Neural mechanisms of mismatch negativity dysfunction in schizophrenia.

Schizophrenia is associated with cognitive deficits that reflect impaired cortical information processing. Mismatch negativity (MMN) indexes pre-attentive information processing dysfunction at the level of primary auditory cortex. This study investigates mechanisms underlying MMN impairments in schizophrenia using event-related potential, event-related spectral decomposition (ERSP) and resting state functional connectivity (rsfcMRI) approaches. For this study, MMN data to frequency, intensity and duration-deviants were analyzed from 69 schizophrenia patients and 38 healthy controls. rsfcMRI was obtained from a subsample of 38 patients and 23 controls. As expected, schizophrenia patients showed highly significant, large effect size (P=0.0004, d=1.0) deficits in MMN generation across deviant types. In ERSP analyses, responses to deviants occurred primarily the theta (4-7 Hz) frequency range consistent with distributed corticocortical processing, whereas responses to standards occurred primarily in alpha (8-12 Hz) range consistent with known frequencies of thalamocortical activation. Independent deficits in schizophrenia were observed in both the theta response to deviants (P=0.021) and the alpha-response to standards (P=0.003). At the single-trial level, differential patterns of response were observed for frequency vs duration/intensity deviants, along with At the network level, MMN deficits engaged canonical somatomotor, ventral attention and default networks, with a differential pattern of engagement across deviant types (P<0.0001). Findings indicate that deficits in thalamocortical, as well as corticocortical, connectivity contribute to auditory dysfunction in schizophrenia. In addition, differences in ERSP and rsfcMRI profiles across deviant types suggest potential differential engagement of underlying generator mechanisms.

Expectancy-related modulations of neural oscillations in continuous performance tasks.

Analysis of neural oscillations in the electroencephalogram (EEG) during cognitive tasks provides valuable information about underlying neuronal processing not accessible by other methods such as event-related potentials (ERPs) and the BOLD signal in fMRI. We investigated neural substrates of motor preparation and expectancy by analyzing neural oscillations of healthy subjects performing the AX continuous performance task (AX-CPT), a task widely used to evaluate processes such as cognitive control, motor preparation and anticipatory and sustained attention. The task consists of letters presented sequentially on a monitor, and subjects are required to respond only when they see the letter A (cue) followed by the letter X (target). In this study, to emphasize expectation and motor preparation, three versions of AX-CPT were used in which the overall propensity to respond was differentially modulated, by changing the probability of the letter sequences. Neural activity was investigated in three time windows following presentation of the cue: sensory, evaluation and preparation. Alpha power was reduced following cue onset similarly in all versions of the task in both the sensory and evaluation periods, but in the later preparation period there were task dependent modulations. Alpha was decreased when an infrequent cue increased the chance of a response, and increased when a propensity to respond had to be overcome, possibly reflecting an anticipatory attentional mechanism to gate visuo-motor processing. Beta power was modulated by task and cue in both evaluation and preparation periods. In the latter, beta power reflected the propensity to respond and correlated both with amplitude of the contingent negative variation (CNV), an ERP that reflects response preparation, and with reaction time. Some clinical populations such as patients with schizophrenia or attention-deficit disorder show specific deficits when performing the AX-CPT. These results provide a basis for investigating the differential neural underpinnings of oscillatory cognitive control deficits observed in various patient populations.

Planejamento estético na implantodontia: considerações anatômicas, cirúrgicas e protéticas / Aesthetic planning in implant dentistry: anatomical, surgical and prosthetic considerations

Na implantodontia moderna o conceito de restabelecer função sem maior preocupação com a estética está ultrapassado. O planejamento atual tem que devolver função e estética de forma previsível, e para isso, as variáveis biológicas e suas conseqüências nos tecidos perimplantares e periodontais devem ser conhecidas. O objetivo desse estudo é, através de uma revisão da literatura, apontar as condições anatômicas, cirúrgicas e protéticas adequadas para prever resultados estéticos no tratamento com implantes

In the modern implantology the concept of re-establish function without more concern with aesthetic is overshot. The present treatment planning has to restore function and aesthetic in the foreseeable way, and to do chat, the biological variables and their consequences in the periimplant and periodontal soft tissues must be know. The purpose of this paper is, through the literature review, point the anatomic, surgical and prosthetic appropriate conditions to foresee aesthetic results in the treatment with dental implants

Non-invasive diagnosis of acute rejection in kidney transplants with delayed graft function.

Delayed graft function (DGF) often occurs in kidney transplants from deceased donors. We wanted to provide studies giving more accurate non-invasive tests for acute rejection (AR). Using real-time PCR, we examined the expression of cytolytic molecules such as perforin, granzyme B, and fas-ligand along with serpin proteinase inhibitor-9. We also measured the expression of FOXP3, a characteristic gene of T-regulatory cells known to be involved in AR. These studies were conducted on peripheral blood monocytes, urinary cells, and 48 surveillance kidney biopsies taken from a total of 35 patients with DGF. Of these patients, 20 had a histopathological diagnosis of AR, whereas other 28 had characteristics of acute tubular necrosis (ATN). Expression of cytolytic and apoptotic-associated genes in the biopsy tissue, peripheral blood leukocytes, and urinary cells was significantly higher in patients with AR than that in patients with ATN. Diagnostic parameters associated with FOXP3 gene expression were most accurate in peripheral blood leukocytes and urine cells with sensitivity, specificity, positive and negative predictive values, and accuracy between 94 and 100%. Our study shows that quantification of selected genes in peripheral blood leukocytes and urinary cells from renal transplant patients with DGF may provide a useful and accurate non-invasive diagnosis of AR.

Evaluation of apoptosis in peripheral blood lymphocytes of renal transplant patients.

The aim of this study was to evaluate the occurrence of apoptosis and the expression of FasL and IL-2 genes in apoptotic peripheral blood mononuclear cells (PBMC) at different posttransplant periods. Three groups of patients were studied: group 1, kidney transplant recipients at least 1 year posttransplant (n = 17); group 2, kidney transplant recipients at least 5 years posttransplant (n = 15); and a control group composed of 7 healthy subjects. Apoptosis was detected by annexin flow cytometry and gene expression by reverse transcription polymerase chain reactions. The percentage of apoptotic cells was significantly higher in groups 1 (42 +/- 4%) and 2 (37 +/- 3%) than the controls (27 +/- 2%; P < .0001). Apoptotic cells in group 1 was significantly higher than in group 2 (P < .005). A significant difference in FasL expression was observed between groups 1 and 2 (P < .001) and the immunosuppressive regimen. These findings suggest that PBMC of kidney transplant recipients are more susceptible to activation-induced cell death and that the Fas-FasL pathway is involved in this process.

Prolactin and growth hormone secretion after thyrotrophin-releasing hormone infusion and dopaminergic (DA2) blockade in infertile patients with minimal/mild endometriosis.

BACKGROUND: The origin of infertility in patients with endometriosis without tubal occlusion has not yet been clearly defined. Several reports show an abnormal pituitary-ovarian axis in this group of patients. Moreover, prolactin (PRL) and growth hormone (GH) secretion is closely related to reproductive status. This study aimed to evaluate PRL and GH secretion after metoclopramide and thyrotrophin-releasing hormone (TRH) infusion in infertile patients with minimal/mild endometriosis. METHODS: A total of 64 women participated in the study: 33 fertile patients without endometriosis; 10 fertile patients with minimal/mild endometriosis; and 21 infertile patients with minimal/mild endometriosis. TRH or metoclopramide was administered randomly in two sequential menstrual cycles (cycle days 3-5). Serum PRL and GH secretion before and after dopaminergic type 2 (DA2) receptor blockade and TRH were compared. RESULTS: Higher serum PRL levels were observed in patients with endometriosis at baseline and after 15 and 30 min of TRH administration. Also, infertile patients with endometriosis had lower serum estradiol levels than fertile patients. Moreover, the dopaminergic blockade did not result in abnormal PRL or GH secretion. CONCLUSIONS: Decreased serum estradiol levels and altered PRL secretion after TRH administration in infertile patients with minimal/mild endometriosis are related to ovulatory dysfunction and infertility in this group of patients without tubal occlusion.

Growth hormone and prolactin secretion after metoclopramide administration (DA2 receptor blockade) in fertile women.

In this report, we will describe the results of a cross-sectional study to assess PRL and GH secretion during the early follicular phase in 22 fertile patients after metoclopramide administration in order to achieve a dopaminergic DA2 receptor blockade. Blood samples were collected at - 15, 0, 15, 30, 45 and 60 minutes. PRL, GH, estradiol, IGF-I, TSH, glucose, and insulin were measured in the samples taken at - 15 and 0 minutes. The existence of a correlation between GH and PRL secretion was investigated. All patients presented normal serum levels of estradiol, prolactin, insulin, fasting glucose and IGF-I. Serum GH levels were not changed after metoclopramide infusion (p = 0.302), but there was a significant alteration in serum PRL (p = 0.0001) with the highest levels after 30 (mean: 237.20 ng/ml +/- 95.86) and 45 (mean: 211.80 ng/ml +/- 83.24) minutes. Serum GH levels did not correlate with serum PRL levels after the dopaminergic DA2 blockade. We conclude that GH secretion was not modulated by a direct effect of type 2 dopamine receptor.

Covert visual spatial orienting and saccades: overlapping neural systems.

We used functional magnetic resonance imaging (fMRI) to investigate the functional anatomical relationship between covert orienting of visual spatial attention and execution of saccadic eye movements. Brain areas engaged by shifting spatial attention covertly and by moving the eyes repetitively toward visual targets were compared and contrasted directly within the same subjects. The two tasks activated highly overlapping neural systems and showed that common parietal and frontal regions are more activated during the covert task than the overt oculomotor condition. The possible nature of the relationship between these two operations is discussed.

Muscimol-induced inactivation of monkey frontal eye field: effects on visually and memory-guided saccades.

Muscimol-induced inactivation of the monkey frontal eye field: effects on visually and memory-guided saccades. Although neurophysiological, anatomic, and imaging evidence suggest that the frontal eye field (FEF) participates in the generation of eye movements, chronic lesions of the FEF in both humans and monkeys appear to cause only minor deficits in visually guided saccade generation. Stronger effects are observed when subjects are tested in tasks with more cognitive requirements. We tested oculomotor function after acutely inactivating regions of the FEF to minimize the effects of plasticity and reallocation of function after the loss of the FEF and gain more insight into the FEF contribution to the guidance of eye movements in the intact brain. Inactivation was induced by microinjecting muscimol directly into physiologically defined sites in the FEF of three monkeys. FEF inactivation severely impaired the monkeys' performance of both visually guided and memory-guided saccades. The monkeys initiated fewer saccades to the retinotopic representation of the inactivated FEF site than to any other location in the visual field. The saccades that were initiated had longer latencies, slower velocities, and larger targeting errors than controls. These effects were present both for visually guided and for memory-guided saccades, although the memory-guided saccades were more disrupted. Initially, the effects were restricted spatially, concentrating around the retinotopic representation at the center of the inactivated site, but, during the course of several hours, these effects spread to flanking representations. Predictability of target location and motivation of the monkey also affected saccadic performance. For memory-guided saccades, increases in the time during which the monkey had to remember the spatial location of a target resulted in further decreases in the accuracy of the saccades and in smaller peak velocities, suggesting a progressive loss of the capacity to maintain a representation of target location in relation to the fovea after FEF inactivation. In addition, the monkeys frequently made premature saccades to targets in the hemifield ipsilateral to the injection site when performing the memory task, indicating a deficit in the control of fixation that could be a consequence of an imbalance between ipsilateral and contralateral FEF activity after the injection. There was also a progressive loss of fixation accuracy, and the monkeys tended to restrict spontaneous visual scanning to the ipsilateral hemifield. These results emphasize the strong role of the FEF in the intact monkey in the generation of all voluntary saccadic eye movements, as well as in the control of fixation.

A pressure system for the microinjection of substances into the brain of awake monkeys.

We describe a method for placing pressure microinjections of drugs or anatomical tracers in physiologically defined sites in the brain of awake monkeys. This method provides a means to record neuronal activity from the tip of an injection cannula so that an injection can be made at a physiologically defined location. It uses pressure in a closed system to precisely control the amount of fluid injected and provides a visible means for monitoring injection volume. The injection cannula is easy to make with readily available components and can be used repeatedly for multiple recording sessions and injections.

The primate frontal eye field and the generation of saccadic eye movements: comparison of lesion and acute inactivation/activation studies.

The frontal eye field (FEF) of monkeys has been repeatedly implicated in the generation of saccadic eye movements by various experimental approaches. Electrical stimulation of most of the FEF produces saccadic eye movements, many cells have activities related to saccades, and it has anatomical connections with many other oculomotor areas. Surprisingly, complete lesions of the FEF have remarkably little effect on oculomotor behavior. Only when more cognitive aspects are tested is a deficit clearly detected. In contrast, acute inactivation of the FEF of monkeys with the GABA agonist muscimol produced much more severe oculomotor impairment. This difference is probably due to the acute nature of the muscimol effect, which does not allow time for reorganization of the control of eye movements before testing begins. In addition, acute activation of the FEF with the GABA antagonist bicuculline caused the monkey to make irrepressible saccades of the same dimensions as those electrically elicited at the site. These experiments further confirm the strong involvement of the FEF in the control of saccadic eye movements and fixation.

Acute activation and inactivation of macaque frontal eye field with GABA-related drugs.

1. This project tests the behavioral effects of reversible activation and inactivation of sites within the frontal eye field of rhesus monkeys with microinjections of the gamma-aminobutyric acid (GABA)-related drugs bicuculline and muscimol. 2. Muscimol injections impaired the monkeys' ability to make both visually and memory-guided saccades to targets at the center of the area represented by the injection site. The latencies of saccades to targets in regions flanking the injection were increased. For memory-guided saccades, saccades in the direction opposite to that represented by the injection site, were made with shorter latency than controls and often occurred before the movement cue. 3. Bicuculline injections produced irrepressible saccades equivalent to the saccade vector represented by the injection site, often in a staircase of several closely spaced movements. 4. Both substances decreased the accuracy of fixation of a central light. The distribution of points of fixation on different trials was diffuse, and the angle of gaze tended to deviate towards the side of the injection. 5. The results of these acute injections are similiar to those observed in the superior colliculus and are much more substantial than the effects observed in the long term after surgical removal of the frontal eye field. The results of this study promote a central role for the frontal eye field in the generation of all voluntary saccades and in the control of fixation.

Physiological correlate of fixation disengagement in the primate's frontal eye field.

1. We recorded from the frontal eye field (FEF) of rhesus monkeys while they performed the gap task in which the fixation point disappears 200 ms before the appearance of the peripheral saccadic target. This gap allows the disengagement of fixation to begin before the acquisition of saccade coordinates, thereby greatly reducing saccade latency ("gap effect"). Very short-latency saccades obtained in this gap task have been called "express saccades". 2. We studied 145 FEF neurons that had presaccadic activity on conventional saccade tasks. When tested in the gap task with a 200-ms gap, nearly half of these neurons (69) increased their discharge rate in response to the disappearance of the fixation target. We call this increase a fixation-disengagement discharge (FDD). The mean latency of the start of the FDD relative to the fixation light extinction was 149 +/- 36 (SD) ms. 3. Gap-task trials with the saccade target in the cell's response field were randomly intermixed with trials having the target opposite to the cell's field. The FDD was present in both cases: on trials into the response field, the FDD was followed by the cell's presaccadic burst. On trials opposite the cell's field, the FDD activity was suppressed prior to the saccade. 4. The FDD was most likely to be found in cells that had the movement type of presaccadic activity, i.e., movement cells and visuomovement cells. FDD was observed in 57% of visuomovement cells A, B, and C, 50% with movement activity, and 18% purely visual.(ABSTRACT TRUNCATED AT 250 WORDS)

[Development and current aspects of occupational health in Brazil]. / Evolução e aspectos atuais da saúde do trabalhador no Brasil.

The main objective of this study is to describe and analyze the health situation of workers in Brazil in the 1980s, as a process with technical, political, socioeconomic, and cultural dimensions. The main sources of data and information were: the Brazilian Institute of Geography and Statistics (IBGE), the National Institute of Social Security (INSS), and international agencies like the International Labor Office (ILO), the World Health Organization (WHO), and available specialized literature. The severity of the workers' patterns of morbidity and mortality emerges from this analysis, as well as the inadequacy of the public policies implemented by the State to deal with these issues and find efficient solutions. The study also points out the importance of the social process that occurred in this decade, with the participation of workers and health professionals, which was responsible for important achievements, particularly in the field of legislation. In conclusion, some issues and challenges for further improvement of the workers' quality of life, through the improvement of health and working conditions, are presented.

[From occupational medicine to workers' health]. / Da medicina do trabalho à saúde do trabalhador.

The evolution of the concepts and practice of occupational medicine, occupational health and workers' health is tentatively reviewed. An attempt is made to answer the following questions: what were the major characteristics of occupational medicine throughout its evolution? How and why did occupational medicine evolve into occupational health? Why has the "occupational health model" become inadequate? Within what context did workers' health arise? What are the principal characteristics of workers' health?

Disparity selective units in the superior colliculus of the opossum.

Binocular visual responses can be recorded in two regions of the superficial layers of the superior colliculus of the opossum. The direct binocular region (DBR) represents the binocular portion of the contralateral hemifield whereas the rostral pole (RP) represents the binocular portion of the ipsilateral hemifield. In the present study single units from both of these regions were tested with binocular and monocular stimulation. Most cells in both regions showed response facilitation when both eyes were simultaneously stimulated and, when tested with different binocular disparities, most cells showed broadly-tuned disparity selectivity. DBR units usually preferred disparities near zero whereas RP units had a wider range of preferred disparities, with a tendency toward positive (crossed) values. This data indicates that the superior colliculus of the opossum could provide a neural substrate for a coarse analysis of depth and also might help control vergence eye movements. The different ranges of disparity selectivity of DBR and RP are consistent with the previously reported monocular receptive-field data and suggest that DBR and RP analyze different depths of the 3-dimensional visual scene.