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Redistribution of fibronectin and keratin localization patterns in early wounded confluent PtK2 cells.

Single and double-label immunofluorescence were used to study the fibronectin (FN) and keratins (Ks) localization patterns in early wounded confluent PtK2 cells. A time-course study (0 hr, 2 hr, 6 hr and 24 hr) gives the following results: before wounding, the FN localizations of confluent cells are composed of curved and sometimes branched strands or fibrils. The Ks network is formed by radial fluorescent filaments connecting the Ks centers near the nuclei with a linear fluorescence underlying the cell membrane. Two hr after, the FN localizations are redistributed at the cell-cell contact areas. The radial Ks filaments are compacted around the nuclei, some of them delineate the cytoplasmic periphery of the wounded cells. Six hr later, the method shows redistributed FN localizations at the cell-cell contact areas. An alveolar pattern is formed enclosing each of the adjacent cells. The codetected Ks filaments are retracted around the nuclei. The underlying cell-cell contact areas are also well demonstrated. It may be noted that these areas are FN-labelled. Twenty-four hr after wounding, the FN alveolar pattern persists. The redistributed Ks filaments have some similarity to those seen before wounding.

Animals↗

Propagation of local motion correspondence.

We examined how the direction of apparent motion in one part of a scene can propagate and constrain motion direction in another part. The stimulus scene consisted of an array of dots all moving in the same physical direction at the same time. According to the proximity rule, the dots in the interior of the array should appear to move rightward and the dots at the edges should appear to oscillate horizontally. However, we found that: (1) with long frame durations, the interior dots also appeared to oscillate; (2) with shorter frame durations, the likelihood that the subjects perceived rightward motion at the center of the array increased; (3) oscillation was observed at the edges regardless of frame duration; (4) when opaque objects were placed on both the left and right sides of the array as occluders, only rightward motion was observed both in the center and at the edges of the occluders independent of frame duration; (5) in all cases, similar results were obtained with both foveal and peripheral viewing of either the center or the edge; and (6) with longer frame durations, the interior area within which oscillations were observed became larger. These findings suggest that signals for motion correspondence (oscillation) can gradually propagate to distant units (roughly 30 deg/sec). This can be explained by a locally-connected iterative network model.

Female↗

Substance P in the human brain.

The distribution of substance P immunoreactive sites was investigated by immunoenzymatic methods in a large series of paraffin embedded human brain sections from the collection assembled by Oscar and Cécile Vogt several decades ago, as well as from more recent post-mortem material. These studies demonstrated that substance P immunoreactivity was preserved in archival material permitting a detailed account of the localization of immunoreactive cell bodies, fibre networks and tracts in the human brain. Previous observations made on experimental animals and man were confirmed and extended. Additionally, substance P immunoreactive cell bodies were seen in most cortical areas and novel features were noted in the distribution of substance P-containing elements in the tuberal region, corpus striatum, substantia nigra (particularly in relationship to blood vessels) and in association with melanin-containing cells. Reconstruction of some substance P pathways was attempted by the analysis of semi-serial sections in more than one plane. Immunocytochemistry, in combination with image analysis, enabled some measurements of the differential concentrations of substance P immunoreactive material to be made and allowed a close correlation of this with defined anatomical landmarks or enkephalin immunoreactive sites.

Brain↗

Age-dependent reduction of gamma oscillations in the mouse hippocampus in vitro.

Normal brain ageing is associated with a decline in hippocampal memory functions. Neuronal oscillations in the gamma frequency band have been implicated in various cognitive tasks. In this study we test the effect of normal brain ageing on gamma oscillations in the mouse hippocampus in vitro. gamma Oscillations were evoked by either 10 microM carbachol or 100 nM kainate in ventral hippocampus slices from young (>5 month) and aged (>22 month) C57Bl/J6 mice. In slices from young mice carbachol-induced gamma oscillations were more regular and more coherent than those induced by kainate. Compared with young, the power in the 20-80 Hz frequency range in area CA3 of slices from aged mice was reduced to 14% for kainate-induced oscillations and to 7% for carbachol-induced oscillations, whereas waveform, dominant frequency and coherence of the oscillation were unchanged. Local network properties were assessed by paired-pulse stimulation of Schaffer collateral/commissural fibers. The excitatory synaptic response in stratum radiatum of CA3 was reduced, in correlation with the antidromic population spike, but functional inhibition in CA3 and CA1 was unaffected. Changes in local network properties could not explain the reduced gamma oscillation strength. Since oscillations driven by two different pathways are similarly affected with age, an age-dependent effect on tonic depolarizing drive of principal cells is unlikely to explain the current results. Other mechanisms, including a change with age in the use-dependent modulation of synaptic strength, should account for the impaired gamma oscillations in the aged hippocampus that may contribute to age-dependent memory impairment.

Age Factors↗

A review of Japanese telemedicine research and global co-operation.

We can trace 229 telemedicine trials in Japan. Of these, 150 were active in 1998, including 73 in radiology, 24 in home care, 22 in medical imaging, 20 in pathology, 5 in ophthalmology, and 3 in dentistry. Some of them have been reformed into practical daily activities. However, activities using the same method work in some local areas but not in others. Typical successful cases will be presented and discussed. We are constructing Japan-Canada cooperation in numerous areas using several communicative methods: ordinary telephone, ordinary Internet, ISDN (2B/6B), and an offline network using optical memory cards (which patients carry). We have introduced successful domestic cases into global cooperation. Some of them will be useful for exchanging medical information among developing countries.

Humans↗

[Functional localization of vestibular cerebral representations in human using functional magnetic resonance imaging].

OBJECTIVE: To study human vestibular cerebral representations by combining right-sided ice-water stimulation at 0 degree C with blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) and to evaluate the value of this method in the functional localization of human vestibular cortex. METHODS: Twenty right-handed volunteers (12 men and 8 women) received unilateral irrigation of the right external auditory meatu for 15 s with 15 ml of water at 0 degrees C during fMRI in complete darkness. The functional imaging of brain cortex was acquired with a 1.5-T MRI scanner (Signa Infinity Twin + Excite; General Electric Co., USA). The successive functional images from each subject were analyzed as a group with statistical parametric mapping software (SPM 99). RESULTS: Ultimately, data obtained from 17 subjects were analyzed (3 subjects were eliminated from data because of head movement exceeding 2 mm). The group analysis showed bilateral (particularly left-sided) cortical activation, associated with caloric stimulus involving in temporoparietal junction extending into the posterior insula, supramarginal gyrus in the inferior parietal lobe, precuneus, supplementary motor area (SMA), the ventrolateral portion of the occipital lobe, cuneus and lingual gyrus, superior temporal gyrus and cingular cortex. CONCLUSIONS: Ice-water stimulation at 0 degree C in fMRI reveals a widespread cortical network involved in vestibular signal processing in human. As the functional localization of vestibular cortex could be determined precisely, ice-water stimulation at 0 degree C in fMRI would hold great promise as a sensitive and reproducible tool for the research in human vestibular cortex.

Adult↗

Equity of access to tertiary hospitals in Wales: a travel time analysis.

BACKGROUND: The objective of the study was to investigate the implications for equity of geographical access for population subgroups arising from hypothetical scenarios of change in configuration of National Health Service tertiary hospital service provision located in Wales. METHODS: For each of three scenarios, the status quo and centralization of services to one of two locations, we used a travel time road length matrix in geographical information software to calculate the proportion of the population living within 30, 60, 90 and 120 min travel of each hospital site and the associated mean, median and 90th percentile travel times. We analysed data for the total resident population of Wales, for residents aged 75 or more years, for residents of the most deprived 10 per cent of enumeration districts, and for residents of rural areas. RESULTS: Centralization of services reduces geographical access for all population subgroups. Access varies between population subgroups, both between and within different scenarios of service configuration. A change in service configuration may improve access for one subgroup but reduce access for another. The interpretation may also vary according to whether the defined cut point for comparing access is based on short or long travel times. Measurements of absolute and relative access are sensitive to the assumed travel speeds. CONCLUSION: Access for the total population does not imply equity of access for subgroups of the population. Comparisons of access between scenarios are dependent on which measure of access is the indicator of choice. Results are sensitive to the road network travel speeds and further local validation may be necessary. This method can provide explicit information to health service planners on the effects on equity of access from a change in service configuration.

Catchment Area, Health↗

Histotopographic and ultrastructural study on the lymphatic network of the pancreas in the guinea pig.

The localization of absorbing lymph vessels was studied in the normal guinea pig pancreas by light microscopy (serial semithin sections) and transmission electron microscopy (ultrathin sections). Absorbing lymph vessels were observed both in the interlobular and intralobular areas where they can be localized close to the adenomeres. Lymph vessels were also seen in the interlobular areas located next to the islets of Langerhans and to groups of endocrine cells (n = 8-10) not showing a vascular organization comparable with islets of Langerhans. All lymph vessels in the pancreas are absorbing lymph vessels, characterized by a very thin endothelial wall, anchoring filaments and the absence of a definitive basal membrane. Adjacent endothelial cells form end-to-end, overlapping and interdigitating intercellular junctions. Valves were present both in the interlobular and intralobular lymph vessels.

Animals↗

Neural correlates of processing facial identity based on features versus their spacing.

Adults' expertise in recognizing facial identity involves encoding subtle differences among faces in the shape of individual facial features (featural processing) and in the spacing among features (a type of configural processing called sensitivity to second-order relations). We used fMRI to investigate the neural mechanisms that differentiate these two types of processing. Participants made same/different judgments about pairs of faces that differed only in the shape of the eyes and mouth, with minimal differences in spacing (featural blocks), or pairs of faces that had identical features but differed in the positions of those features (spacing blocks). From a localizer scan with faces, objects, and houses, we identified regions with comparatively more activity for faces, including the fusiform face area (FFA) in the right fusiform gyrus, other extrastriate regions, and prefrontal cortices. Contrasts between the featural and spacing conditions revealed distributed patterns of activity differentiating the two conditions. A region of the right fusiform gyrus (near but not overlapping the localized FFA) showed greater activity during the spacing task, along with multiple areas of right frontal cortex, whereas left prefrontal activity increased for featural processing. These patterns of activity were not related to differences in performance between the two tasks. The results indicate that the processing of facial features is distinct from the processing of second-order relations in faces, and that these functions are mediated by separate and lateralized networks involving the right fusiform gyrus, although the FFA as defined from a localizer scan is not differentially involved.

Adolescent↗

Managed care and the delivery of primary care to the elderly and the chronically ill.

OBJECTIVE: To analyze primary care staffing in HMOs and to review the literature on primary care organization and performance in managed care organizations, with an emphasis on the delivery of primary care to the elderly and chronically ill. DATA SOURCES/STUDY SETTING: Analysis of primary care staffing: InterStudy HMO census data on primary care (n = 1,956) and specialist (n = 1,777) physician staffing levels from 1991 through 1995. Primary care organization and performance for the chronically ill and elderly were analyzed using a review of published research. STUDY DESIGN: For the staffing-level models, the number of primary care and specialist physicians per 100,000 enrollees was regressed on HMO characteristics (HMO type [group, staff, network, mixed], HMO enrollment, federal qualification, profit status, national affiliation) and community characteristics (per capita income, population density, service area size, HMO competition). For the review of organization and performance, literature published was summarized in a tabular format. PRINCIPAL FINDINGS: The analysis of physician staffing shows that group and staff HMOs have fewer primary care and specialist physicians per 100,000 enrollees than do network and mixed HMOs, which have fewer than IPAs. Larger HMOs use fewer physicians per 100,000 enrollees than smaller HMOs. Federally qualified HMOs have fewer primary care and specialist physicians per 100,000 enrollees. For-profit, nationally affiliated, and Blue Cross HMOs have more primary care and specialist physicians than do local HMOs. HMOs in areas with high per capita income have more PCPs per 100,000 and a greater proportion of PCPs in the panel. HMO penetration decreases the use of specialists, but the number of HMOs increases the use of primary care and specialist physicians in highly competitive markets. Under very competitive conditions, HMOs appear to compete by increasing access to both PCPs and specialists, with a greater emphasis on access to specialists. The review of research on HMO performance suggests that access to PCPs is better in MCOs. But access to specialists and hospitals is lower and more difficult in MCOs than FFS. Data do not suggest that processes of care, given access, are different in MCOs and FFS. MCO enrollees are more satisfied with financial aspects of a health plan and less satisfied with other aspects of health plan organization. There are potential problems with outcomes, with some studies finding greater declines among the chronically ill in MCOs than FFS. We found a variety of innovative care programs for the elderly, based on two fundamentally different approaches: organization around primary care or organizing around specialty care. Differences between the performance of the two approaches cannot be evaluated because of the small amount of research done. It is difficult to say how well particular programs perform and if they can be replicated. The innovative programs described in the literature tend to be benchmark programs developed by HMOs with a strong positive reputation.

Aged↗

Development of an integrated and sustainable rural service for people with diabetes in the Scottish Highlands.

INTRODUCTION: The number of people with diabetes is increasing leading to a greater burden on health care services. The impact of the growing prevalence is accentuated by remote and rural demographic and geographic characteristics. Highland is a sparsely populated remote and rural area in the north of Scotland, characterised by poor access to health-care services and pockets of marked deprivation. Centralised policy developments demanding local implementation compounded the pressures on a system that already had waiting times of over 90 weeks for some people with diabetes. A regional review of services, engaging stakeholders from all disciplines and geographical locations was required to develop acceptable and sustainable solutions. This article describes the extensive mapping process involved, how solutions were derived, and suggests a new service structure to encompass remote health-care issues. METHODS: Health-care professionals with an interest in diabetes were identified and workshops were organised to include the remote areas of Highland. Patient and carers views were ascertained through workshops and supplemented by written submissions. Using the redesign methodology the patient pathway was mapped, noting service deficiencies and good practice. The information gathered was constructed into a service-level map representing the patient journey. A conference was organised to develop solutions to the issues raised during the mapping process. From these solutions a new service configuration was constructed. RESULTS: Over 300 health-care professionals patients and carers contributed. Fourteen workshops were held across the region including the remote areas, providing 15 local maps of the patient pathways subsequently amalgamated into a service-level map. The current patient pathway in Highland follows a traditional and dichotomous cycle of care in the primary and secondary care setting, partly reflecting the rural nature of healthcare in the Highlands. Four main areas for service improvement were identified: a reduction in waiting times for secondary care out patients; an improvement in communication between health-care professionals; further education for both health-care professionals and patients; and the use and role of allied health professionals. Seventeen solutions were recommended, including the introduction of a managed clinical network, use of an integrated IT system, use of a remote access consultation clinic, and web-based peer education and group sessions for allied health professionals. A new service configuration was proposed with the patient at the centre of a non-hierarchical system using standardised referral letters with a seamless flow of information. CONCLUSION: Local processes for the implementation of government directives are imposing pressures on relatively smaller organisations. These pressures develop as a result of attempts to ensure local ownership and in overcoming the difficulties unique to the remote and rural setting. Further evaluation of the implementation of initiatives to solve the issues of service planning in remote areas is needed to clarify their level of effectiveness.

Diabetes Mellitus↗

An evaluation of three community-based projects to improve care for incontinence.

The Australian National Continence Management Strategy commissioned the implementation and evaluation of three community-based projects designed to improve care for people with incontinence by improving the detection and treatment of urinary incontinence. Projects were located in demographically diverse areas, overseen by co-operating professional groups with an interest in continence and aimed at facilitating a pathway of care for those with incontinence. Project activities focused on health care provider training and improving local referral networks, as well as raising public awareness. Multifaceted evaluation of each project was designed to inform principles for a national approach to continence care. The evaluation indicated that providers involved in each project became more confident in their ability to manage incontinence, had significantly increased knowledge of issues around incontinence and became more aware of local options for referral. However, there was little evidence that projects achieved an increase in seeking professional help among those with incontinence. From the evaluation, six principles were developed to guide future models of community-based continence care.

Aged↗

Use of non-linear EEG measures to characterize EEG changes during mental activity.

Non-linear EEG analysis provides a possibility for studying the dynamical changes in cortical networks related to mental activity. In this study the correlation dimension D2 was used to study local changes in complexity, and the mutual dimension Dm was used to assess changes in the dynamical coupling between different brain areas. EEGs were recorded in 25 healthy subjects under three conditions: (1) eyes closed, (2) eyes open, and (3) mental arithmetic with eyes closed (serial subtraction of 7s from 1000). In the eyes-closed condition, D2 was lower at parieto-occipital sites. D2 increased during the eye-open and arithmetic conditions. Contrary to the D2, the Dm showed no regional differences in the eyes closed condition. A clear increase in Dm was seen during eyes open and arithmetic. We conclude that both the correlation dimension and the mutual dimension are very sensitive to EEG changes during simple visual information processing and during mental arithmetic. However, these measures seem to be relatively non-specific, and correlate only weakly with performance on the arithmetic task.

Adult↗

Central integration of swallow and airway-protective reflexes.

The relationship between the timing of respiration and swallowing has been proven not to be random. Using pseudorabies virus (PRV) as a transsynaptic neural tracer, a basis for the central integration of swallowing and airway-protective reflexes can be located in the neural circuits projecting to swallowing-related muscles. The premotor neurons (PMNs) that constitute the swallowing central pattern generators, interneuronal networks able to initiate repetitive rhythmic muscle activity independent of sensory feedback, connect with multiple areas of the brainstem and other areas of the central nervous system. Those PMNs that project to muscles used in swallowing have been localized within the nucleus of the solitary tract (NTS) and its adjacent reticular formation, and they are synaptically linked both to peripheral afferents and to cortical swallowing areas. Bartha PRV, an attenuated vaccine strain of swine alpha-herpesvirus with a long postinjection survival rate and the ability to produce controlled infections that spread in a hierarchical manner within synaptically linked neurons, can specifically label neurons projecting to PMNs of a given circuit. Thus, it has been used to isolate two neuroanatomically distinct subnetworks of PMNs involved in the buccopharyngeal and esophageal phases of swallowing. Use of PRV as a neural tracer shows that during the buccopharyngeal phase of swallowing, vagal afferents from the pharynx and larynx and from the superior laryngeal nerve terminate in the intermediate and interstitial subnuclei of the NTS. Motoneurons projecting to the pharynx and larynx are located in the semicompact and loose formations of the nucleus ambiguus (NA). Neural tracing with PRV also shows that esophageal PMNs have direct synaptic contact with esophageal motoneurons in the compact formation of the NA. Moreover, esophageal PMNs are localized exclusively to the central subnucleus of the NTS, a site that also is the sole point of termination of esophageal vagal afferents. Using PRV, one can identify third-order (neurons projecting to PMNs) esophageal neurons in sites where pharyngeal PMNs have been noted. Injection of PRV into the esophagus and subsequent detection using immunofluorescence found a subpopulation of neurons in the intermediate and interstitial subnuclei of the NTS. This subpopulation projects to pharyngeal motoneurons and buccopharyngeal PMNs, and it is synaptically linked to esophageal PMNs. The synaptic link between buccopharyngeal and esophageal PMNs provides a potential anatomic substrate within the NTS for the central integration of esophageal peristalsis with the pharyngeal phase of swallowing and airway-protective reflexes. Human studies and animal models investigating esophagoglottal closure and pharyngo-upper esophageal sphincter (pharyngo-UES) contractile reflexes have located the neural pathways that mediate airway-protective reflexes. Similar studies and models using two PRV strains injected simultaneously into different swallowing and respiration-related muscle groups may identify synaptic connectivity between laryngeal, esophageal, and pharyngeal PMNs and, thus, may help to demonstrate the central integration of swallowing and airway-protective reflexes.

Deglutition↗

The professional carers' group: supporting group work for young sexual abusers.

OBJECTIVE: A centralized treatment project, for young people who have sexually abused others, describes how group-based work with potentially isolated local professionals may help a treatment program to maintain a systemic perspective. METHOD: The paper reviews relevant literature and outlines the context, format and goals of a Professional Carers' Group. RESULTS: Recurring themes, observed during the 30-week treatment programs, are subjected to clinical analysis. Two key areas are discussed: (1) cognitive-emotional processing of common reactions to work with sexual abuse; and (2) inter-professional communication to balance the requirements of child protection and therapy. CONCLUSION: Concurrent work with local professional networks may promote the clinical effectiveness of a treatment program for young perpetrators of sexual abuse. A Professional Carers' Group is one relatively low-cost approach which may help to integrate the work of a central treatment facility with that of distant, community-based, agencies.

Adolescent↗

P2X(2) receptor immunoreactivity in the dorsal vagal complex and area postrema of the rat.

Adenosine 5'-triphosphate (ATP) can function as a fast synaptic transmitter through its actions on ionotropic (P2X) and metabotropic (P2Y) receptors in neuronal tissue. The ionotropic receptors have been classified into seven subtypes (P2X(1)-P2X(7)) by molecular cloning. However, they are difficult to distinguish pharmacologically owing to an absence of specific agonists and antagonists. In this study we used neuroanatomical methods to determine the origin and neurochemical phenotype of the P2X(2) subtype of purinoceptor in the dorsal medulla of the rat. Using immunohistochemistry we observed dense networks of P2X(2) receptor immunoreactive labelled fibres and terminals in the dorsal vagal complex and area postrema, as well as labelled cell bodies in the dorsal vagal nucleus and the area postrema. The P2X(2) receptor was localized presynaptically in vagal afferent fibres and terminals in the nucleus tractus solitarius at the ultrastructural level by combining injections of an anterograde tracer (biotin dextran amine) into the nodose ganglion with pre-embedding immunogold visualization of P2X(2) immunoreactivity. Terminals immunoreactive for the P2X(2) receptor in the nucleus tractus solitarius were found to contain glutamate, but not GABA immunoreactivity by post-embedding immunogold-labelling techniques. In cell bodies in the area postrema, dual immunofluorescence also indicated that P2X(2) receptor immunoreactive cells are glutamatergic but not GABAergic. The P2X(2) receptor was localized to vagal preganglionic neurons in the dorsal vagal nucleus that were identified by prior intraperitoneal injections of the retrograde tracer FluoroGold. No cells immunoreactive for the P2X(2) receptor were observed in the nucleus tractus solitarius. The localization of P2X(2) receptor immunoreactivity presynaptically in vagal afferent terminals indicates that the receptor may be involved in modulating transmitter release from vagal afferent fibres. Furthermore, the presence of the P2X(2) receptor in vagal preganglionic cells and in glutamatergic cells of the area postrema implies that it may, respectively, play a role in regulation of vagal efferent cell activity and modulation of excitatory outputs from the area postrema to other brain regions.

Animals↗

A comparison of optimal MIMO linear and nonlinear models for brain-machine interfaces.

The field of brain-machine interfaces requires the estimation of a mapping from spike trains collected in motor cortex areas to the hand kinematics of the behaving animal. This paper presents a systematic investigation of several linear (Wiener filter, LMS adaptive filters, gamma filter, subspace Wiener filters) and nonlinear models (time-delay neural network and local linear switching models) applied to datasets from two experiments in monkeys performing motor tasks (reaching for food and target hitting). Ensembles of 100-200 cortical neurons were simultaneously recorded in these experiments, and even larger neuronal samples are anticipated in the future. Due to the large size of the models (thousands of parameters), the major issue studied was the generalization performance. Every parameter of the models (not only the weights) was selected optimally using signal processing and machine learning techniques. The models were also compared statistically with respect to the Wiener filter as the baseline. Each of the optimization procedures produced improvements over that baseline for either one of the two datasets or both.

Action Potentials↗

Anatomical differences in the mirror neuron system and social cognition network in autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social and emotional skills, the anatomical substrate of which is still unknown. In this study, we compared a group of 14 high-functioning ASD adults with a group of controls matched for sex, age, intelligence quotient, and handedness. We used an automated technique of analysis that accurately measures the thickness of the cerebral cortex and generates cross-subject statistics in a coordinate system based on cortical anatomy. We found local decreases of gray matter in the ASD group in areas belonging to the mirror neuron system (MNS), argued to be the basis of empathic behavior. Cortical thinning of the MNS was correlated with ASD symptom severity. Cortical thinning was also observed in areas involved in emotion recognition and social cognition. These findings suggest that the social and emotional deficits characteristic of autism may reflect abnormal thinning of the MNS and the broader network of cortical areas subserving social cognition.

Adult↗