Synchrotron-Based Fourier Transform Infrared Microspectroscopy (µFTIR) Study on the Effect of Alzheimer's Aß Amorphous and Fibrillar Aggregates on PC12 Cells.

Amyloid plaques made of aggregated Aß amyloid peptide are a pathological hallmark in brains affected by Alzheimer's disease (AD). Moreover, the amyloid peptide may play a major role in the onset and development of the disease in association to other factors such as oxidative stress. Although the molecular nature of the amyloid toxic species is still unknown, there is experimental evidence pointing to their nonfibrillar nature. In the present paper, we report the use of synchrotron Fourier transform infrared microspectroscopy (µFTIR) for the study of the effect of two different types of Alzheimer's Aß(1-40) aggregates (amyloid fibrils and granular nonfibrillar aggregates) on PC12 cultured cells. The principal component analysis (PCA) of the infrared spectra has been complemented with a correlation analysis, which permits one to study different spectroscopic parameters as a function of peptide aggregation. The results show that the treatment of PC12 cells with amorphous aggregates generates a higher degree of oxidation in the vicinity of the amyloid aggregates than the treatment with preformed amyloid fibrils. These results, which permit, for the first time, the in situ colocalization of amyloid aggregates and oxidized macromolecules in cell culture, are in agreement with previous data from our group, showing that oxidation was higher in regions surrounding amyloid plaques in human brain samples affected by AD.

Mobilization of arsenic and other trace elements of health concern in groundwater from the Salí River Basin, Tucumán Province, Argentina.

The Salí River Basin in north-west Argentina (7,000 km(2)) is composed of a sequence of Tertiary and Quaternary loess deposits, which have been substantially reworked by fluvial and aeolian processes. As with other areas of the Chaco-Pampean Plain, groundwater in the basin suffers a range of chemical quality problems, including arsenic (concentrations in the range of 12.2-1,660 µg L(-1)), fluoride (50-8,740 µg L(-1)), boron (34.0-9,550 µg L(-1)), vanadium (30.7-300 µg L(-1)) and uranium (0.03-125 µg L(-1)). Shallow groundwater (depths up to 15 m) has particularly high concentrations of these elements. Exceedances above WHO (2011) guideline values are 100% for As, 35% for B, 21% for U and 17% for F. Concentrations in deep (>200 m) and artesian groundwater in the basin are also often high, though less extreme than at shallow depths. The waters are oxidizing, with often high bicarbonate concentrations (50.0-1,260 mg L(-1)) and pH (6.28-9.24). The ultimate sources of these trace elements are the volcanic components of the loess deposits, although sorption reactions involving secondary Al and Fe oxides also regulate the distribution and mobility of trace elements in the aquifers. In addition, concentrations of chromium lie in range of 79.4-232 µg L(-1) in shallow groundwater, 129-250 µg L(-1) in deep groundwater and 110-218 µg L(-1) in artesian groundwater. All exceed the WHO guideline value of 50 µg L(-1). Their origin is likely to be predominantly geogenic, present as chromate in the ambient oxic and alkaline aquifer conditions.

Sources and controls for the mobility of arsenic in oxidizing groundwaters from loess-type sediments in arid/semi-arid dry climates - evidence from the Chaco-Pampean plain (Argentina).

In oxidizing aquifers, arsenic (As) mobilization from sediments into groundwater is controlled by pH-dependent As desorption from and dissolution of mineral phases. If climate is dry, then the process of evaporative concentration contributes further to the total concentration of dissolved As. In this paper the principal As mobility controls under these conditions have been demonstrated for Salí River alluvial basin in NW Argentina (Tucumán Province; 7000 km(2)), which is representative for other basins or areas of the predominantly semi-arid Chaco-Pampean plain (1,000,000 km(2)) which is one of the world's largest regions affected by high As concentrations in groundwater. Detailed hydrogeochemical studies have been performed in the Salí River basin where 85 groundwater samples from shallow aquifers (42 samples), deep samples (26 samples) and artesian aquifers (17 samples) have been collected. Arsenic concentrations range from 11.4 to 1660 µg L(-1) leaving 100% of the investigated waters above the provisional WHO guideline value of 10 µg L(-1). A strong positive correlation among As, F, and V in shallow groundwaters was found. The correlations among those trace elements and U, B and Mo have less significance. High pH (up to 9.2) and high bicarbonate (HCO(3)) concentrations favour leaching from pyroclastic materials, including volcanic glass which is present to 20-25% in the loess-type aquifer sediments and yield higher trace element concentrations in groundwater from shallow aquifers compared to deep and artesian aquifers. The significant increase in minor and trace element concentrations and salinity in shallow aquifers is related to strong evaporation under semi-arid climatic conditions. Sorption of As and associated minor and trace elements (F, U, B, Mo and V) onto the surface of Fe-, Al- and Mn-oxides and oxi-hydroxides, restricts the mobilization of these elements into groundwater. Nevertheless, this does not hold in the case of the shallow unconfined groundwaters with high pH and high concentrations of potential competitors for adsorption sites (HCO(3), V, P, etc.). Under these geochemical conditions, desorption of the above mentioned anions and oxyanions occurs as a key process for As mobilization, resulting in an increase of minor and trace element concentrations. These geochemical processes that control the concentrations of dissolved As and other trace elements and which determine the groundwater quality especially in the shallow aquifers, are comparable to other areas with high As concentrations in groundwater of oxidizing aquifers and semi-arid or arid climate, which are found in many parts of the world, such as the western sectors of the USA, Mexico, northern Chile, Turkey, Mongolia, central and northern China, and central and northwestern Argentina.

Sequential analysis of fMRI images: A new approach to study human epileptic networks.

PURPOSE: The aim of this study was to introduce a new approach for analysis of functional magnetic resonance imaging (fMRI) data in order to illustrate the temporal development of the blood oxygenation level-dependent (BOLD) signal changes induced by epileptic seizures. METHOD: In order to sequentially analyze the fMRI images acquired during epileptic seizures, a continuous series of echo planar imaging (EPI) scans covering the complete period of a seizure was acquired. Data were segmented into 10-s blocks. Each block, representing a unique experimental condition, was contrasted with a neutral (no seizure) baseline condition. Visual comparison of the activations from one block to the next highlighted the course of activations and deactivations during the seizure event. This analysis was applied to three independent seizures of one patient with peri-rolandic epilepsy secondary to chronic encephalitis: one seizure before epilepsy surgery and two after unsuccessful tailored resection. Observations were compared to results from invasive subdural electroencephalography (EEG) monitoring, single-photon emission computed tomography (SPECT) coregistered to MRI (SISCOM), and independent component analysis (ICA), a model-free method of BOLD-signal analysis. RESULTS: The initial increase in BOLD signal occurred 10-40 s before clinical onset in the same location compared to the seizure-onset zone determined by invasive subdural evaluation and SISCOM. Sequential involvement of cortical and subcortical structures was in agreement with SISCOM, intracranial EEG recordings, and ICA results. DISCUSSION: In selected patients, sequential analysis of changes in BOLD signal induced by epileptic seizures might represent a useful approach for investigating the temporal development of brain activity during epileptic seizures, thereby allowing imaging of those cerebral structures involved in seizure generation and propagation.

Identifying the structures involved in seizure generation using sequential analysis of ictal-fMRI data.

UNLABELLED: The aim of this study was to investigate if sequential analysis of BOLD signal changes induced by seizures is useful for preoperative identification of the site of seizure onset in patients with pharmaco-resistant focal epilepsy. METHOD: We analyzed BOLD raw data from 5 patients with focal medically refractory epilepsy who experienced partial seizures during fMRI as part of a preoperative evaluation. To sequence the changes in BOLD signal seizure-induced, each seizure epoch was divided into groups of five consecutive images (ten-second blocks). t-maps were calculated continuously from 120 s before the onset of clinical/EEG seizure onwards by comparing two consecutive groups of five images. Time lag between each comparison was 2 s. Relative changes in BOLD signal between two consecutive groups of five images along the seizure epoch were determined. Results were compared with those of subtraction ictal SPECT coregistered with MRI (SISCOM) and intracranial EEG (2 patients). RESULTS: A typical seizure was registered in each patient. After sequential analysis, a well-localized and statistically significant (t: 7-14) area of signal increase was consistently found at seizure initiation in each patient. This area invariably preceded the onset of clinical/electrical seizure by several seconds (6-52 s); was concordant with SISCOM results in all but one patient; and overlapped with the ictal onset zone determined by intracranial EEG in those 2 patients who underwent invasive-EEG recordings. Complete resection of this initial area of signal increase resulted in seizure remission. Three out of four patients who underwent epilepsy surgery remained seizure-free. CONCLUSION: Sequential analysis of ictal-fMRI data may be useful to precisely and non-invasively delineate the ictal onset zone within the brain; and provide insights into the cerebral substrates involved in the generation and propagation of seizures.

A voxel-based diffusion tensor imaging study of temporal white matter in patients with schizophrenia.

Diffusion tensor imaging (DTI) is a relatively new technique used to detect changes in the anisotropic diffusion of white matter. The study of the disruption of brain connectivity may increase our understanding of cognitive deficits associated with schizophrenia. Here we analysed DTI data in 25 patients with DSM-IV schizophrenia and 24 healthy controls. Two complementary measures, fractional anisotropy (FA) and the apparent diffusion coefficient (ADC), were considered and analysed using voxel-based morphometry. Declarative memory functions were also investigated and their associations with DTI data were analysed. FA was significantly reduced, and the ADC increased in the left sub-gyral white matter of the temporal lobe, which involves the posterior part of the fornix. In the schizophrenic group, females had lower FA than males in the genu of the corpus callosum. Memory functions correlate with FA values. These data provide further evidence for the disruption of white matter connectivity in the left medial temporal lobe, and for its contribution to the declarative memory deficit in schizophrenia.

Cerebellar deficits in schizophrenia are associated with executive dysfunction.

Cerebellar abnormalities have been documented in schizophrenia in postmortem, functional and volumetric neuroimaging studies. This study aims to establish the relationship between structural changes in the cerebellum and executive dysfunction in patients with schizophrenia using voxel-based morphometry. We compared 28 outpatients with 28 healthy controls. A widely used executive battery and the voxel-based morphometry approach were used to investigate possible structural cerebellum changes on magnetic resonance imaging. Working memory dysfunctions in schizophrenia correlated with grey matter in both cerebellar hemispheres and vermis. Mental flexibility dysfunctions also correlated with reductions in white matter volume in bilateral cerebellum. This evidence supports the contribution of cerebellar grey and white matter deficits to executive dysfunctions observed in schizophrenia.

Brain response to complex visual stimuli in Parkinson's patients with hallucinations: a functional magnetic resonance imaging study.

Visual hallucinations (VH) in Parkinson's disease (PD) have been associated with gray matter reductions in visual associative areas and with abnormal patterns of brain activation in posterior and frontal regions. However, all previous fMRI studies have used simple visual stimuli. The objective of our study was, therefore, to compare the pattern of brain activation during a one-back face detection task. We examined 10 PD patients with VH, 10 PD patients without VH, and 10 controls matched for age and education. The fMRI task consisted in three blocks of 21-face stimuli (activation condition) and three blocks of 21-colored mosaics (control condition). Subjects were asked to press a key when two identical stimuli were presented consecutively. During the face condition, compared with patients without VH, hallucinating PD patients showed significant reductions in the activation of several right prefrontal areas, such as the inferior (BA 10,47), superior (BA 6/8), middle frontal (BA 8), and anterior cingulate gyrus (BA 31/32). In the control condition, we found a hyperactivation in the hallucinating PD sample compared with the nonVH patients in the right inferior frontal gyrus. A dysfunction of the frontal areas associated with the control of attention could predispose to VH through an abnormal processing of relevant and irrelevant visual stimuli.

Oroalimentary automatisms induced by electrical stimulation of the fronto-opercular cortex in a patient without automotor seizures.

Despite being a common sign in focal epilepsies, the exact symptomatogenic zone for oroalimentary automatisms remains largely unknown. We describe a patient with refractory complex partial seizures secondary to a right temporoparietal malformation of cortical development who underwent prolonged video/EEG monitoring with subdural electrodes. During his typical seizures, the patient manifested decreased awareness but never automatisms. However, during electrical cortical stimulation of two electrodes located over the right inferior frontal gyrus, oroalimentary automatisms with preserved consciousness were elicited, with no afterdischarges detected in the adjacent electrodes. These two electrodes were distant from the seizure onset zone and were not involved in seizure propagation. This case provides evidence that fronto-opercular cortex may be involved in the generation of oroalimentary automatisms.

Activation patterns of the primary auditory cortex in normal-hearing subjects: a functional magnetic resonance imaging study.

CONCLUSIONS: These results demonstrate that functional magnetic resonance imaging (fMRI) is an optimal tool to investigate the auditory cortex. The study suggests that there is a medio-lateral gradient of responsiveness to high frequencies medially and low frequencies laterally. The contralateral auditory cortex is more responsive than the ipsilateral cortex to tones presented monaurally. OBJECTIVES: To demonstrate the activation of the primary auditory cortex in normal-hearing subjects using fMRI and to examine the response and topographic location of activation in the human auditory brain to stimulation with two different frequencies in a large group of volunteers. SUBJECTS AND METHODS: Scanning was performed on a 1.5 Tesla MR with head gradient coils and a birdcage radiofrequency coil. Multiplanar echo-planar images were acquired in 32 subjects aged between 18 and 49 years. Two groups were defined, according to age (group A, 18 to <35 years old; group B, 35 to <50 years old). We studied normal-hearing subjects scanned while listening to auditory stimuli: narrative text in one volunteer and non-speech noise (pure tones 750 Hz and pure tones 2 KHz) in all subjects. RESULTS: For both tone frequencies, auditory activation was observed bilaterally across the supratemporal plane in 29 of the 32 subjects (90.62%) with a probability level of p<0.001. In Heschl's gyrus (HG) contralateral to the stimulated ear, the extent of activation was generally greater than in homolateral HG. There were no statistical differences in HG activation according to age or sex. The 750 Hz tone activated more voxels in the medial area of the transverse temporal gyrus (TTG) whereas the 2000 Hz tone activated more voxels in the lateral TTG.

Brote de leptospirosis humana en la provincia Guantánamo / Outbreak of human leptospirosis in Guantánamo province

Se realizó una caracterización de la epidemia ocurrida en la provincia Guantßnamo durante los meses de octubre y noviembre de 2005, así como de las actividades desarrolladas para su control. Se comprobó que existían factores propicios para su desarrollo, esto trajo consigo que a partir de la semana estadística 42 se notificara un alza en el número de atenciones médicas con cuadros clínicos y elementos epidemiológicos. Se notificaron un total de 885 casos sospechosos, 61 fueron confirmados microbiológicamente para una positividad de 6,9 por ciento. Los municipios con mayor riesgo fueron Niceto Pérez, la ciudad de Guantßnamo y Manuel Tames. Se llevaron a cabo de forma inmediata una serie de actividades con el apoyo multisectorial e interdisciplinario de distintas organizaciones, que permitieron controlar la situación en un lapso menor de un mes. El estudio de este brote demostró que la leptospirosis continúa siendo un problema de salud en Cuba y que para su control se necesitan unificar esfuerzos y recursos.

A characterization of the epidemic occurred in Guantßnamo province during October and November 2005, and as well as of the activities developed for its control was made. The existence of favourable factors was confirmed, and as a result from the 42nd statistical week on there was an increase in the number of medical attentions with clinical pictures and epidemiologic elements. 885 suspected cases were notified, 61 were microbiologically confirmed, accounting for a positivity of 6.9 percent. The municipalities with the highest risk were Niceto Pérez, Guantßnamo city, and Manuel Tames. Some activities were immediately carried out, with the multisectorial and interdisciplinary support from different organizations, allowing the control of the situation in less than a month. The study of this outbreak showed that leptospirosis is still a health problem in Cuba, and that it is necessary to join efforts and resources to control it.

[Outbreak of human leptospirosis in Guantánamo Province]. / Brote de leptospirosis humana en la Provincia Guantánamo.

A characterization of the epidemic occurred in Guantánamo province during October and November 2005, and as well as of the activities developed for its control was made. The existence of favourable factors was confirmed, and as a result from the 42nd statistical week on there was an increase in the number of medical attentions with clinical pictures and epidemiologic elements. 885 suspected cases were notified, 61 were microbiologically confirmed, accounting for a positivity of 69%. The municipalities with the highest risk were Niceto Pérez, Guantánamo city, and Manuel Tames. Some activities were immediately carried out, with the multisectorial and interdisciplinary support from different organizations, allowing the control of the situation in less than a month. The study of this outbreak showed that leptospirosis is still a health problem in Cuba, and that it is necessary to join efforts and resources to control it.