Subsurface imaging of silicon nanowire circuits and iron oxide nanoparticles with sub-10 nm spatial resolution.

Non-destructive subsurface characterization of nanoscale structures and devices is of significant interest in nanolithography and nanomanufacturing. In those areas, the accurate location of the buried structures and their nanomechanical properties are relevant for optimization of the nanofabrication process and the functionality of the system. Here we demonstrate the capabilities of bimodal and trimodal force microscopy for imaging silicon nanowire devices buried under an ultrathin polymer film. We resolve the morphology and periodicities of silicon nanowire pairs. We report a spatial resolution in the sub-10 nm range for nanostructures buried under a 70 nm thick polymer film. By using numerical simulations we explain the role of the excited modes in the subsurface imaging process. Independent of the bimodal or trimodal atomic force microscopy approach, the fundamental mode is the most suitable for tracking the topography while the higher modes modulate the interaction of the tip with the buried nanostructures and provide subsurface contrast.

Improved measurement of intersession latency in mfVEPs.

PURPOSE: The purpose of the study is to present a method (Selfcorr) by which to measure intersession latency differences between multifocal VEP (mfVEP) signals. METHODS: The authors compared the intersession latency difference obtained using a correlation method (Selfcorr) against that obtained using a Template method. While the Template method cross-correlates the subject's signals with a reference database, the Selfcorr method cross-correlates traces across subsequent recordings taken from the same subject. RESULTS: The variation in latency between intersession signals was 0.8 ± 13.6 and 0.5 ± 5.0 ms for the Template and Selfcorr methods, respectively, with a coefficient of variability CV_TEMPLATE = 15.83 and CV_SELFCORR = 5.68 (n = 18, p = 0.0002, Wilcoxon). The number of analyzable sectors with the Template and Selfcorr methods was 36.7 ± 8.5 and 45.3 ± 8.7, respectively (p = 0.0001, paired t test, two tailed). CONCLUSIONS: The Selfcorr method produces smaller intersession mfVEP delays and variability over time than the Template method.

From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-ß.

Cancer cells have the ability to migrate from the primary (original) site to other places in the body. The extracellular matrix affects cancer cell migratory capacity and has been correlated with tissue-specific spreading patterns. However, how the matrix orchestrates these behaviors remains unclear. Here, we investigated how both higher collagen concentrations and TGF-ß regulate the formation of H1299 cell (a non-small cell lung cancer cell line) spheroids within 3D collagen-based matrices and promote cancer cell invasive capacity. We show that at low collagen concentrations, tumor cells move individually and have moderate invasive capacity, whereas when the collagen concentration is increased, the formation of cell clusters is promoted. In addition, when the concentration of TGF-ß in the microenvironment is lower, most of the clusters are aggregates of cancer cells with a spheroid-like morphology and poor migratory capacity. In contrast, higher concentrations of TGF-ß induced the formation of clusters with a notably higher invasive capacity, resulting in clear strand-like collective cell migration. Our results show that the concentration of the extracellular matrix is a key regulator of the formation of tumor clusters that affects their development and growth. In addition, chemical factors create a microenvironment that promotes the transformation of idle tumor clusters into very active, invasive tumor structures. These results collectively demonstrate the relevant regulatory role of the mechano-chemical microenvironment in leading the preferential metastasis of tumor cells to specific tissues with high collagen concentrations and TFG-ß activity.

Quantifying 3D chemotaxis in microfluidic-based chips with step gradients of collagen hydrogel concentrations.

Cell migration is an essential process involved in crucial stages of tissue formation, regeneration or immune function as well as in pathological processes including tumor development or metastasis. During the last few years, the effect of gradients of soluble molecules on cell migration has been widely studied, and complex systems have been used to analyze cell behavior under simultaneous mechano-chemical stimuli. Most of these chemotactic assays have, however, focused on specific substrates in 2D. The aim of the present work is to develop a novel microfluidic-based chip that allows the long-term chemoattractant effect of growth factors (GFs) on 3D cell migration to be studied, while also providing the possibility to analyze the influence of the interface generated between different adjacent hydrogels. Namely, 1.5, 2, 2.5 and 4 mg ml-1 concentrations of collagen type I were alternatively combined with 5, 10 or 50 ng ml-1 concentrations of PDGF and VEGF (as a negative control). To achieve this goal, we have designed a new microfluidic device including three adjacent chambers to introduce hydrogels that allow the generation of a collagen concentration step gradient. This versatile and simple platform was tested by using dermal human fibroblasts embedded in 3D collagen matrices. Images taken over a week were processed to quantify the number of cells in each zone. We found, in terms of cell distribution, that the presence of PDGF, especially in small concentrations, was a strong chemoattractant for dermal human fibroblasts across the gels regardless of their collagen concentration and step gradient direction, whereas the effects of VEGF or collagen step gradient concentrations alone were negligible.

Paroxysmal MEG activity in obsessive compulsive patients without SSRIs therapy.

We describe a fronto-temporal paroxysmal rhythmic activity registered by magnetoencephalography (MEG) in two patients with obsessive compulsive disorder (OCD) without SSRIs treatment. The localization of the activity involves cingulate cortex and frontal areas. We think that these MEG findings are related to the disease itself, rather than representing pharmacological SSRIs effect.

[Frontal seizures recorded by magnetoencephalography. Case report]. / Crisis frontales registradas mediante magnetoencefalografía. Caso clínico.

INTRODUCTION: This paper reports the usefulness of magnetoencephalography (MEG) in the anatomical localization of the onset and spread of seizures. CASE REPORT: In a 34-year-old male patient who suffered from drug-resistant complex partial seizures (sometimes generalized) with loss of awareness, magnetic resonance imaging revealed a probable left frontobasal cortical dysplasia. Ictal scalp electroencephalogram showed left frontotemporal theta waves. Electrocorticography (ECoG) registered interictal polyspike discharges and located the seizure onset in the lateral orbital side of the left frontal lobe. Three seizures were registered by MEG, clinically similar to the ones usually experienced by the patient. MEG ictal spike dipole location showed seizure onset coming from the left inferior frontal gyrus (as the ECoG), spreading on to other frontal areas, insula and temporal lobe, all in the left hemisphere. CONCLUSION: MEG may be considered as a useful diagnosis modality in the study of partial seizure physiopathology as well as in its presurgical evaluation.

Continuous-wavelet-transform analysis of the multifocal ERG waveform in glaucoma diagnosis.

The vast majority of multifocal electroretinogram (mfERG) signal analyses to detect glaucoma study the signals' amplitudes and latencies. The purpose of this paper is to investigate application of wavelet analysis of mfERG signals in diagnosis of glaucoma. This analysis method applies the continuous wavelet transform (CWT) to the signals, using the real Morlet wavelet. CWT coefficients resulting from the scale of maximum correlation are used as inputs to a neural network, which acts as a classifier. mfERG recordings are taken from the eyes of 47 subjects diagnosed with chronic open-angle glaucoma and from those of 24 healthy subjects. The high sensitivity in the classification (0.894) provides reliable detection of glaucomatous sectors, while the specificity achieved (0.844) reflects accurate detection of healthy sectors. The results obtained in this paper improve on the previous findings reported by the authors using the same visual stimuli and database.

Cortical organization for receptive language functions in Chinese, English, and Spanish: a cross-linguistic MEG study.

Chinese differs from Indo-European languages in both its written and spoken forms. Being a tonal language, tones convey lexically meaningful information. The current study examines patterns of neurophysiological activity in temporal and temporoparietal brain areas as speakers of two Indo-European languages (Spanish and English) and speakers of Mandarin-Chinese were engaged in a spoken-word recognition task that is used clinically for the presurgical determination of hemispheric dominace for receptive language functions. Brain magnetic activation profiles were obtained from 92 healthy adult volunteers: 30 monolingual native speakers of Mandarin-Chinese, 20 Spanish-speaking, and 42 native speakers of American English. Activation scans were acquired in two different whole-head MEG systems using identical testing methods. Results indicate that (a) the degree of hemispheric asymmetry in the duration of neurophysiological activity in temporal and temporoparietal regions was reduced in the Chinese group, (b) the proportion of individuals who showed bilaterally symmetric activation was significantly higher in this group, and (c) group differences in functional hemispheric asymmetry were first noted after the initial sensory processing of the word stimuli. Furthermore, group differences in the degree of hemispheric asymmetry were primarily due to greater degree of activation in the right temporoparietal region in the Chinese group, suggesting increased participation of this region in the spoken word recognition in Mandarin-Chinese.

Correlation of ultrasound bone velocity with dual-energy X-ray bone absorptiometry in rat bone specimens.

RATIONALE AND OBJECTIVES: To investigate bone mass measurements by ultrasound bond velocity (UBV) in bone specimens obtained from experimental animals. METHODS: The authors made UBV measurements in 40 femurs and tibias dissected from Sprague-Dawley rats (14 weeks-old, mean weight 290 g) and compared them with bone densitometric measurements made on the same material using dual-energy x-ray absorptiometry (DXA). RESULTS: The coefficient of variation for UBV measurements, based on values obtained in five femurs and five tibias at different times, was 0.2% and 0.3% respectively. Regression studies yielded a correlation between UBV and bone mineral density in femur of r = 0.87 (P < 0.0001) and with bone mineral content of r = 0.65 (P < 0.0001); in the tibia similar levels of significance were obtained. The correlation between femur weight and UBV was r = 0.51 (P < 0.0005) and with bone mineral content it was r = 0.79 (P < 0.0001). Partial correlation between UBV and femur bone mineral density, with respect to bone weight, was r = 0.68 (P < 0.001), and with femur bone mineral content was r = 0.71 (P < 0.0001). In the tibia measurements were similarly significant. CONCLUSIONS: Measurements of bone mass made with ultrasound transmission velocity are precise correlate well with DXA measurements.

Spatio-temporal patterns of brain magnetic activity during a memory task in Alzheimer's disease.

The brain magnetic activity patterns in a high load probe-letter (targets and distractors) memory task were examined in patients with Alzheimers's disease (AD) and elderly controls. Control subjects showed a higher number of activity sources over the temporal and parietal cortex between 400 and 700 ms after stimulus onset. However, AD patients showed a higher number of sources over the frontal motor areas, including Broca's and the insula. The number of activity sources on the left parietal areas in response to the target stimuli predicted the AD score oncognitive (MMSE, CAMCOG) and functional staging (FAST) scales. These results suggest that a high information load reveals a deficient functioning of phonological store and reduced task-related activity in temporal and parietal areas, manifesting in a rapid information trace decay. The increased levels of activity in motor areas may reflect a compensatory strategy in an attempt to facilitate rehearsal speed.

Etidronate versus clodronate in the prevention of postovariectomy bone loss. An experimental study in rats.

OBJECTIVE: We compared the diphosphonates etidronate and clodronate to find out which was more effective in inhibiting the loss of bone mass after ovariectomy in rats. METHODS: Five lots of female Sprague Dawley rats, each containing 15 rats (14 wks old; mean weight 290 g), were kept under identical living conditions (12 hrs of light and 12 hrs of darkness), habitat, and diet following the current norms of the European Economic Community. One lot was kept as a control; one lot underwent sham ovariectomy (Sham-OVX); and the remaining 3 lots were anesthesized and underwent double ovariectomy (OVX). One lot of ovariectomized rats was given etidronate by esophageal tube, 5 mg/kg/day (OVX-E); one lot was treated with intraperitoneal clodronate, 5 mg/kg/3 days (OVX-Cl). The remaining lot was not manipulated (OVX). The animals' right femurs were then dissected for measurements of the bone mineral content. RESULTS AND CONCLUSION: Bone densitometry revealed that loss of bone mass 2 months after ovariectomy in the OVX-Cl group was 2.3%, not differing from that of the control group; bone loss in the OVX-E group was 11.7%, significantly different from the control group and from the OVX-Cl group (p < 0.001). These results show that clodronate is superior to etidronate in inhibiting osteopenia after ovariectomy in rats.

[The evaluation of heterosexual transmission of the human immunodeficiency virus by nucleic acid amplification technics]. / Evaluación de la transmisión heterosexual del virus de la inmunodeficiencia humana por técnicas de amplificación de ácidos nucleicos.

Heterosexual couples of individuals infected by HIV represent a group of high risk of virus infection. We have investigated the presence of fragments of the HIV genome with a new nucleic acid amplification technique (PCR or polymerase chain reaction) in lymphocytes from 33 seronegative couples with anti-HIV antibodies, most of which were heroin addicts. 12 of the 33 couples (36%) had positive PCR for a gag HIV amplimer in the absence of antibodies. 4 of them (12%) also showed reactivity for sequences from an env amplimer. A control group of 7 patients with AIDS and 4 seropositive couples showed reactivity to gag and env in all. It is concluded that silent HIV infection may frequently develop in heterosexual couples of infected individuals.

[Cognition and neural networks, a new perspective based on functional neuroimaging]. / Cognición y redes neurales, una nueva perspectiva desde la neuroimagen funcional.

AIM: We went through a critical review of the current status of neuroimaging studies of cognition. Thus, we argue why the use of a neuronal network perspective could led us to a better understanding of cognition than a localizationism perspective. METHOD: The question about how cognitive functions are organized in the brain, comes from the very early lesions studies. Electrocortical stimulation and the intracorotid amytal procedure collaborate together with lesions studies to increase the knowledge about the organization of cognitive functions in the brain. Functional neuroimaging could help to this issue answering the following questions: where, when and how the activity is produced in the brain. Many of the functional neuroimaging studies have addressed the question of where the activity is located, but very few has been concentrated into describe the spatio temporal profiles of brain activity, and then how the neural networks which support cognition are organized. Taking into account just one of this perspectives (where or when) we could achieve a reductionism view of the problem. CONCLUSIONS: Executive function, memory or language are more distributed than located in just one area, even the different subprocesses that are included in each of this functions are supported by a network rather than a particular area. We analyze the current available functional neuroimaging techniques under this view and its possibilities to describe the neural networks which support cognition.

[The neuromagnetic correlates of language]. / Correlatos neuromagnéticos del lenguaje.

Studies of language using different functional neuroimaging techniques have shown the cortical structures to be involved in the functions of language, both in control subjects and in patients with different neurological pathologies who are to undergo brain surgery. Magnetoencephalography (MEG) is a totally non-invasive technique that measures the magnetic fields generated by the flow of intracellular current produced in the dendrites of the pyramidal neurones. MEG also offers the possibility of lateralizing language, so enabling us to know which areas of language lie within the dominant hemisphere and to establish the temporal patterns that reveal the organisation, either in sequence or in parallel, of the different areas that are activated. This will provide us with a deeper understanding of the physiological foundations upholding both language and other cognitive processes.

[Magnetoencephalographic study in patients with cognitive impairment]. / Estudio magnetoencefalográfico en pacientes con deterioro cognitivo.

INTRODUCTION: In early stages, dementia is a neurodegenerative process with difficult diagnosis. Although well defined clinically, its neurophysiological, neuroradiological and metabolic diagnosis is still unsuccessful. PATIENTS AND METHOD: A MEG study using a 148 channel whole head magnetometer (Magnes 2500 WH) and evaluation by mini mental state examination (MMSE) was performed in 31 subjects. Statistical analyses was made to correlate number of dipoles of slow waves and neuropsychological variables. RESULTS: The 63.3% (21 patients) show slow waves dipoles in temporal lobes (52.3% were bitemporal). Right temporal lobe has 119.5 23.3 dipoles (averaged value), and left temporal lobe has 126.2 19.8 dipoles (averaged value). The 25% (8 patients) shown slow waves dipoles in parietals lobes, 5 of them biparietal. Correlation between MMSE averaged scores and temporal lobe dipoles was r= 0.84. CONCLUSION: MEG results show that slow waves dipoles number in temporal lobes is related with low scores in the mini mental state examination. MEG could be a usefully complementary method in evaluation and following of degree of cognitive impairment in these patients

[A magnetoencephalographic study of generalised developmental disorders. A new proposal for their classification]. / Estudio mediante magnetoencefalografia de los trastornos generalizados del desarrollo. Nueva propuesta de clasificacion.

INTRODUCTION: Autistic spectrum disorders (ASD) is a term that is not included in DSM IV or in ICD 10, which are the diagnostic tools most commonly used by clinical professionals but can offer problems in research when it comes to finding homogenous groups. DEVELOPMENT: From a neuropaediatric point of view, there is a need for a classification of the generalised disorders affecting development and for this purpose we used Wing's triad, which defines the continuum of the autistic spectrum, and the information provided by magnetoencephalography (MEG) as grouping elements. Specific generalised developmental disorders were taken as being those syndromes that partially expressed some autistic trait, but with their own personality so that they could be considered to be a specific disorder. ASD were classified as being primary, cryptogenic or secondary. The primary disorders, in turn, express a continuum that ranges from Savant syndrome to Asperger's syndrome and the different degrees of early infantile autism. MEG is a functional neuroimaging technique that has enabled us to back up this classification.

[Rolandic discharges in childhood epilepsy: magnetoencephalographic diagnosis]. / Epilepsia infantil por descargas rolándicas: diagnóstico mediante magnetoencefalografía.

INTRODUCTION: Whole head magnetoencephalography (MEG) systems facilitate simultaneous recording from the entire brain surface and deep structures. Thus MEG may be accepted as a clinically feasible method for the evaluation of epileptic patients not diagnosed with EEG. CLINICAL CASE: A 11 year old female, with tonic generalized seizures since birth. At the present time, seizures consist of initial focal signs followed by fear sensation and both eyes and cephalic deviation to the right, tonic extension of the superior limbs and prolonged apnea. Complementary examinations (EEG, Holter EEG, Video EEG, CT, MRI, SPECT) were normal. MEG study was conclusive, diagnosing sharp waves in the internal face of the left precentral circunvolution. CONCLUSIONS: MEG study s utility in seizures focus localization and pseudo seizures differential diagnosis has been demonstrated.

[Neuromagnetic correlates of dyslexia]. / Correlatos neuromagnéticos de la dislexia.

Dyslexia was first described over a century ago and since then many theories have been put forward to explain it, but we still do not have one single unified theory that explains the problem. Furthermore, over the years a great deal of research work has also been carried out that relates dyslexia with disorders in different brain structures, and yet we still do not have a clear idea of exactly which neurophysiological mechanisms are involved. It has been claimed, however, that the disorder may be caused by specific deficits in the left frontotemporal region or atypical asymmetries in the left perisylvian regions. Lastly, neuroimaging techniques, such as functional magnetic resonance or mapping of the electrical activity in the brain, have helped to further studies into dyslexia over the last decade. Recently, the introduction of magnetoencephalography in the study of the brain has opened up a whole new range of possibilities that will allow most of the controversial points raised by research into dyslexia using neuroimaging techniques to be resolved empirically.

[Clinical features of epilepsy in autism spectrum disorders]. / Clínica de la epilepsia en los trastornos del espectro autista.

Autism is a rare disease, but is currently in vogue. An incidence of 1/1,000 has been estimated for early childhood autism, but in autism spectrum the incidence can reach 30/1,000. The clinical characteristics of autism are cognitive language disorders, lack of social interaction, obsessive behaviours with stereotypic movements and epilepsy. For some authors it is an associated symptom while for others it is a cardinal symptom of the disease. Epilepsy in autism, as an association, was reported as early as 1944 by Leo Kanner, in describing his initial work involving 11 cases and how one of them suffered from epilepsy. In 1960, the prevalence of epilepsy among autistic patients was evaluated and found to be much higher than in the normal population. The figures differ from author to author, but really they depend on age: the higher the age, the greater the prevalence of epilepsy. It was in fact this detail that drew our attention to this issue, and triggered the first questions in our research into autism and epilepsy. The series vary from 4 to 86%, depending on the methodology used to confirm the epilepsy. In our casuistics, between the ages of 1 and 18 years, 20% of these children with autism spectrum disorders suffer some kind of epileptic seizures, and 80% suffer what other researchers call subclinical seizures . In this paper, the symptomatology of the most important subclinical seizures that have been observed in these children is presented; the diseases associated with autism are commented on; the concept of primary and secondary autism is discussed; we explain why seizures occur in autism and their consequences as a neurodevelopmental disorder, and we put forward an interesting hypothesis within our general theory of autism. We also comment on the importance that the use of functional magnetic images in the study of autism has in our research.

[Savant or idiot savant syndrome]. / El síndrome de savant o idiot savant.

Savant syndrome is currently still very mysterious, yet, thanks to the progress made in neuroimaging studies and especially MSI (Magnetic Source Imaging) techniques, a little more is now known about it. The theory, formulated many years ago, about damage to the left hemisphere of the brain has been supported by functional neuroimaging. Its relation to developmental disorders or to autism spectrum disorders is far more justified today and can be explained on the basis of its neuropathology. We present a study based on a review of the scientific literature concerning the syndrome, from the first time it was described back in 1789 by Benjamin Rush up to the present day. We comment on its epidemiology and positive clinical manifestations, involving brilliant artistic talent and dazzling memory, but also the negative aspects suffered by these autistic patients. The most important theories are discussed together with the clinical coincidence with frontotemporal dementia and the responsibility of the right hemisphere when there are alterations in the contralateral hemisphere. The latest contributions made by Positron Emission Tomography and magnetoencephalography will be discussed and a mini-video of a personal case will be projected.