Deficit of temporal dynamics of detection of a moving object during egomotion in a stroke patient: a psychophysical and MEG study

To investigate the temporal dynamics underlying object motion detection during egomotion, we used psychophysics and MEG with a motion discrimination task. The display contained nine spheres moving for 1 second, eight moved consistent with forward observer translation, and one (the target) with independent motion within the scene (approaching or receding). Observers's task was to detect the target. Seven healthy subjects (7HS) and patient PF with an infarct involving the left occipital-temporal cortex participated in both the psychophysical and MEG study. Psychophysical results showed that PF was severely impaired on this task. He was also impaired on the discrimination of radial motion (with even poorer performance on contraction) and 2D direction as well as on detecting motion discontinuity. We used anatomically constrained MEG and dynamic Granger causality to investigate the direction and dynamics of connectivity between the functional areas involved in the object-motion task and compared the results of 7HS and PF. The dynamics of the causal connections among the motion responsive cortical areas (MT, STS, IPS) during the first 200 ms of the stimulus was similar in all subjects. However, in the later part of the stimulus (>200 ms) PF did not show significant causal connections among these areas. Also the 7HS had a strong, probably attention modulatory connection, between MPFC and MT, which was completely absent in PF. In PF and the 7HS, analysis of onset latencies revealed two stages of activations: early after motion onset (200–400 ms) bilateral activations in MT, IPS, and STS, followed (>500 ms) by activity in the postcentral sulcus and middle prefrontal cortex (MPFC). We suggest that the interaction of these early and late onset areas is critical to object motion detection during self-motion, and disrupted connections among late onset areas may have contributed to the perceptual deficits of patient PF.Published versio

Reorganization of retinotopic maps after occipital lobe infarction

Published in final edited form as: J Cogn Neurosci. 2014 June ; 26(6): 1266–1282. doi:10.1162/jocn_a_00538.We studied patient JS, who had a right occipital infarct that encroached on visual areas V1, V2v, and VP. When tested psychophysically, he was very impaired at detecting the direction of motion in random dot displays where a variable proportion of dots moving in one direction (signal) were embedded in masking motion noise (noise dots). The impairment on this motion coherence task was especially marked when the display was presented to the upper left (affected) visual quadrant, contralateral to his lesion. However, with extensive training, by 11 months his threshold fell to the level of healthy participants. Training on the motion coherence task generalized to another motion task, the motion discontinuity task, on which he had to detect the presence of an edge that was defined by the difference in the direction of the coherently moving dots (signal) within the display. He was much better at this task at 8 than 3 months, and this improvement was associated with an increase in the activation of the human MT complex (hMT^+) and in the kinetic occipital region as shown by repeated fMRI scans. We also used fMRI to perform retinotopic mapping at 3, 8, and 11 months after the infarct. We quantified the retinotopy and areal shifts by measuring the distances between the center of mass of functionally defined areas, computed in spherical surface-based coordinates. The functionally defined retinotopic areas V1, V2v, V2d, and VP were initially smaller in the lesioned right hemisphere, but they increased in size between 3 and 11 months. This change was not found in the normal, left hemisphere of the patient or in either hemispheres of the healthy control participants. We were interested in whether practice on the motion coherence task promoted the changes in the retinotopic maps. We compared the results for patient JS with those from another patient (PF) who had a comparable lesion but had not been given such practice. We found similar changes in the maps in the lesioned hemisphere of PF. However, PF was only scanned at 3 and 7 months, and the biggest shifts in patient JS were found between 8 and 11 months. Thus, it is important to carry out a prospective study with a trained and untrained group so as to determine whether the patterns of reorganization that we have observed can be further promoted by training.This work was supported by NIH grant R01NS064100 to L. M. V. Lucia M. Vaina dedicates this article to Charlie Gross, who has been a long-time collaborator and friend. I met him at the INS meeting in Beaune (France), and since then we often discussed the relationship between several aspects of high-level visual processing described in his work in monkeys physiology and my work in neuropsychology. In particular, his pioneering study of biological motion in monkeys' superior temporal lobe has influenced my own work on biological motion and has led us to coauthor a paper on this topic. Working with Charlie was a uniquely enjoyable experience. Alan Cowey and I often spoke fondly about Charlie, a dear friend and close colleague to us both, whose work, exquisite sense of humor, and unbound zest of living we both deeply admired and loved. (R01NS064100 - NIH)Accepted manuscrip

Civiltà della Campania. Anno II, n. 3 (agosto-ottobre 1975)

A. II, n.3 (agosto-ottobre 1975): Il messaggio dell’Assessore Emilio de Feo, P. 3 ; M. Parrilli, Continuità nel turismo regionale, P. 3 ; Napoli nei secoli, P. 5 ; G. Galasso, Tumulti ed elezioni del ’600, P. 6 ; N. Cilento, Nella città medioevale, P. 18 ; B. Gatta, Capri tra Napoleone e Murat, P. 24 ; R. Causa, Gioacchino Toma a Napoli, P. 30 ; A. Assante, Napoli e il suo porto, P. 34 ; G. Grimaldi, Messaggio di fede dell’Anno Santo, P. 40 ; R. Vlad, Musica all’aperto, P. 50 ; M. Stefanile, Viaggio nella storia di Amalfi, P. 52 ; D. Rea, Mappa minore, P. 60 ; M. Prisco , Incontro con la Badia, P. 68 ; P. Amos e A. Gambardella, Il villaggio di Albori, P. 74 ; R. Virtuoso, Giovanni Cuomo ritorna tra i giovani, P. 76 ; V. Panebianco, Il turismo venuto dalla storia, P. 80 ; A.P. Carbone, Le grotte di Pertosa, P. 84 ; F. de Ciuceis, Il mare di Caserta, P. 88 ; E. Tirone, Riti settennali a Guardia Sanframondi, P. 92 ; F. Calabro, Turismo e cultura a Capri, P. 98 ; F. de Ciuceis, Settembre al Borgo, P. 102 ; I. Santoro, Teggiano citta museo, P. 104 ; Notiziario, P. 108

Overview of the FTU results

Since the 2016 IAEA Fusion Energy Conference, FTU operations have been mainly devoted to experiments on runaway electrons and investigations into a tin liquid limiter; other experiments have involved studies of elongated plasmas and dust. The tearing mode onset in the high density regime has been studied by means of the linear resistive code MARS, and the highly collisional regimes have been investigated. New diagnostics, such as a runaway electron imaging spectroscopy system for in-flight runaway studies and a triple Cherenkov probe for the measurement of escaping electrons, have been successfully installed and tested, and new capabilities of the collective Thomson scattering and the laser induced breakdown spectroscopy diagnostics have been explored

Reorganization of Retinotopic Maps after Occipital Lobe Infarction

We studied patient JS who had a right occipital infarct that encroached on visual areas V1, V2v and VP. When tested psychophysically, he was very impaired at detecting the direction of motion in random dot displays where a variable proportion of dots moving in one direction (signal) were embedded in masking motion noise (noise dots). The impairment on this Motion Coherence task was especially marked when the display was presented to the upper left (affected) visual quadrant, contralateral to his lesion. However, with extensive training, by 11 months his threshold fell to the level of healthy subjects. Training on the Motion Coherence task generalized to another motion task, the Motion Discontinuity task, on which he had to detect the presence of an edge that was defined by the difference in the direction of the coherently moving dots (signal) within the display. He was much better at this task at 8 than 3 months, and this improvement was associated with an increase in the activation of the human MT complex (hMT+) and in the kinetic occipital region (KO) as shown by repeated fMRI scans. We also used fMRI to perform retinotopic mapping at 3, 8 and 11 months after the infarct. We quantified the retinotopy and areal shifts by measuring the distances between the center of mass of functionally defined areas, computed in spherical surface-based coordinates. The functionally defined retinotopic areas V1, V2v, V2d and VP were initially smaller in the lesioned right hemisphere, but they increased in size between 3 and 11 months. This change was not found in the normal, left hemisphere, of the patient or in either hemispheres of the healthy control subjects. We were interested in whether practice on the motion coherence task promoted the changes in the retinotopic maps. We compared the results for patient JS with those from another patient (PF) who had a comparable lesion but had not been given such practice. We found similar changes in the maps in the lesioned hemisphere of PF. However, PF was only scanned at 3 and 7 months, and the biggest shifts in patient JS were found between 8 and 11 months. Thus, it is important to carry out a prospective study with a trained and untrained group so as to determine whether the patterns of reorganization that we have observed can be further promoted by training

Does a strict glycemic control during acute coronary syndrome play a cardioprotective effect? Pathophysiology and clinical evidence

A hyperglycemic state, also in non-diabetic subjects, may be associated with acute coronary syndrome (ACS). Aim of this review is to describe the pathophysiologic association between ACS and hyperglycemic state, the protective mechanisms of a tight glycaemic control in ACS on CV outcomes, and the supporting clinical evidence. Several mechanisms may be responsible of a poor CV outcome in subjects with hyperglycemia during ACS. Endothelial NAPDH oxidase-2 (NOX2) activation in response to high glucose alters the balance between Raf/MAPK-dependent vasoconstriction and PI3K/Akt-dependent vasodilation in favour of constriction. Hyperglycaemia induces an overproduction of superoxide by the mitochondrial electron transport chain through different molecular mechanisms. Moreover, hyperglycaemia increases the size of the infarct by causing myocardial cell death through apoptosis and reducing the collateral blood flow. High FFA concentrations lead to toxicity mechanisms in acutely ischemic myocardium. On the other hand, a tight glycaemic control in ACS exerts a cardioprotective action by anti-inflammatory and anti-apoptotic mechanisms, anti-oxidative stress, endothelium protection, FFA reduction, anti-glucotoxic effect, IR and cardiac fuel metabolisms improvement, heart stem cells protection and reduced activation of adrenergic system. Unfortunately, the clinical studies supporting the above pathophysiological background are few and sometimes controversial, more likely due the risk of hypoglycemia linked to the insulin therapy generally used during ACS. Intriguingly, GLP-1 RA and SGLT2i, demonstrated highly effective in the cardiovascular prevention in high-risk subjects without the risk of hypoglycemia, might keep this cardioprotective effect even in acute conditions such as ASC

Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects

Heart failure (HF) affects up to over 20% of patients with type 2 diabetes (T2DM), even more in the elderly. Although, in T2DM, both hyperglycemia and the proinflammatory status induced by insulin resistance are crucial in cardiac function impairment, SGLT2i cardioprotective mechanisms against HF are several. In particular, these beneficial effects seem attributable to the significant reduction of intracellular sodium levels, well-known to exert a cardioprotective role in the prevention of oxidative stress and consequent cardiomyocyte death. From a molecular perspective, patients' exposure to gliflozins' treatment mimics nutrient and oxygen deprivation, with consequent autophagy stimulation. This allows to maintain the cellular homeostasis through different degradative pathways. Thus, since their introduction in the clinical practice, the hypotheses on SGLT2i mechanisms of action have changed: from simple glycosuric drugs, with consequent glucose lowering, erythropoiesis enhancing and ketogenesis stimulating, to intracellular sodium-lowering molecules. This provides their consequent cardioprotective effect, which justifies its significant reduction in CV events, especially in populations at higher risk. Finally, the updated clinical evidence of SGLT2i benefits on HF was summarized. Thus, this review aimed to analyze the cardioprotective mechanisms of sodium glucose transporter 2 inhibitors (SGLT2i) in patients with HF, as well as their clinical impact on cardiovascular events

Impact of gliflozins on cardiac remodeling in patients with type 2 diabetes mellitus & reduced ejection fraction heart failure: A pilot prospective study. GLISCAR study

Aims: Type 2 diabetes mellitus (T2DM) and heart failure are closely related entities and together determine an increased risk of mortality compared to patients suffering from only one of these diseases. Sodium-glucose co-transporter type 2 inhibitors (SGLT-2i) have shown favorable effects on cardiovascular system, particularly on heart failure. Aim of this study is to verify whether in individuals with T2DM and heart failure with reduced ejection fraction (HFrEF) treated with SGLT-2i, echocardiographic signs of favorable reverse remodeling follow longitudinal observation. Methods: 31 subjects with T2DM and HFrEF were finally included. All individuals performed clinical visit, medical history, blood sampling and echocardiography at time 0' and at the end of 6 months of follow-up on SGLT-2i treatment. Results: After 6 months follow-up, left ventricular ejection fraction (LVEF), global work index (GWI), global work efficiency (GWE), global longitudinal strain (GLS), left atrial expansion index (LAEI) and total left atrial emptying fraction (TLAEF), tricuspid annular plane systolic excursion (TAPSE), septal thickness (St), pulmonary artery systolic pressures (PASP) and TAPSE/PASP ratio significantly improved. Conclusions: Despite the lack of a favorable effect on cardiac remodeling, SGLT-2i treatment significantly improved LV systolic and diastolic function, left atrial (LA) reservoir and total emptying function, RV systolic function and pulmonary artery pressure

First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trial

PURPOSE: Erlotinib prolonged survival of unselected patients with advanced non-small-cell lung cancer (NSCLC) who were not eligible for further chemotherapy, and two phase II studies suggested it might be an alternative to first-line chemotherapy. A randomized phase III trial was designed to test whether first-line erlotinib followed at progression by cisplatin-gemcitabine was not inferior in terms of survival to the standard inverse sequence. PATIENTS AND METHODS: Patients with stage IIIB (with pleural effusion or supraclavicular nodes) to IV NSCLC and performance status of 0 to 1 were eligible. With a 95% CI upper limit of 1.25 for the hazard ratio (HR) for death, 80% power, a one-sided α = .025, and two interim analyses, a sample size of 900 patients was planned. RESULTS: At the first planned interim analysis with half the events, the inferiority boundary was crossed, and the Independent Data Monitoring Committee recommended early termination of the study. Seven hundred sixty patients (median age, 62 years; range, 27 to 81 years) had been randomly assigned. Baseline characteristics were balanced between study arms. As of June 1, 2011, median follow-up was 24.3 months, and 536 deaths were recorded (263 in the standard treatment arm and 273 in the experimental arm). Median survival was 11.6 months (95% CI, 10.2 to 13.3 months) in the standard arm and 8.7 months (95% CI, 7.4 to 10.5 months) in the experimental arm. Adjusted HR of death in the experimental arm was 1.24 (95% CI, 1.04 to 1.47). There was no heterogeneity across sex, smoking habit, histotype, and epidermal growth factor receptor (EGFR) mutation. CONCLUSION: In unselected patients with advanced NSCLC, first-line erlotinib followed at progression by cisplatin-gemcitabine was significantly inferior in terms of overall survival compared with the standard sequence of first-line chemotherapy followed by erlotinib

Comparison of intra-procedural vs. post-stenting prolonged bivalirudin infusion for residual thrombus burden in patients with ST-segment elevation myocardial infarction undergoing: the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and angioX) OCT study.

AIMS To compare prolonged bivalirudin infusion vs. an intra-procedural only bivalirudin infusion administration in subjects with ST-segment elevation myocardial infarction (STEMI) regarding residual stent strut thrombosis. METHODS AND RESULTS Multivessel STEMI patients undergoing primary percutaneous coronary intervention (PPCI) and scheduled for a staged percutaneous coronary intervention (PCI) before hospital discharge were selected among those allocated to either prolonged bivalirudin or intra-procedural only bivalirudin infusion in the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and angioX) Treatment-Duration study. Optical coherence tomography (OCT) of the infarct-related artery was performed at the end of PPCI and 4-5 days thereafter during staged intervention. The predefined endpoint was the percentage difference in the number of stent cross-sections with a thrombotic area >5% at the end of PPCI and at the time of staged PCI (ΔThCS). Between September 2013 and November 2015, 137 were randomized to either intra-procedural only bivalirudin infusion (N = 64) or prolonged bivalirudin (N = 73) at 16 European sites. Mean stent area, minimum lumen area, percentage of malapposed struts, and mean percent thrombotic area were comparable after index or staged PCI. The difference in the proportion of frames with percent thrombotic area >5% (ΔTh > 5%) were -7.7 (-22.1 to 5.1) in the intra-procedural bivalirudin infusion group and -8.8 (-23.1 to 2.6) in the prolonged infusion group (P = 0.994). Time from index to follow-up OCT imaging and the infarct vessel artery did not affect this OCT-based endpoint. CONCLUSION A strategy of prolonged bivalirudin infusion after PPCI did not reduce residual stent strut thrombosis when compared with intra-procedural only bivalirudin infusion administration (funded by The Medicines Company and Terumo; MATRIX ClinicalTrials.gov number, NCT01433627)