The role of pH on the thermodynamics and kinetics of muscle biochemistry: An in vivo study by 31P-MRS in patients with myo-phosphorylase deficiency

AbstractIn this study we assessed ΔG′ATP hydrolysis, cytosolic [ADP], and the rate of phosphocreatine recovery using Phosphorus Magnetic Resonance Spectroscopy in the calf muscle of a group of patients affected by glycogen myo-phosphorylase deficiency (McArdle disease). The goal was to ascertain whether and to what extent the deficit of the glycogenolytic pathway would affect the muscle energy balance. A typical feature of this pathology is the lack of intracellular acidosis. Therefore we posed the question of whether, in the absence of pH decrease, the rate of phosphocreatine recovery depends on the amount of phosphocreatine consumed during exercise. Results showed that at the end of exercise both [ADP] and ΔG′ATP of patients were significantly higher than those of matched control groups reaching comparable levels of phosphocreatine concentration. Furthermore, in these patients we found that the rate of phosphocreatine recovery is not influenced by the amount of phosphocreatine consumed during exercise. These outcomes provide experimental evidence that: i) the intracellular acidification occurring in exercising skeletal muscle is a protective factor for the energy consumption; and ii) the influence of pH on the phosphocreatine recovery rate is at least in part related to the kinetic mechanisms of mitochondrial creatine kinase enzyme

Study of hypothalamic metabolism in cluster headache by proton MR spectroscopy

The authors used 1H-MRS to investigate hypothalamic metabolism in 26 patients with cluster headache (CH) and 12 healthy subjects. Hypothalamic N-acetylaspartate/creatine was reduced in patients with CH vs controls (p < 0.01). Dividing the patients into episodic CH outside- and in-cluster periods and chronic CH, the hypothalamic N-acetylaspartate/creatine in all three subgroups of patients was reduced. The reduction of the neuronal marker N-acetylaspartate is consistent with hypothalamic neuronal dysfunction in patients with CH

Multi-level analysis of on-chip optical wireless links

Networks-on-chip are being regarded as a promising solution to meet the on-going requirement for higher and higher computation capacity. In view of future kilo-cores architectures, electrical wired connections are likely to become inefficient and alternative technologies are being widely investigated. Wireless communications on chip may be therefore leveraged to overcome the bottleneck of physical interconnections. This work deals with wireless networks-on-chip at optical frequencies, which can simplify the network layout and reduce the communication latency, easing the antenna on-chip integration process at the same time. On the other end, optical wireless communication on-chip can be limited by the heavy propagation losses and the possible cross-link interference. Assessment of the optical wireless network in terms of bit error probability and maximum communication range is here investigated through a multi-level approach. Manifold aspects, concurring to the final system performance, are simultaneously taken into account, like the antenna radiation properties, the data-rate of the core-to core communication, the geometrical and electromagnetic layout of the chip and the noise and interference level. Simulations results suggest that communication up to some hundreds of \u3bcm can be pursued provided that the antenna design and/or the target data-rate are carefully tailored to the actual layout of the chip

Multi-level analysis of on-chip optical wireless links

Networks-on-chip are being regarded as a promising solution to meet the on-going requirement for higher and higher computation capacity. In view of future kilo-cores architectures, electrical wired connections are likely to become inefficient and alternative technologies are being widely investigated. Wireless communications on chip may be therefore leveraged to overcome the bottleneck of physical interconnections. This work deals with wireless networks-on-chip at optical frequencies, which can simplify the network layout and reduce the communication latency, easing the antenna on-chip integration process at the same time. On the other end, optical wireless communication on-chip can be limited by the heavy propagation losses and the possible cross-link interference. Assessment of the optical wireless network in terms of bit error probability and maximum communication range is here investigated through a multi-level approach. Manifold aspects, concurring to the final system performance, are simultaneously taken into account, like the antenna radiation properties, the data-rate of the core-to core communication, the geometrical and electromagnetic layout of the chip and the noise and interference level. Simulations results suggest that communication up to some hundreds of μm can be pursued provided that the antenna design and/or the target data-rate are carefully tailored to the actual layout of the chip

Dielectric and plasmonic vivaldi antennas for on-chip wireless communication

In this paper, different technologies enabling wireless on-chip communication are investigated. In particular, plasmonic Vivaldi antennas coupled to silicon waveguides and all-dielectric Vivaldi antennas are proposed. The design criteria and the performances of the two antenna configurations are also discussed

Magnetic resonance diagnostic markers in clinically sporadic prion disease: a combined brain magnetic resonance imaging and spectroscopy study

The intra vitam diagnosis of prion disease is challenging and a definite diagnosis still requires neuropathological examination in non-familial cases. Magnetic resonance imaging has gained increasing importance in the diagnosis of prion disease. The aim of this study was to compare the usefulness of different magnetic resonance imaging sequences and proton magnetic resonance spectroscopy in the differential diagnosis of patients with rapidly progressive neurological signs compatible with the clinical diagnosis of sporadic prion disease. Twenty-nine consecutive patients with an initial diagnosis of possible or probable sporadic prion disease, on the basis of clinical and electroencephalography features, were recruited. The magnetic resonance protocol included axial fluid-attenuated inversion recovery-T2- and diffusion-weighted images, and proton magnetic resonance spectroscopy of the thalamus, striatum, cerebellum and occipital cortex. Based on the clinical follow-up, genetic studies and neuropathology, the final diagnosis was of prion disease in 14 patients out of 29. The percentage of correctly diagnosed cases was 86% for diffusion-weighted imaging (hyperintensity in the striatum/cerebral cortex), 86% for thalamic N-acetyl-aspartate to creatine ratio (cutoff ≤1.21), 90% for thalamic N-acetyl-aspartate to myo-inositol (mI) ratio (cutoff ≤1.05) and 86% for cerebral spinal fluid 14-3-3 protein. All the prion disease patients had N-acetyl-aspartate to creatine ratios ≤1.21 (100% sensitivity and 100% negative predictive value) and all the non-prion patients had N-acetyl-aspartate to myo-inositol ratios >1.05 (100% specificity and 100% positive predictive value). Univariate logistic regression analysis showed that the combination of thalamic N-acetyl-aspartate to creatine ratio and diffusion-weighted imaging correctly classified 93% of the patients. The combination of thalamic proton magnetic resonance spectroscopy (10 min acquisition duration) and brain diffusion-weighted imaging (2 min acquisition duration) may increase the diagnostic accuracy of the magnetic resonance scan. Both sequences should be routinely included in the clinical work-up of patients with suspected prion disease

Extra-Visual Functional and Structural Connection Abnormalities in Leber's Hereditary Optic Neuropathy

We assessed abnormalities within the principal brain resting state networks (RSNs) in patients with Leber's hereditary optic neuropathy (LHON) to define whether functional abnormalities in this disease are limited to the visual system or, conversely, tend to be more diffuse. We also defined the structural substrates of fMRI changes using a connectivity-based analysis of diffusion tensor (DT) MRI data. Neuro-ophthalmologic assessment, DT MRI and RS fMRI data were acquired from 13 LHON patients and 13 healthy controls. RS fMRI data were analyzed using independent component analysis and SPM5. A DT MRI connectivity-based parcellation analysis was performed using the primary visual and auditory cortices, bilaterally, as seed regions. Compared to controls, LHON patients had a significant increase of RS fluctuations in the primary visual and auditory cortices, bilaterally. They also showed decreased RS fluctuations in the right lateral occipital cortex and right temporal occipital fusiform cortex. Abnormalities of RS fluctuations were correlated significantly with retinal damage and disease duration. The DT MRI connectivity-based parcellation identified a higher number of clusters in the right auditory cortex in LHON vs. controls. Differences of cluster-centroid profiles were found between the two groups for all the four seeds analyzed. For three of these areas, a correspondence was found between abnormalities of functional and structural connectivities. These results suggest that functional and structural abnormalities extend beyond the visual network in LHON patients. Such abnormalities also involve the auditory network, thus corroborating the notion of a cross-modal plasticity between these sensory modalities in patients with severe visual deficits

In vivo magnetic resonance diagnostic surrogate markers in prion diseases (Contract n. QLK4-CT-2002-01763)

The clinical diagnosis of TSE is challenging as there is currently no non-invasive in vivo diagnostic test with 100% accuracy and a number of dementing disorders either degenerative or vascular must be considered in the differential diagnosis. At present, a definite diagnosis of CJD relies on neuropathological findings and, therefore, new markers are highly desirable in living patients. The purpose of this project is to test the usefulness of a totally non invasive technique, such as magnetic resonance spectroscopy and imaging, in identifying and evaluating in vivo brain indicators of TSE infection and progression

Diagnostica delle malattie da prioni

Convegno internazionale focalizzato sui meccanismi fisiopatogenetici delle malattie da prioni, aspetti clinici e di diagnostica strumental