Tactile stimulation during development alters behaviour and neuroanatomical organization of normal rats

The purpose of this study was to examine the anatomical and behavioural sequelae in the normal brain associated with tactile stimulation treatment during development. Using a split litter design, male and female rats were randomly assigned to either the tactile stimulation group (tactile stimulation for 15 min, three times/day, from postnatal day 3 to 21), or the no-tactile stimulation group. In adulthood, the rats were tested on the Whishaw tray reaching task, activity box, novel object recognition, and elevated plus maze. Following behavioural testing, rats were sacrificed for Golgi-Cox analysis. Dendritic length, dendritic branching, and spine density were analyzed in two areas of the prefrontal cortex (mPFC and OFC) and spine density in the amygdala. Tactile stimulation significantly altered rat behaviour on the novel object recognition task and Whishaw tray reaching task, but failed to have an effect on behaviour in the elevated plus maze or activity box. Importantly, tactile stimulation dramatically altered dendritic morphology in the prefrontal cortex and amygdala of both male and female rats. Tactile stimulation significantly increased dendritic branching, dendritic length, and spine density in all brain regions examined. These findings demonstrate that similar to early adversity, positive experiences early in development can dramatically alter neuroplasticity.     

Structural organization of the presynaptic density at identified synapses in the locust central nervous system

In a synaptic active zone, vesicles aggregate around a densely staining structure called the presynaptic density. We focus on its three-dimensional architecture and a major molecular component in the locust. We used electron tomography to study the presynaptic density in synapses made in the brain by identified second-order neuron of the ocelli. Here, vesicles close to the active zone are organized in two rows on either side of the presynaptic density, a level of organization not previously reported in insect central synapses. The row of vesicles that is closest to the density's base includes vesicles docked with the presynaptic membrane and thus presumably ready for release, whereas the outer row of vesicles does not include any that are docked. We show that a locust ortholog of the Drosophila protein Bruchpilot is localized to the presynaptic density, both in the ocellar pathway and compound eye visual neurons. An antibody recognizing the C-terminus of the Bruchpilot ortholog selectively labels filamentous extensions of the presynaptic density that reach out toward vesicles. Previous studies on Bruchpilot have focused on its role in neuromuscular junctions in Drosophila, and our study shows it is also a major functional component of presynaptic densities in the central nervous system of an evolutionarily distant insect. Our study thus reveals Bruchpilot executes similar functions in synapses that can sustain transmission of small graded potentials as well as those relaying large, spike-evoked signals.     

Serum levels of sCD137 (4-1BB) ligand are prognostic factors for progression in acute myeloid leukemia but not in non-Hodgkin's lymphoma

CD178 (Fas/APO-1 ligand) and CD137 ligand (CD137L) have previously been described in sera of patients with various malignancies and play an important role in the pathogenesis of various diseases. Recently, we demonstrated that low levels of soluble (s) CD137L and high levels of sCD178 correlate significantly with a long progression free survival in patients with myelodysplastic syndrome (MDS). In this study, we correlated sCD137L and sCD178 levels in sera of 42 samples of patients with acute myeloid leukemia (AML) and 46 samples of patients with non-Hodgkin's lymphoma (NHL) with stages, subtypes, and the clinical course of the diseases and determined cut-off values with maximum probability for significant differentiation between cases with higher/lower probability for progress free survival. In contrast to patients with MDS, surprisingly no correlation between sCD178 levels and different subtypes and stages or with prognosis in AML or NHL were observed. Regarding sCD137L, NHL-patients displayed lower levels compared with AML. Statistically significant higher median levels of sCD137L are present in patients with undifferentiated AML (M1/M2, 1,470 pg/mL), poor cytogenetic risk (288 pg/mL) and higher levels of BM-blasts (186 pg/mL) compared with patients with monocytoid AML (M4/M5, 89 pg/mL), intermediate cytogenetic risk (59 pg/mL) and lower levels of BM-blasts (14 pg/mL) respectively. Furthermore, in AML patients sCD137L levels correlate significantly with the probabilities to achieve complete remission (CR), stay in CR or with progress of the disease. Taken together, our data demonstrate that sCD137L can be used as a prognostic factor not only in MDS but also in AML.     

Management of far-field R wave sensing for the avoidance of inappropriate mode switch in dual chamber pacemakers: results of the FFS-test study

Background and Objective: Far-field R wave sensing (FFS) in the atrial channel of dual chamber pacemakers is a relevant source for inappropriate mode switch from the DDD mode to the DDI or VDI mode. Inappropriate loss of atrioventricular synchrony due to false positive mode switch is hemodynamically disadvantageous, may induce atrial tachyarrhythmias, can lead to pacemaker syndrome, and impairs the reliability of pacemaker Holter data. The aim of the study was to determine whether individual adjustment of the postventricular atrial blanking period (PVAB) based on an additional test is effective in avoiding inappropriate mode switch due to FFS when compared with standard programming of the PVAB.
Methods: A total of 207 patients were supplied with a St. Jude Medical Identity DR® or Identity ADx DR® dual chamber pacemaker for sinus nodal disease (n = 84), atrioventricular block (n = 79), binodal disease (n = 35), or other indications (n = 9). At hospital discharge, they were randomized to an individually optimized PVAB (n = 100) or to a control group with the PVAB left at the nominal of 100 msec (n = 107). Primary endpoint was the occurrence of inappropriate mode switch due to FFS within 3 months after pacemaker implantation assessed by stored electrograms of the pacemaker.
Results: At the 3-month follow-up, 28/107 (26%) patients with the standard programming of the PVAB showed at least one episode of inappropriate mode switch due to FFS versus 10/100 (10%) patients with optimized PVAB (P < 0.01). The optimized PVAB was shorter than the nominal PVAB in about one-third of patients and longer in about two-third of patients. Different atrial lead localizations were not associated with the occurrence of inappropriate mode switch.
Conclusions: Individual adjustment of the PVAB significantly reduces the incidence of inappropriate mode switch due to FFS.     

Cardiac pacing in a patient with diaphragm pacing for congenital central hypoventilation syndrome (Ondine's curse)

Mechanical ventilation support and diaphragm pacing has improved the prognosis of patients with idiopathic congenital central hypoventilation syndrome (CCHS; Ondine's curse). However, severe bradyarrhythmias may occur. This report is about a patient who was supplied with a bilateral diaphragm pacing system at early childhood. At the age of 17 years, he experienced multiple syncopes due to sinus nodal arrest, which was successfully treated by the implantation of a dual chamber pacemaker.