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Much has been said about the rapid penetration of HMOs. Yet, little attention has been given to another, equally important trend--the consolidation of hospitals into local systems and networks. The number of local hospital clusters has increased significantly in recent years. They are now taking the lead in the majority of markets across the country in forming integrated systems.
The laminar distribution of cholinergic axons was analyzed quantitatively in the visual cortex of adult cats by using immunocytochemistry with a monoclonal antibody against choline acetyltransferase (ChAT). ChAT(+) fibers and varicosities were counted at different locations within area 17 and the distribution patterns in various animals were compared. Choline acetyltransferase-immunoreactivity was localized in fine, varicose fibers, which were present in all layers of the visual cortex. The density of labeled fibers was highest in layer I, which contained 14% of all fibers and 19.5% of all varicosities, and decreased toward deeper layers. The number of varicosities decreased more markedly toward deeper layers than the frequency of fibers. These distribution patterns were very consistent, showing only slight intra- and interindividual variability.
The lamprey brainstem contains a 'command system' which descends into the spinal cord to activate motor networks and initiate locomotion. In the present study, partial lesions were made in the rostral spinal cord in order to spare various tracts and determine which tracts carry the descending command signal to the spinal cord. Sparing the medial areas of the rostral spinal cord usually blocked both sensory-evoked and spontaneous locomotion, while sparing the lateral regions of the rostral spinal cord did not abolish voluntary locomotor activity. Either the ventrolateral or dorsolateral spinal tracts could support the initiation of locomotion. Brainstem structures rostral to the mesencephalon were not necessary for the initiation of locomotor behavior. The data indicate that the lateral spinal tracts contain a significant part of the descending command pathway for locomotion. In contrast, the medial spinal tracts were neither necessary nor usually sufficient to support locomotor behavior, suggesting that the larger reticulospinal Muller cells, which project in these tracts, do not contribute significantly to the initiation of locomotion.
A partnership between the Specialist Health Promotion Service of NHS Tayside and Dundee City Council developed a project, 'Discover Health', to bring health information to the public. The two main formats used were traditional leaflets and Internet access via the People's Network, both available in public libraries. The steering group for the project was made up of staff from both organisations. The NHS side secured the funding; the Council side provided the accommodation and information and communication technologies. The partnership worked well, and the project is continuing, with expansion in the pipeline for other areas within Tayside. The various aspects of the functioning of the partnership are discussed. A literature review of similar initiatives is included.
PURPOSE OF REVIEW: This review examines our current understanding of the chemoattractant network for lymphocyte trafficking and discusses the recent findings in this area. RECENT FINDINGS: The universe of chemoattractants is expanding. Although the approximately 40 chemokines by themselves provide an extensive network of chemotactic signals, it is now clear that nonchemokine molecules such as lipid mediators, pathogen-derived products, antimicrobial peptides, complement products, and other normal constituents of our body are also chemotactic and regulate lymphocyte trafficking. The past several years has witnessed important progress in the area of lymphocyte trafficking: CD45+CD4+CD3- lymphoid tissue inducer cells express CXCR5 and CCR7 and migrate toward lymphoid tissue--organizing stromal cells. Sphingosine 1-phosphate and homeostatic chemokines regulate lymphocyte localization in lymph nodes and egress to circulation. Upon antigen priming, regulatory T cells rapidly upregulate CXCR5 to migrate and suppress germinal center T and B cells. Plasmacytoid dendritic cells can migrate to lymph nodes through high endothelial venule cells, and chemokines and nonchemokine G-protein--coupled seven-transmembrane domain receptor ligands such as chemerin can regulate pDC migration. Gut dendritic cells and retinoic acid induce the expression of alpha4beta7 and CCR9 on T cells for their homing to the gut. Leukotriene B4 and interleukin-8, known chemoattractants for myeloid cells, are also selective chemoattractants for cytotoxic effector T cells. SUMMARY: Immune cells migrate within the vast and dense network of chemoattractants. This greater chemotactic network comprehensively controls lymphoid organogenesis, homeostatic immune cell migration, and effector cell dispatch to clear pathogens.
The localization of neurons, fibers, and terminals containing tyrosine hydroxylase (TH)-like immunoreactivity was studied in the brain of the crested newt by using an antiserum to rat phaeochromocytoma tyrosine hydroxylase. Immunoreactive cells and fibers were found in the spinal cord, the medulla oblongata (lateral periventricular areas), and the acousticolateral area. In the tegmentum mesencephali, two bilateral clusters of labelled cells were localized in the ventrolateral periventricular gray extending toward the caudal hypothalamus. In the hypothalamic tuberal lobes, the TH-like reactive neurons, frequently of CSF-contacting type, lined the dorsal wall of the lateral infundibular recesses. A thick network of TH-like reactive nerve fibers and terminals was observed in the perivascular zone of the median eminence and in the adenohypophysial pars intermedia. A number of labelled cell bodies were also found in the dorsal thalamus (pars intercalaris diencephali), the paraventricular organ, and the ventral wall of the preoptic recess. In the telencephalon, immunoreactive innervation was identified in the striatum, together with immunopositive cell bodies in the olfactory bulbs. The pattern of organization of TH-immunoreactive systems in the newt showed, except for some peculiarities (e.g., the labelled cell bodies in dorsal thalamus), close similarities to the arrangement typical of mammals.
A review of recent literature suggests that the brainstem may play a more fundamental role in the elaboration of adaptive behaviors than has often been assumed. This view is indicated by current reports documenting the substantial behavioral repertoire of decerebrate animals and by the recent findings that electrical stimulation of localized areas in all major levels of the brainstem can induce complex and coordinated behaviors, including eating, grooming and attack. Indeed, behaviors elicited from sites in the caudal brainstem evidence unexpected goal specificity and stimulus control over response topography. Additional neuroanatomical and behavioral data are reviewed which further implicate caudal brainstem networks in process of reward and aversion. From these and other findings it is argued that integrating mechanisms for the expression of many aspects of species-characteristic behaviors are intrinsic to the brainstem. In line with this view, rostral hypothalamic-limbic mechanisms, while perhaps contributing refinement to the integration of behaviors, may best be viewed as phylogenetically newer control mechanisms making the expression of species-characteristic behaviors subordinate to additional class of exteroceptive and interoceptive stimuli.
Subtle changes in a subject's breathing rate or depth, which occur naturally during rest at low frequencies (<0.1 Hz), have been shown to be significantly correlated with fMRI signal changes throughout gray matter and near large vessels. The goal of this study was to investigate the impact of these low-frequency respiration variations on both task activation fMRI studies and resting-state functional connectivity analysis. Unlike MR signal changes correlated with the breathing motion ( approximately 0.3 Hz), BOLD signal changes correlated with across-breath variations in respiratory volume ( approximately 0.03 Hz) appear localized to blood vessels and regions with high blood volume, such as gray matter, similar to changes seen in response to a breath-hold challenge. In addition, the respiration-variation-induced signal changes were found to coincide with many of the areas identified as part of the 'default mode' network, a set of brain regions hypothesized to be more active at rest. Regions could therefore be classified as being part of a resting network based on their similar respiration-induced changes rather than their synchronized neuronal activity. Monitoring and removing these respiration variations led to a significant improvement in the identification of task-related activation and deactivation and only slight differences in regions correlated with the posterior cingulate at rest. Regressing out global signal changes or cueing the subject to breathe at a constant rate and depth resulted in an improved spatial overlap between deactivations and resting-state correlations among areas that showed deactivation.
Several studies among adult populations showed that an array of outdoor and indoor sources of particles emissions contributed to personal exposures to atmospheric particles, with tobacco smoke playing a prominent role (J. Expo. Anal. Environ. Epidemiol. 6 (1996) 57, Environ. Int. 24 (1998) 405, Arch. Environ. Health 54 (1999) 95). The Vesta study was carried out to assess the role of exposure to traffic emissions in the development of childhood asthma. In this paper, we present data on 68 children aged 8-14 years, living in the metropolitan areas of Paris (n = 30), Grenoble (n = 15) and Toulouse (n = 23), France, who continuously carried, over 48 h, a rucksack that contained an active PM2.5 sampler. Data about home indoor sources were collected by questionnaires. In parallel, daily concentrations of PM10 in ambient air were monitored by local air quality networks. The contribution of indoor and outdoor factors to personal exposures was assessed using multiple linear regression models. Average personal exposure across all children was 23.7 microg/m3 (S.D. = 19.0 microg/m3), with local means ranging from 18.2 to 29.4 microg/m3. The final model explains 36% of the total between-subjects variance, with environmental tobacco smoke contributing for more than a third to this variability; presence of pets at home, proximity of the home to urban traffic emissions, and concomitant PM10 ambient air concentrations were the other main determinants of personal exposure.
Maintenance of forests biodiversity is intimately related on the one hand to the species and community-related ecological needs of flora and fauna living in the forest and on the other hand the disturbance regimes of the specific forest type. Populations of plants and animals need minimum biotopes for their ontogeny; for assuring their survival they depend on a minimum of connected suitable areas. Specific traits of forest types are based upon different disturbance regimes, ranging from small-scale internal processes (e.g. regeneration, growth, senescence, mortality, gap dynamics) generating normal forest cycles (i.e. regular sequences, e.g. regeneration, optimum, decay phases) to potentially chaotic and large-scale, frequently external, disturbances, e.g. fire, landslides, or beetle attacks. Forest protection may meet the needs of these very different demands by varied protected area networks going from small (>100 ha), medium (1000 ha) to large-scale reserves (National Parks, several thousands of ha). According to this triple protection concept not only graduated threshold numbers, but also threshold sizes and threshold areas for forest protection must be defined. To realize this concept the regional and local conditions (forest area, forest cover percentage, forest composition, socio-economic targets) must always be taken in consideration.
The small guanosine triphosphate (GTP)-binding protein ADP-ribosylation factor (ARF) 6 regulates membrane recycling to regions of plasma membrane remodeling via the endocytic pathway. Here, we show that GTP-bound ARF6 interacts with Sec10, a subunit of the exocyst complex involved in docking of vesicles with the plasma membrane. We found that Sec10 localization in the perinuclear region is not restricted to the trans-Golgi network, but extends to recycling endosomes. In addition, we report that depletion of Sec5 exocyst subunit or dominant inhibition of Sec10 affects the function and the morphology of the recycling pathway. Sec10 is found to redistribute to ruffling areas of the plasma membrane in cells expressing GTP-ARF6, whereas dominant inhibition of Sec10 interferes with ARF6-induced cell spreading. Our paper suggests that ARF6 specifies delivery and insertion of recycling membranes to regions of dynamic reorganization of the plasma membrane through interaction with the vesicle-tethering exocyst complex.
PURPOSE: To develop a completely automated method based on image processing techniques and artificial neural networks for the interpretation of combined [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) images for the diagnosis and staging of lung cancer. METHODS: A total of 87 patients who underwent PET/CT examinations due to suspected lung cancer comprised the training group. The test group consisted of PET/CT images from 49 patients suspected with lung cancer. The consensus interpretations by two experienced physicians were used as the 'gold standard' image interpretation. The training group was used in the development of the automated method. The image processing techniques included algorithms for segmentation of the lungs based on the CT images and detection of lesions in the PET images. Lung boundaries from the CT images were used for localization of lesions in the PET images in the feature extraction process. Eight features from each examination were used as inputs to artificial neural networks trained to classify the images. Thereafter, the performance of the network was evaluated in the test set. RESULTS: The performance of the automated method measured as the area under the receiver operating characteristic curve, was 0.97 in the test group, with an accuracy of 92%. The sensitivity was 86% at a specificity of 100%. CONCLUSIONS: A completely automated method using artificial neural networks can be used to detect lung cancer with such a high accuracy that the application as a clinical decision support tool appears to have significant potential.
Autism is a neurodevelopmental disorder with a range of clinical presentations. These presentations vary from mild to severe and are referred to as autism spectrum disorders. The most common clinical sign of autism spectrum disorders is social interaction impairment, which is associated with verbal and non-verbal communication deficits and stereotyped and repetitive behaviors. Thanks to recent brain imaging studies, scientists are getting a better idea of the neural circuits involved in autism spectrum disorders. Indeed, functional brain imaging, such as positron emission tomography, single foton emission tomography and functional MRI have opened a new perspective to study normal and pathological brain functioning. Three independent studies have found anatomical and rest functional temporal lobe abnormalities in autistic patients. These alterations are localized in the superior temporal sulcus bilaterally, an area which is critical for perception of key social stimuli. In addition, functional studies have shown hypoactivation of most areas implicated in social perception (face and voice perception) and social cognition (theory of mind). These data suggest an abnormal functioning of the social brain network in autism. The understanding of the functional alterations of this important mechanism may drive the elaboration of new and more adequate social re-educative strategies for autistic patients.
Age changes of microstructure of granular layer of the cortex of human cerebellum superior lobe (the area of clivus, posterior lateral regions of right and left tetrangular lobules) were studied in annual intervals from birth up to 20 yrs using computer analysis of optic images. Enlargement of the area of profile fields of cell groups in apical and basal regions of cerebellar folia from birth up to 14-15 yrs and differences between hemispheres in clasterization of granular layer were demonstrated. The data on age changes of cellular aggregations obtained allowed to formulate a hypothesis on autonomic local sensory networks of human cerebellar cortex associated with granular layer of cerebellar cortex that are considered as structural elements of module organization of the latter.
It is time for all providers, physicians, hospital executives and ancillary providers to find creative ways to meet the healthcare needs of their local communities. More efficient systems of health care delivery will come from noncompetitive partnerships based on shared visions, collaborations, openess, honesty and integrity. RHP can be a catalyst for physicians and other providers in the Kansas City area and throughout the state to respond to the challenges and opportunities that lie before them.
BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that can lead to malignancies over time. Sphingosine-1-phosphate (S1P) receptor signaling affects lymphocyte trafficking and vascular integrity, influencing intestinal inflammation. This study aimed to identify S1P-related key genes in UC. METHODS: Differentially expressed genes (DEGs) between the UC and control groups were analyzed in the GSE87473 (training) dataset. Genes overlapping between the DEGs and S1P-related genes were considered candidate genes. These genes were incorporated into machine learning algorithms and subjected to expression analysis to identify key genes. Gene functions were determined through a gene–gene interaction network, enrichment analysis, and immune cell infiltration analysis. In addition, transcription factor–mRNA and mRNA–miRNA–lncRNA networks were constructed. Finally, reverse transcription–quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the expression of key candidate genes in UC and control tissues. RESULTS: This study identified two key genes (SPHK2 and SPNS2) associated with UC. Notably, SPHK2 expression was lower and SPNS2 expression was higher in the UC group in both training and validation datasets and in clinical UC tissues (RT-qPCR). The area under the curve values of SPHK2 and SPNS2 exceeded 0.7 in both datasets, indicating that the genes had good diagnostic efficacy for UC. Consistently, the nomogram showed that the two genes had promising diagnostic value in UC. SPHK2 and SPNS2 were found to be localized to the plasma membrane. The correlations of the two genes with different immune cells showed significantly opposite trends. In particular, SPHK2 had the strongest positive correlation with M2 macrophages (r = 0.6) and the strongest negative correlation with neutrophils. Moreover, mRNA–miRNA–lncRNA and transcription factor– mRNA networks of the key genes were constructed. CONCLUSION: This study suggests that SPHK2 and SPNS2 are key genes associated with UC, highlighting their potential as effective diagnostic biomarkers.
Market surveys show that a dramatic organizational and economic restructuring of medical care delivery is taking place at the local level. These changes suggest a trend in which a finite number of umbrella corporations within each local area will be established and will control the majority of medical care provided. Information systems will play a critical role in determining the success or failure of these organizations.
We have investigated the arrangement and function of actin filament bundles in Sertoli cell ectoplasmic specializations found adjacent to junctional networks and in areas of adhesion to spermatogenic cells. Tissue was collected, from ground squirrel (Spermophilus spp.) testes, in three ways: seminiferous tubules were fragmented mechanically; segments of intact epithelium and denuded tubule walls were isolated by using EDTA in a phosphate-buffered salt solution; and isolated epithelia and denuded tubule walls were extracted in glycerol. To determine the arrangement of actin bundles, the tissue was fixed, mounted on slides, treated with cold acetone (-20 degrees C), and then exposed to nitrobenzoxadiazole-phallacidin. Myosin was localized using immunofluorescence. To investigate the hypothesis that ectoplasmic specializations are contractile, glycerinated models were exposed to exogenous ATP and Ca++; then contraction was assessed qualitatively by using nitrobenzoxadiazole-phallacidin as a marker. Actin bundles in ectoplasmic specializations adjacent to junctional networks circumscribe the bases of Sertoli cells. When intact epithelia are viewed from an angle perpendicular to the epithelial base, honeycomb staining patterns are observed. Filament bundles in Sertoli cell regions adjacent to spermatogenic cells dramatically change organization during spermatogenesis. Initially, the bundles circle the region of contact between the developing acrosome and nucleus. They then expand to cover the entire head. As the spermatid flattens, filaments on one side of the now saucer-shaped head orient themselves parallel to the germ cell axis while those on the other align perpendicularly to it. Before sperm release, all filaments course parallel to the rim of the head. Contrary to the results we obtained with myoid cells, we could not convincingly demonstrate myosin in ectoplasmic specializations or induce contraction of glycerinated models. Our data are consistent with the hypothesis that actin in ectoplasmic specializations of Sertoli cells may be more skeletal than contractile.