Autonomic nervous system in the control of energy balance and body weight: personal contributions.

The prevalence of obesity is increasing in the industrialized world, so that the World Health Organization considers obesity as a "pandemia" in rich populations. The autonomic nervous system plays a crucial role in the control of energy balance and body weight. This review summarizes our own data and perspectives, emphasizing the influence exerted by autonomic nervous system on energy expenditure and food intake, which are able to determine the body weight. Activation of the sympathetic discharge causes an increase in energy expenditure and a decrease in food intake, while reduction of food intake and body weight loss determines a reduction of the sympathetic activity. On the other hand, pathophysiological mechanisms of the obesity involve alterations of the sympathetic nervous system in accordance with the "Mona Lisa Hypothesis," an acronym for "most obesities known are low in sympathetic activity." Furthermore, the parasympathetic influences on the energy expenditure are analyzed in this review, showing that an increase in parasympathetic activity can induce a paradoxical enhancement of energy consumption.

Deregulation of HOX B13 expression in urinary bladder cancer progression.

Urinary bladder cancer is a common malignancy in industrialized countries. More than 90% of bladder cancer originates in the transitional cells. Bladder transitional cancer prognosis is, according to the most recent definition related to the level of tumor infiltration, characterized by two main phenotypes, Non Muscle Invasive Bladder Transitional Cancer (NMIBC) and Muscle Invasive Bladder Transitional Cancer (MIBC). The genetic profile and the clinical course of the two subtypes are completely different, however among NMIBC the prognosis is not completely predictable, since 20% of the cases experience a relapse, even in the form of MIBC. It has recently been reported that the chromosomal region 12q13-15, containing crucial cancer genes such as MDM2, CDK4, GLI and an entire cluster of HOX genes, is amplified in bladder cancer. HOX genes codify for transcriptionl factor, involved in embryonal development and cancer progression, with main nuclear expression. Particularly it was also described the strong involvement of HOX B13 in several tumors of urogenital system. In this study we have been investigated, by immunohistochemisty and quantitative Real Time PCR, the HOX B13 expression in bladder cancer evolution and progression, evaluating its ability to discriminate between NMIBC and MBCI phenotypes. Cytoplasmic HOX B13 delocalization significantly relates with muscle invasion (p 0.004). In addition in the series of NMIBC nuclear HOX B13 expression loss is significantly associated to shorter disease free survival (p-value=0.038) defining a potential prognostic role. Overexpression of HOX B13 in more aggressive phenotype is also demonstrate at gene level by quantitative RT-PCR. The de-regulation and delocalization of HOX B13 in urinary bladder cancer supports again the important role of HOX genes in tumor evolution and represents a starting point to establish an integrated analysis, in which HOX genes represent important prognostic and predictive markers for bladder cancer.

Recent advances in the biology of germ cell tumors: implications for the diagnosis and treatment.

Testicular germ cell tumors (TGCT), are the most frequent solid malignant tumors in men 20-40 yr of age, and the most frequent cause of death from solid tumors in this age group. TGCT can be subdivided into seminoma and nonseminoma germ cell tumors (NSGCT), including embryonal cell carcinoma, choriocarcinoma, yolk sac tumor, and teratoma. Seminomas and NSGCT do not only present distinctive clinical features, but they also show significant differences as far as therapy and prognosis are concerned. Many novel markers have given further advantages to discriminate between histological subgroups. In addition, therapeutic approaches for the treatment of TGCT have been proposed: humanized antibodies against receptors/surface molecules on cancer cells, inhibitors of serine-threonine, and tyrosine kinases, and others. The review will focus on the recent advances in the research of molecular alterations identified in TGCT and on novel targeted anti-neoplastic strategies that might help to treat chemotherapy-resistant TGCT.

Movement velocity effects on kinaesthetic localisation of spatial positions.

In the present study, we examined how subjects locate spatial positions and code them in short-term memory. In the first experiment, blindfolded subjects were asked to perform movements in the near or far peripersonal space (criterion movement, CM). Then, subjects had to reach the end-point of CM (reproduction movement, RM). Movements could be performed either slowly or rapidly. Also, CM and RM could be performed with the same (congruent conditions) or different velocity (incongruent conditions). The results showed that performance was accurate in the two congruent conditions. Conversely, in the incongruent conditions, subjects made undershoot errors when the CM was fast and overshoot errors when it was slow. In the second experiment, blindfolded subjects also performed CM and RM in congruent or incongruent conditions. However, the CM and RM could start from the same or different position. We found again undershoot errors when the CM was fast and RM was slow and overshoot errors in the reverse condition. The results of both experiments suggest that the information about movement velocity contributes to the kinaesthetic coding in memory of a spatial location to be reached with arm movement.

Influence of visual distractors on movement trajectory.

In the present study, we explored the influence of a visual distractor on the trajectory of movements made to join two dots. The two dots could be unconnected (D) or connected by a straight (L) or curved line, convex either to the left (LL) or to the right (RL). The connecting line constituted the visual distractor. In Experiment 1, subjects were asked to perform the joining movement as straight as possible. The results showed that hand trajectory moved to the left of the midsagittal axis in LL and to the right in RL, while it was almost straight both in L and D. In Experiment 2, subjects were explicitly required to follow the connecting line during their movements to verify whether, in the previous experiment, they had used curved lines as guide for their movements. An increase of movement time and different hand paths showed that this was not the case. In Experiment 3, subjects were asked to move as straight as possible without vision of their hand. Hand trajectories were shifted to the left in all experimental conditions, but the leftward shift was greater in LL than in all other conditions, and also greater in D and L than in RL. These findings suggest that the visual distractor influenced hand trajectory by attracting subject's attention and competing with target for motor response. It is hypothesized that the attracting influence operated by the distractor was sustained by involuntary attentional mechanisms.

Influence of perceptual factors on line bisection.

In the present study we investigated whether masking/perceptual factors may influence line bisection performance in normal subjects. We carried out two experiments. In Experiment 1 the stimuli consisted of a line flanked at each end by: (1) parallel arrows, (2) oblique arrows, (3) or oblique geometrical figures. Of the two pairs of labels, one pair converged on the line and appeared to mask the flanked portion of the line. The results showed the presence of a bisection bias in the direction opposite to location of masking labels. In Experiment 2 we examined if orientation factors might have contributed to the observed bisection bias. The stimuli consisted of a line flanked by only one pair of oblique geometrical figures. The results showed that bisection bias was always in the direction opposite to label location, independently of the direction pointed out by oblique figures. These findings suggest that masking/perceptual factors may influence bisection performance in normal subjects.

Hand-centred coding of target location in visuo-spatial working memory.

The aim of the present experiment was to determine the frame of reference used to encode a visually specified target location, in a simple, visuo-spatial short-term-memory task, using delayed manual pointing. Subjects were required to remember the location of a single, visually presented stimulus, over delays of 3 and 30 s, and to recall its location by pointing to it with the tip of a stylus with eyes closed. There were two starting positions for the hand: one near the body, proximal to the target area, the other far from the body, i.e., beyond the target area. Two groups of twelve subjects participated in the experiment. One group observed the target locations in the light, the other group observed the target LEDs in the dark. The results showed a large (between 10-30%) and consistent undershoot of the remembered target location with respect to the hand's starting position, in the sagittal axis, both when the hand started from the near and from the far position. That is, from the far starting position. pointing errors lay consistently beyond the actual target location as seen from the subject's viewpoint. Further, this undershoot error in the remembered target location increased over time delay. These results are in favour of the hypothesis that the visual target locations were encoded in a hand-centred frame of reference in spatial short-term memory. They also implicate the use of motor- or action-related representations in visuo-spatial working memory.

Independent coding of target distance and direction in visuo-spatial working memory.

The organization of manual reaching movements suggests considerable independence in the initial programming with respect to the direction and the distance of the intended movement. It was hypothesized that short-term memory for a visually-presented location within reaching space, in the absence of other allocentric reference points, might also be represented in a motoric code, showing similar independence in the encoding of direction and distance. This hypothesis was tested in two experiments, using adult human subjects who were required to remember the location of a briefly presented luminous spot. Stimuli were presented in the dark, thus providing purely egocentric spatial information. After the specified delay, subjects were instructed to point to the remembered location. In Exp. 1, temporal decay of location memory was studied, over a range of 4-30 s. The results showed that (a) memory for both the direction and the distance of the visual target location declined over time, at about the same rate for both parameters; however, (b) errors of distance were much greater in the left than in the right hemispace, whereas direction errors showed no such effect; (c) the distance and direction errors were essentially uncorrelated, at all delays. These findings suggest independent representation of these two parameters in working memory. In Exp. 2 the subjects were required to remember the locations of two visual stimuli presented sequentially, one after the other. Only after both stimuli had been presented did the subject receive a signal from the experimenter as to which one was to be pointed to. The results showed that the encoding of a second location selectively interfered with memory for the direction but not for the distance of the to-be-remembered target location. As in Exp. 1, direction and distance errors were again uncorrelated. The results of both experiments indicate that memory for egocentrically-specified visual locations can encode the direction and distance of the target independently. Use of motor-related representation in spatial working memory is thus strongly suggested. The findings are discussed in the context of multiple representations of space in visuo-spatial short-term memory.

Effects of stimulus asymmetry on line bisection.

There is an upward bias in bisecting radial and vertical lines under visual guidance. We investigated whether illusory visual factors might contribute to a previously reported representational upward bias in this task. In two experiments, subjects performed a line-bisection task along the three orthogonal axes (horizontal, radial, vertical). In Experiment 1, the stimuli consisted of a line terminated at each end by two equal- or different-sized bars. In Experiment 2, the stimuli were formed by a line terminated by two equal- or different-sized directional labels: SOPRA ("top") and SOTTO ("bottom"). The results showed a bisection bias towards the smaller bar (Experiment 1) and the smaller directional label (Experiment 2) on all three spatial axes, supporting the existence of an illusory visual effect. Contrary to a previous report, the data failed to show any representational (semantic) bias related to directional label meaning. These findings suggest that perceptual/attentional factors play a significant role in normal subjects' upward bias.

Visual illusion and action.

The role of allocentric cues on movement control was investigated in the present study. Pointing movements directed to the more distant vertex of closed and open configurations of the Muller-Lyer illusion, as well as to the vertex of control lines, were studied in four experimental conditions. In the first (full-vision condition) subjects saw both stimulus and their hand before and during movement, in the second (non-visual feedback condition) they saw the stimulus, but not their hand during movement. In the two remaining conditions (no-vision conditions) vision of the scene and the hand was precluded. Pointing was executed 0 sec (no vision 0 sec delay condition) or 5 sec (no-vision 5 sec delay condition) after the light was switched off. The Muller-Lyer illusion affected pointing kinematics with respect to the control lines. Subjects undershot and overshot the vertex location, respectively, of the closed and open configuration. Correspondingly, the entire kinematics were changed. The main result was, however, a gradually increasing effect of the perceptual illusion when pointing was executed from memory compared to the full-vision condition. These data are discussed according to the hypothesis that the system underlying visual perception in the allocentric frame of reference and that involved in motor action can functionally interact. The strength of this interaction depends upon the efficiency of the egocentric frame of reference by which motor actions are constructed.

Unconscious updating of grasp motor program.

Grasp modification during prehension movements was studied in response to slight variations of somesthetic information about object size. Three experiments were carried out. In experiment 1 eight subjects were required to reach and grasp an object whose size could either increase or decrease, whereas its visual image remained unmodified. The object size was changed during the experiment with uninformed subjects after a block of trials during which visual and somesthetic information were congruent. At the end of the experiment subjects were required to reproduce the size of the object with their fingers (matching test). Results showed that maximal grip aperture during prehension as well as finger aperture in the matching test were modified according to variation in object size, although no subject realized that the object had changed during the experiment. Grasp time was also altered by object size change. Greater and earlier adaptation in maximal grip aperture, as well as perturbation of grasp time, were observed for decrease than for increase in object size. However, complete compensation was never reached for both parameters. Constant confidence in vision could have prevented both complete compensation and conscious detection of object change. This was investigated in two additional experiments. In experiment 2 visual information was made unreliable by informing subjects about variation in grasped object size. This led to greater and earlier modification in maximal grip aperture than in experiment 1. Grasp time was kept almost constant regardless of size variation. In experiment 3 vision of the stimulus was prevented and no information on change in object size was given to subjects. The results of experiment 3 were similar to those of experiment 1, although modification in maximal grip aperture was larger for increase in object size. Correspondingly, grasp time was more affected by increase than by decrease in object size. The results of the three experiments suggest that kinematic parameters usually considered as dependent on object properties, such as maximal grip aperture, were modified in order to compensate perturbation of temporal parameters. This modification induced a "pragmatic" knowledge of object size (as showed by the results of the matching test), although awareness was not reached.

The role of proprioception in the control of prehension movements: a kinematic study in a peripherally deafferented patient and in normal subjects.

In this study we investigated the role of proprioception in the control of prehension movements, with particular reference to the grasp component. Grasp and transport kinematics were studied in a peripherally deafferented patient and in five healthy subjects. Two experiments were carried out: the prehension experiment and the grasp perturbation experiment. In the prehension experiment both the patient and the control subjects were required to reach and grasp three objects of different size, located at three different distances, both with and without visual feedback. In the grasp perturbation experiment a mechanical perturbation was applied to the fingers during prehension movements, again executed with and without visual feedback. In the prehension experiment temporal parameters of the patient's movements were generally slowed, with greater variability on some measures. However, over the first phase of the movement the pattern of the patient's hand opening and transport acceleration, scaled to object size and distance, was the same as that of controls, both with and without visual feedback. On the contrary, during the final phase of the movement (the finger closure phase and deceleration) the patient's performance differed significantly from the controls. These phases were abnormally lengthened and frequent movement adjustments were observed. In the grasp perturbation experiment the patient was not able to compensate for the perturbations applied to the fingers, even with visual feedback. The data allowed us to investigate also the respective contribution of proprioception and of vision of the hand in the control of prehension. We compared prehension kinematics in two conditions: (a) with visual but no proprioceptive feedback (in the patient) and (b) with proprioceptive but no visual feedback (in the controls). In both experiments proprioceptive control was more efficient than visual control. The results of this study are interpreted in favour of the strict dependence of prehension control on proprioception. The first phase of the movement, however, can be appropriately planned and executed without the necessity of either proprioceptive or visual information about the hand.

Study of selective reaching and grasping in a patient with unilateral parietal lesion. Dissociated effects of residual spatial neglect.

In the present study we investigated the possibility of a dissociation between the visual control of reaching and the visual control of grasping in a prehension task. To this purpose we studied the kinematics of prehension movements in a patient with a right parietal lesion and in six right-handed healthy control subjects. The task we used was one in which the subjects had to reach and grasp target objects in the presence or absence of a simultaneously presented distractor object. All stimuli were presented in the space ipsilateral to the lesion. The distractor could be either of the same or different size to the target object and was presented either to the right or to the left of the target. The following parameters of the prehension 'transport' component were analysed: wrist trajectory, transport time, tangential peak velocity, acceleration. Maximal finger aperture, time to maximal finger aperture, peak acceleration and time to peak acceleration of grip aperture were the parameters of the 'grasping' component analysed. The results showed that, although the patient had no misreaching, her hand trajectory deviated abnormally towards the distractor position when the distractor was to the right (ipsilateral) side of the target. In contrast, the grasp kinematics was not affected by the distractors, even when the size of the right distractor was different from the target. It appears, therefore, that the attentional shift towards the ipsilesional side, typical of neglect patients, determines a surprising dissociation in motor control. In the presence of a right distractor, the patient plans and partially executes a reaching movement towards that object and simultaneously performs a grasping movement towards a second object, i.e. the centrally located target. The presentation of distractors had no effects on the prehension kinematics of the control subjects.

Coordination between the transport and the grasp components during prehension movements.

In this study, the possible influence of the transport on the grasp component of prehension movements was investigated. The first phase of the transport (acceleration phase) and of the grasp (finger aperture phase) kinematics were studied under conditions of visual and non-visual object presentation (prehension experiment). In the non-visual condition, object size was estimated by haptics and object position was estimated by proprioception. Eight subjects were required to reach and grasp three objects of different size located at two distances. An additional experiment (matching experiment) was carried out to control the scaling of object size in two conditions. The results showed that in the matching experiment size estimation for large objects was similar in the two conditions, whereas small stimuli were underestimated in the haptic condition. In the prehension experiment, maximal finger aperture and velocity of finger aperture were greater in the non-visual than in the visual condition, and the difference was greater for small than for large stimuli. Moreover, in both conditions, finger opening was larger for prehension movements directed to the far than to the near objects, but only for smaller stimuli. Hand trajectory variability increased in the non-visual condition and with the distance, whereas finger opening variability was only affected by the non-visual condition. For smaller stimuli, increased finger opening with distance was positively correlated with the increase in wrist variability in the visual condition, but not in the non-visual condition. Furthermore, increased finger opening between visual and non-visual conditions was correlated with the increase in wrist variability, for smaller objects at the near object location.(ABSTRACT TRUNCATED AT 250 WORDS)

Prehension movements directed to approaching objects: influence of stimulus velocity on the transport and the grasp components.

In this investigation we studied the influence of object velocity on the transport and on the grasp components of prehension movements directed to approaching objects. Three experiments were carried out. In the first experiment six subjects were required to reach and grasp a sphere that approached them with a constant velocity. The effects of four velocities were studied. The results showed that the end point of the arm movement changed with object velocity: nearer the body with higher than with lower object velocities. Transport velocity increased with movement amplitude and the deceleration phase decreased in duration with higher object velocities. On the contrary the grasp component was not affected by object velocity. The second experiment was a control experiment carried out in order to verify whether a possible influence of object velocity on the grasp could be revealed in an experimental condition in which grasp planning relies without doubt on visual computation of all object features. In this experiment object velocity and object size were randomly varied. The results showed that the grasp was not influenced by object velocity, whereas it was sensitive to changes of object size. The third experiment had the two-fold aim of establishing (1) whether transport velocity was influenced by object velocity once the location in space at which the object had to be grasped was fixed and (2) whether the grasp kinematics differed for prehension movements directed respectively to stationary or to moving objects. Results showed that the first part of the transport is affected only by distance, whereas the deceleration phase decreased with increasing object velocity. This last result suggests that subjects minimized object displacements in order to grasp the sphere correctly. The grasp component differed between the conditions of stationary and moving stimuli only in the relative timing between finger aperture and closure phases. The closure phase decreased in the condition of moving stimuli. The results of the three experiments indicate the dependence of transport parameters on object velocity, whereas grasp parameters appear to be unaffected.

Temporal coupling between transport and grasp components during prehension movements: effects of visual perturbation.

The temporal coupling between the transport and grasp components of prehension movements was investigated through two experiments. In Experiment 1, six normal subjects were required to reach and grasp each of three spheres located at three different distances (Blocked trials). In Experiment 2, a visual perturbation paradigm was used in which the location of the object to be reached and grasped could change at the beginning of arm movement (Perturbed trials). The same subjects participated in both experiments. Kinematics of wrist trajectory (transport component) and of distance between thumb and index finger (grasp component) were analyzed. The results of Experiment 1 showed that the two components could be temporally coupled during their time course. In Experiment 2, the visual perturbation affected both the components, but different times were required by each component to reorganize the movement towards the new target. These different times caused the decoupling of those events that appeared synchronized in Experiment 1. Finally, evidence was found to suggest that planning of grip formation takes into account not only the perceived characteristics of the object, but also the time planned by the transport component to reach the object.

[Facilitating and inhibiting effects of the orientation of attention using peripheral cues]. / Effetti facilitatori e inibitori dell' orientamento dell'attenzione con segnali periferici.

The attentional field resulting from the presentation of peripheral cues; which were either informative or non informative about the position of the imperative stimulus, was studied. Different time intervals between cue and stimulus (120, 300, 600 ms) were used. The results showed facilitation of the response with the informative cue and inhibition with the non informative cue. This happened for the longest cue-stimulus intervals and when the position of the cue and the position of the stimulus were congruent. Also order of cue presentation (i.e., either informative followed by the non informative cue or vice versa) proved important in producing facilitatory and inhibitory effects.

[Endo-periodontal relations. Microbiological and clinical aspects]. / Relazioni endo-parodontali. Aspetti microbiologici e clinici.

Periodontics and endodontics share common objectives and common field of interest. Both disciplines treat lesions of the periodontal tissues; in their marginal aspect the first, in the periapical aspect the latter. These relationships have not been well understood for a long time. This article is a review of the literature on the topic aimed at clarifying the anatomic, microbiological, pathogenetic relationship in the periodontal and endodontic lesions.

[Kinematic study of reaching-grasping movements in the monkey]. / Studio cinematico dei movimenti di raggiungimento-prensione nella scimmia.

Kinematics of reaching-grasping movement towards stimuli of three different sizes located at two different distances were studied in one monkey (Macaca nemestrina). Transport and manipulation components were analyzed using the ELITE system. Transport time, peak velocity and deceleration phase of velocity were influenced by stimulus size, whilst acceleration phase remained unmodified. Peak velocity clearly increased with distance, while transport time remained constant (isochrony ). The main parameters of manipulation component were all influenced by stimulus size but they did not vary with distance. A comparison with kinematic data obtained from human subjects was made.

[Kinematic study of the temporal coupling between the components of transport and manipulation during reaching and grasping movements]. / Studio cinematico dell'accoppiamento temporale tra le componenti di trasporto e manipolazione durante i movimenti di raggiungimento-prensione.

In this study the temporal coupling between transport and manipulation components of prehension movements was tested. For this purpose two experiments were carried out. In Experiment 1 six normal subjects were required to reach and grasp one of three spheres located at three different distances (Blocked trials). In Experiment 2 a visual perturbation paradigm was used in which the location of the object to be reached and grasped could change at onset of arm movement (Perturbed trials). The results of this study exclude a temporal coupling between events of transport and manipulation components. On the contrary they suggest that manipulation component organizes its time course having information about the time required to reach the object.