Functional mapping of the human insula: Data from electrical stimulations.

Electrical stimulations of the insula performed during stereo-electro-encephalography (SEEG) reproduce the ictal symptoms observed during the development of insular seizures and are also a unique opportunity to provide a functional mapping of the insular cortex. We provide here a functional mapping of the insular cortex obtained by electrical stimulation, based on our previous work and a review of literature. The most frequent responses to insula stimulation were somatosensory sensations followed by visceral responses. Then, in decreasing order of frequency, auditory sensations, vestibular illusions, speech impairment, gustato-olfactory sensations and motor reactions were evoked. A bipolar organization could be evidenced with a posterior part assigned to somatosensory functions and notably to pain perception; and an anterior part assigned to visceral functions. Although some degree of spatial segregation could be evidenced, there was a clear spatial overlap between the representations of the different types of responses. These data provide a better understanding of physiological insular functions, insula seizures semiology and a prediction of post-surgical deficits. Insula is the only cortical region where stimulations demonstrate such a multi-modal representation, perhaps supporting its integrative functions of polymodal inputs.

Semiology of insular lobe seizures.

After the early attempts of intra-operative electrocorticography and insulectomy in the 1950s, the notion of insular lobe seizures was largely forgotten for decades. It is only since the late 1990s that the recent technique of stereo-electroencephalography (SEEG) enabled preoperative diagnosis of insular origin seizures and thus gave rise to a renewed interest for this ill-defined electroclinical entity. Owing to the multiple functional roles of insula and its extensive connectivity with adjacent as well as distant brain structures, insular lobe seizures present with a combination or series of diverse subjective and objective symptoms. In this review, we summarize current knowledge on the semiology of insular origin seizures. The following two distinct forms of clinical presentation have been recognized: 1) Seizures with predominant insulo-perisylvian symptoms, most notably paraesthesia and cervico-laryngeal discomfort. The former typically involves a large/bilateral cutaneous territory and can be perceived as cold, hot, or painful sensations. The latter ranges from slight dyspnea to strong sensation of strangulation. Other symptoms include epigastric discomfort/nausea, hypersalivation, auditory, vestibular, gustatory, and aphasic symptoms. 2) Nocturnal hyperkinetic seizures with/without tonic elevation of upper limbs, masquerading as fronto-mesial seizures. Patients are usually not fully aware of their symptoms despite preserved contact and organized behavior to others. Ipsilateral eye blinking can be observed. These two patterns often occur in succession or simultaneously. This characteristic combination and progression of ictal symptoms orients us strongly towards an insular origin of seizure, a better understanding of which is a crucial key to further optimize modern SEEG strategy.

EEG analysis in anti-NMDA receptor encephalitis: Description of typical patterns.

OBJECTIVE: To describe different electroencephalogram (EEG) patterns and epileptic features in patients with anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE), their timeline in the course of the disease, their correlation with clinical data and outcome. METHODS: We retrospectively analyzed EEG recordings between November 2007 and June 2016 in 24 consecutive patients. RESULTS: Three EEG patterns were described: Excessive Beta Activity range 14-20 Hz (EBA) in 71% of patients, Extreme Delta Brush (EDB) in 58% and Generalized Rhythmic Delta Activity (GRDA) in 50%. They followed a chronological organization in the course of the disease: EBA appeared first, followed by EDB and then GRDA, as the median time of appearance for EBA, EDB and GRDA was respectively 10, 16.5 and 21.5 days. The presence of GRDA was strongly associated with concomitant abnormal movements (p < 0.001). CONCLUSION: This study focuses on EEG and epileptic abnormalities in anti-NMDARE. Beyond EDB that were already reported (Schmitt et al., 2012), GRDA seems to be a very frequent pattern. Its rhythmic aspect should not be misinterpreted as seizure or status epilepticus, to avoid antiepileptic treatments intensification. SIGNIFICANCE: This study comforts the importance of EEG in anti-NMDARE, with a better description of EEG abnormalities for a better treatment management.

Assessment of climate change effects on mountain ecosystems through a cross-site analysis in the Alps and Apennines.

Mountain ecosystems are sensitive and reliable indicators of climate change. Long-term studies may be extremely useful in assessing the responses of high-elevation ecosystems to climate change and other anthropogenic drivers from a broad ecological perspective. Mountain research sites within the LTER (Long-Term Ecological Research) network are representative of various types of ecosystems and span a wide bioclimatic and elevational range. Here, we present a synthesis and a review of the main results from ecological studies in mountain ecosystems at 20 LTER sites in Italy, Switzerland and Austria covering in most cases more than two decades of observations. We analyzed a set of key climate parameters, such as temperature and snow cover duration, in relation to vascular plant species composition, plant traits, abundance patterns, pedoclimate, nutrient dynamics in soils and water, phenology and composition of freshwater biota. The overall results highlight the rapid response of mountain ecosystems to climate change, with site-specific characteristics and rates. As temperatures increased, vegetation cover in alpine and subalpine summits increased as well. Years with limited snow cover duration caused an increase in soil temperature and microbial biomass during the growing season. Effects on freshwater ecosystems were also observed, in terms of increases in solutes, decreases in nitrates and changes in plankton phenology and benthos communities. This work highlights the importance of comparing and integrating long-term ecological data collected in different ecosystems for a more comprehensive overview of the ecological effects of climate change. Nevertheless, there is a need for (i) adopting co-located monitoring site networks to improve our ability to obtain sound results from cross-site analysis, (ii) carrying out further studies, in particular short-term analyses with fine spatial and temporal resolutions to improve our understanding of responses to extreme events, and (iii) increasing comparability and standardizing protocols across networks to distinguish local patterns from global patterns.

Evaluation of DNA typing as a positive identification method for soft and hard tissues immersed in strong acids.

Identification of human remains can be hindered by several factors (e.g., traumatic mutilation, carbonization or decomposition). Moreover, in some criminal cases, offenders may purposely adopt various expedients to thwart the victim's identification, including the dissolution of body tissues by the use of corrosive reagents, as repeatedly reported in the past for Mafia-related murders. By means of an animal model, namely porcine samples, we evaluated standard DNA typing as a method for identifying soft (muscle) and hard (bone and teeth) tissues immersed in strong acids (hydrochloric, nitric and sulfuric acid) or in mixtures of acids (aqua regia). Samples were tested at different time intervals, ranging between 2 and 6h (soft tissues) and 2-28 days (hard tissues). It was shown that, in every type of acid, complete degradation of the DNA extracted from soft tissues preceded tissue dissolution and could be observed within 4h of immersion. Conversely, high molecular weight DNA amenable to STR analysis could be isolated from hard tissues as long as cortical bone fragments were still present (28 days for sulfuric acid, 7 days for nitric acid, 2 days for hydrochloric acid and aqua regia), or the integrity of the dental pulp chamber was preserved (7 days, in sulfuric acid only). The results indicate that DNA profiling of acid-treated body parts (in particular, cortical bone) is still feasible at advanced stages of corrosion, even when the morphological methods used in forensic anthropology and odontology can no longer be applied for identification purposes.

Long-term EEG in adults: sleep-deprived EEG (SDE), ambulatory EEG (Amb-EEG) and long-term video-EEG recording (LTVER).

Long-term EEG in adults includes three modalities: sleep deprived-EEG lasting 1 to 3 hours, 24 hours ambulatory-EEG and continuous prolonged video-EEG lasting from several hours to several days. The main indications of long-term EEG are: syndromic classification of epilepsy; search for interictal discharges when epilepsy is suspected or for the purpose of therapeutic evaluation; positive diagnosis of paroxysmal clinical events; and pre-surgical evaluation of drug-resistant epilepsy. Sleep deprived-EEG and ambulatory-EEG are indicated to detect interictal discharges in order to validate a syndromic classification of epilepsy when standard EEG is negative. These exams can help in evaluating treatment efficacy, especially when clinical evaluation is difficult. Long-term video EEG is indicated for drug-resistant epilepsy, to analyze electro-clinical correlations in a pre-surgical evaluation context, and to refine a positive diagnosis when paroxysmal clinical events are frequent.

Graphitic carbon in a nanostructured titanium oxycarbide thin film to improve implant osseointegration.

A nanostructured coating layer on titanium implants, able to improve their integration into bones and to protect against the harsh conditions of body fluids, was obtained by Ion Plating Plasma Assisted, a method suitable for industrial applications. A titanium carbide target was attached under vacuum to a magnetron sputtering source powered with a direct current in the 500-1100 W range, and a 100 W radio frequency was applied to the sample holder. The samples produced at 900 W gave the best biological response in terms of overexpression of some genes of proteins involved in bone turnover. We report the characterization of a reference and of an implant sample, both obtained at 900 W. Different micro/nanoscopic techniques evidenced the morphology of the substrates, and X-ray Photoelectron Spectroscopy was used to disclose the surface composition. The layer is a 500 nm thick hard nanostructure, composed of 60% graphitic carbon clustered with 15% TiC and 25% Ti oxides.

[French guidelines on electroencephalogram]. / Recommandations françaises sur l'électroencéphalogramme.

Electroencephalography allows the functional analysis of electrical brain cortical activity and is the gold standard for analyzing electrophysiological processes involved in epilepsy but also in several other dysfunctions of the central nervous system. Morphological imaging yields complementary data, yet it cannot replace the essential functional analysis tool that is EEG. Furthermore, EEG has the great advantage of being non-invasive, easy to perform and allows control tests when follow-up is necessary, even at the patient's bedside. Faced with the advances in knowledge, techniques and indications, the Société de Neurophysiologie Clinique de Langue Française (SNCLF) and the Ligue Française Contre l'Épilepsie (LFCE) found it necessary to provide an update on EEG recommendations. This article will review the methodology applied to this work, refine the various topics detailed in the following chapters. It will go over the summary of recommendations for each of these chapters and underline proposals for writing an EEG report. Some questions could not be answered by the review of the literature; in those cases, an expert advice was given by the working and reading groups in addition to the guidelines.

[Childhood cerebral vasculitis]. / Vascularites du système nerveux central.

Central nervous system vasculitides are defined as the invasion of the vascular wall by blood-borne inflammatory cells. In childhood, they may be classified according to their trigger event (infectious vs. non-infectious), their temporal course (time-limited vs. chronic), and the size of the affected vessel. Diseases apparently confined to the central nervous system are also distinguished from secondary forms, associated with infection or rheumatic or systemic inflammatory disorders. Large-vessel vasculitis, the most frequent form, causes stroke and presents with acute focal deficits. MR, or more seldom contrast angiography is required for the positive diagnosis, while the child's medical history conveys the etiological diagnosis. The clinical manifestations of small-vessel vasculitis include headaches, seizures, focal deficits, cognitive decline, and behavior changes that can occur insidiously over a few weeks or a few months. The diagnosis is based on the associated clinical and biological symptoms in secondary forms and on cerebromeningeal biopsy in primary forms. Secondary forms of vasculitides are treated according to the etiology. The injury of large basal arteries is often observed after infection, especially varicella, and is also called transient focal cerebral arteriopathy (TCA) or post-varicella arteriopathy (PVA). This focal, monophasic, and time-limited entity is highly specific of childhood. There are no arguments in the current literature supporting the hypothesis that an aggressive immunomodulatory treatment would be more effective, in terms of recurrence rate or functional outcome, than aspirin alone. In contrast, the diffuse, prolonged, and aggressive course of the rare primary vasculitis of the central nervous system requires a prolonged immunosuppressive treatment. The management of associated symptoms, treatment-related adverse effects, and sequelae is based on a multidisciplinary approach.

A comprehensive e-prescribing model to allow representing, comparing, and analyzing available systems.

BACKGROUND: Even though ePrescribing systems are now available in many healthcare systems and have been a crucial milestone of the roadmaps towards eHealth in the last years, there is still a large heterogeneity among functionalities and performances of different systems. OBJECTIVE: In this paper, we propose an updated comprehensive model for the ePrescribing process able to represent, analyze, and compare current systems and to support the design of new, more general, systems suitable also to sustain the ePrescription process in National Healthcare Systems. METHODS: After a preliminary literature review, we identified six main phases of the ePrescribing process, namely Assign, Transmit, Dispense, Administer, Monitor, and Analysis Decision. Each phase produces a digital object characterized by formal properties that ensure the collection of appropriate data and information and works as input for the next one. The impact, in terms of benefits, of ePrescribing on governance, drug surveillance, and quality of care at the individual, territorial, and governmental levels are related to the formal properties of the digital objects created at the end of each phase. RESULTS AND CONCLUSIONS: The model-based implementation of each phase has an impact on the quality of care, the access to care, and the effectiveness of care delivery. The model does not cover cost evaluation, but the benefits identified can be used as basis for cost-benefit or cost-effectiveness analysis of heterogeneous systems.

Measuring the characteristic function of the work distribution.

We propose an interferometric setting for the ancilla-assisted measurement of the characteristic function of the work distribution following a time-dependent process experienced by a quantum system. We identify how the configuration of the effective interferometer is linked to the symmetries enjoyed by the Hamiltonian ruling the process and provide the explicit form of the operations to implement in order to accomplish our task. We finally discuss two physical settings, based on hybrid optomechanical-electromechanical devices, where the theoretical proposals discussed in our work could find an experimental demonstration.

Surface analysis and osteoblasts response of a titanium oxi-carbide film deposited on titanium by ion plating plasma assisted (IPPA).

Titanium is the most widely used material in orthopaedic and dental implantoprosthesis due to its superior physical properties and enhanced biocompatibility due to the spontaneous formation of a passivating layer of titanium oxides which, however, does not form good chemical bonds with bone and tends to brake exposing bulk titanium to harsh body fluids releasing titanium particles which may prime an inflammation response and a fibrotic tissue production. In order to avoid these possible problems and to enhance the biocompatibility of titanium implants, modifications of titanium surfaces by many different materials as hydroxyapatite, titanium nitride, titanium oxide and titanium carbide have been proposed. The latter is shown to be an efficient protection for the titanium implant in the harsh conditions of biological tissues and, compared to untreated titanium, acting like an osteoblast stimulation factor increasing in vitro production of proteins involved in osteogenesis. These results were confirmed by in vivo experiments in rabbits: implants covered by the titanium carbide (TiC) layer were faster and better osseointegrated than untreated titanium implants. The TiC layer was deposited by a Pulsed Laser Deposition (PLD) device which allowed only one deposition per cycle, shown to be unsuitable for industrial applications. Therefore the main objective of the present work was to replace PLD process with an Ion Plating Plasma Assisted (IPPA) deposition process, which is suitable for industrial upgrading. By this technique, nanostructured TiOx-TiCy-C has been deposited on titanium after sandblasting with 120 micron zirconia spheres. XPS analyses revealed the presence of about 33% carbon (50% of which is present as free carbon), 39% oxygen and 28% titanium (37% of which is bound to carbon to form TiC and 63% is bound to oxygen to form non stoichiometric oxides). Surface mechanical response of as-deposited coatings has been performed by nanoindentation techniques. Focused Ion Beam micrographs showed bigger differences on the obtained nanostructure compared to the PLD coating structure; in vitro tests confirm for IPPA produced coatings an improvement in stimulating osteoblasts to produce mRNA's of proteins involved in the ossification process, this latter case they resulted to be faster and more efficient. The proposed treatement is expected to improve the good results obtained by PLD, in vivo as well.

Sudden transition between classical and quantum decoherence.

We study the dynamics of quantum and classical correlations in the presence of nondissipative decoherence. We discover a class of initial states for which the quantum correlations, quantified by the quantum discord, are not destroyed by decoherence for times t<[symbol: see text]. In this initial time interval classical correlations decay. For t>[symbol: see text], on the other hand, classical correlations do not change in time and only quantum correlations are lost due to the interaction with the environment. Therefore, at the transition time [symbol: see text] the open system dynamics exhibits a sudden transition from classical to quantum decoherence regime.

Somatotopic organization of pain responses to direct electrical stimulation of the human insular cortex.

The question whether pain encoding in the human insula shows some somatotopic organization is still pending. We studied 142 patients undergoing depth stereotactic EEG (SEEG) exploration of the insular cortex for pre-surgical evaluation of epilepsy. 472 insular electrical stimulations were delivered, of which only 49 (10.5%) elicited a painful sensation in 38 patients (27%). Most sites where low intensity electric stimulation produced pain, without after-discharge or concomitant visually detectable change in EEG activity outside the insula, were located in the posterior two thirds of the insula. Pain was located in a body area restricted to face, upper limb or lower limb for 27 stimulations (55%) and affected more than one of these regions for all others. The insular cortex being oriented parallel to the medial sagittal plane we found no significant difference between body segment representations in the medio-lateral axis. Conversely a somatotopic organization of sites where stimulation produced pain was observed along the rostro-caudal and vertical axis of the insula, showing a face representation rostral to those of upper and lower limbs, with an upper limb representation located above that of the lower limb. These data suggest that, in spite of large and often bilateral receptive fields, pain representation shows some degree of somatotopic organization in the human insula.

Autobiographic memory: phenomenological aspects, personal semantic knowledge, generic events and characters (one case of pure retrograde memory recovery).

Tulving et al. [Brain Cogn 8 (1988) 3-20] proposed an operational distinction concerning memory between a semantic component consisting of general information about the individual's past and an episodic component, containing memories of specific events that can be situated in space and time. After a mild head trauma and in the context of professional troubles, patient FF displayed a pure retrograde amnesia concerning both his biographical identity and semantic memories. The patient could no longer access his memories. However, these did not seem completely lost since his answers to tests concerning historical events were better than random, his answers to a television quiz were automatic, he showed temporal transfer phenomena (ecmnesia) and since he retrieved the entirety of his memories within nine months. The patient FF illustrates the loss of retrograde autobiographic memory and the recovery of episodic memories, which requires three elements: a sense of subjective time, an autonoetic awareness (the ability to be aware of subjective time) and a "self" that can travel in subjective time.

[Searching for lost memory: memory loss and recovery mechanisms observed in a patient with pure retrograde amnesia]. / A la recherche de la mémoire perdue: nature des troubles et mode de récupération d'un cas d'amnésie rétrograde pure.

We describe a patient who developed acute reversible amnesia characterized by impaired recollection of past events with preserved anterograde memory. This occurred after a mild head trauma and in the context of occupational stress. Isolated retrograde amnesia affected autobiographical memory (with lost of identity lasting a few days) and semantic knowledge. Isolated retrograde amnesia subsided for nine months. The patient was no longer able to access to his memories, which did not seem completely lost. Some answers to tests concerning historical events were better than those given at random; his answers to a TV quiz were automatic or he exhibited temporal transfer phenomena (ecmnesia). Gradual, progressive, irregular and spontaneous or "flash" recovery, which was also facilitated by dreams, associations or contextual clues. The persistent and vivid familiarity of the retrieved memories are reported here together with the organization of long-term memory and the clinical and neuropsychological traits of functional isolated retrograde amnesia.

Somatosensory and pain responses to stimulation of the second somatosensory area (SII) in humans. A comparison with SI and insular responses.

Somatosensory and pain responses to direct intracerebral stimulations of the SII area were obtained in 14 patients referred for epilepsy surgery. Stimulations were delivered using transopercular electrodes exploring the parietal opercular cortex (SII area), the suprasylvian parietal cortex (SI area) and the insular cortex. SII responses were compared to those from adjacent SI and insular cortex. In the three areas we elicited mostly somatosensory responses, including paresthesiae, temperature and pain sensations. The rate of painful sensations (10%) was similar in SII and in the insula, while no painful sensation was evoked in SI. A few non-somatosensory responses were evoked by SII stimulation. Conversely various types of non-somatosensory responses (auditory, vegetative, vestibular, olfacto-gustatory, etc.) were evoked only by insular stimulation, confirming that SII, like SI, are mostly devoted to the processing of somatosensory inputs whereas the insular cortex is a polymodal area. We also found differences in size and lateralization of skin projection fields of evoked sensations between the three studied areas, showing a spatial resolution of the somatotopic map in SII intermediate between those found in SI and insula. This study shows the existence of three distinct somatosensory maps in the suprasylvian, opercular and insular regions, and separate pain representations in SII and insular cortex.

[Experience of a peripheral center in the surgical treatment of hepatic metastasis from colorectal cancer]. / Esperienza di un centro periferico nel trattamento chirurgico delle metastasi epatiche da cancro colorettale.

Surgical resection is still the first therapeutic option in patients with resectable colorectal cancer metastatic to the liver. Application of radiofrequency energy has been used in patients who did not meet the criteria for resectability and yet were candidates for a liver-directed procedure based upon the presence of liver-only disease. Hepatic resection has evolved in the last two or three decades from a procedure with associated mortality rate of up to 20% in the early 80s to usually less than 5% in patients undergoing liver resection thereafter. This improvement in morbidity and mortality is multifactorial; despite the increased safety of liver operations, hepatic resection still remains a complex surgical procedure with serious potential morbidity. The experience with liver resections and/or radiofrequency ablations, for colorectal cancer metastatic to the liver, performed at a medium-volume center (15 cases in 4 years) is presented. Some features of the metastatic disease, including the number, size and location of metastases are identified. The perioperative mortality is 0, morbidity for non surgical complications is 40%. In this series the reported overall 1-yr survival is 80%, 2-yr is 67%. This paper reviews the experienced factors that have defined the morbidity and mortality associated with liver surgery.

[Use of totally implantable venous system in cancer patients. Surgical technique and initial clinical experience]. / L'utilizzo dei sistemi venosi totalmente impiantabili nel paziente neoplastico. Note di tecnica e nostra iniziale esperienza.

The experience with a totally implanted venous system (TIVS) in 27 cancer patients (15 males and 12 women) is reviewed, stressing simplicity of the cut down technique, which was successfully performed in 92.7% of patients. The common: est complications are described; port infection (7.4%), subclavian vein thrombosis (3.7%), and cutaneous necrosis (3.7%) at the port level. It is concluded that TIVS is a useful device for prolonged drugs administration and the cut down technique is indicated especially in the outpatients setting.