40 research outputs found

    A TMS/EEG protocol for the causal assessment of the functions of the oscillatory brain rhythms in perceptual and cognitive processes

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    The combined use of transcranial magnetic stimulation (TMS), electroencephalogram (EEG), and behavioral performance allows investigation of causal relationships between neural markers and their functional relevance across a number of perceptual and cognitive processes. Here, we present a protocol for combining and applying these techniques on human subjects. We describe correlation approach and causal approach to disentangle the role of different oscillatory parameters, namely alpha frequency and amplitude that control for accuracy and metacognitive abilities, respectively, in a visual detection task. For complete details on the use and execution of this protocol, please refer to Di Gregorio et al. (2022)

    M1-P15 as a cortical marker for transcallosal inhibition: A preregistered TMS-EEG study

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    In a recently published study combining transcranial magnetic stimulation and electroencephalography (TMS-EEG), an early component of TMS-evoked potentials (TEPs), i.e., M1-P15, was proposed as a measure of transcallosal inhibition between motor cortices. Given that early TEPs are known to be highly variable, further evidence is needed before M1-P15 can be considered a reliable index of effective connectivity. Here, we conceived a new preregistered TMS-EEG study with two aims. The first aim was validating the M1-P15 as a cortical index of transcallosal inhibition by replicating previous findings on its relationship with the ipsilateral silent period (iSP) and with performance in bimanual coordination. The second aim was inducing a task-dependent modulation of transcallosal inhibition. A new sample of 32 healthy right-handed participants underwent behavioral motor tasks and TMS-EEG recording, in which left and right M1 were stimulated both during bimanual tasks and during an iSP paradigm. Hypotheses and methods were preregistered before data collection. Results show a replication of our previous findings on the positive relationship between M1-P15 amplitude and the iSP normalized area. Differently, the relationship between M1-P15 latency and bimanual coordination was not confirmed. Finally, M1-P15 amplitude was modulated by the characteristics of the bimanual task the participants were performing, and not by the contralateral hand activity during the iSP paradigm. In sum, the present results corroborate our previous findings in validating the M1-P15 as a cortical marker of transcallosal inhibition and provide novel evidence of its task-dependent modulation. Importantly, we demonstrate the feasibility of preregistration in the TMS-EEG field to increase methodological rigor and transparency

    Angiogenic impairment of the vascular endothelium: a novel mechanism and potential therapeutic target in muscular dystrophy

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    Dystrophin, the missing or defective protein in Duchenne muscular dystrophy, is expressed not only in muscle cells but also in vascular endothelial cells (ECs). In this study, we assessed the effects of dystrophin deficiency on the angiogenic capacities of ECs

    Defecography: a still needful exam for evaluation of pelvic floor diseases

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    The aim of this discussion is to describe what is a defecography, how we have to perform it, what can we see and to present the main physio-pathological illnesses of pelvic floor and anorectal region that can be studied with this method and its advantages over other screening techniques. Defecography is a contrastographic radiological examination that highlights structural and functional pelvic floor diseases. Upon preliminary ileum-colic opacification giving to patient radiopaque contrast, are first acquired static images (at rest, in maximum voluntary contraction of the pelvic muscles, while straining) and secondarily dynamic sequences (during evacuation), allowing a complete evaluation of the functionality of the anorectal region and the pelvic floor. Defecography is an easy procedure to perform widely available, and economic, carried out in conditions where the patient experiences symptoms, the most realistic possible. It can be still considered reliable technology and first choice in many patients in whom the clinic alone is not sufficient and it is not possible or necessary to perform a study with MRI

    Microparticles produced by activated platelets carry a potent and functionally active angiogenic signal in subjects with crohn’s disease

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    Microparticles (MPs) are submicron vesicles shed from various cell types upon activation, stimulation, and death. Activated platelets are an important source of circulating MPs in subjects with inflammatory diseases, including Crohn’s disease (CD). Angiogenesis is a hallmark of inflammation in CD and plays an active role in sustaining disease progression, while targeting angiogenesis may be an effective approach to block colitis. In this study, we analyzed the angiogenic content of the MPs produced by activated platelets in subjects with CD. We also evaluated whether the angiogenic signal carried by these MPs was functionally active, or able to induce angiogenesis. We found that, in subjects with CD, MPs produced by activated platelets contain significantly higher levels of angiogenic mRNAs, such as epidermal growth factor (EGF), platelet-derived growth factor-α (PDGFα), fibroblast growth factor (FGF-2), and angiopoietin-1 (ANGPT1), compared to MPs isolated from control subjects. They also contain significantly higher levels of prototypical angiogenic proteins, including vascular endothelial growth factor (VEGF), angiopoietin-1, endoglin, endothelin-1, pentraxin 3, platelet factor-4, plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinases-1 (TIMP-1), and thrombospondin 1. The protein content of these MPs is functionally active, since it has the ability to induce a robust angiogenic process in an endothelial cell/interstitial cell co-culture in vitro assay. Our results reveal a potential novel mechanism through which the angiogenic signal is delivered in subjects with CD, with potentially important clinical and therapeutic implications

    Sharing motor plans while acting jointly: a TMS study

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    When acting together, we may represent not only our own individual goals but also a collective goal. Although behavioural evidence suggests that agents' motor plans might be related to collective goals, direct neurophysiological evidence of whether collective goals are motorically represented is still scarce. The aim of the present transcranial magnetic stimulation (TMS) study is to begin to fill this gap. A participant and a confederate were asked to sequentially perform a two-choice reaction time task by acting on pressure sensors. In their own turn, they saw a cue indicating whether to lift their fingers from (or to press them on) a pressure sensor to shoot a ball across the screen as fast as possible. The confederate responded with the right hand, the participant with the left hand. While the confederate acted on the sensor, the participant's motor evoked potentials (MEPs) were collected from the right Extensor Carpi Ulnaris. If participants represent their own and the confederate's actions as being directed to a collective goal, MEPs amplitude should be modulated according to the action the confederate should perform. To test this conjecture, we contrasted three conditions: a Joint condition, in which both players worked together with their collective goal being to shoot the ball to get it to a common target, a Parallel condition, in which the players performed exactly the same task but received independent outcomes for their performance, and a Competitive condition, in which the outcome of the game still depended on the other player performance, but without the collective goal feature. Results showed no MEPs modulation according to the confederate's action in the Joint condition. Post-hoc exploratory analyses both provide some hints about this negative finding and also suggest possible improvements (i.e., adopting a different dependent variable, avoiding task-switching between conditions) for testing our hypothesis that collective goal can be represented motorically

    Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease.

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    Sonic hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh + MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. The goal of this study was to test the hypothesis that, in humans with peripheral artery disease (PAD), there is increased number of circulating Shh + MPs. This was done by assessing the number of Shh + MPs in plasma of patients with PAD and control subjects without PAD. We found significantly higher number of Shh + MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs—produced either by endothelial cells, platelets, leukocytes, and erythrocytes—was not different between PAD patients and controls. We also found a significant association between the number of Shh + MPs and the number of collateral vessels in the ischemic limbs of PAD patients. Interestingly, the concentration of Shh protein unbound to MPs—which was measured in MP-depleted plasma—was not different between subjects with PAD and the controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel information on Shh signaling during ischemia in humans, with potentially important biological and clinical implications

    Electrocardiographic Alternans: A New Approach

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    Alternans is an electrophysiological phenomenon consisting in a beat-to-beat variation of the morphology of an electrocardiographic (ECG) waveform. Literature has particularly studied T-wave alternans (TWA) because it has been widely recognized as a noninvasive and clinically useful index to predict occurrence of malignant ventricular arrhythmias and, eventually, sudden cardiac death. Historically, alternans of other segments of ECG, like P wave (PWA), or QRS complex (QRSA) gained less interest than TWA, but this is an incomplete vision of the action potential (AP). AP is influenced by electrical activity of all myocardial cells, so it is reasonable that all ECG waveforms could be affected by alternans phenomenon. ECG alternans (ECGA) can be intended as the prevalent nature of alternans. This study aimed to use the heart-rate adaptive match filter (AMF) method, previously applied for TWA applications, to detect ECGA. AMF effectiveness was tested on simulated alternating ECG (alternans-amplitude range: 10 μV–200 μV), characterized by single- and multiple-wave alternans (always of the same amplitude and morphology). AMF method proved to be specific, being able to recognize ECGA absence, and particularly sensitive to TWA. In general, in case of singular-wave alternans, AMF correctly identified the type of alternans and correctly determined its amplitude (mean error: 0%). When TWA was combined to PWA or QRSA, only TWA was identified with an overestimation of its amplitude (mean error: 23%). In conclusion, overall AMF proved its effectiveness and specificity in revealing and discriminating ECGA

    HepPar1-Positive Circulating Microparticles Are Increased in Subjects with Hepatocellular Carcinoma and Predict Early Recurrence after Liver Resection

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    Circulating microparticles (MPs) are novel potential biomarkers in cancer patients. Their role in hepatocellular carcinoma (HCC) is under intensive investigation. In this study, we tested the hypothesis that MPs expressing the antigen HepPar1 are increased in the blood of subjects with HCC and may serve as markers of early recurrence after liver resection (LR). We studied 15 patients affected by HCC undergoing LR, and used flow cytometry to assess the number of circulating HepPar1+ MPs. Ten subjects without HCC (five with liver cirrhosis and five with healthy livers) were used as controls. After LR, HCC patients underwent a follow-up to check for early recurrence, which occurred in seven cases. The number of circulating HepPar1+ MPs was significantly higher in subjects affected by HCC, compared to individuals without cancer (p < 0.01). We also found that, among HCC patients, the number of circulating HepPar1+ MPs, measured before LR, was significantly higher in those who displayed early recurrence compared to those without recurrence (p = 0.02). Of note, other types of circulating MPs, such as those derived from endothelial cells (CD144+) or those produced by the activated endothelium (CD144+/CD62+), were not associated with HCC, nor could they predict HCC recurrence. HepPar1+ MPs deserve further investigation as novel biomarkers of disease and prognosis in HCC patients

    Les espaces blancs du livre : usages et significations

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    White is a very mysterious colour, which seems impenetrable. Its connotations are numerous and universal, even if the colour is very often associated with the ideas of blank and emptiness. In books, white is necessary for all the stages of the creation. When the author is writing the book, he uses the "white" of the blank page in order to start creating. It also helps the writer to organize its thoughts and make it text having sense. White then takes a huge importance concerning the layout stage, especially through its negative spaces. Finally, when the reader is reading, it is still here, flying between the letters so the reader can learn about the text, take notes and develop his own thought. Why having so many blank spaces? How could we interpret it?Le blanc : une couleur particulièrement mystérieuse et en apparence impénétrable. Riche en connotations universelles et millénaires, elle n’en reste pas moins l’apanage du rien, du vide. Dans le livre, le blanc est un objet singulier et nécessaire à toutes les étapes de la création d’un projet éditorial. Lors de l’écriture du texte par l’écrivain, il est le terreau fertile de la création. Il permet également à l’auteur d’organiser sa pensée et de donner du sens à son texte. Le blanc prend ensuite une dimension essentielle lorsque le livre est mis en page, notamment à travers ses marges. Enfin, au moment de la lecture, il est toujours là, se glissant entre les lettres, pour permettre au lecteur de prendre connaissance du texte, de l’annoter, voire de développer sa réflexion à partir de celui-ci. Pourquoi « laisser du blanc » ? Quel sens donner à ces lignes dites vides qui sont pourtant bien présentes
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