Chlamydiaceae and Chlamydia-like organisms in the koala (Phascolarctos cinereus)--organ distribution and histopathological findings.

Chlamydial infections in koalas can cause life-threatening diseases leading to blindness and sterility. However, little is known about the systemic spread of chlamydiae in the inner organs of the koala, and data concerning related pathological organ lesions are limited. The aim of this study was to perform a thorough investigation of organs from 23 koalas and to correlate their histopathological lesions to molecular chlamydial detection. To reach this goal, 246 formalin-fixed and paraffin embedded organ samples from 23 koalas were investigated by histopathology, Chlamydiaceae real-time PCR and immunohistochemistry, ArrayTube Microarray for Chlamydiaceae species identification as well as Chlamydiales real-time PCR and sequencing. By PCR, two koalas were positive for Chlamydia pecorum whereas immunohistochemical labelling for Chlamydiaceae was detected in 10 tissues out of nine koalas. The majority of these (n=6) had positive labelling in the urogenital tract related to histopathological lesions such as cystitis, endometritis, pyelonephritis and prostatitis. Somehow unexpected was the positive labelling in the gastrointestinal tract including the cloaca as well as in lung and spleen indicating systemic spread of infection. Uncultured Chlamydiales were detected in several organs of seven koalas by PCR, and four of these suffered from plasmacytic enteritis of unknown aetiology. Whether the finding of Chlamydia-like organisms in the gastrointestinal tract is linked to plasmacytic enteritis is unclear and remains speculative. However, as recently shown in a mouse model, the gastrointestinal tract might play a role being the site for persistent chlamydial infections and being a source for reinfection of the genital tract.

Facilitar la teoría de la mente en niños con alteraciones del lenguaje

The ability to recognize mental states in oneself and others, or the theory of mind, has been a widely studied topic in last years. Traditionally, these studies have focused on the understanding of false belief, one of the most important milestones in its development. Studies conducted with children with language difficulties suggest that they have a delay in false belief acquisition. On the other hand, numerous studies have established a relationship between the understanding of false belief and language skills. In particular, it has been suggested that training based in labelling objects with double perspective facilitates the understanding of false belief. The aim of the present study is to test the effect of the structuration level of labelling training in a group of children with difficulties in language development. A total of 14 children, aged between 58 and 107 months, were trained in 3 sessions, and a pre-test and a post-test were administered to evaluate the effects of the training. The results confirm a delay in false belief understanding in children with developmental language difficulties, and suggest that the structured labelling training is effective to improve this understanding

Aplicação da espectroscopia de ressonância magnética nuclear para estudos de difusão molecular em líquidos: a técnica DOSY

Diffusion coefficients provide uniquely detailed and easily interpreted information on molecular organization and phase structure. They are quite sensitive to structural changes, and to binding and association phenomena, in particular for liquid colloidal or macromolecular systems. This paper describes the principles of diffusion measurements in liquids by pulsed magnetic field gradient spin-echo (PFG-SE) NMR spectroscopy. The important PFG-SE technique known as DOSY is presented and discussed. This is a noninvasive technique that can provide individual multicomponent translational diffusion coefficients with good precision in a few minutes, without the need for radioactive isotopic labelling.

In vivo co-ordinated interactions between inhibitory systems to control glutamate mediated hippocampal excitability.

We present an overview of the long-term adaptation of hippocampal neurotransmission to cholinergic and GABAergic deafferentation caused by excitotoxic lesion of the medial septum. Two months after septal microinjection of 2.7 nmol a -amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), a 220% increase of GABA A receptor labelling in the hippo- campal CA3 and the hilus was shown, and also changes in hippocampal neurotransmission characterised by in vivo microdialysis and HPLC. Basal amino acid and purine extra- cellular levels were studied in control and lesioned rats. In vivo effects of 100 m M KCl perfusion and adenosine A 1 receptor blockade with 1,3-dipropyl- 8-cyclopentylxanthine (DPCPX) on their release were also investigated. In lesioned animals GABA, glutamate and glutamine basal levels were decreased and taurine, adenosine and uric acid levels increased. A similar response to KCl infusion occurred in both groups except for GABA and glutamate, which release decreased in lesioned rats. Only in lesioned rats, DPCPX increased GABA basal level and KCl-induced glutamate release, and decreased glutamate turnover. Our results evidence that an excitotoxic septal lesion leads to increased hippocampal GABA A receptors and decreased glutamate neurotransmis- sion. In this situation, a co-ordinated response of hippocampal retaliatory systems takes place to control neuron excitability.

Positron emission tomography in the diagnosis and staging of pancreatic and neuroendocrine tumors

Tutkimuksen tausta ja tavoitteet: Viimeaikaisesta perinteisten kuvantamismenetelmien kehityksestä huolimatta sekä haima- että neuroendokriinisten (NE) kasvaimien diagnostiikka on haastavaa. Uudentyyppinen kuvantamismenetelmä, fuusio positroniemissiotomografia-tietokonetomografia (PET/TT), on lupaava näiden kasvainten erotusdiagnostiikassa ja levinneisyyden arvioinnissa. Huolimatta alustavista lupaavista tutkimustuloksista, PET/TT:n rooli on toistaiseksi vielä epäselvä sekä haima- että NE-kasvaimissa eikä se näin ollen ole vakiintunut kliiniseen hoitokäytäntöön. Väitöskirjatyön tavoitteena oli selvittää PET/TT -menetelmän käyttökelpoisuutta haima- ja NE-kasvaimien diagnostiikassa. Kahden ensimmäisen osatyön prospektiivisessa tutkimuksessa potilaat, joilla epäiltiin haimakasvainta, kuvannettiin PET/TT:llä käyttäen merkkiaineena fluorideoxyglukoosia (¹⁸F-FDG) kasvaimen aineenvaihdunnan arvioimiseksi ja kasvaimen verenvirtausta arviointiin käyttäen merkkiaineena radiovettä (¹⁵O-H₂O). Kolmen muun osatyön tavoitteena oli selvittää dihydroxyfenylalaniini (18F-DOPA) PET -menetelmää erilaisten NE-kasvaimien diagnostiikassa ja levinneisyyden arvioinnissa. Tulokset: Haimakasvaimien ensivaiheen diagnostiikassa ¹⁸F-FDG-PET/TT:llä oli korkeampi diagnostinen tarkkuus verrattuna titokoneleike- (TT) ja magneettikuvantamiseen (MK) (89% vs. 76% ja 79%). Etenkin pahanlaatuiseksi epäillyn sappitiehytahtauman erotusdiagnostiikassa ¹⁸F-FDG-PET/TT:n positiivinen ennustearvo (92%) oli korkea. Haimasyövän levinneisyyden arvioinnissa ¹⁸F-FDG-PET/TT:n herkkyys oli huono (30%) paikallisen taudin osoittamisessa. Sen sijaan etäpesäkkeiden osoittamisessa ¹⁸F-FDG-PET/TT oli merkittävästi herkempi menetelmä verrattuna TT ja magneettikuvantamiseen (88% vs. 38%). Verrattaessa erilaisten haimakasvaimien ja normaalin haimakudoksen aineenvaihduntaa ja verenvirtausta, aineenvaihdunta/verenvirtaus suhde oli merkittävästi korkeampi pahanlaatuisissa haimakasvaimissa (P<0.05). Lisäksi kasvaimen korkea aineenvaihdunta/verenvirtaus suhde viittasi huonompaan taudin ennusteeseen. ¹⁸F-DOPA-PET löysi seitsemän kahdeksasta insulinoomasta ja oli positiivinen myös kahdella potilaalla, joilla todettiin haiman saarakesoluhyperplasia. Perustuen alustaviin tuloksiin, rutiinikäytössä oleva karbidopa esilääke ennen ¹⁸F-DOPA-PET kuvantamista peitti insulinooma löydöksen kahdella potilaalla kolmesta. NE-kasvaiminen diagnostiikassa 82 potilaan aineisto osoitti ¹⁸F-DOPA PET kuvantamisen tarkkuudeksi 90%. Etenkin feokromosytoomien ensivaiheen diagnostiikassa ja NE-kasvaimen uusiutumaa epäiltäessä menetelmän tarkkuus oli korkea. Kokonaisuudessaan 59%:lla aineiston potilaista ¹⁸F-DOPA-PET kuvantamisella oli vaikutusta kliinisiin hoitoratkaisuihin. Johtopäätökset: PET/TT käyttäen merkkiaineena ¹⁸F-FDG:tä ja radiovettä osoittautui käyttökelpoiseksi menetelmäksi haimakasvaimien erotusdiagnostiikassa. Lisäksi ¹⁸F-FDG-PET/TT oli hyödyllinen haimasyövän etäpesäkkeiden arvioinnissa. Tutkimus osoitti myös ¹⁸F-DOPA-PET kuvantamisen olevan luotettava menetelmä insulinoomien ja muiden vatsan alueen NE-kasvaimien ensivaiheen diagnostiikassa sekä levinneisyyden arvioinnissa, etenkin muiden kuvantamislöydösten ollessa ristiriitaisia. PET kuvantamisella oli merkittävä vaikutus potilaiden kliiniseen hoitokäytäntöön sekä haima- että NE-kasvaimissa.

Veus ignorades: representacions socials, subjectivitat i resiliència en persones grans amb pèrdua d’autonomia funcional

Els processos per a l’aprovació i la implementació de la Llei per a l’Autonomia personal i l’Atenció a les Persones en situació de Dependència (LAPAD) han donat lloc a un intens debat polític i social que, coincidint també amb les millores en la provisió de serveis i els avenços mèdics, ha contribuït a un procés de classificació i d’etiquetatge basats en els dèficits de les persones que es troben en aquestes circumstàncies. Aquesta visió anul·la el subjecte i la seva experiència singular i condiciona l’abordatge dels models d’atenció i de cura. L’estudi pretén fer una aproximació a les persones grans amb pèrdua d’autonomia funcional, fent emergir les seves veus, que expressen com perceben, interpreten, afronten i es reajusten a la nova situació. Partint d’un enfocament constructivista, basat en la subjectivitat, es fa un recorregut sobre els models de la discapacitat que han reeixit en l’activitat científica dels darrers anys, els mecanismes de regulació de les pèrdues que defensen les teories del cicle vital i les aportacions que s’han fet sobre el model de la resiliència aplicat a les persones que envelleixen. El resultats de l’estudi mostren com les representacions i els significats que les persones grans atribueixen a la seva experiència s’inscriuen en les seves trajectòries vitals, donant un sentit únic i singular a la forma de viure i de respondre a la pèrdua d’autonomia funcional i les seves conseqüències. Aquelles que expressen una vivència d’integritat respecte de la vida viscuda, amb predomini d’afectes positius envers un mateix i els altres, que conserven l’esperança i el desig de continuar vivint, s’ajusten a les pèrdues de manera més satisfactòria que aquelles que expressen desconfiança i una certa amargor respecte de la pròpia vida. D’això se’n deriva que els espais d’escolta i d’acompanyament poden ser un recurs vàlid i necessari en el qual, a través de la paraula i el testimoni narrat, el subjecte pugui repensar i resignificar les seves experiències.

Imaging of the Vulnerable Atherosclerotic Plaque. Pre-Clinical Evaluation of PET Tracers for Vascular Inflammation

Atherosclerosis is a vascular inflammatory disease causing coronary artery disease, myocardial infarct and stroke, the leading causes of death in Finland and in many other countries. The development of atherosclerotic plaques starts already in childhood and is an ongoing process throughout life. Rupture of a plaque and the following occlusion of the vessel is the main reason for myocardial infarct and stroke, but despite extensive research, the prediction of rupture remains a major clinical problem. Inflammation is considered a key factor in the vulnerability of plaques to rupture. Measuring the inflammation in plaques non-invasively is one potential approach for identification of vulnerable plaques. The aim of this study was to evaluate tracers for positron emission tomography (PET) imaging of vascular inflammation. The studies were performed with a mouse model of atherosclerosis by using ex vivo biodistribution, autoradiography and in vivo PET and computed tomography (CT). Several tracers for inflammation activity were tested and compared with the morphology of the plaques. Inflammation in the atherosclerotic plaques was evaluated as expression of active macrophages. Systematic analysis revealed that the uptake of 18F-FDG and 11C-choline, tracers for metabolic activity in inflammatory cells, was more prominent in the atherosclerotic plaques than in the surrounding healthy vessel wall. The tracer for αvβ3 integrin, 18Fgalacto- RGD, was also found to have high potential for imaging inflammation in the plaques. While 11C-PK11195, a tracer targeted to receptors in active macrophages, was shown to accumulate in active plaques, the target-to-background ratio was not found to be ideal for in vivo imaging purposes. In conclusion, tracers for the imaging of inflammation in atherosclerotic plaques can be tested in experimental pre-clinical settings to select potential imaging agents for further clinical testing. 18F-FDG, 18F-galacto-RGD and 11C-choline choline have good properties, and further studies to clarify their applicability for atherosclerosis imaging in humans are warranted.

Rhizodeposition of organic carbon by plants with contrasting traits for resource acquisition: responses to different fertility regimes

Background and aims Rhizodeposition plays an important role in mediating soil nutrient availability in ecosystems. However, owing to methodological difficulties (i.e., narrow zone of soil around roots, rapid assimilation by soil microbes) fertility-induced changes in rhizodeposition remain mostly unknown. Methods We developed a novel long-term continuous 13C labelling method to address the effects of two levels of nitrogen (N) fertilization on rhizodeposited carbon (C) by species with different nutrient acquisition strategies. Results Fertility-induced changes in rhizodeposition were modulated by root responses to N availability rather than by changes in soil microbial biomass. Differences among species were mostly related to plant biomass: species with higher total leaf and root biomass also had higher total rhizodeposited C, whereas species with lower root biomass had higher specific rhizodeposited C (per gram root mass). Experimental controls demonstrated that most of the biases commonly associated with this type of experiment (i.e., long-term steady-state labelling) were avoided using our methodological approach. Conclusions These results suggest that the amount of rhizodeposited C from plants grown under different levels of N were driven mainly by plant biomass and root morphology rather than microbial biomass. They also underline the importance of plant characteristics (i.e., biomass allocation) as opposed to traits associated with plant resource acquisition strategies in predicting total C rhizodeposition.

The Child Protection System from the Perspective of Young People: Messages from 3 Studies

This article reports findings and reflections based on the results of three different research projects conducted between 2008 and 2013 and focusing on the perspective of young care leavers in Spain. The overall aim was to examine these young people’s perceptions and evaluations of how they were treated while in the public care system, mainly residential care. Reviewing these qualitative studies, the most common and relevant issues highlighted by young people were related to the following themes: (a) entering care; (b) stability and emotional bonds in care; (c) education; (d) friends; (e) labelling, stigmatization, rights and opportunities; (f) autonomy and responsibility versus overprotection; (g) contact with parents, siblings and extended family; (h) maltreatment in care; and (i) leaving care. One of the main elements used in their assessments was comparison (i) between their previous situation within their birth family and the quality of care experienced in the residential home; and (ii) between what these young people commonly refer to as “normal children” and children in care. Recommendations deriving from their advice and opinions are also debated

O sistema globalmente harmonizado de classificação e rotulagem de produtos químicos (GHS): uma introdução para sua aplicação em laboratórios de ensino e pesquisa acadêmica

The present article provides an overview of the Globally Harmonised System of Classification, Labelling and Packaging of Chemicals (GHS) and its implementation in Brazil. Although Classification and Packaging is beyond the scope of the responsibility of academic chemists, labelling of chemicals used in academic laboratories will be required by the competent authorities to ensure the safety of students and staff. Therefore, academic teachers and researchers responsible should be familiarised with the GHS principles outlined here and at least be able to label, by applying these principles, mixtures of substances previously classified by the competent authorities.

Produtos químicos perigosos utilizados em laboratórios de ensino: proposta e exemplos para indicação de seus perigos no rótulo

Typically hundreds of different chemical products stored in small flasks which cannot accommodate labels large enough to bear all information required by the Globally Harmonised System of Classification, Labelling and Packaging of Chemicals (GHS) are used in academic laboratories. To overcome this restriction Brazilian legislation permits communication of the dangers of chemical products to trained laboratory workers/students by alternative means. Here we describe an alternative label system, developed by the German Social Accident Insurance (DGUV), which allows hazard communication to trained workers/students via a labelling system, using pictograms and highly condensed hazard statements to alert about dangerous chemical products.

Imaging of Dopamine and Serotonin Transporters. Pre-clinical Studies with Radiotracers for Positron Emission Tomography

The action of the neurotransmitters dopamine (DA) and serotonin (5-HT) at synapses is terminated by their rapid reuptake into presynaptic nerve endings via plasma membrane dopamine (DAT) and serotonin (SERT) transporters. Alterations in the function of these transporters have been suggested as a feature of several neurological and neuropsychiatric diseases, such as Parkinson’s disease (PD), depression, and anxiety. A suitable clinical method for studying these transporters non-invasively in vivo is positron emission tomography (PET) utilizing radiopharmaceuticals (tracers) labelled with short-lived positron-emitting radionuclides. The aim of this study was to evaluate in rats two novel radiotracers, [¹⁸F]beta -CFT-FP and ¹⁸FFMe-McN, for imaging DAT and SERT, respectively, using in vitro, ex vivo and in vivo methods. Substituting an N-methyl in [¹⁸F]beta-CFT, a well known DAT tracer, with a ¹⁸Ffluoropropyl group significantly changed the properties of the tracer. [¹⁸F]beta- CFT showed slow kinetics and metabolism, and a high specific uptake in the striatum, whereas [¹⁸F]beta-CFT-FP showed fast kinetics and metabolism, and a moderate specific uptake in the striatum. [¹⁸F]betaCFT-FP was selective for DAT; but [¹⁸F]beta-CFT also bound to the noradrenaline transporter. [¹⁸F]beta-CFT-FP may be a suitable PET tracer for imaging the striatal DAT sites, but a tracer with a higher affinity is needed for imaging extrastriatal DAT sites. In rats, ¹⁸FFMe-McN showed high target-to-non-target ratios, specificity and selectivity for SERT, but slow kinetics. However, ¹⁸FFMe-McN reveals potential for imaging SERT, at least in pre-clinical studies. In addition, the sensitivities of [¹⁸F]beta CFT and [¹⁸ F]FDOPA (a precursor of DA) for detecting mild nigrostriatal hypofunction were compared in an animal model of PD. The uptake of [¹⁸F]FDOPA was significantly affected by compensatory effects in dopaminergic cells, whereas [¹⁸F]beta-CFT was more sensitive and therefore more suitable for PET studies of mild dopaminergic symptoms. In conclusion, both novel tracers, [¹⁸F]-CFT-FP and ¹⁸FFMe-McN, have potential, but are not optimal PET tracers for DAT and SERT imaging in rats, respectively. [¹⁸F]beta-CFT is superior to [18F]FDOPA for imaging mild nigral lesions in rat brains.

PET and MR imaging in Parkinson’s disease patients with cognitive impairment. A study of dopaminergic dysfunction, amyloid deposition, cortical hypometabolism and brain atrophy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. It is characterized by a severe loss of substantia nigra dopaminergic neurons leading to dopamine depletion in the striatum. PD affects movement, producing motor symptoms such as rigidity, tremor and bradykinesia. Non-motor symptoms include autonomic dysfunction, neurobehavioral problems and cognitive impairment, which may lead to dementia. The pathophysiological basis of cognitive impairment and dementia in PD is unclear. The aim of this thesis was to study the pathophysiological basis of cognitive impairment and dementia in PD. We evaluated the relation between frontostriatal dopaminergic dysfunction and the cognitive symptoms in PD patients with [18F]Fdopa PET. We also combined [C]PIB and [¹⁸F]FDG PET and magnetic resonance imaging in PD patients with and without dementia. In addition, we analysed subregional striatal [¹⁸F]Fdopa PET data to find out whether a simple ratio approach would reliably separate PD patients from healthy controls. The impaired dopaminergic function of the frontostriatal regions was related to the impairment in cognitive functions, such as memory and cognitive processing in PD patients. PD patients with dementia showed an impaired glucose metabolism but not amyloid deposition in the cortical brain regions, and the hypometabolism was associated with the degree of cognitive impairment. PD patients had atrophy, both in the prefrontal cortex and in the hippocampus, and the hippocampal atrophy was related to impaired memory. A single 15-min scan 75 min after a tracer injection seemed to be sufficient for separating patients with PD from healthy controls in a clinical research environment. In conclusion, the occurrence of cognitive impairment and dementia in PD seems to be multifactorial and relates to changes, such as reduced dopaminergic activity, hypometabolism, brain atrophy and rarely to amyloid accumulation.

Konventionaalisen jätehuollon kehittäminen Loviisan voimalaitoksella

Tämän diplomityön tarkoituksena oli löytää kehityskohteita Fortumin Loviisan ydinvoimalaitoksen konventionaalisesta, eli tavanomaisesta, jätehuollosta. Tavoitteena oli löytää erityisesti keinoja kaatopaikkajätteen määrän vähentämiseksi sekä lajittelun tehostamiseksi. Myös jätelainsäädännön kokonaisuudistuksen vaikutukset jätehuollon toimintaan olivat työn kannalta keskeisessä roolissa. Työ tehtiin jätehuoltosuunnitelman rakennetta noudattaen. Jätehuoltosuunnitelma koostuu alkukartoituksesta sekä jätehuoltosuunnitelman laatimisesta ja toteutuksesta. Varsinaisina kehitystarpeiden kartoittamismenetelminä käytettiin viranomaisvaatimusten selvittämistä, toiminnan tarkastelua, jätehuoltokyselyä voimalaitoksen työntekijöille, benchmarkingia sekä valittujen hyötykäyttö- ja loppusijoitusmenetelmien kustannusvertailua. Tulokseksi saatiin, että jätteiden lajittelua voitaisiin tehostaa ennen kaikkea lisäämällä työntekijöiden koulutusta. Lajittelun helpottamiseksi ohjeistuksen tulee olla paremmin saatavilla sekä voimalaitoksen omalle henkilöstölle kuin urakoitsijoillekin. Ongelmajätehuollossa eniten ongelmia ilmeni ongelmajätepakkausten merkitsemisessä jätteiden syntypaikoilla. Tähän ratkaisuna ehdotettiin kokeiltavaksi jätteiden syntykohteisiin sijoitettavia jätekortteja, joista pakkaajat voisivat helposti tarkistaa tarvittavat merkinnät. Myös mustan jäteöljyn keräämistä olisi mahdollista parantaa, jotta suurempi osa siitä saataisiin hyödynnettyä materiaalina. Kaatopaikkajätteen määrän vähentämiseksi työssä ehdotettiin sekajätteen viemistä kaatopaikan sijaan poltettavaksi. Muutoksen seurauksena voimalaitoksen jätehuollon kustannukset saattavat lisääntyä, mutta ympäristön kannalta muutos tulisi olemaan positiivinen.

Neurobiology of pathological gambling. Brain imaging and epidemiological studies

Pathological gambling, a form of behavioral addiction, refers to maladaptive, compulsive gambling behavior severely interfering with an individual’s normal life. The prevalence of pathological gambling has been estimated to be 1–2% in western societies. The reward deficiency hypothesis of addiction assumes that individuals that have, or are prone, to addictions have blunted mesolimbic dopamine reward signaling, which leads to compulsive reward seeking in an attempt to compensate for the malfunctioning brain reward network. In this research project, the effects of gambling were measured using brain [11C] raclopride PET during slot machine gambling and possible brain structural changes associated with pathological gambling using MRI. The subjects included pathological gamblers and healthy volunteers. In addition, impulse control disorders associated with Parkinson’s disease were investigated by using brain [18F]fluorodopa PET and conducting an epidemiological survey. The results demonstrate mesolimbic dopamine release during gambling in both pathological gamblers and healthy volunteers. Striatal dopamine was released irrespective of the gambling outcome, whether the subjects won or not. There was no difference in gambling induced dopamine release between pathological gamblers and control subjects, although the magnitude of the dopamine release correlated with gambling related symptom severity in pathological gamblers. The results also show that pathological gambling is associated with extensive abnormality of brain white matter integrity, as measured with diffusion tensor imaging, similar to substance-addictions. In Parkinson’s disease patients with impulse control disorders, enhanced brain [18F] fluorodopa uptake in the medial orbitofrontal cortex was observed, indicating increased presynaptic monoamine function in this region, which is known to influence signaling in the mesolimbic system and reward processing. Finally, a large epidemiological survey in Finnish Parkinson’s disease patients showed that compulsive behaviors are very common in Parkinson disease and they are strongly associated with depression. These findings demonstrate the role of dopamine in pathological gambling, without support for the concept of reward deficiency syndrome.