Etiska dilemman vid vård och bemötande av patienter med cancer i livets slutskede : En intervjustudie om akutvårdares upplevelser

Akutvårdare är tränade att rädda liv och att hantera akuta sjukdomsfall. Att lindra dö-ende patienters lidande är ibland målet med vården vilket kan medföra etiska dilemman. Syftet med studien var att fördjupa akutvårdares förståelse och kunskap gällande etiska dilemman vid prehospital vård och bemötande av patienter med cancer i livets slutskede. Studiens centrala frågeställningar var: 1. Hur upplever akutvårdare vård och bemötande av patienter med cancer i livets slutskede i den prehospitala vården? 2. Vilka konfliktsituationer uppstår vid etiskt beslutsfattande? Den tidigare forskningen påvisade att etik är ett svårt ämne och att det behövs mera utbildning inom området. Studien ingick i GROW-projektet, ett projekt inom ramen för Arcada Patientsäkerhets- och Lärocenter. Materialet samlades in genom fyra temaintervjuer med akutvårdare från ett räddningsverk i södra Finland. Det insamlade materialet analyserades enligt en modell för kvalitativ innehållsanalys. Resultatet delades in i fyra huvudkategorier: -att bemöta patienter och anhöriga, -akutvårdares personliga uppfattningar, -organisation, ledarskap och samarbete samt -etiska aspekter. I resultatet framkom att akutvårdarna upplevde patienternas anhöriga som en utmaning i flera situationer. Bland de etiska dilemman som kan ses i resultatet har akutvårdarna upplevt att bristfällig dokumentering av DNR-beslut i flera fall har lett till etiska konfliktsituationer. Resultatet visade på att det behövs en utveckling av samarbetet mellan akutvården och hemsjukvården. Akutvårdarna upplevde att det i vissa situationer var oklart vilka uppgifter som ska skötas av vem i vården av patienter med cancer i livets slutskede och att bristen på klara riktlinjer har lett till att akutvården och hemsjukvården har ifrågasatt varandras agerande. Utgående från studiens resultat skapades ett simuleringscase som kan användas i den etiska undervisningen i Arcada.Paramedics are trained to save lives and to handle acute illness. To relieve suffering of dying patients are sometimes the purpose of the care which can bring ethical dilemmas. The purpose of the study was to immerse paramedics understanding and knowledge about ethical dilemmas in prehospital treatment and care of patients with cancer in the end of life. The central questions of the study was: 1. How do the paramedics experience care and treatment of patients with cancer in the end of life in the prehospital care? 2. What conflicts arise in ethical decisionmaking? The previous research showed that ethics is a difficult subject and that there is need for more education in the area. The thesis was a part of the GROW-project, a project under Arcada Patient Safety and Learning Center. The material was gathered through four thematic interviews with paramedics from a fire department in southern Finland. The collected material was analyzed with a model for qualitative method. The result was divided in four categories: -to meet patients and relatives, -paramedics’ personal comprehension, -organization, leadership and co-operation and -ethical aspects. It emerged that the paramedics experienced the patients’ relatives as a challenge in several situations. Among the ethical dilemmas which can be seen in the result, the paramedics have experienced that deficient documentation of DNR-decisions in several cases has led to ethical conflicts. The result showed that development of co-operation between emergency care and home health care is needed. The paramedics felt that in some situations it was unclear which task should be managed by whom in the care of patients with cancer in the end of life and the lack of clear guidelines has led to that the emergency care and the home health care question each other’s actions. Based on the study’s result there was created a simulation case which can be used in the ethical education at Arcada.Ensihoitajat ovat koulutettuja pelastamaan ihmishenkiä ja käsittelemään akuutteja sairauskohtauksia. Joskus hoidon tavoite on lievittää kuolevan potilaan kärsimystä mikä voi aiheuttaa eettisiä haasteita. Tutkimuksen tavoite on syventää ensihoitajien ymmärtäväisyyttä ja osaamista eettisissä haasteissa elämän loppuvaiheessa olevien syöpäpotilaiden hoitamisessa ja kohtaamisessa ensihoidossa. Tutkimuksen keskeiset tutkimuskysymykset olivat: 1. Miten ensihoitajat kokevat elämän loppuvaiheessa olevien syöpäpotilaiden hoitamista ja kohtaamista ensihoidossa? 2. Mitkä ristiriitaisia tilanteita syntyy eettisessä päätöksenteossa? Aikaisempi tutkimus osoitti että etiikka on vaikea aihe ja että aiheesta tarvitaan lisää koulutusta. Tutkimus oli osa GROW-projektia, projekti kuuluu Arcadan Potilasturvallisuus- ja Oppimiskeskukseen. Tutkimusmateriaalin keräämiseksi tehtiin teemahaastatteluja joihin osallistui neljä ensihoitajaa yhdeltä pelastuslaitokselta Etelä-Suomesta. Kerätty materiaali analysoitiin kvalitatiivisen sisältöanalyysin avulla. Tulos jaettiin neljään pääluokkaan: -potilaiden ja omaisten kohtaaminen, -ensihoitajien henkilökohtaisia käsityksiä, -organisaatio, johtajuus ja yhteistyö ja -eettisiä näkökulmia. Tutkimustulos osoitti että ensihoitajat kokenevat potilaiden omaiset haasteina useammassa tilanteessa. Tuloksessa näkyvät eettisien haasteiden seassa muun muassa että ensihoitajat olivat kokeneet että DNR-päätöksien puutteellinen dokumentointi ovat johtaneet eettisiin konflikteihin useammassa tilanteessa. Tutkimus osoitti että ensihoidon ja kotisairaanhoidon välisessä yhteistyössä tarvitaan kehitystä. Ensihoitajat kokivat että joissain tilanteissa oli epäselvää kenen tehtävää oli hoitaa tiettyjä asioita hoidettaessa elämän loppuvaiheessa olevia syöpäpotilaita ja että puutteelliset ohjeet ovat johtaneet siihen että ensihoito ja kotisairaanhoito ovat kyseenalaistaneet toistensa toimintaa. Tutkimustuloksen perusteella kehitettiin simulaatiotilanteen jota voi käyttää eettisessä opetuksessa Arcadassa

Storage of neural histamine and histaminergic neurotransmission is VMAT2 dependent in the zebrafish

Monoaminergic neurotransmission is greatly dependent on the function of the vesicular monoamine transporter VMAT2, which is responsible for loading monoamines into secretory vesicles. The role of VMAT2 in histaminergic neurotransmission is poorly understood. We studied the structure and function of the histaminergic system in larval zebrafish following inhibition of VMAT2 function by reserpine. We found that reserpine treatment greatly reduced histamine immunoreactivity in neurons and an almost total disappearance of histamine-containing nerve fibers in the dorsal telencephalon and habenula, the most densely innervated targets of the hypothalamic histamine neurons. The reserpine treated larvae had an impaired histamine-dependent dark-induced flash response seen during the first second after onset of darkness, implying that function of the histaminergic network is VMAT2 dependent. Levels of histamine and other monoamines were decreased in reserpine treated animals. This study provides conclusive evidence of the relevance of VMAT2 in histaminergic neurotransmission, further implying that the storage and release mechanism of neural histamine is comparable to that of other monoamines. Our results also reveal potential new insights about the roles of monoaminergic neurotransmitters in the regulation of locomotion increase during adaptation to darkness.Peer reviewe

The histaminergic neurotransmitter system : its development and role in neuronal plasticity in zebrafish, Danio rerio

The histaminergic neurotransmitter system is a modulatory system which regulates many functions in the vertebrate brain. In the mammalian brain, histaminergic neurons fire during waking and are involved in maintaining sleep-wake homeostasis. Furthermore, histamine has been implicated in neurodegenerative disorders. Patients suffering from Alzheimer s disease, Parkinson s disease and narcolepsy have alterations in this system. Histamine is produced from the amino acid ι-histidine by histidine decarboxylase (HDC). The aims of this study were to characterize the histaminergic system in zebrafish, a nonmammalian vertebrate, and to identify novel mechanisms in which the histaminergic system is involved. We found that histamine receptor ligands altered the behavior in larval zebrafish in a dose-dependent manner. Cloning and sequence analysis of the histamine receptors indicated that the zebrafish histamine receptors were similar to the corresponding mammalian receptors. We also studied the neurotransmitter phenotype of histaminergic neurons by immunohistochemistry and confocal microscopy and found that these neurons resemble those of rats. Immunohistochemical comparison of the histaminergic system in male and female adult brain revealed no significant differences in location, distribution, or neuron number, and thereby no differences between the sexes were observed. We studied the functions of the histaminergic system in hdc knockdown animals (morpholino oligonucleotide approach), and found that the neurotransmitter was important for mediating rapid behavioral responses to environmental cues, and that these behavioral responses were driven via the histamine receptor hrh1. We studied the interaction of histamine with a wakefulness associated neuropeptide system, hypocretin/orexin (hcrt), which is implicated in narcolepsy. We reported a novel mechanism for histamine that regulates development of the hcrt neurons. Transient knockdown of hdc with morpholino oligonucleotides and pharmacological inactivation of hrh1 with pyrilamine reduced the number of hcrt mRNA-positive neurons in zebrafish larvae. This effect was rescued by overexpression of hdc mRNA. Since histaminergic neurons play important roles in the central nervous system, we were interested in identifying factors that regulates the development of the histaminergic neurons themselves. We found that in the Alzheimer s disease-associated gene, presenilin1 (psen1), mutant zebrafish, the histaminergic system was altered. During the developmental and larval stages, the histamine neuron number was significantly reduced in psen1 mutants, whereas at the young adult age there was a significant increase in histamine neuron number in psen1 mutants in comparison to wild-type fish. These results showed us that psen1 was essential for the development and normal functioning of the histaminergic neurotransmitter system. Histamine is metabolized by histamine N-methyltransferase (HNMT), followed by monoamine oxidase (MAO). We studied the effect that pharmacological inhibition of MAO has on the locomotor behavior of fish. We found that pharmacological inhibition of the MAO enzyme mainly affects the serotonin system in zebrafish, with characteristic behavioral consequences that could be rescued. Taken together, the results of this thesis provide evidence that the histaminergic neurotransmitter system in zebrafish is similar to that in mammals. These results show that the zebrafish is an excellent tool in studies to provide novel insights into neurotransmitter system functions in the vertebrate central nervous system on both the mechanistic and behavioral levels. We found that the histaminergic system is important for rapid behavioral responses, affects the development of the hcrt neurotransmitter system, and is itself regulated in a temporal manner by psen1.Det histaminerga neurotransmittersystemet är ett modulatoriskt system som reglerar många funktioner i hjärnan hos vertebrater. Genom interaktion med receptorer i olika hjärnområden är histamin involverat i flera komplexa funktioner, från hormonal kontroll till kognition. Neuronalt histamin är främst känt för sin roll i övergången från sömn till vakenhet, i och med att dessa neuroner är aktiva när individen vaknar. Trots att neuronalt histamin studerats under flera årtionden, är det fortfarande oklart vilka faktorer som styr de histaminerga neuronernas utveckling, samt hur systemet samverkar med andra neurotransmittersystem på molekylär nivå. Förändringar i det histaminerga neurotransmittersystemet har kopplats till neurodegenerativa sjukdomar såsom Alzheimers sjukdom, Parkinsons sjukdom och narkolepsi. Trots detta är det oklart huruvida det histaminerga systemet är involverat i etiologin av sjukdomarna. Målsättningarna med denna avhandling var att karakterisera det histaminerga systemet i sebrafisk, och att identifiera nya mekanismer som medieras via det histaminerga systemet. Vi fann stora likheter mellan sebrafiskens och mammaliers histaminerga neurotransmittersystem, vilket tyder på att nya rön kan extrapoleras från fisk till däggdjur. Histamin produceras från aminosyran ι-histidin genom en reaktion katalyserad av histidindekarboxylas. Kortvarig inhibering av produktionen av histamin i sebrafiskyngel, resulterade i en beteendeförändring. De individer som saknade histamin var oförmögna att reagera på samma sätt som kontrollfiskarna på en snabb förändring i omgivningen. Resultaten indikerar att histamin är viktigt vid reglering av finmotorik, vilket även detekterats i patienter som diagnostiserats med Gilles de la Tourette syndrom. Dessutom fann vi att histamin via histamin receptor 1 reglerar utvecklingen av hypocretin/orexin (hcrt) systemet, vilket i sin tur är det neurotransmittersystem som kopplats till narkolepsi. Eftersom histamin medverkar i flera neuronala processer, identifierade vi en faktor essentiell för utvecklingen av histaminerga neuroner. Vi fann att presenilin 1, en gen associerad med Alzheimers sjukdom, reglerar utvecklingen av histaminerga neuroner. Resultaten sammanställda i denna avhandling visar att sebrafisken lämpar sig väl i studier angående det histaminerga systemet. Resultaten visar att sebrafisken utgör en utmärkt modell för nya rön i vertebraters centrala nervsystem, både på en mekanistisk och beteende nivå. Vi fann att det histaminerga systemet är viktigt för snabba beteendeförändringar, påverkar utvecklingen av hcrt neuroner och är självt reglerat av presenilin 1. Dessa resultat ger en ny infallsvinkel i studier av neurodegenerativa sjukdomar, såsom narkolepsi och Alzheimers sjukdom

Artificial selection on relative brain size reveals a positive genetic correlation between brain size and proactive personality in the guppy

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The bullies are the leaders of the next generation : Inherited aminergic neurotransmitter system changes in socially dominant zebrafish, Danio rerio

We studied the social hierarchy in zebrafish and assessed differences in neurotransmitters and behavior in the F1 generation offspring of dominant and subordinate zebrafish (Danio rerio). We used behavioral assays to study locomotion, ability to complete cognitive tasks, social interaction and aggression. To study the neurochemical changes, we applied quantitative polymerase chain reaction, high pressure liquid chromatography and immunohistochemistry. Social hierarchies were formed both by males and females when animals were kept in same sex pairs in the dyadic dominant-subordinate hierarchy test. The offspring of dominant animals were the leaders in social interactions, however aggression in the mirror-test was not altered in any group. Serotonin and noradrenaline levels were lower in the F1 generation subordinate animals when compared with dominant animals, but not compared with animals that were naive to social hierarchy. The mRNA level of the rate-limiting enzyme in histamine synthesis, histidine decarboxylase, was significantly lower in dominant and subordinate larval zebrafish when compared with control animals. In the dominant adult zebrafish tyrosine hydroxylase 1 mRNA level was lower compared with control animals, whereas tyrosine hydroxylase 2 mRNA was not different. The result was verified with immunohistochemistry. There were gender specific differences between the dominant and subordinate animals, where the dominant females performed better in cognitive tasks such as the T-maze than subordinate females. This was not observed in males, as the behavior of the dominant and subordinate males did not differ. These results add to the understanding of the plastic nature of the central nervous system and show that neurochemical features in aminergic neurotransmitter systems are associated with social leadership and dominance.Peer reviewe

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

Clinical and polysomnographic course of childhood narcolepsy with cataplexy.

Our aim was to investigate the natural evolution of cataplexy and polysomnographic features in untreated children with narcolepsy with cataplexy. To this end, clinical, polysomnographic, and cataplexy-video assessments were performed at diagnosis (mean age of 10 ± 3 and disease duration of 1 ± 1 years) and after a median follow-up of 3 years from symptom onset (mean age of 12 ± 4 years) in 21 children with narcolepsy with cataplexy and hypocretin 1 deficiency (tested in 19 subjects). Video assessment was also performed in two control groups matched for age and sex at first evaluation and follow-up and was blindly scored for presence of hypotonic (negative) and active movements. Patients' data at diagnosis and at follow-up were contrasted, compared with controls, and related with age and disease duration. At diagnosis children with narcolepsy with cataplexy showed an increase of sleep time during the 24 h; at follow-up sleep time and nocturnal sleep latency shortened, in the absence of other polysomnographic or clinical (including body mass index) changes. Hypotonic phenomena and selected facial movements decreased over time and, tested against disease duration and age, appeared as age-dependent. At onset, childhood narcolepsy with cataplexy is characterized by an abrupt increase of total sleep over the 24 h, generalized hypotonia and motor overactivity. With time, the picture of cataplexy evolves into classic presentation (i.e., brief muscle weakness episodes triggered by emotions), whereas total sleep time across the 24 h decreases, returning to more age-appropriate levels

Tutors' perceptions of use of tablet computers in PBL sessions

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Molecular psychiatry of zebrafish

Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CNS) disorders. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity disorder (ADHD), aggression, post-traumatic stress and substance abuse. Critically evaluating the advantages and limitations of larval and adult fish tests, we suggest that zebrafish models become a rapidly emerging new field in modern molecular psychiatry research