Quantification of cortical proprioceptive processing through a wireless and miniaturized EEG amplifier.

Corticokinematic coherence (CKC) is computed between limb kinematics and cortical activity (e.g. MEG, EEG), and it can be used to detect, quantify and localize the cortical processing of proprioceptive afference arising from the body. EEG-based studies on CKC have been limited to lab environments due to bulky, non-portable instrumentations. We recently proposed a wireless and miniaturized EEG acquisition system aimed at enabling EEG studies outside the laboratory. The purpose of this work is to compare the EEG-based CKC values obtained with this device with a conventional wired-EEG acquisition system to validate its use in the quantification of cortical proprioceptive processing. Eleven healthy right-handed participants were recruited (six males, four females, age range: 24-40 yr). A pneumatic-movement actuator was used to evoke right index-finger flexion-extension movement at 3 Hz for 4 min. The task was repeated both with the wireless-EEG and wired-EEG devices using the same 30-channel EEG cap preparation. CKC was computed between the EEG and finger acceleration. CKC peaked at the movement frequency and its harmonics, being statistically significant (p < 0.05) in 8-10 out of 11 participants. No statistically significant differences (p < 0.05) were found in CKC strength between wireless-EEG (range 0.03-0.22) and wired-EEG (0.02-0.33) systems, that showed a good agreement between the recording systems (3 Hz: r = 0.57, p = 0.071, 6 Hz: r = 0.82, p = 0.003). As expected, CKC peaked in sensors above the left primary sensorimotor cortex contralateral to the moved right index finger. As the wired-EEG device, the tested wireless-EEG system has proven feasible to quantify CKC, and thus can be used as a tool to study proprioception in the human neocortex. Thanks to its portability, the wireless-EEG used in this study has the potential to enable the examination of cortical proprioception in more naturalistic conditions outside the laboratory environment. Clinical Relevance-Our study will contribute to provide innovative technological foundations for future unobtrusive EEG recordings in naturalistic conditions to examine human sensorimotor system.

Design and Validation of a Wireless Body Sensor Network for Integrated EEG and HD-sEMG Acquisitions.

Sensorimotor integration is the process through which the human brain plans the motor program execution according to external sources. Within this context, corticomuscular and corticokinematic coherence analyses are common methods to investigate the mechanism underlying the central control of muscle activation. This requires the synchronous acquisition of several physiological signals, including EEG and sEMG. Nevertheless, physical constraints of the current, mostly wired, technologies limit their application in dynamic and naturalistic contexts. In fact, although many efforts were made in the development of biomedical instrumentation for EEG and High Density-surface EMG (HD-sEMG) signal acquisition, the need for an integrated wireless system is emerging. We hereby describe the design and validation of a new fully wireless body sensor network for the integrated acquisition of EEG and HD-sEMG signals. This Body Sensor Network is composed of wireless bio-signal acquisition modules, named sensor units, and a set of synchronization modules used as a general-purpose system for time-locked recordings. The system was characterized in terms of accuracy of the synchronization and quality of the collected signals. An in-depth characterization of the entire system and an head-to-head comparison of the wireless EEG sensor unit with a wired benchmark EEG device were performed. The proposed device represents an advancement of the State-of-the-Art technology allowing the integrated acquisition of EEG and HD-sEMG signals for the study of sensorimotor integration.

[Acute renal failure after videolaparoscopic surgery: an avoidable complication?]. / L'insufficianza renale acuta postchirurgia laparoscopica: evitabile complicanza?

Videolaparoscopic surgery exposes the abdominal organs to the mechanical effect of pneumoperitoneum at pressure values between 12 and 15 mm Hg, which are considered safe. Nevertheless, experimental data have shown that this pressure range can represent a hemodynamic risk factor as it may induce a decrease in the venous return to the right ventricle, a decrease in cardiac output, and activation of the sympathetic nervous system and renin angiotensin system. We report two cases of acute renal failure that occurred soon after videolaparoscopy in young female patients without any evidence of ongoing renal disease. Patient A was 29 years old and was submitted to videolaparoscopic surgery in a follow-up program after surgical treatment of ovarian cancer; patient B was 15 years old and was submitted to the surgical removal of a monolateral ovarian cyst. In neither of the cases was it necessary to perform hemodialysis. Patient A underwent a renal biopsy under ultrasound guidance; optic microscopy showed only in ra- and extraglomerular capillary congestion. In both cases the acute renal failure resolved completely and the patients where discharged with normal renal function. Taking in to account that normal renal venous pressure levels are around 4 mmHg we think that a) a 15 mmHg pneumoperitoneum may represent a risk factor during videolaparoscopic surgery mainly if the patient's extracellular volume is not properly expanded; b) administration of nonsteroidal anti-inflammatory drugs in order to prevent surgical pain may inhibit vasodilatory prostaglandin availability; c) onset of oliguria during the surgical procedure suggests that extracellular volume expansion is required.

[Update of the Italian Society of Nephrology Project No. 1 of the 2004-2006 SIN programme]. / Update sul progetto SIN n. 1 del programma SIN 2004-2006: qualità e accreditamento delle strutture di nefrologia, dialisi e trapianto.

In the last few years the Italian Society of Nephrology has addressed many technical-scientific and management aspects to better patient satisfaction. Project No. 1 of the 2004-2006 programme on 'Quality and Accreditation of National Renal Units' focuses on four essential points. The first is the questionnaire mailed to all the Presidents and Regional Delegates on the relationship between Nephrology units, Local Government Health-System and the Regional Healthcare Agency. The results evidence that the 'political' decision-making power of nephrologists decreases in the absence of a national strategy. The second point, in collaboration with the National Census Group, includes the quality analysis and the standardization of resources (human and structural) and management of the Renal Units. The third point is based on 'Educational Courses for Quality and Accreditation' held in Rome (3-5 October 2005: L'Accreditamento all'Eccellenza dell'Unita' Operativa di Nefrologia, Dialisi e Trapianto; 17-19 October 2005: Il Manuale di Accreditamento della Specialità di Nefrologia). The courses aim at training members responsible for each region to hold courses in their specific region to create a network including each single Renal Unit to create an acceptable homogenous language on the models of analysis and on the correct use of 'The Guide for Excellence Accreditation'. The fourth point concerns both the on-line Guide for Excellence Accreditation and 'Peer Review Accreditation' and the NEQUASY (Nephrology Quality System) project. The manual must be 'user friendly' allowing each Centre to self-evaluate using national and regional standards.

Structural and functional response of meiofauna rocky assemblages to sewage pollution.

Despite meiofauna being one of the most popular tool for detecting the ecological effects of different sources of impact, the application of structured experimental designs to this benthic component is typically neglected, especially in subtidal rocky shores. In this study, an asymmetrical design was used to detect hard-bottom meiofaunal abundance and biodiversity response to sewage discharge. Sampling was carried out at a depth of 3-4 m by SCUBA diving, by means of a modified manual corer. Six replicate cores were collected at three sites (80-100 m apart), at each of three locations (one purportedly impacted [I] and two controls [Cs]). A total of 84,994 specimens were collected. The outfall affected meiofaunal assemblages in terms of taxon richness, by determining a significant reduction of the number of taxa in the disturbed location, and community structure, by causing functional changes in terms of a decrease of the abundance of nematodes and an increase of the hydrozoan component. Nematodes and syllid polychaetes showed significant lower average abundance at I. Multivariate analyses showed that both meiofaunal assemblage and syllids were significantly different at I compared with Cs. The sewage outfall also affected patterns of spatial distribution at the scale of site (100 m apart) and of replicate units (centimetres apart), both in syllids and in nematodes. Our results provide evidence that the selection of multiple controls is crucial to prevent the widespread risk of Type II error, highlighting the need of more accurate experimental designs when dealing with meiofauna.

Aneurysm of arteriovenous fistula in uremic patients: is endograft a viable therapeutic approach?

One of the complications of arteriovenous fistulas in chronic hemodialyzed patients is the onset of an aneurysm which can be at risk of rupture. Traditional surgical repair is not always feasible and may not be successful in these cases, leading therefore to the loss of a functioning vascular access and requiring in any case the temporary use of a central venous catheter to allow regular hemodialysis sessions. We applied to this kind of aneurysm the same experience developed in the management of major arterial aneurysms and we considered endografting repair a good alternative in this case. In this paper we present the successful treatment of an arteriovenous fistula aneurysm using that technique. A distal radio-cephalic arteriovenous fistula in one of our patients presented an aneurysm with high risk of rupture. The endografting repair with percutaneous insertion of a WallgraftTM endoprosthesis was well tolerated and the vascular access could be used the day after, without the need for a central venous catheter insertion.

[The integrated approach between Health Organisation accreditation and professional excellence accreditation]. / L'integrazione tra accreditamento istituzionale e accreditamento professionale di eccellenza.

Later than in other industrialized areas, Health Organisation accreditation has become popular in our country during the last few years as a result of legislation requiring accreditation for healthcare providers of the National Health Service. Out of the two accreditation models, for regulation and public accountability (institutional) and professional, voluntary self-developed (for excellence), Institutional accreditation process has been slowly growing with the adoption of generic structural and organisational standards, which have been set up and managed directly by government. The recently undertaken second model is a peer review assessment activity that originates from a comparison with explicit standards during reciprocal visits carried out by professional organisations. The basis for the assessment is primarily clinical and patient oriented. The healthcare quality of Institutional accreditation is guaranteed mainly through the achievement of predetermined standards for risk management and organisation. On the other hand, the excellence accreditation, whose aim is to implement the continuous improvement of quality, depends on the context and the changes that result from new knowledge and scientific progress. The model operates according to values, which can change in the long run. It measures the effort to improve performances while special care is required to define standards through peer consensus. Once the prescribed model of accreditation is adopted, as is the case for Health Organisation accreditation, it is essential to have flexible patient-oriented tools ensuring that new knowledge and scientific progress complete the assessment and audit.

Glide2, a second glial promoting factor in Drosophila melanogaster.

The fly glial cell deficient/glial cell missing (glide/gcm) gene codes for a transcription factor that induces gliogenesis. Lack of its product eliminates lateral glial cells in the embryonic nervous system. Here we identify a second gene, glide2, that is homologous to glide/gcm in the binding domain and that is also necessary and sufficient to promote glial differentiation. glide2 codes for a transcription factor that displays a weaker and delayed expression compared with glide/gcm. The two genes, which are located 27 kb apart and share cis-regulatory elements, are able to auto- and cross-regulate, indicating that they form a gene complex. Finally, we show that lack of both products eliminates all lateral glial cells, which means that the two genes contain all the fly lateral glial promoting activity.

Human medulloblastoma cell line DEV is a potent tool to screen for factors influencing differentiation of neural stem cells.

The aim of our study was to investigate whether a human neural cell line could be used as a reliable screening tool to examine the functional conservation, in humans, of transcription factors involved in neuronal or glial specification in other species. Gain-of-function experiments were performed on DEV cells, a cell line derived from a human medulloblastoma. Genes encoding nine different transcription factors were tested for their influence on the process of specification of human DEV cells towards a neuronal or glial fate. In a first series of experiments, DEV cells were transfected with murine genes encoding transcription factors known to be involved in the neuronal differentiation cascade. Neurogenins-1, -2, and -3; Mash-1; and NeuroD increased the differentiation of DEV cells towards a neuronal phenotype by a factor of 2-3.5. In a second series of experiments, we tested transcription factors involved in invertebrate glial specification. In the embryonic Drosophila CNS, the development of most glial cells depends on the master regulatory gene glial cell missing (gcm). Expression of gcm in DEV cells induced a twofold increase of astrocytic and a sixfold increase of oligodendroglial cell types. Interestingly, expression of tramtrack69, which is required in all Drosophila glial cells, resulted in a fourfold increase of only the oligodendrocyte phenotype. Expression of the related tramtrack88 protein, which is not expressed in the fly glia, or the C. elegans lin26 protein showed no effect. These results show that the Drosophila transcription factor genes tested can conserve their function upon transfection into the human DEV cells, qualifying this cell line as a screening tool to analyze the mechanisms of neuronal and glial specification.

A novel mode of asymmetric division identifies the fly neuroglioblast 6-4T.

Asymmetric cell divisions and segregation of fate determinants are crucial events in the generation of cell diversity. Fly neuroblasts, the precursors that self-reproduce and generate neurons, represent a clear example of asymmetrically dividing cells. Less is known about how neurons and glial cells are generated by multipotent precursors. Flies provide the ideal model system to study this process. Indeed, neuroglioblasts (NGBs) can be specifically identified and have been shown to require the glide/gcm fate determinant to produce glial cells, which otherwise would become neurons. Here, we follow the division of a specific NGB (NGB6-4T), which produces a neuroblast (NB) and a glioblast (GB). We show that, to generate the glioblast, glide/gcm RNA becomes progressively unequally distributed during NGB division and preferentially segregates. Subsequently, a GB-specific factor is required to maintain glide/gcm expression. Both processes are necessary for gliogenesis, showing that the glial vs. neuronal fate choice is a two-step process. This feature, together with glide/gcm subcellular RNA distribution and the behavior of the NGB mitotic apparatus identify a novel type of division generating cell diversity.

Notch signaling represses the glial fate in fly PNS.

By using gain-of-function mutations it has been proposed that vertebrate Notch promotes the glial fate. We show in vivo that glial cells are produced at the expense of neurons in the peripheral nervous system of flies lacking Notch and that constitutively activated Notch produces the opposite phenotype. Notch acts as a genetic switch between neuronal and glial fates by negatively regulating glial cell deficient/glial cells missing, the gene required in the glial precursor to induce gliogenesis. Moreover, Notch represses neurogenesis or gliogenesis, depending on the sensory organ type. Numb, which is asymmetrically localized in the multipotent cell that produces the glial precursor, induces glial cells at the expense of neurons. Thus, a cell-autonomous mechanism inhibits Notch signaling.

Relapsing seroma in a uremic patient bearing a PTFE graft as vascular access.

UNLABELLED: Seroma is one of the most frequent complications of PTFE vascular grafts and its etiology is still unclear. CASE REPORT: A 51 year-old male on regular dialytic treatment for seven years underwent the surgical implantation of a vascular prosthesis of homologous safena due to the thrombosis of his native artero-venous fistula. Several years earlier the patient had suffered the amputation of the left forearm because of electric shock. A few months later the vascular prosthesis was replaced with a PTFE vascular graft as a result of aneurysm formation and thrombosis. During the following days a non pulsating swelling occurred near the arterial anasto-mosis. Ultrasonography, doppler sonography and aspiration confirmed the diagnosis of seroma and it was surgically removed. Some weeks later a new seroma was observed in the same site and associated with a skin ulcer. A new surgical removal had no benefit and about one month later a perigraft collection was found along with signs of bacterial infection. For this reason the patient underwent the surgical excision of the PTFE graft and a vascular access was warranted by placing a Tesio TM catheter. Usually surgery is considered mandatory in seromas larger than 2 cm in diameter and showing continuous growth. In our patient the poor vascular status might have suggested a more conservative management even with a seroma diameter of about 7 cm. Nevertheless the high risk of systemic infection prompted us to remove the PTFE graft.

Some fly sensory organs are gliogenic and require glide/gcm in a precursor that divides symmetrically and produces glial cells.

In flies, the choice between neuronal and glial fates depends on the asymmetric division of multipotent precursors, the neuroglioblast of the central nervous system and the IIb precursor of the sensory organ lineage. In the central nervous system, the choice between the two fates requires asymmetric distribution of the glial cell deficient/glial cell missing (glide/gcm) RNA in the neuroglioblast. Preferential accumulation of the transcript in one of the daughter cells results in the activation of the glial fate in that cell, which becomes a glial precursor. Here we show that glide/gcm is necessary to induce glial differentiation in the peripheral nervous system. We also present evidence that glide/gcm RNA is not necessary to induce the fate choice in the peripheral multipotent precursor. Indeed, glide/gcm RNA and protein are first detected in one daughter of IIb but not in IIb itself. Thus, glide/gcm is required in both central and peripheral glial cells, but its regulation is context dependent. Strikingly, we have found that only subsets of sensory organs are gliogenic and express glide/gcm. The ability to produce glial cells depends on fixed, lineage related, cues and not on stochastic decisions. Finally, we show that after glide/gcm expression has ceased, the IIb daughter migrates and divides symmetrically to produce several mature glial cells. Thus, the glide/gcm-expressing cell, also called the fifth cell of the sensory organ, is indeed a glial precursor. This is the first reported case of symmetric division in the sensory organ lineage. These data indicate that the organization of the fly peripheral nervous system is more complex than previously thought.

Gliogenesis depends on glide/gcm through asymmetric division of neuroglioblasts.

Some neurons and glial cells originate from neuroblasts and glioblasts, stem cells that delaminate from the ectoderm of developing fly embryos. A second class of glial cells and neurons differentiates from multipotent precursors, the neuroglioblasts. The differentiation of both glial cell types depends on glial cell deficient/glial cell missing (glide/gcm). Although it has been shown that this transcription factor promotes gliogenesis at the expense of neurogenesis, the cellular mechanisms underlying this fate choice are poorly understood. Using loss and gain of function glide/gcm mutations here we show that the cell fate choice takes place in the neuroglioblast, which divides and produces a glioblast and a neuroblast. Such choice requires the asymmetric distribution of glide/gcm RNA, which accumulates preferentially on one side of the neuroglioblast and is inherited by one cell, the presumptive glioblast. Interestingly, glial cells can differentiate from cells that delaminate as neuroglioblasts or they can arise from cells that start expressing glide/gcm several hours after delamination of a neuroblast. Altogether, these findings identify a novel type of asymmetric cell division and disclose the lineage relationships between glia and neurons. They also reveal the mode of action of the glide/gcm promoting factor.

Prevalence of hypertension in patients on peritoneal dialysis: results of an Italian multicentre study.

BACKGROUND: The tenet that peritoneal dialysis is capable of either normalizing or improving blood pressure control in uraemic patients is based on outdated or monocentric experiences. Therefore, we assessed the prevalence of hypertension and the efficacy of antihypertensive therapy in a large, multicentric cohort of patients on peritoneal dialysis. METHODS: Twenty seven out of the 50 centres belonging to the Italian Co-operative Peritoneal Dialysis Study Group took part in the study. The main patient selection criteria were: peritoneal dialysis therapy for at least 3 months and no peritonitis or changes in dialysis technique for at least 1 month. Clinical blood pressure was measured according to WHO/ISH guidelines. Ambulatory blood pressure monitoring was carried out using a SpaceLabs 90207 recorder. Hypertension was defined according to WHO/ISH criteria and staged according to the criteria of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (JNC), 5th Report. Ambulatory blood pressure monitoring recordings were used to evaluate white-coat hypertension, blood pressure load and the dipping phenomenon. RESULTS: Five hundred and four subjects were evaluated. Hypertension was prevalent in 88.1% of the population, and 362 out of 444 hypertensive patients were on antihypertensive therapy. JNC staging revealed that 188 patients had moderate to severe hypertension. Blood pressure load was pathological in 77.3% of the patients receiving antihypertensive treatment. White-coat hypertension was identified in 9.1% of the hypertensive patients not on antihypertensive therapy, and 53.1% of the patients were non-dippers. CONCLUSIONS: The study demonstrates that hypertension is a dramatic, unsolved problem in uraemic patients treated with peritoneal dialysis, and casts doubts on the effectiveness of our current peritoneal dialysis strategies and pharmacological management of hypertension.

GCMB, a second human homolog of the fly glide/gcm gene.

Glial cells play fundamental roles in neurogenesis. In addition, defective or abnormal gliogenesis is associated with severe diseases. To understand the molecular basis of such diseases, it is crucial to identify the genes promoting normal gliogenesis. Here we identify GCMB, which encodes a human protein homologous to the fly glial promoting factor glial cell deficient/glial cell missing (glide/gcm).

Continuous ambulatory peritoneal dialysis and sclerosing encapsulating peritonitis: tamoxifen as a new therapeutic agent?

Sclerosing encapsulating peritonitis (SEP) is a serious complication of long-term continuous ambulatory peritoneal dialysis (CAPD), very likely related to a persisting expression of the transforming growth factor beta1 (TGFbeta1) gene on peritoneal mesothelial cells. We report the case of a 67-year-old uremic woman who developed SEP eight years after being placed on CAPD, complicated by eight episodes of bacterial peritonitis. CAPD was therefore stopped and the patient transferred to hemodialysis. The diagnosis of SEP was confirmed by physical findings (vomiting, abdominal pain with palpable mass, ileus, cachexia) and CT data. The patient was treated with tamoxifen (10 mg/day) for three months, and gradually recovered, a subsequent CT showing a significant reduction of the thickness of peritoneal and intestinal loops. Tamoxifen probably interferes with TGFbeta1 and may be useful in the treatment of this CAPD complication.

Positive autoregulation of the glial promoting factor glide/gcm.

Fly gliogenesis depends on the glial-cell-deficient/glial-cell-missing (glide/gcm) transcription factor. glide/gcm expression is necessary and sufficient to induce the glial fate within and outside the nervous system, indicating that the activity of this gene must be tightly regulated. The current model is that glide/gcm activates the glial fate by inducing the expression of glial-specific genes that are required to maintain such a fate. Previous observations on the null glide/gcmN7-4 allele evoked the possibility that another role of glide/gcm might be to maintain and/or amplify its own expression. Here we show that glide/gcm does positively autoregulate in vitro and in vivo, and that the glide/gcmN7-4 protein is not able to do so. We thereby provide the first direct evidence of both a target and a regulator of glide/gcm. Our data also demonstrate that glide/gcm transcription is regulated at two distinct steps: initiation, which is glide/gcm-independent, and maintenance, which requires glide/gcm. Interestingly, we have found that autoregulation requires the activity of additional cell-specific cofactors. The present results suggest transcriptional autoregulation is a mechanism for glial fate induction.

Glial differentiation does not require a neural ground state.

Glial cells differentiate from the neuroepithelium. In flies, gliogenesis depends on the expression of glial cell deficient/glial cell missing (glide/gcm). The phenotype of glide/gcm loss- and gain-of-function mutations suggested that gliogenesis occurs in cells that, by default, would differentiate into neurons. Here we show that glide/gcm is able to induce cells even from a distinct germ layer, the mesoderm, to activate the glial developmental program, which demonstrates that gliogenesis does not require a ground neural state. These findings challenge the common view on the establishment of cell diversity in the nervous system. Strikingly, ectopic glide/gcm overrides positional information by repressing the endogenous developmental program. These findings also indicate that glial differentiation tightly depends on glide/gcm transcriptional regulation. It is likely that glide/gcm homologs act similarly during vertebrate gliogenesis.