A role for fast rhythmic bursting neurons in cortical gamma oscillations in vitro

Basic cellular and network mechanisms underlying gamma frequency oscillations (30-80 Hz) have been well characterized in the hippocampus and associated structures. In these regions, gamma rhythms are seen as an emergent property of networks of principal cells and fast-spiking interneurons. In contrast, in the neocortex a number of elegant studies have shown that specific types of principal neuron exist that are capable of generating powerful gamma frequency outputs on the basis of their intrinsic conductances alone. These fast rhythmic bursting (FRB) neurons (sometimes referred to as "chattering" cells) are activated by sensory stimuli and generate multiple action potentials per gamma period. Here, we demonstrate that FRB neurons may function by providing a large-scale input to an axon plexus consisting of gap-junctionally connected axons from both FRB neurons and their anatomically similar counterparts regular spiking neurons. The resulting network gamma oscillation shares all of the properties of gamma oscillations generated in the hippocampus but with the additional critical dependence on multiple spiking in FRB cells.     

sE‐selectin for stratifying outcome in rheumatoid arthritis

Objectives

To determine the usefulness of sE‐selectin as a marker for early diagnosis and stratification of rheumatoid arthritis.

Methods

We investigated several markers of disease activity, including circulating adhesion molecules and other standard laboratory tests, in a 2–3 year followup analysis of patients with rheumatoid arthritis.

Results

The mean ± SD levels of sE‐selectin (91.68 ± 31.8 ng/ml versus 49.83 ± 14.76 ng/ml) and rheumatoid factor (375.7 ± 394.4 U versus 44.66 ± 37.63 U) were strongly elevated in severe (n = 15) versus mild (n = 7) courses of disease. Statistical calculation of mean and standard deviation revealed that sE‐selectin represents a highly significant marker for the presence of persistent and aggressive disease over time, regardless of therapeutic intervention and observation time points (P = 0.0004). Notably, regression analysis identified constant values for all parameters analyzed and, therefore, a stable course of the disease could be predicted from the beginning.

Conclusion

sE‐selectin appears to be a powerful marker to predict the severity of rheumatoid arthritis.

     

Novel approach to discriminate left bundle branch block from nonspecific intraventricular conduction delay using pacing-induced functional left bundle branch block

Purpose

Left bundle branch block (LBBB) has a predictive value for response to cardiac resynchronization therapy as reported by Zareba et al. (Circulation 123(10):1061–1072, 2011). However, based on ECG criteria, the discrimination between complete LBBB and nonspecific intraventricular conduction delay is challenging. We tested the hypothesis that discrimination can be performed using standard electrophysiological catheters and a simple stimulation protocol.

Methods

Fifty-nine patients were analyzed retrospectively. Patients were divided into groups of narrow QRS (n?=?20), wide QRS of right bundle branch block (RBBB) morphology (n?=?14), and wide QRS of LBBB morphology (n?=?25). Using a diagnostic catheter placed in the coronary sinus, left ventricular activation was assessed during intrinsic conduction as well as during right ventricular (RV) stimulation.

Results

In patients with narrow QRS and RBBB, the Q-LV/QRS ratio was 0.43?±?0.013 (n?=?20) and 0.41?±?0.026 (n?=?14), respectively. In patients with LBBB morphology, the Q-LV/QRS split up into a group of patients with normal (0.43?±?0.022, n?=?7) and a group with delayed left ventricular activation (0.75?±?0.016, n?=?18). By direct comparison of the Q-LV/QRS ratio during intrinsic conduction with the Q-LV/QRS ratio during RV pacing leading to a functional LBBB, a clear distinction between a group of “true LBBB” and another group of “apparent LBBB”/nonspecific intraventricular conduction delay (NICD) could be generated.

Conclusions

We present a novel and practical method that might facilitate discrimination between patients with apparent LBBB and true LBBB by comparing Q-LV/QRS ratios during intrinsic activation and during RV stimulation. Although this method can already be directly applied, validation by 3D electrical mapping and prospective correlation to cardiac resynchronization therapy (CRT) response will be required for further translation into clinical practice.

     

Mitral annular calcification in the elderly – Quantitative assessment

PurposeTo determine the reliability of subjective and objective quantification of mitral annular calcification (MAC) in elderly patients with severe aortic stenosis, to define quantitative sex- and age-related reference values of MAC, and to correlate quantitative MAC with mitral valve disease.MethodsIn this retrospective, IRB-approved study, we included 559 patients (268 females, median age 81 years, inter-quartile range 77–85 years) with severe aortic stenosis undergoing CT. Four independent readers performed subjective MAC categorization as follows: no, mild, moderate, and severe MAC. Two independent readers performed quantitative evaluation of MAC using the Agatston score method (Agatston_MAC). Mitral valve disease was determined by echocardiography.ResultsSubjective MAC categorization showed high inter-reader agreement for no (k ?= ?0.88) and severe MAC (k ?= ?0.75), whereas agreement for moderate (k ?= ?0.59) and mild (k ?= ?0.45) MAC was moderate. Intra-reader agreement for subjective MAC categorization was substantial (k ?= ?0.69 and 0.62). Inter- and intra-reader agreement for Agatston_MAC were excellent (ICC ?= ?0.998 and 0.999, respectively), with minor inconsistencies in MAC involving the left ventricular outflow tract/aortic valve. There were significantly more women than men with MAC (n ?= ?227, 85% versus n ?= ?209, 72%; p ?< ?0.001), with a significantly higher Agatston_MAC (median 597, range 81–2055 versus median 244; range 0–1565; p ?< ?0.001), particularly in patients ≥85 years of age. Agatston_MAC showed an area-under-the-curve of 0.84 to diagnose mitral stenosis, whereas there was no association of Agatston_MAC with mitral regurgitation (p ?> ?0.05).ConclusionsOur study in elderly patients with severe aortic stenosis shows that quantitative MAC scoring is more reliable than subjective MAC assessment. Women show higher Agatston_MAC scores than men, particularly in the elderly population. Agatston_MAC shows high accuracy to diagnose mitral stenosis.     

Differential CD26-mediated activation of the CD3 and CD2 pathways after CD6-depleted allogeneic bone marrow transplantation

Patients who have undergone allogeneic bone marrow transplantation (allo-BMT) are susceptible to a variety of opportunistic infectious complications in the months to years after engraftment. Impaired in vitro T-cell functions have been documented in these patients, and these T-cell dysfunctions contribute to the prolonged immune deficiency after allo-BMT. In the present study, we examined the expression of CD26 as well as the reconstitution of CD26-mediated T-cell costimulation via the CD3 and CD2 pathways at various times in patients aged greater than 18 years after CD6-positive, T-cell depleted allo- BMT. We found that the percentage of CD26- and CD3-positive cells, as well as the levels of expression of both antigens, was lower than in normal controls during the first 4 months after CD6-depleted allo-BMT. Subsequently, the amount of lymphocytes expressing CD3 and CD26 and the quantitative surface expression of CD3 and CD26 were not significantly different in patients and normal controls. Functional studies showed that CD26-mediated T-cell proliferation via the CD3 pathway was considerably improved and almost reached normal levels by 1 year, whereas recovery of CD26-mediated T-cell proliferation via the CD2 pathway was delayed for at least 2 years after CD6-depleted allo-BMT. As CD26 involvement in the regulation of human thymocyte activation is restricted preferentially to the CD3 pathway--unlike its involvement with both CD3 and CD2 pathways of peripheral T cells--our results suggest that the different effects of CD26-mediated costimulation via the CD3 and CD2 pathways after CD6-depleted allo-BMT may be a reflection of peripheral T-cell immaturity in those individuals, similar to that seen in mature medullary thymocytes or cord T lymphocytes.