Reduced metal transferrin binding in neurological diseases

By employing G75 gel-filtration chromotography, it has been demonstrated that human plasma gallium speciation (and by implication, Al speciation) is bimodal. Normally, gallium was predominantly bound to a high molecular weight fraction which was presumably transferrin. Literature reviews and experimental work throughout this thesis provided evidence to support this idea. An aluminium-transferrin species was assumed to be relatively non-toxic and a protective function for this complex has been suggested. A second, low molecular weight species of gallium was observed and its identity has been suggested to be citrate. The results of this thesis support the concept citrate was a gallium binding ligand present in the plasma, but there was another species (tentatively identified as phosphate) which bound gallium to a much greater degree than did citrate in the majority of samples studied. The consequence of a low molecular weight species of aluminium is the possibility that this leads to a more rapid, uncontrolled deposition of the metal in the brain compared to a transferrin mediated mechanism. Plasma speciation studies in Alzheimer's disease, Parkinson's disease, Down's syndrome, and neonates has revealed an altered ratio of the two gallium species found in control subjects. In all groups there was an increase in the potentially more neurotoxic low molecular weight species. These observations have led to a suggested mechanism of accumulation of metals in the brain, which is known to occur in the first three groups. Possible pathogenic mechanisms are described. The results can also offer an explanation to the reported increased sensitivity to the toxic effects of aluminium in the neonate. Speciation studies on normal plasma has shown the balance between high and low molecular weight species of gallium to be influenced by many physiological factors. There appears to be a fine equilibrium between both species which can be altered without any great difficulty. Therefore, in the diseased groups studied, it is possible that there are subtle biochemical changes within the circulatory system to affect the equilibrium which results in an increased low molecular weight species of aluminium. Furthermore, it has been demonstrated that there is a group of normal controls with no clinical signs of Alzheimer's or Parkinson's disease which have reduced transferrin binding. This indicates there is a population of healthy people who are at risk to the development of either disease.

General features of Multiple System Atrophy

Multiple system atrophy (MSA) is a rare movement disorder and a member of a group of neurodegenerative diseases referred to collectively as the ‘parkinsonian syndromes’. Characteristic of these syndromes is that the patient exhibits symptoms of ‘parkinsonism’, viz., a range of problems involving movement, most typically manifest in Parkinson’s disease (PD) itself1, but also seen in progressive supranuclear palsy (PSP), and to some extent in dementia with Lewy bodies (DLB). MSA is a relatively ‘new’ descriptive term and is derived from three previously described diseases, viz., olivopontocerebellar atrophy, striato-nigral degeneration, and Shy-Drager syndrome. The classical symptoms of MSA include parkinsonism, ataxia, and autonomic dysfunction.6 Ataxia describes a gross lack of coordination of muscle movements while autonomic dysfunction involves a variety of systems that regulate unconscious bodily functions such as heart rate, blood pressure, bladder function, and digestion. Although primarily a neurological disorder, patients with MSA may also develop visual signs and symptoms that could be useful in differential diagnosis. The most important visual signs may include oculomotor dysfunction and problems in pupil reactivity but are less likely to involve aspects of primary vision such as visual acuity, colour vision, and visual fields. In addition, the eye-care practitioner can contribute to the management of the visual problems of MSA and therefore, help to improve quality of life of the patient. Hence, this first article in a two-part series describes the general features of MSA including its prevalence, signs and symptoms, diagnosis, pathology, and possible causes.

Visual signs and symptoms of Multiple System Atrophy

Multiple system atrophy (MSA) is a rare movement disorder and a member of a group of neurodegenerative diseases, which include Parkinson’s disease (PD) and progressive supranuclear palsy (PSP), and referred to as the ‘parkinsonian syndromes’. Although primarily a neurological disorder, patients with MSA may also develop visual signs and symptoms that could be useful in differential diagnosis. In addition, the eye-care practitioner may contribute to the management of visual problems of MSA patients and therefore, help to improve quality of life. This second article in the series considers the visual signs and symptoms of MSA with special reference to those features most useful in differential diagnosis of the parkinsonian syndromes.

The Intelligent System of the Hearing Investigation

This paper describes a prototype of the intelligent system of the hearing investigation developed by the Tver State Technical University. The problem of automatic diagnostics, considered as the recognition problem of object not completely determined on set of the diseases classes’ descriptions, is discussed. The management strategy of the hearing investigation is proposed.

Placental contribution to the origins of sexual dimorphism in health and diseases: sex chromosomes and epigenetics

Sex differences occur in most non-communicable diseases, including metabolic diseases, hypertension, cardiovascular disease, psychiatric and neurological disorders and cancer. In many cases, the susceptibility to these diseases begins early in development. The observed differences between the sexes may result from genetic and hormonal differences and from differences in responses to and interactions with environmental factors, including infection, diet, drugs and stress. The placenta plays a key role in fetal growth and development and, as such, affects the fetal programming underlying subsequent adult health and accounts, in part for the developmental origin of health and disease (DOHaD). There is accumulating evidence to demonstrate the sex-specific relationships between diverse environmental influences on placental functions and the risk of disease later in life. As one of the few tissues easily collectable in humans, this organ may therefore be seen as an ideal system for studying how male and female placenta sense nutritional and other stresses, such as endocrine disruptors. Sex-specific regulatory pathways controlling sexually dimorphic characteristics in the various organs and the consequences of lifelong differences in sex hormone expression largely account for such responses. However, sex-specific changes in epigenetic marks are generated early after fertilization, thus before adrenal and gonad differentiation in the absence of sex hormones and in response to environmental conditions. Given the abundance of X-linked genes involved in placentogenesis, and the early unequal gene expression by the sex chromosomes between males and females, the role of X- and Y-chromosome-linked genes, and especially those involved in the peculiar placenta-specific epigenetics processes, giving rise to the unusual placenta epigenetic landscapes deserve particular attention. However, even with recent developments in this field, we still know little about the mechanisms underlying the early sex-specific epigenetic marks resulting in sex-biased gene expression of pathways and networks. As a critical messenger between the maternal environment and the fetus, the placenta may play a key role not only in buffering environmental effects transmitted by the mother but also in expressing and modulating effects due to preconceptional exposure of both the mother and the father to stressful conditions.

Changes in microbial diversity associated with two coral species recovering from a stressed state in a public aquarium system:Microbial diversity associated with aquarium corals

Coral diseases are a major factor in the decline of coral reefs worldwide, and a large proportion of studies focusing on disease causation use aquaria to control variables that affect disease occurrence and development. Public aquaria can therefore provide an invaluable resource to study the factors contributing to health and disease. In November 2010 the corals within the main display tank at the Horniman Museum and Gardens, London, UK, underwent a severe stress event due to reduced water quality, which resulted in death of a large number of coral colonies. Three separate colonies of two species of reef coral, Seritopora hystrix and Montipora capricornis showing signs of stress and acute tissue loss were removed from the display tank and placed in a research tank with improved water quality. Both coral species showed a significant difference in 16S rRNA gene bacterial diversity between healthy and stressed states (S. hystrix; ANOSIM, R=0.44, p=0.02 and M. capricornis; ANOSIM, R=0.33, p=0.01), and between the stressed state and the recovering corals. After four months the bacterial communities had returned to a similar state to that seen in healthy corals of the same species. The bacterial communities associated with the two coral species were distinct, despite them
being reared under identical environmental conditions. Despite the environmental perturbation being identical different visual signs were seen in each species and distinctly different bacterial communities associated with the stressed state occurred within them. Recovery of the visually healthy state was associated with a return of the bacterial community, within two months, to the pre-disturbance state. These observations suggest that coral-associated microbial communities are remarkably resilient and return to a very similar stable state following disturbance.

Mechanisms underlying activation of neural stem cells in the adult central nervous system

À la fin du 19e siècle, Dr. Ramón y Cajal, un pionnier scientifique, a découvert les éléments cellulaires individuels, appelés neurones, composant le système nerveux. Il a également remarqué la complexité de ce système et a mentionné l’impossibilité de ces nouveaux neurones à être intégrés dans le système nerveux adulte. Une de ses citations reconnues : “Dans les centres adultes, les chemins nerveux sont fixes, terminés, immuables. Tout doit mourir, rien ne peut être régénérer” est représentative du dogme de l’époque (Ramón y Cajal 1928). D’importantes études effectuées dans les années 1960-1970 suggèrent un point de vue différent. Il a été démontré que les nouveaux neurones peuvent être générés à l’âge adulte, mais cette découverte a créé un scepticisme omniprésent au sein de la communauté scientifique. Il a fallu 30 ans pour que le concept de neurogenèse adulte soit largement accepté. Cette découverte, en plus de nombreuses avancées techniques, a ouvert la porte à de nouvelles cibles thérapeutiques potentielles pour les maladies neurodégénératives. Les cellules souches neurales (CSNs) adultes résident principalement dans deux niches du cerveau : la zone sous-ventriculaire des ventricules latéraux et le gyrus dentelé de l’hippocampe. En condition physiologique, le niveau de neurogenèse est relativement élevé dans la zone sous-ventriculaire contrairement à l’hippocampe où certaines étapes sont limitantes. En revanche, la moelle épinière est plutôt définie comme un environnement en quiescence. Une des principales questions qui a été soulevée suite à ces découvertes est : comment peut-on activer les CSNs adultes afin d’augmenter les niveaux de neurogenèse ? Dans l’hippocampe, la capacité de l’environnement enrichi (incluant la stimulation cognitive, l’exercice et les interactions sociales) à promouvoir la neurogenèse hippocampale a déjà été démontrée. La plasticité de cette région est importante, car elle peut jouer un rôle clé dans la récupération de déficits au niveau de la mémoire et l’apprentissage. Dans la moelle épinière, des études effectuées in vitro ont démontré que les cellules épendymaires situées autour du canal central ont des capacités d’auto-renouvellement et de multipotence (neurones, astrocytes, oligodendrocytes). Il est intéressant de noter qu’in vivo, suite à une lésion de la moelle épinière, les cellules épendymaires sont activées, peuvent s’auto-renouveller, mais peuvent seulement ii donner naissance à des cellules de type gliale (astrocytes et oligodendrocytes). Cette nouvelle fonction post-lésion démontre que la plasticité est encore possible dans un environnement en quiescence et peut être exploité afin de développer des stratégies de réparation endogènes dans la moelle épinière. Les CSNs adultes jouent un rôle important dans le maintien des fonctions physiologiques du cerveau sain et dans la réparation neuronale suite à une lésion. Cependant, il y a peu de données sur les mécanismes qui permettent l'activation des CSNs en quiescence permettant de maintenir ces fonctions. L'objectif général est d'élucider les mécanismes sous-jacents à l'activation des CSNs dans le système nerveux central adulte. Pour répondre à cet objectif, nous avons mis en place deux approches complémentaires chez les souris adultes : 1) L'activation des CSNs hippocampales par l'environnement enrichi (EE) et 2) l'activation des CSNs de la moelle épinière par la neuroinflammation suite à une lésion. De plus, 3) afin d’obtenir plus d’information sur les mécanismes moléculaires de ces modèles, nous utiliserons des approches transcriptomiques afin d’ouvrir de nouvelles perspectives. Le premier projet consiste à établir de nouveaux mécanismes cellulaires et moléculaires à travers lesquels l’environnement enrichi module la plasticité du cerveau adulte. Nous avons tout d’abord évalué la contribution de chacune des composantes de l’environnement enrichi à la neurogenèse hippocampale (Chapitre II). L’exercice volontaire promeut la neurogenèse, tandis que le contexte social augmente l’activation neuronale. Par la suite, nous avons déterminé l’effet de ces composantes sur les performances comportementales et sur le transcriptome à l’aide d’un labyrinthe radial à huit bras afin d’évaluer la mémoire spatiale et un test de reconnaissante d’objets nouveaux ainsi qu’un RNA-Seq, respectivement (Chapitre III). Les coureurs ont démontré une mémoire spatiale de rappel à court-terme plus forte, tandis que les souris exposées aux interactions sociales ont eu une plus grande flexibilité cognitive à abandonner leurs anciens souvenirs. Étonnamment, l’analyse du RNA-Seq a permis d’identifier des différences claires dans l’expression des transcripts entre les coureurs de courte et longue distance, en plus des souris sociales (dans l’environnement complexe). iii Le second projet consiste à découvrir comment les cellules épendymaires acquièrent les propriétés des CSNs in vitro ou la multipotence suite aux lésions in vivo (Chapitre IV). Une analyse du RNA-Seq a révélé que le transforming growth factor-β1 (TGF-β1) agit comme un régulateur, en amont des changements significatifs suite à une lésion de la moelle épinière. Nous avons alors confirmé la présence de cette cytokine suite à la lésion et caractérisé son rôle sur la prolifération, différentiation, et survie des cellules initiatrices de neurosphères de la moelle épinière. Nos résultats suggèrent que TGF-β1 régule l’acquisition et l’expression des propriétés de cellules souches sur les cellules épendymaires provenant de la moelle épinière.

The mating system of the true fruit flyBactrocera tryoniand its sister-species, Bactrocera neohumeralis

The frugivorous “true” fruit fly, Bactrocera tryoni (Queensland fruit fly), is presumed to have a nonresourced-based lek mating system. This is largely untested, and contrary data exists to suggest Bactrocera tryoni may have a resource-based mating system focused on fruiting host plants. We tested the mating system of Bactrocera tryoni, and its close sibling Bactrocera neohumeralis, in large field cages using laboratory reared flies. We used observational experiments that allowed us to determine if: (i) mating pairs were aggregated or nonaggregated; (ii) mating system was resource or nonresource based; (iii) flies utilized possible landmarks (tall trees over short) as mate-rendezvous sites; and (iv) males called females from male-dominated leks. We recorded nearly 250 Bactrocera tryoni mating pairs across all experiments, revealing that: (i) mating pairs were aggregated; (ii) mating nearly always occurred in tall trees over short; (iii) mating was nonresource based; and (iv) that males and females arrived at the mate-rendezvous site together with no evidence that males preceded females. Bactrocera neohumeralis copulations were much more infrequent (only 30 mating pairs in total), but for those pairs there was a similar preference for tall trees and no evidence of a resource-based mating system. Some aspects of Bactrocera tryoni mating behavior align with theoretical expectations of a lekking system, but others do not. Until evidence for unequivocal female choice can be provided (as predicted under a true lek), the mating system of Bactrocera tryoni is best described as a nonresource based, aggregation system for which we also have evidence that land-marking may be involved.

Detection of viral diseases in shrimp Litopenaeus vannamei in Iran with emphasis on white spot disease prevention by using marine alga extract

Nowadays, following was expanded shrimp breeding and culture; viral diseases have been main problem which threatened shrimp industry in the country. Therefore, shrimp samples were obtained from different stages of Litopenaeus vannmei life cycle (larval, post larval, juveniles, adults and broodstocks) based on clinical signs in the breeding center and shrimp farming from Bushehr, Khozestan and Sistan and Baluchestan provinces. Viral diseases were detected by PCR (Polymerase Chain Reaction), histopathology and transmission electron microscopy (TEM) methods. Results of the PCR were indicated present white spot virus (WSV) in juveniles, sub adults and adults shrimp with medium intensity from three provinces, but it was not showed in larval and post larval stages. Histopathological sections were indicated hypertrophy and basophilic Cowdry type A formation in nucleus cells of gill, haematopoietic, lymphoid and epithelial's cuticles and intestinal tissues which was associated with small vacuoles increased in B cells of hepatopancreas tissue of infection shrimps. Transmission electronic microscopic studies were demonstrated that the length and diameter virus was detected, respectively, 300 ± 20 nm and 75 ± 5 nm. Considerable, results of the PCR were only displayed IHHNV in juvenile, adult and broodstock shrimps from breeding and farming center of Bushehr province. The main lesion pathology was formed eosinophilic Cowdry type A in nucleus cells of gill, haematopoietic, lymphoid and epithelial's cuticles and intestinal tissues. Whereas penaeid shrimps are lack specific immune system, hence, in the present study was used of marine alga (Lurensia snideria) collected from along costal Persian Gulf of Bushehr province for viral diseases were prevented. Powder alga extract were added with a ratio of 1 % to shrimp diet. Total haemocyte count (THC) and total protein plasma (TPP) were increased after 5 days of oral administration diets. When shrimps were infected by with spot virus experimentally, THC and TPP gradually were increased in both two groups (shrimps fed with diet containing alga extract and without alga extract) after 48h. Nevertheless; THC, TPP and survival of shrimp fed with diet containing alga extract were more than shrimp control in 15 days. So, oral administration Lurensia snideria extract was capable prevention infected L. vannamei via stimulant specific immune system.

Clonagem e expressão do gene que codifica o inibidor de quimotripsina de Erythrina velutina WILLD. - caracterização e avaliação de seu potencial farmacológico

Proteinases are enzymes distributed widely founded in several organisms and perform many different functions, from maintaining homeostasis to the worsening of some diseases such as cancer, autoimmune diseases and infections. The proteins responsible of controlling the action of these enzymes are the inhibitors, that are classified based on their target proteases and are founded since simple organisms, such as bacteria, to higher organisms, such as larger plants and mammals. Plant proteinase inhibitors act by reducing or inactivating the activity of target proteases, thus, these proteins have been studied as potential tools in the treatment of diseases related to protease activities. In this context, an inhibitor of chymotrypsin from Erythrina velutina, called EvCI was previously purified and it was observed that this protein plays in vitro anticoagulant activity and anti-inflammatory activity in in vivo model. Aiming to reduce the environmental impact caused by the purification EvCI in high amounts and to facilitate the process of obtaining this protein, the recombinant chymotrypsin inhibitor from Eryhrina velutina was produced after cloning and expression in Escherichia coli. The bacteria were grown in LB medium and after induction of the expression this material was subjected to procedures for cell lysis and the product was applied on Nickel-affinity column. The proteins adsorbed were digested by thrombin and applied on Chymotrypsin-Sepharose affinity column, obtaining the purified inhibitor, named recEvCI. After electrophoresis, the recombinant inhibitor showed an approximately molecular mass of 17 kDa, and reduced the chymotrypsin and elastase activities in vitro. The recombinant inhibitor was sequenced and was found similar amino acids residues when compared to other inhibitors deposited in the database, with some modifications. recEvCI showed high stability under pH variations and reducing conditions, maintaining its activity around 80%. This protein increased the blood coagulation time in vitro by acting on the intrinsic pathway and did not show cytotoxicity against strains of mouse 3T3 fibroblasts and RAW 264.7 macrophages. recEvCI showed microbicide activity related to release of nitric oxide and consequently the activation of macrophages, futhermore having proinflammatory effects assessed by increased release of TNF-α. These results indicate that recEvCI can be biotechnologically used as a new tool in the control of coagulation-related diseases as well as can be an activating agent of the immune system in immunosuppressed individuals

Diagnóstico ecográfico de tumores anexiais: modelos do grupo international ovary tumor analysis (IOTA) versus classificação gynecologic imaging report and data system (GI-RADS)

A ecografia é o exame de primeira linha na identificação e caraterização de tumores anexiais. Foram descritos diversos métodos de diagnóstico diferencial incluindo a avaliação subjetiva do observador, índices descritivos simples e índices matematicamente desenvolvidos como modelos de regressão logística, continuando a avaliação subjectiva por examinador diferenciado a ser o melhor método de discriminação entre tumores malignos e benignos. No entanto, devido à subjectividade inerente a esta avaliação tornouse necessário estabelecer uma nomenclatura padronizada e uma classificação que facilitasse a comunicação de resultados e respectivas recomendações de vigilância. O objetivo deste artigo é resumir e comparar diferentes métodos de avaliação e classificação de tumores anexiais, nomeadamente os modelos do grupo International Ovary Tumor Analysis (IOTA) e a classificação Gynecologic Imaging Report and Data System (GI-RADS), em termos de desempenho diagnóstico e utilidade na prática clínica.

Mechanisms underlying activation of neural stem cells in the adult central nervous system

À la fin du 19e siècle, Dr. Ramón y Cajal, un pionnier scientifique, a découvert les éléments cellulaires individuels, appelés neurones, composant le système nerveux. Il a également remarqué la complexité de ce système et a mentionné l’impossibilité de ces nouveaux neurones à être intégrés dans le système nerveux adulte. Une de ses citations reconnues : “Dans les centres adultes, les chemins nerveux sont fixes, terminés, immuables. Tout doit mourir, rien ne peut être régénérer” est représentative du dogme de l’époque (Ramón y Cajal 1928). D’importantes études effectuées dans les années 1960-1970 suggèrent un point de vue différent. Il a été démontré que les nouveaux neurones peuvent être générés à l’âge adulte, mais cette découverte a créé un scepticisme omniprésent au sein de la communauté scientifique. Il a fallu 30 ans pour que le concept de neurogenèse adulte soit largement accepté. Cette découverte, en plus de nombreuses avancées techniques, a ouvert la porte à de nouvelles cibles thérapeutiques potentielles pour les maladies neurodégénératives. Les cellules souches neurales (CSNs) adultes résident principalement dans deux niches du cerveau : la zone sous-ventriculaire des ventricules latéraux et le gyrus dentelé de l’hippocampe. En condition physiologique, le niveau de neurogenèse est relativement élevé dans la zone sous-ventriculaire contrairement à l’hippocampe où certaines étapes sont limitantes. En revanche, la moelle épinière est plutôt définie comme un environnement en quiescence. Une des principales questions qui a été soulevée suite à ces découvertes est : comment peut-on activer les CSNs adultes afin d’augmenter les niveaux de neurogenèse ? Dans l’hippocampe, la capacité de l’environnement enrichi (incluant la stimulation cognitive, l’exercice et les interactions sociales) à promouvoir la neurogenèse hippocampale a déjà été démontrée. La plasticité de cette région est importante, car elle peut jouer un rôle clé dans la récupération de déficits au niveau de la mémoire et l’apprentissage. Dans la moelle épinière, des études effectuées in vitro ont démontré que les cellules épendymaires situées autour du canal central ont des capacités d’auto-renouvellement et de multipotence (neurones, astrocytes, oligodendrocytes). Il est intéressant de noter qu’in vivo, suite à une lésion de la moelle épinière, les cellules épendymaires sont activées, peuvent s’auto-renouveller, mais peuvent seulement ii donner naissance à des cellules de type gliale (astrocytes et oligodendrocytes). Cette nouvelle fonction post-lésion démontre que la plasticité est encore possible dans un environnement en quiescence et peut être exploité afin de développer des stratégies de réparation endogènes dans la moelle épinière. Les CSNs adultes jouent un rôle important dans le maintien des fonctions physiologiques du cerveau sain et dans la réparation neuronale suite à une lésion. Cependant, il y a peu de données sur les mécanismes qui permettent l'activation des CSNs en quiescence permettant de maintenir ces fonctions. L'objectif général est d'élucider les mécanismes sous-jacents à l'activation des CSNs dans le système nerveux central adulte. Pour répondre à cet objectif, nous avons mis en place deux approches complémentaires chez les souris adultes : 1) L'activation des CSNs hippocampales par l'environnement enrichi (EE) et 2) l'activation des CSNs de la moelle épinière par la neuroinflammation suite à une lésion. De plus, 3) afin d’obtenir plus d’information sur les mécanismes moléculaires de ces modèles, nous utiliserons des approches transcriptomiques afin d’ouvrir de nouvelles perspectives. Le premier projet consiste à établir de nouveaux mécanismes cellulaires et moléculaires à travers lesquels l’environnement enrichi module la plasticité du cerveau adulte. Nous avons tout d’abord évalué la contribution de chacune des composantes de l’environnement enrichi à la neurogenèse hippocampale (Chapitre II). L’exercice volontaire promeut la neurogenèse, tandis que le contexte social augmente l’activation neuronale. Par la suite, nous avons déterminé l’effet de ces composantes sur les performances comportementales et sur le transcriptome à l’aide d’un labyrinthe radial à huit bras afin d’évaluer la mémoire spatiale et un test de reconnaissante d’objets nouveaux ainsi qu’un RNA-Seq, respectivement (Chapitre III). Les coureurs ont démontré une mémoire spatiale de rappel à court-terme plus forte, tandis que les souris exposées aux interactions sociales ont eu une plus grande flexibilité cognitive à abandonner leurs anciens souvenirs. Étonnamment, l’analyse du RNA-Seq a permis d’identifier des différences claires dans l’expression des transcripts entre les coureurs de courte et longue distance, en plus des souris sociales (dans l’environnement complexe). iii Le second projet consiste à découvrir comment les cellules épendymaires acquièrent les propriétés des CSNs in vitro ou la multipotence suite aux lésions in vivo (Chapitre IV). Une analyse du RNA-Seq a révélé que le transforming growth factor-β1 (TGF-β1) agit comme un régulateur, en amont des changements significatifs suite à une lésion de la moelle épinière. Nous avons alors confirmé la présence de cette cytokine suite à la lésion et caractérisé son rôle sur la prolifération, différentiation, et survie des cellules initiatrices de neurosphères de la moelle épinière. Nos résultats suggèrent que TGF-β1 régule l’acquisition et l’expression des propriétés de cellules souches sur les cellules épendymaires provenant de la moelle épinière.

Development of the Andalusian Registry of Patients Receiving Community Case Management, for the follow-up of people with complex chronic diseases.

Background: Complex chronic diseases are a challenge for the current configuration of Health services. Case management is a service frequently provided for people with chronic conditions and despite its effectiveness in many outcomes, such as mortality or readmissions, uncertainty remains about the most effective form of team organization, structures, and the nature of the interventions. Many processes and outcomes of case management for people with complex chronic conditions cannot be addressed with the information provided by electronic clinical records. Registries are frequently used to deal with this weakness. The aim of this study was to generate a registry-based information system of patients receiving case management to identify their clinical characteristics, their context of care, events identified during their follow-up, interventions developed by case managers, and services used. Methods and design: The study was divided into three phases, covering the detection of information needs, the design and its implementation in the healthcare system, using literature review and expert consensus methods to select variables that would be included in the registry. Objective: To describe the essential characteristics of the provision of ca re lo people who receive case management (structure, process and outcomes), with special emphasis on those with complex chronic diseases. Study population: Patients from any District of Primary Care, who initiate the utilization of case management services, to avoid information bias that may occur when including subjects who have already been received the service, and whose outcomes and characteristics could not be properly collected. Results: A total of 102 variables representing structure, processes and outcomes of case management were selected for their inclusion in the registry after the consensus phase. Total sample was composed of 427 patients, of which 211 (49.4%) were women and 216 (50.6%) were men. The average functional level (Barthel lndex) was 36.18 (SD 29.02), cognitive function (Pfeiffer) showed an average of 4.37 {SD 6.57), Chat1son Comorbidity lndex, obtained a mean of 3.03 (SD 2.7) and Social Support (Duke lndex) was 34.2 % (SD 17.57). More than half of patients include in the Registry, correspond lo immobilized or transitional care for patients discharged from hospital (66.5 %). The patient's educational level was low or very low (50.4%). Caregivers overstrain (Caregiver stress index), obtained an average value of 6.09% (SD 3.53). Only 1.2 % of patients had declared their advanced directives, 58.6 had not defined the tutelage and the vast majority lived at home 98.8 %. Regarding the major events recorded at RANGE Registry, 25.8 % of the selected patients died in the first three months, 8.2 % suffered a hospital admission at least once time, 2.3%, two times, and 1.2% three times, 7.5% suffered a fall, 8.7% had pressure ulcer, 4.7% had problems with medication, and 3.3 % were institutionalized. Stroke is the more prevalent health problem recorded (25.1%), followed by hypertension (11.1%) and COPD (11.1%). Patients registered by NCMs had as main processes diabetes (16.8%) and dementia (11.3 %). The most frequent nursing diagnoses referred to the self-care deficit in various activities of daily living. Regarding to nursing interventions, described by the Nursing Intervention Classification (NIC), dementia management is the most used intervention, followed by mutual goal setting, caregiver and emotional support. Conclusions: The patient profile who receive case management services is a chronic complex patient with severe dependence, cognitive impairment, normal social support, low educational level, health problems such as stroke, hypertension or COPD, diabetes or dementia, and has an informal caregiver. At the first follow up, mortality was 19.2%, and a discrete rate of readmissions and falls.

Incorporation of the Health Care System in the West

A reflection is made, from an interpretative perspective, on the historical evolution of health care in the West. It starts from the moment that this became a way to intervene the sick and an instrument for healing diseases, focusing on original documents and written sources which account for results of historical research, which range from XV century until today. To do this, it tries to understand the health care as an ideographic body of knowledge consisting of five pieces of a puzzle composed by: the state policy of hospitals accumulation implemented in Spain, the accumulation of medical practices in what is currently Germany, the hospital wards in England, the nosological rationality in France, and the US sanitizing machine; all these movements as producers of closely linked health care developments, that are nothing more than collective actions regulated by social norms around health.

Using health-related quality of life instruments for children with long-term conditions : On the basis of a national quality registry system

Introduction: There has been a continuous development of new technologies in healthcare that are derived from national quality registries. However, this innovation needs to be translated into the workflow of healthcare delivery, to enable children with long-term conditions to get the best support possible to manage their health during everyday life. Since children living with long-term conditions experience different interference levels in their lives, healthcare professionals need to assess the impact of care on children’s day-to-day lives, as a complement to biomedical assessments. Aim: The overall aim of this thesis was to explore and describe the use of instruments about health-related quality of life (HRQOL) in outpatient care for children with long-term conditions on the basis of a national quality registry system. Methods: The research was conducted by using comparative, cross-sectional and explorative designs and data collection was performed by using different methods. The questionnaire DISABKIDS Chronic Generic Measure -37 was used as well as semi-structured interviews and video-recordings from consultations. Altogether, 156 children (8–18 years) and nine healthcare professionals participated in the studies. Children with Type 1 Diabetes (T1D) (n 131) answered the questionnaire DISABKIDS and children with rheumatic diseases, kidney diseases and T1D (n 25) were interviewed after their consultation at the outpatient clinic after the web-DISABKIDS had been used. In total, nine healthcare professionals used the HRQOL instrument as an assessment tool during the encounters which was video-recorded (n 21). Quantitative deductive content analysis was used to describe content in different HRQOL instruments. Statistical inference was used to analyse results from DISABKIDS and qualitative content analysis was used to analyse the interviews and video-recordings. Results: The findings showed that based on a biopsychosocial perspective, both generic and disease-specific instruments should be used to gain a comprehensive evaluation of the child’s HRQOL. The DISABKIDS instrument is applicable when describing different aspects of health concerning children with T1D. When DISABKIDS was used in the encounters, children expressed positive experiences about sharing their results with the healthcare professional. It was discovered that different approaches led to different outcomes for the child when the healthcare professionals were using DISABKIDS during the encounter. When an instructing approach is used, the child’s ability to learn more about their health and how to improve their health is limited. When an inviting or engaging approach is used by the professional, the child may become more involved during the conversations. Conclusions: It could be argued that instruments of HRQOL could be used as a complement to biomedical variables, to promote a biopsychosocial perspective on the child’s health. According to the children in this thesis, feedback on their results after answering to web-DISABKIDS is important, which implies that healthcare professionals need to prioritize time for discussions about results from HRQOL instruments in the encounters. If healthcare professionals involve the child in the discussion of the results of the HRQOL, misinterpreted answers could be corrected during the conversation. Concurrently, this claims that healthcare professionals invite and engage the child.