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Andrea Mechelli

Publications and source records attributed to Andrea Mechelli.

25 records · Page 2Linked to original sources

[Primary plasma cell leukemia. A fulminant case].

Primary plasma cell leukemia is a rare variant of malignant monoclonal gammapathies with de novo presentation in the leukemic phase. Only few series enrolling more than 20 patients have been reported in the literature. The authors deal with a patient who had a fulminant presentation of primary plasma cell leukemia with fatal outcome. Diagnosis of primary plasma cell leukemia was established based on Kyle's criteria, which include an absolute plasma cell count greater than 2 x 10(9)/L or a relative plasma cell number comprising greater than 20% of peripheral blood cells. The patient died within three days of diagnosis because of Streptococcus pneumoniae septic shock and multiple organ failure. This case report is worth of note due to the rarity of primary plasma cell leukemia and also because fulminant presentation is not commonly recognized among patients with malignant gammapathies.

Aged↗

Are subitizing and counting implemented as separate or functionally overlapping processes?

Enumeration of small groups of four or fewer objects is very fast and accurate (often called "subitizing"), but gets slower and more error prone for more than four items ("counting"). Many theories have been proposed to account for this dichotomy, most suggesting that "subitizing" and "counting" are two qualitatively different and separable processes. Others, in contrast, have proposed that the two operations reflect two different levels along a continuum of complexity. In this paper we present a PET study that attempts to characterize subitizing and counting at a neural level in order to investigate whether they are implemented as separate or functionally overlapping processes. Subjects performed an enumeration task on visual arrays of dots that varied in numerosity (1-4 and 6-9 dots) and spatial arrangement (canonical and random). The results demonstrated a common network for subitizing and counting that comprises extrastriate middle occipital and intraparietal areas. The intensity and spatial extent of this network were modulated by the number of dots and their spatial arrangement: activation increased as the number of items in the visual array increased, reaching maximum peak and extent for counting 6-9 randomly arranged items. Direct comparison between subitizing and counting showed that counting, relative to subitizing, was correlated with increased activity in this occipitoparietal network, while subitizing did not show areas of increased activation with respect to counting. Results speak against the idea of the two processes being implemented in separable neural systems.

Adult↗

Effective connectivity and intersubject variability: using a multisubject network to test differences and commonalities.

This article is about intersubject variability in the functional integration of activity in different brain regions. Previous studies of functional and effective connectivity have dealt with intersubject variability by analyzing data from different subjects separately or pretending the data came from the same subject. These approaches do not allow one to test for differences among subjects. The aim of this work was to illustrate how differences in connectivity among subjects can be addressed explicitly using structural equation modeling. This is enabled by constructing a multisubject network that comprises m regions of interest for each of the n subjects studied, resulting in a total of m x n nodes. Constructing a network of regions from different subjects may seem counterintuitive but embodies two key advantages. First, it allows one to test directly for differences among subjects by comparing models that do and do not allow a particular connectivity parameter to vary over subjects. Second, a multisubject network provides additional degrees of freedom to estimate the model's free parameters. Any neurobiological hypothesis normally addressed by single-subject or group analyses can still be tested, but with greater sensitivity. The common influence of experimental variables is modeled by connecting a virtual node, whose time course reflects stimulus onsets, to the sensory or "input" region in all subjects. Further experimental changes in task or cognitive set enter through modulation of the connections. This approach allows one to model both endogenous (or intrinsic) variance and exogenous effects induced by experimental design. We present a functional magnetic resonance imaging study that uses a multisubject network to investigate intersubject variability in functional integration in the context of single word and pseudoword reading. We tested whether the effect of word type on the reading-related coupling differed significantly among subjects. Our results showed that a number of forward and backward connections were stronger for reading pseudowords than words, and, in one case, connectivity showed significant intersubject variability. The discussion focuses on the implications of our findings and on further applications of the multisubject network analysis.

Adult↗

The importance of distributed sampling in blocked functional magnetic resonance imaging designs.

In this study we demonstrate the importance of distributed sampling of peristimulus time in blocked design fMRI studies. Distributed sampling ensures all the components of an event-related hemodynamic response are sampled and avoids the bias incurred when stimulus presentation is time-locked to data acquisition. We found that differences in the temporal offset between stimulus presentation and data acquisition had a significant effect on some language-related activations. These effects, induced by simply shifting stimulus presentation by a fraction of the interscan interval, suggest that fixed sampling does indeed bias estimated responses, even in blocked designs.

Adult↗

Heat shock proteins and their role in heart injury.

Heat shock protein (HSP) synthesis arises transiently as a tool to protect cellular homeostasis after exposure to heat and a wide spectrum of stressful and potentially deleterious stimuli. HSPs are "molecular chaperones" that recognize and form a complex with incorrectly folded or denatured proteins, which ultimately leads to correct folding, compartmentalization, or degradation. Accumulating evidence has implicated HSPs as mediators of myocardial protection, particularly in experimental models of ischemia and reperfusion injury. Impaired myocardial performance, which results from many factors, including hypoxia, is one of the main mechanisms responsible for heart failure in the critically ill patient. In this setting, different protective functions have been attributed to HSPs, which include repairing ion channels, restoring redox balance, interacting with nitric oxide-induced protection, inhibiting proinflammatory cytokines, and preventing apoptosis pathway activation. On this basis, novel therapeutic strategies by means of promising pharmacologic interventions and/or gene transfection techniques are being investigated for their potential to enhance HSP expression by myocardial cells, with the goal of improving the outcome of the critically ill patient.

Apoptosis↗