Cholesterol dysregulation in peripheral blood mononuclear cells of Alzheimer's disease.

Cholesterol and the immune system are involved in Alzheimer's Disease (AD). To investigate the relations among them, we compared the cholesterol content in peripheral blood mononuclear cells (PBMC) of cognitively healthy controls and patients with mild cognitive impairment (MCI) and AD in two independent samples. Free cholesterol content of PBMC was lower in MCI and AD patients, and was modulated by APOE genotype. A decrease of CD8+ and an increase of CD16+ was also found in AD patients. These results suggest that cholesterol levels in PBMCs may represent an early signature of the disease and support the involvement of immune system in AD.

Hybrid Composite-Metal Stack Drilling with Different Minimum Quantity Lubrication Levels.

Hybrid stack drilling is a very common operation used in the assembly of high-added-value components, which combines the use of composite materials and metallic alloys. This process entails the complexity of machining very dissimilar materials, simultaneously, on account of the interactions that are produced between them, during machining. This study analyzed the influence of Minimum Quantity Lubrication (MQL) on the performance of diamond-coated carbide tools when drilling Ti/carbon fiber reinforced plastics (CFRP)/Ti stacks. The main wear mechanism observed was diamond-coating detachment, followed by fragile breaks in the main cutting-edge. The tests done with the lower lubrication levels have shown an important adhesion of titanium (mainly on the secondary cutting-edge) and a higher friction between the tool and the workpiece, producing higher temperatures on the cutting region and a thermal softening effect on the workpiece. These phenomena affect the evolution of cutting power consumption with tool wear in the titanium layer. Regarding the quality of the test specimen, no significant differences were observed between the lubrication levels tested.

Impact of sleep loss before learning on cortical dynamics during memory retrieval.

Evidence shows that sleep loss before learning decreases activation of the hippocampus during encoding and promotes forgetting. But it remains to be determined which neural systems are functionally affected during memory retrieval after one night of recovery sleep. To investigate this issue, we evaluated memory for pairs of famous people's faces with the same or different profession (i.e., semantically congruent or incongruent faces) after one night of undisturbed sleep in subjects who either underwent 4hours of acute sleep restriction (ASR, N=20) or who slept 8hours the pre-training night (controls, N=20). EEG recordings were collected during the recognition memory task in both groups, and the cortical sources generating this activity localized by applying a spatial beamforming filter in the frequency domain. Even though sleep restriction did not affect accuracy of memory performance, controls showed a much larger decrease of alpha power relative to a baseline period when compared to sleep-deprived subjects. These group differences affected a widespread frontotemporoparietal network involved in retrieval of episodic/semantic memories. Regression analyses further revealed that associative memory in the ASR group was negatively correlated with alpha power in the occipital regions, whereas the benefit of congruency in the same group was positively correlated with delta power in the left lateral prefrontal cortex. Retrieval-related decreases of alpha power have been associated with the reactivation of material-specific memory representations, whereas increases of delta power have been related to inhibition of interferences that may affect the performance of the task. We can therefore draw the conclusion that a few hours of sleep loss in the pre-training night, though insufficient to change the memory performance, is sufficient to alter the processes involved in retrieving and manipulating episodic and semantic information.

Progressive reduction of sleep time and quality in rats with hepatic encephalopathy caused by portacaval shunts.

Patients with liver cirrhosis show sleep disturbances. Insight into their relationship with hepatic encephalopathy (HE) can be obtained using animal models of HE. The aims of this work were to assess (1) whether rats with portacaval shunts (PCS), a model of HE, show alterations in sleep and if they are similar to those in patients with HE; (2) Whether hyperammonemia plays a role in these sleep alterations; and (3) the time course of sleep alterations in these animal models. Rats were subjected to PCS to induce HE. Another group of rats was fed an ammonium-containing diet to induce hyperammonemia. Polysomnographic recordings were acquired for 24 h and sleep architecture was analyzed in control, PCS, and hyperammonemic rats at 4, 7, and 11 weeks after surgery or diet, respectively. PCS rats show a significant reduction in rapid eye movement (REM) and non-rapid eye movement (NREM) sleep time and increased sleep fragmentation, whereas reduced sleep occurs at 4 weeks and worsens at 7 and 11 weeks, sleep fragmentation appears at 7 weeks and worsens at 11 weeks. Hyperammonemic rats show decreased REM sleep, starting at 7 weeks and worsening at 11 weeks, with no changes in NREM sleep or sleep fragmentation. Therefore, PCS rats are a good model to study sleep alterations in HE, their mechanisms, and potential treatment. Mild hyperammonemia mainly impacts mechanisms involved in REM generation and/or maintenance but does not seem to be involved in sleep fragmentation.

Associative memory deficits in mild cognitive impairment: the role of hippocampal formation.

Neuropathological events featuring early stages of Alzheimer's disease (AD) appear in the entorhinal cortex (EC), subiculum (SB) and cornu ammonis 1 (CA1) of hippocampus, which may account for associative memory deficits in non-demented people with mild cognitive impairment (MCI). To test this hypothesis in vivo, we investigated whether volume changes in these regions are related to failures in associative memory in MCI as compared to cognitively normal (CN) elderly subjects. Volume changes in EC and hippocampal subfields were determined by using deformation-based morphometry techniques applied to probabilistic cytoarchitectonic maps derived from post mortem human brains. CN subjects were distinguished from MCI patients by firstly identifying local volume differences in EC and hippocampus, and then evaluating the way in which these anatomical changes correlated with performance in a non-intentional face-location association task. MCI patients not only performed worse than CN elders in building new associations, but they were further unable to benefit from semantic encoding to improve episodic binding. According to our initial hypothesis, local volume reductions in both EC and hippocampal CA accounted for group differences in associative memory whereas atrophy in CA, but not in EC, accounted for semantic encoding of associations. Two main conclusions can be drawn from the present study: i) access to semantic information during encoding does not reduce the episodic deficit in MCI; and ii) EC and hippocampal CA, two regions early affected by AD neuropathology, are responsible, at least partially, for associative memory deficits observed in MCI patients.

Functional neural networks underlying semantic encoding of associative memories.

Evidence suggests that theta oscillations recruit distributed cortical representations to improve associative encoding under semantically congruent conditions. Here we show that positive effects of semantic context on encoding and retrieval of associations are mediated by changes in the coupling pattern between EEG theta sources. During successful encoding of semantically congruent face-location associations, the right superior parietal lobe showed enhanced theta phase synchronization with other regions within the lateral posterior parietal lobe (PPL) and left medial temporal lobe (MTL). However, functional coordination involving the inferior parietal lobe was higher in the incongruent condition. These results suggest a differential engagement of top-down and bottom-up mechanisms during encoding of semantically congruent and incongruent episodic associations, respectively. Although retrieval processes operated on a similar neural network, the main difference with the study phase was the larger amount of functional links shown by the lateral prefrontal cortex with regions of the MTL and PPL. All together, these results suggest that theta oscillations mediate, at least partially, the positive effect of semantic congruence on associative memory by (i) optimizing top-down attentional mechanisms through enhanced theta phase synchronization between dorsal regions of the PPL and MTL and (ii) by adjusting the control of automatic attention to sensory and contextual information reactivated in the MTL through functional connections with the inferior parietal lobe during both encoding and retrieval processes.

Precise timing accounts for posttraining sleep-dependent enhancements of the auditory mismatch negativity.

Memory consolidation is a long-lasting dynamic process by which new acquired information is transformed at different analysis levels, from molecules to cognition, without additional practice. Results from a previous study on event-related potentials (ERPs) suggest that part of the neural events promoting changes in the electrophysiological correlates of enhanced automatization in a sound discrimination task occur during sleep. These data were reanalyzed in the present study at the single-trial level, and results indicated that the first night of sleep succeeding training is absolutely required to improve the timing consistency of cortical neural assemblies involved in automatic sound-change detection, as revealed by a significant reduction in the latency-jitter of the MMN response across trials. This change in the regularity of the brain response to previously trained sounds facilitated involuntary switch of attention towards the same sounds when they were task irrelevant, as reflected by the P3a emergence after posttraining sleep. Both responses were, however, prevented in subjects deprived of sleep the night following training in the sound discrimination task. We hypothesize that the reduction in the MMN latency-jitter, which, in turn, triggered an automatic shift of attention, might result from a change in synaptic efficacy and/or neural excitability, rather than from changes in firing synchronization and/or size of representation.

Recurrence pattern of esophageal cancer after esophagectomy with two-field lymphadenectomy.

AIM: To analyze the pattern of recurrence of esophageal carcinoma after a curative-intention surgical resection. PATIENTS: Ninety-two patients with non-metastatic esophageal carcinoma were included. Ninety percent of patients were male, and the mean age of this series was 61 years. The most frequent histologic subtype was squamous cell carcinoma. Fifty percent of tumors were at or above the tracheal bifurcation. All patients were submitted for transthoracic subtotal esophagectomy plus two-field radical lymphadenectomy, leaving no apparent residual disease. No adjuvant therapy was applied to any patient. RESULTS: Follow-up was complete for 76 out of 80 patients surviving the operation. Thirty-four tumoral recurrences were detected for a disease-free survival af 39% at 9 years after surgery. All recurrences were detected during the first two years after treatment. Tumoral relapse was related to the presence of T3 or T4 tumors, with positive lymph nodes, squamous cell carcinoma subtype and supracarinal location. Nine percent of patients had a distant relapse, 15% had a locorregional relapse and 12% a combination of both. Distant relapse presented significantly earlier. There was no statistical association between type of recurrence and clinico-pathological or surgical features. CONCLUSIONS: After radical surgery for carcinoma of the esophagus, half of the patients relapse in the following two years. Distant metastases happen to appear earlier in the follow-up, but the most frequent recurrence is the locorregional one.

Penetrating chest gunshot wounds: conservative treatment.

Gunshot wounds, and in particular chest gunshot wounds, are becoming a growing problem in daily practice at many hospitals. Many authors propose a conservative attitude in certain cases. We present a patient with a chest gunshot wound successfully solved under conservative means and videothoracoscopic removal of the bullet.

Sensory and motor attentional modulation during the manual gap effect in humans: a high-density ERP study.

The present study investigated reaction time (RT) and event-related potential (ERP) differences between gap and step conditions using visual stimulation and manual responses. RTs during the gap condition were facilitated with respect to those of the step condition. The ERPs, which were obtained from electrodes placed at 58 scalp sites, showed differences when the gap and step conditions were compared for the following components: an early positive component centred at the vertex, an enhanced P1 component, a frontal negativity, a negative lateralized motor potential, and an increased P3. All these results suggest that the facilitation induced by the gap is mediated by a modulation of the neural circuits involved in sensory, motor, and cognitive functions.

Protective effect of vagotomy on the gastric mucosa in a stress model in rats.

INTRODUCTION: The use of vagotomy is classically based on its inhibiting effects on acid secretion. Vagotomy induces both cellular and endocrine changes that may be involved in protective actions. Our aim was to study morphologic changes induced by vagotomy on the gastric mucosa and their relation to stress protection in the short, medium and long term. MATERIAL AND METHODS: An immobilization and cold stress model was used with 80 Wistar rats divided into two groups--control (with and without stress) and vagotomy (at 7, 30 and 120 days). Changes induced in the gastric mucosa by stress were studied with and without vagotomy, as well as relationship between these changes and the intended protective action. RESULTS: Bleeding showed a very significant relation to stress (p < 0.0001). Bleeding incidence exhibited a significant difference between vagotomised and non-vagotomised rats (p < 0.0001) in the short, medium and long term (vagotomy was protective against stress). Regeneration signs related significantly to vagotomy (p < 0.0001) but not stress (p = 0.208). However, no significant relationship was found between the protective action and the presence of regeneration signs (p = 1). CONCLUSIONS: Vagotomy has tropic effects on the gastric mucosa and is protective against stress. This protective action is maintained in the short, medium and long term. However, these changes are not sufficient to explain protection. An adaptation phenomenon mediated by hormonal and peptidic factors may be involved in this action.

Auditory information processing during human sleep as revealed by event-related brain potentials.

The main goal of this review is to elucidate up to what extent pre-attentive auditory information processing is affected during human sleep. Evidence from event-related brain potential (ERP) studies indicates that auditory information processing is selectively affected, even at early phases, across the different stages of sleep-wakefulness continuum. According to these studies, 3 main conclusions are drawn: (1) the sleeping brain is able to automatically detect stimulus occurrence and trigger an orienting response towards that stimulus if its degree of novelty is large; (2) auditory stimuli are represented in the auditory system and maintained for a period of time in sensory memory, making the automatic-change detection during sleep possible; and (3) there are specific brain mechanisms (sleep-specific ERP components associated with the presence of vertex waves and K-complexes) by which information processing can be improved during non-rapid eye movement sleep. However, the remarkably affected amplitude and latency of the waking-ERPs during the different stages of sleep suggests deficits in the building and maintenance of a neural representation of the stimulus as well as in the process by which neural events lead to an orienting response toward such a stimulus. The deactivation of areas in the dorsolateral pre-frontal cortex during sleep contributing to the generation of these ERP components is hypothesized to be one of the main causes for the attenuated amplitude of these ERPs during human sleep.

Complex sound processing during human REM sleep by recovering information from long-term memory as revealed by the mismatch negativity (MMN).

Perceptual learning is thought to be the result of neural changes that take place over a period of several hours or days, allowing information to be transferred to long-term memory. Evidence suggests that contents of long-term memory may improve attentive and pre-attentive sensory processing. Therefore, it is plausible to hypothesize that learning-induced neural changes that develop during wakefulness could improve automatic information processing during human REM sleep. The MMN, an objective measure of the automatic change detection in auditory cortex, was used to evaluate long-term learning effects on pre-attentive processing during wakefulness and REM sleep. When subjects learned to discriminate two complex auditory patterns in wakefulness, an increase in the MMN was obtained in both wake and REM states. The automatic detection of the infrequent complex auditory pattern may therefore be improved in both brain states by reactivating information from long-term memory. These findings suggest that long-term learning-related neural changes are accessible during REM sleep as well.

The initial orienting response during human REM sleep as revealed by the N1 component of auditory event-related potentials.

The large N1 wave of the auditory event-related potentials (ERPs) typically occurring to the first stimulus after a long silent interval seems to be associated with the involuntary initial-orienting response. Since the mechanisms involved in the generation of this brain response are assumed to be activated automatically, the present study aims at determining whether this electrophysiological response can also be elicited during human REM sleep, the sleep stage considered most sensitive to external stimuli. To achieve this goal, the auditory N1 wave was analyzed in wakefulness and REM sleep for frequency deviant tones delivered in several positions (1, 2, 4 and 6) within homogenous stimulus trains separated by different intervals of silence (3, 6 and 9 s), the intra-train stimulus interval being 600 ms. A significant increment in the amplitude of the N1 component for the first deviant tone, as compared with deviants delivered in remaining positions, was observed in both brain states, independently of the inter-train interval length. This result cannot be explained by a release-from-refractoriness effect, since only one deviant was presented in each train and the inter-deviant interval hardly changed from one train to another. The increase in N1 to the first stimulus of the train, probably due to the contribution of the neuronal elements responsible for the supratemporal and non-specific components, may be explained by changes in the silent interval, rather than by variations in the stimulus frequency. The enhanced N1 could be reflecting a general increase in sensory sensitivity associated with the arousal factor of the orienting response. These findings suggest that the brain maintains the potential ability to trigger the brain events responsible for the OR elicitation, even during REM sleep.

Colonic carcinogenesis in vagotomyzed rats.

INTRODUCTION: An increased incidence of colorectal cancer (CRC) has been reported in patients with peptic ulcer disease treated with truncal vagotomy. Inhibition of gastric acid output and its hormonal consequence, hypergastrinemia, have been considered risk factors for the development of CRC. The aim of the present study was to determine whether truncal vagotomy increases, in the short (7 days) and long term (120 days), the incidence of CRC in a model of carcinogenesis. MATERIAL AND METHOD: We used 86 Wistar rats distributed in 7 groups to which DMH (1,2-dimethylhydrazine dihydrochloride) was administered for the induction of colon tumors, at doses of 5 and 20 mg/kg of weight. The first three groups were used as control groups; the rats of the four other groups underwent a truncal vagotomy with pyloroplasty and Heller myotomy prior to the administration of DMH. Finally, we compared the incidence of colonic tumors in vagotomized vs non-vagotomized groups receiving the same dose of DMH. RESULTS: In the non-vagotomized rats that received low doses of DMH (5 mg/kg of weight), mortality was 0% and 0% developed cancer as compared to 40% and 0%, respectively, of rats vagotomized 7 days before the administration of DMH and 20% and 0%, respectively, of rats vagotomized 120 days before the administration of DMH. After the administration of high doses of DMH, mortality was 50% and 80% developed cancer as compared to 100% and 0%, respectively, of rats vagotomized 7 days before the administration of DMH and 61.11% and 42.8%, respectively, of rats vagotomized 120 days before the administration of DMH. CONCLUSION: Truncal vagotomy does not increase the incidence of CRC induced by DMH in the rat.

[Clinical value of EEG coherence as electrophysiological index of cortico-cortical connections during sleep]. / Valor clínico de la coherencia EEG como índice electrofisiológico de conectividad córtico-cortical durante el sueño.

OBJECTIVE: The technique of EEG coherence gives a non-invasive objective index of the functional relations between the different regions of the cerebral cortex. The main objectives of this study were firstly to obtain methodological information to facilitate its use in any context, whether clinical or in investigation, and secondly to draw attention to the results obtained with this technique during the different phases of sleep, both in healthy persons and in certain clinical conditions where its use in evaluation and/or diagnosis has been shown. DEVELOPMENT: The results derived from the application of coherence analysis during normal sleep show the existence of a high level of interhemisphere connectivity during all phases of sleep. This result has fomented its use in the evaluation and diagnosis of disorders in which it is suspected that there are anomalies in the relation between the two hemispheres, such as neurological changes (agenesis of the corpus callosum, AIDS), psychiatric disorders (depression) and in the prognosis of states of coma. Also, progressive neurone degeneration and neurochemical deficits characteristic of Alzheimer-type dementia suggest that the coherence EEG during the REM phase may give electrophysiological indices in the establishment of the diagnosis and prognosis of the disorder. CONCLUSION: This study shows that the coherence technique is a useful tool when establishing the pattern of cortico-cortical interactions subjacent to different functional states of the brain, both in healthy persons and in those with the different diseases in which there are alterations in cerebral function.

Spectral features of EEG alpha activity in human REM sleep: two variants with different functional roles?

Evidence suggests that an important contribution of spectral power in the alpha range is characteristic of human REM sleep. This contribution is, in part, due to the appearance of well-defined bursts of alpha activity not associated with arousals during both tonic and phasic REM fragments. The present study aims at determining if the REM-alpha bursts constitute a different alpha variant from the REM background alpha activity. Since previous findings showed a selective suppression of background alpha activity over occipital regions during phasic REM fragments and, on the other hand, the density of alpha bursts seem to be independent of the presence or absence of rapid eye movements, one expects to find the same spectral power contribution of alpha bursts in tonic and phasic REM fragments. The results indicated that REM-alpha bursts showed a similar power contribution and topographic distribution (maximum energy over occipital regions) both in tonic and phasic REM fragments. This suggests that two variants of alpha activity with different functional roles are present during the human REM sleep: i) background alpha activity, modulated over occipital regions by the presence of rapid eye movements, which may be an electrophysiological correlate of the visual dream contents; and ii) REM-alpha bursts, independent of the presence of rapid eye movements, which could be facilitating the connection between the dreaming brain and the external world, working as a micro-arousal in this brain state.

Decay time of the auditory sensory memory trace during wakefulness and REM sleep.

In a repetitive auditory stimulus sequence, deviant infrequent tones typically elicit a component of auditory event-related potentials termed mismatch negativity (MMN). The elicitation of MMN is assumed to reflect the existence of a memory trace of the standard stimulus that has a decay time of about 10 s and is strengthened by repetition of the standards. The main aim of the present study was to test the decay time of the sensory memory trace during rapid-eye movement (REM) sleep vs. wakefulness, as indexed by the MMN. Subjects were presented 10 tone trains, separated by 3, 6, or 9 s of silence, during waking and REM sleep. Each train consisted of 9 standards of 1000 Hz and 1 deviant of 2000 Hz that occurred at position 1, 2, 4, or 6. The waking deviants elicited a frontocentral negativity with a scalp topography equivalent to the MMN component. During REM sleep, the negative component showed the same scalp distribution only for the 3-s intertrain interval (ITI). In this brain state, the MMN amplitude was smaller and decreased with prolongation of the ITI. These results suggest a weaker sensory memory trace formation and a premature decay time of such a memory trace during REM sleep as compared with wakefulness.

Prognostic influence of p53 nuclear overexpression in colorectal carcinoma.

PURPOSE: The aim of this study was to test the prognostic influence of p53 nuclear overexpression in colorectal carcinoma. METHODS: We performed an analysis of the prognostic influence of the nuclear overexpression of p53 with immunohistochemistry in 126 cases of colorectal carcinoma operated on in our hospital between 1987 and 1992, with a minimum follow-up time of 60 months (5 years). RESULTS: Our results show a statistically significant prognostic influence of p53 overexpression on disease-free survival time, but not on the overall survival time, in univariate analysis, but this influence is lost in multivariate analysis. CONCLUSIONS: Our results confirm recent reports by other authors that failed to show the independent prognostic value of p53 in colorectal carcinoma.