Cell types and coincident synapses in the ellipsoid body of Drosophila

Cellular ultrastructures for signal integration are unknown in any nervous system. The ellipsoid body (EB) of the Drosophila brain is thought to control locomotion upon integration of various modalities of sensory signals with the animal internal status. However, the expected excitatory and inhibitory input convergence that virtually all brain centres exhibit is not yet described in the EB. Based on the EB expression domains of genetic constructs from the choline acetyl transferase (Cha), glutamic acid decarboxylase (GAD) and tyrosine hydroxylase (TH) genes, we identified a new set of neurons with the characteristic ring‐shaped morphology (R neurons) which are presumably cholinergic, in addition to the existing GABA‐expressing neurons. The R1 morphological subtype is represented in the Cha‐ and TH‐expressing classes. In addition, using transmission electron microscopy, we identified a novel type of synapse in the EB, which exhibits the precise array of two independent active zones over the same postsynaptic dendritic domain, that we named ‘agora’. This array is compatible with a coincidence detector role, and represents ~8% of all EB synapses in Drosophila. Presumably excitatory R neurons contribute to coincident synapses. Functional silencing of EB neurons by driving genetically tetanus toxin expression either reduces walking speed or alters movement orientation depending on the targeted R neuron subset, thus revealing functional specialisations in the EB for locomotion control.     

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.     

Test‐retest reliability of the default mode network in a multi‐centric fMRI study of healthy elderly: Effects of data‐driven physiological noise correction techniques

Understanding how to reduce the influence of physiological noise in resting state fMRI data is important for the interpretation of functional brain connectivity. Limited data is currently available to assess the performance of physiological noise correction techniques, in particular when evaluating longitudinal changes in the default mode network (DMN) of healthy elderly participants. In this 3T harmonized multisite fMRI study, we investigated how different retrospective physiological noise correction (rPNC) methods influence the within‐site test‐retest reliability and the across‐site reproducibility consistency of DMN‐derived measurements across 13 MRI sites. Elderly participants were scanned twice at least a week apart (five participants per site). The rPNC methods were: none (NPC), Tissue‐based regression, PESTICA and FSL‐FIX. The DMN at the single subject level was robustly identified using ICA methods in all rPNC conditions. The methods significantly affected the mean z‐scores and, albeit less markedly, the cluster‐size in the DMN; in particular, FSL‐FIX tended to increase the DMN z‐scores compared to others. Within‐site test‐retest reliability was consistent across sites, with no differences across rPNC methods. The absolute percent errors were in the range of 5–11% for DMN z‐scores and cluster‐size reliability. DMN pattern overlap was in the range 60–65%. In particular, no rPNC method showed a significant reliability improvement relative to NPC. However, FSL‐FIX and Tissue‐based physiological correction methods showed both similar and significant improvements of reproducibility consistency across the consortium (ICC = 0.67) for the DMN z‐scores relative to NPC. Overall these findings support the use of rPNC methods like tissue‐based or FSL‐FIX to characterize multisite longitudinal changes of intrinsic functional connectivity. Hum Brain Mapp 37:2114–2132, 2016. © 2016 Wiley Periodicals, Inc.