM-A presentation, as shown by bead adhesion and confocal microscopy experiments. Redistribution of JAM-A resulted in an increased leukocyte adhesion and transmigration, which could be inhibited with antibodies against JAM-A or by lovastatin-treatment, but not with the peroxisome proliferator activated receptor gamma-agonist pioglitazone.

Conclusions

This study demonstrates that redistribution of JAM-A in endothelial cells after stimulation with pro-atherogenic oxidized lipoproteins results in increased transmigration of mononuclear cells. This inflammatory dispersal of JAM-A could be counteracted with statins, revealing a novel aspect of their mechanism of action.     

Identification of psychopathological course trajectories in schizophrenia

Course trajectory analyses have been performed primarily for treatment response in acute episodes of schizophrenic disorders. As yet, corresponding data for the long-term course are lacking. Within a multicenter prospective observational study, 268 patients with schizophrenia were assessed at discharge from hospital and followed up after 6, 12, 18, and 24 months. A latent class growth analysis was performed on the scores from the Positive and Negative Syndrome Scale (PANSS). A two-class conditional latent class model showed the best data fit (Entropy: 0.924). The model divided the sample into a group with amelioration in all PANSS subscales (60%) and a group with stable positive/negative and deteriorating general psychopathology symptoms (40%). Global functioning (GAF score), gender, age, living situation and involuntary admission predicted course trajectory class membership. The model was predictive of significant differences between the two groups in health care service costs and quality of life. The results underline the heterogeneous course of the illness, which ranged from amelioration to deterioration over a 2-year period. Statistical models such as trajectory analysis could help to identify more homogenous subtypes in schizophrenia.     

Effects of pyrophosphate delivery in a peritoneal dialysis solution on bone tissue of apolipoprotein-E knockout mice with chronic kidney disease

Vascular calcification (VC) is a risk factor for cardiovascular mortality in the setting of chronic kidney disease (CKD). Pyrophosphate (PPi), an endogenous molecule that inhibits hydroxyapatite crystal formation, has been shown to prevent the development of VC in animal models of CKD. However, the possibility of harmful effects of exogenous administration of PPi on bone requires further investigation. To this end, we examined by histomorphometry the bone of CKD mice after intraperitoneal PPi administration. After CKD creation or sham surgery, 10-week-old female apolipoprotein-E knockout (apoE^?/?) mice were randomized to one non-CKD group or 4 CKD groups (n = 10–35/group) treated with placebo or three distinct doses of PPi, and fed with standard diet. Eight weeks later, the animals were killed. Serum and femurs were sampled. Femurs were processed for bone histomorphometry. Placebo-treated CKD mice had significantly higher values of osteoid volume, osteoid surface and bone formation rate than sham-placebo mice with normal renal function. Slightly higher osteoid values were observed in CKD mice in response to very low PPi dose (OV/BV, O.Th and ObS/BS) and, for one parameter measured, to high PPi dose (O.Th), compared to placebo-treated CKD mice. Treatment with PPi did not modify any other structural parameters. Mineral apposition rates, and other parameters of bone formation and resorption were not significantly different among the treated animal groups or control CKD placebo group. In conclusion, PPi does not appear to be deleterious to bone tissue in apoE^?/? mice with CKD, although a possible stimulatory PPi effect on osteoid formation may be worth further investigation.     

Atrial fibrillation and heart failure: Is atrial fibrillation a disease?

Atrial fibrillation in heart failure often occur together. The relationship between atrial fibrillation and heart failure has remained a subject of research. The main manifestation of the violation of hydrodynamics in heart failure is the increased end-diastolic pressure, which is transmitted through the intercommunicated system (left ventricle–left atrium–pulmonary veins–alveolar capillaries) causing increased pulmonary wedge pressure with the danger for pulmonary edema. End-diastolic pressure is the sum of left ventricle diastolic pressure and left atrial systolic pressure. Stopping the mechanical systole of the left atrium can reduce the pressure in the system in heart failure. Atrial fibrillation stops the mechanical systole of the left atrium and decreases the intercommunicating pressure and pulmonary wedge pressure. It is possible that atrial fibrillation is a mechanism for protection from increasing end-diastolic pressure and pulmonary wedge pressure, and prevents the danger of pulmonary edema. This hypothesis may explain the relationship between heart failure and atrial fibrillation and their frequent association.     

Prediction of anemia on enhanced computed tomography of the thorax using virtual non-contrast reconstructions

To determine if anemia can be predicted on enhanced computed tomography (CT) examinations of the thorax using virtual non-contrast (VNC) images, in order to support clinicians especially in diagnosing primary asymptomatic patients in daily routine.In this monocentric study, 100 consecutive patients (50 with proven anemia), who underwent a contrast-enhanced CT examination of the thorax due to various indications were included. Attenuation was measured in the descending thoracic aorta, the intraventricular septum, and the left ventricle cavity both in the conventional contrast-enhanced and in the VNC images.Two experienced radiologists annotated the delineation of a dense interventricular septum or a hyperattenuating aortic wall sign for all patients.Hemoglobin levels were then correlated with the measured attenuation values, as well as the visualization of the aortic wall or interventricular septum.Good correlation was shown between hemoglobin levels and CT attenuation values of the left ventricular cavity (r = .59), aorta (r = .56), and ratio between left ventricular cavity and the intraventricular septum (r = .57). Receiver operating characteristic curve revealed ≤ 36.5 hounsfield units (left ventricular cavity) as the threshold for diagnosing anemia. Predicting anemia by visualization of a hyperattenuating aortic wall or a dense interventricular septum yielded a specificity of 98% and 92%, respectively.Predicting anemia on enhanced CT examinations using VNC is feasible. A threshold value of ≤ 36.5 hounsfield units (left ventricular cavity) best defines anemia. Aortic wall or interventricular septum visualization on VNC is a specific anemia indicator.     

Angiopoietin 2 mediates microvascular and hemodynamic alterations in sepsis

Septic shock is characterized by increased vascular permeability and hypotension despite increased cardiac output. Numerous vasoactive cytokines are upregulated during sepsis, including angiopoietin 2 (ANG2), which increases vascular permeability. Here we report that mice engineered to inducibly overexpress ANG2 in the endothelium developed sepsis-like hemodynamic alterations, including systemic hypotension, increased cardiac output, and dilatory cardiomyopathy. Conversely, mice with cardiomyocyte-restricted ANG2 overexpression failed to develop hemodynamic alterations. Interestingly, the hemodynamic alterations associated with endothelial-specific overexpression of ANG2 and the loss of capillary-associated pericytes were reversed by intravenous injections of adeno-associated viruses (AAVs) transducing cDNA for angiopoietin 1, a TIE2 ligand that antagonizes ANG2, or AAVs encoding PDGFB, a chemoattractant for pericytes. To confirm the role of ANG2 in sepsis, we i.p. injected LPS into C57BL/6J mice, which rapidly developed hypotension, acute pericyte loss, and increased vascular permeability. Importantly, ANG2 antibody treatment attenuated LPS-induced hemodynamic alterations and reduced the mortality rate at 36 hours from 95% to 61%. These data indicate that ANG2-mediated microvascular disintegration contributes to septic shock and that inhibition of the ANG2/TIE2 interaction during sepsis is a potential therapeutic target.