Co-existence of ethanol-related respiratory and motivational learning processes based on a tactile discrimination procedure in neonatal rats.

In rats, high ethanol doses during early postnatal life exert deleterious effects upon brain development that impact diverse social and cognitive abilities. This stage in development partially overlaps with the third human gestational trimester, commonly referred to as the brain growth spurt period. At this stage in development, human fetuses and rat neonates (postnatal days [PD] 3-9) exhibit relatively high respiratory rates that are affected by subteratogenic ethanol doses. Recent studies suggest conditioned breathing responses in the developing organism, given that there are explicit associations between exteroceptive stimuli and the state of ethanol intoxication. Furthermore, studies performed with near-term rat fetuses suggest heightened sensitivity to ethanol's motivational effects. The present study was meant to analyze the unconditioned effects of ethanol intoxication and the possible co-occurrence of learning mechanisms that can impact respiratory plasticity, and to analyze the preference for cues that signal the state of intoxication as well as the effects of the drug, related with motor stimulation. Neonatal rats were subjected to differential experiences with salient tactile cues explicitly paired or not paired with the effects of vehicle or ethanol (2.0 g/kg). A tactile discrimination procedure applied during PDs 3, 5, 7, and 9 allowed the identification of the emergence of ethanol-derived non-associative and associative learning processes that affect breathing plasticity, particularly when considering apneic disruptions. Ethanol was found to partially inhibit the disruptions that appeared to be intimately related with stressful circumstances defined by the experimental procedure. Tactile cues paired with the drug's effects were also observed to exert an inhibitory effect upon these breathing disruptions. The level of contingency between a given tactile cue and ethanol intoxication also resulted in significant changes in the probability of seeking this cue in a tactile preference test. In addition, the state of intoxication exerted motor-stimulating effects. When contrasting the data obtained via the analysis of the different dependent variables, it appears that most ethanol-derived changes are modulated by positive and/or negative (anti-anxiety) reinforcing effects of the drug. As a whole, the study indicates co-existence of ethanol-related functional changes in the developing organism that simultaneously affect respiratory plasticity and preference patterns elicited by stimuli that signal ethanol's motivational effects. These results emphasize the need to consider significant alterations due to minimal ethanol experiences that argue against "safe" levels of exposure in a critical stage in brain development.

The small GTPase Rheb is required for spermatogenesis but not oogenesis.

The process of germ cell development is under the tight control of various signaling pathways, among which the PI3K-Akt-mTOR pathway is of critical importance. Previous studies have demonstrated sex-specific roles for several components of this pathway. In the current study, we aimed to evaluate the role of Rheb, a member of the small GTPase superfamily and a critical component for mTORC1 activation, in male and female gametogenesis. The function of Rheb in development and the nervous system has been extensively studied, but little is known about its role in the germ line. We have exploited genetic approaches in the mouse to study the role of Rheb in the germ line and have identified an essential role in spermatogenesis. Conditional knockout (cKO) of Rheb in the male germ line resulted in severe oligoasthenoteratozoospermia and male sterility. More detailed phenotypic analyses uncovered an age-dependent meiotic progression defect combined with subsequent abnormalities in spermiogenesis as evidenced by abnormal sperm morphology. In the female, however, germ-cell specific inactivation of Rheb was not associated with any discernible abnormality; these cKO mice were fertile with morphologically unremarkable ovaries, normal primordial follicle formation, and subsequent follicle maturation. The absence of an abnormal ovarian phenotype is striking given previous studies demonstrating a critical role for the mTORC1 pathway in the maintenance of primordial follicle pool. In conclusion, our findings demonstrate an essential role of Rheb in diverse aspects of spermatogenesis but suggest the existence of functionally redundant factors that can compensate for Rheb deficiency within oocytes.

The Healthgrid White Paper.

Over the last four years, a community of researchers working on Grid and High Performance Computing technologies started discussing the barriers and opportunities that grid technologies must face and exploit for the development of health-related applications. This interest lead to the first Healthgrid conference, held in Lyon, France, on January 16th-17th, 2003, with the focus of creating increased awareness about the possibilities and advantages linked to the deployment of grid technologies in health, ultimately targeting the creation of a European/international grid infrastructure for health. The topics of this conference converged with the position of the eHealth division of the European Commission, whose mandate from the Lisbon Meeting was "To develop an intelligent environment that enables ubiquitous management of citizens' health status, and to assist health professionals in coping with some major challenges, risk management and the integration into clinical practice of advances in health knowledge." In this context "Health" involves not only clinical procedures but covers the whole range of information from molecular level (genetic and proteomic information) over cells and tissues, to the individual and finally the population level (social healthcare). Grid technology offers the opportunity to create a common working backbone for all different members of this large "health family" and will hopefully lead to an increased awareness and interoperability among disciplines. The first HealthGrid conference led to the creation of the Healthgrid association, a non-profit research association legally incorporated in France but formed from the broad community of European researchers and institutions sharing expertise in health grids. After the second Healthgrid conference, held in Clermont-Ferrand on January 29th-30th, 2004, the need for a "white paper" on the current status and prospective of health grids was raised. Over fifty experts from different areas of grid technologies, eHealth applications and the medical world were invited to contribute to the preparation of this document.

A web service-based Grid portal for Edgebreaker compression.

BACKGROUND: In health applications, and elsewhere, 3D data sets are increasingly accessed through the Internet. To reduce the transfer time while maintaining an unaltered 3D model, adequate compression and decompression techniques are needed. Recently, Grid technologies have been integrated with Web Services technologies to provide a framework for interoperable application-to-application interaction. OBJECTIVES: The paper describes an implementation of the Edgebreaker compression technique exploiting web services technology and presents a novel approach for using such services in a Grid Portal. The Grid portal, developed at the CACT/ISUFI of the University of Lecce, allows the processing and delivery of biomedical images (CT--computerized tomography--and MRI--magnetic resonance images) in a distributed environment, using the power and security of computational Grids. METHODS: The Edgebreaker Compression Web Service has been deployed on a Grid portal and allows compressing and decompressing 3D data sets using the Globus toolkit GSI (Globus Security Infrastructure) protocol. Moreover, the classical algorithm has been modified extending the compression to files containing more than one object. RESULTS AND CONCLUSIONS: An implementation of the Edgebreaker compression technique and related experimental results are presented. A novel approach for using the compression web service in a Grid portal allowing storing and preprocessing of huge 3D data sets, and subsequent efficient transmission of results for remote visualization is also described.

[Treatment of complex anal and rectovaginal fistulas using the endorectal mucosal flap technique]. / Trattamento delle fistole anali e rettovaginali complesse con la tecnica del lembo mucoso endorettale.

BACKGROUND: Aim of the study is to evaluate the advantages of the surgical technique for the treatment of complex anal and rectovaginal fistulas by means of an endorectal mucosal flap and the removal of the fistular tract. The surgical removal of a fistular tract can lead to incontinence troubles, mostly for high complex transsphincteric fistulas. The endorectal mucosal flap technique involves the meticulous care of the sphincterial structures and of the mucosa of the anal canal, and is, in personal opinion, the best technique for the treatment of such fistulas. METHODS: The procedure used involves: meticulous study of the anatomic characteristics of the fistula; excision of the secondary opening up to the sphincters level with an elliptic excision of the skin by avoiding keyhole deformities; excision of the primary opening from inside the anal canal, with the interruption of the muscular fibers and their reconstruction; the preparation of an endorectal mucosal flap that is transposed to cover the primary opening of the fistula. 21 patients were treated with this technique, 17 were complex anal fistulas, two were associated to Crohn's disease, and of two rectovaginal fistulas, one was found in a patient with Crohn's disease. RESULTS: Recurrences were found in five patients (24%), after a median follow-up of 20 months. The delay of fistular healing, over a month, was found in 50% of the cases. No patient had continence troubles. CONCLUSIONS: The mucosal flap technique is a simple procedure, adequate in preserving the sphincteric function and in preventing deformities of the anal canal. However, it has not demonstrated clear benefits in terms of recurrences compared to other techniques, but it is highly considered for the treatment of complex anal fistulas, in terms of continence and for the earlier and better healing of the wounds and for the better tolerance of the patient.

Primary neuroendocrine carcinoma of the liver: difficult diagnosis of a rare neoplasm.

Primary neuroendocrine neoplasms of the liver are extremely rare: about 30 cases only have been described in the literature. We report the case of a 42-year-old woman with a ten-year evolution. According to the previously reported cases, primary neuroendocrine carcinoma of the liver is usually multicentric, often mimicking liver metastases. The demonstration of the hepatic origin of a neuroendocrine carcinoma is often arduous. A careful surgical exploration and a prolonged follow-up are mandatory. The treatment of choice is surgical resection when possible. For progressive and unresectable disease, hepatic arterial chemoembolization may be considered. However, the prognosis of liver neuroendocrine tumours is much more favorable than that of hepatocellular carcinoma and progression has to be demonstrated before instauration of potentially harmful therapies.

Improved equipment for abdominal fetal electrocardiogram recording: description and clinical evaluation.

Reliable computer-based equipment for transabdominal or indirect recording of fetal electrocardiogram (FECG) is described. The proposed equipment allows a real-time displaying of the signals (fetal + maternal ECG) without averaging procedures and it does not require the employment of a shielded room; moreover, it is user-friendly to medical personnel. An elementary form of semi-automatic computation of the fetal heart rate (FHR) was also implemented. The equipment simultaneously acquires three signals from seven electrodes, six placed on the maternal abdomen following the three space axes, and one placed on the left leg as a indifferent electrode. The signals are magnified and analogically filtered before undergoing digital finite impulse response (FIR) filter. Then the signals are displayed on the screen of a personal computer (PC). The PC also provides the possibility of storing the acquired signals for further analysis of elaborations. The quality of the recordings allows the analysis of both the rapid and slow electrical phenomena of the fetal heart, and it is not significantly influenced by the occurrence at the same time of uterine contractions. The performance of this method was assessed in 140 pregnant women with gestation periods of 29-42 weeks. In 131 cases (93.6%) the fetal QRS complex was detected and the FHR was obtained. A reliable evaluation of P and QRS waves and of ST interval, in spite of the interference of the maternal complexes, was possible in 102 cases (72.8%).