Neuroscience is a relatively small and emerging clinical pharmacy specialism focusing on drug therapy for neurological disease. Against a professional momentum for specialist practice within pharmacy, there is paucity both of relevant research, and a clearly defined role for specialist pharmacy practice in neuroscience. A qualitative research study was undertaken, using constructivist grounded theory method, to explore how hospital based pharmacists practicing in neuroscience define and develop their role and specialism. Data were concurrently generated and analysed, through verbatim transcription of telephone interviews with fourteen pharmacists. Data analysis resulted in the identification of three processes: (1) Acquiring and utilising knowledge in practice; (2) Gatekeeping access to drug therapies; (3) Integrating into the neuroscience service. The key findings within each process are: (1) Pharmacists utilise different forms of knowledge and there can be barriers to gaining knowledge. Pharmacists identify strengths in their breadth of clinical knowledge and holistic consideration of patients’ drug therapy. (2) Pharmacists act as barriers to drug therapy but also act to expedite and secure access to drug therapy. (3) Pharmacists act as an organisational nexus between pharmacy and neuroscience services and identify the importance in practice of forming working relationships within neuroscience services, underpinned by trust. The study identified a basic social process: Maintaining an overview of drug therapy for patients with neurological disease. This process conceptualises the tensions experienced by the pharmacists between their role as near-patient facing clinical specialists, but also as pharmacist generalists. The study findings have implications for supporting pharmacy practice in neuroscience.

Made available in DSpace on 2014-06-11T19:22:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-11-09Bitstream added on 2014-06-13T20:28:36Z : No. of bitstreams: 1 oliveirafilho_n_me_botfm.pdf: 437599 bytes, checksum: 2c2b9a8d5b382a17722a829414485894 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Nos últimos anos o interesse na ocorrência de hiperglicemia no perioperatório de pacientes adultos e pediátricos sem o diagnóstico prévio de diabetes vem aumentando. A maioria dos estudos que demonstram associação entre hiperglicemia e complicações no pós-operatório em pediatria foi realizada em crianças vítimas de trauma ou cirurgia cardíaca. Dados referentes à associação entre hiperglicemia e morbidades em crianças submetidas à ressecção de tumores do sistema nervoso central são escassos na literatura. Avaliar a incidência de hiperglicemia no perioperatório de crianças submetidas à neurocirurgia para ressecção de tumores do sistema nervoso central e correlacionar os níveis de glicemia do perioperatório com a ocorrência de complicações no pós-operatório e identificar os fatores de risco para hiperglicemia perioperatória. Dados de prontuários foram coletados em uma ficha padronizada com informações referentes ao procedimento anestésico-cirúrgico e condições perioperatórias dos pacientes. Hiperglicemia perioperatória foi definida como valores de glicemia ≥150 mg/dL. Análise binária multivariável para identificar fatores de risco de hiperglicemia. Efeitos e diferenças foram considerados estatisticamente significativos se p < 0,05. Foram incluídos 109 pacientes no estudo. A incidência de hiperglicemia foi de 2,9% no pré-operatório, 10,4% no intra-operatório, 42,4% na admissão da UTI e 52,8% considerando a média das glicemias nas primeiras 24h. Níveis mais elevados de glicemia na admissão da UTI (164,2 ± 36,4 e 144,8 ± 42,7 / p=0,004) e nas primeiras 24h (145,3 ± 19,7 e 137,0 ± 25,5 / p= 0,047) foram observadas nos pacientes que cursaram com complicações no pós-operatório. Os pacientes que apresentaram hiperglicemia na admissão da UTI tiveram um maior tempo de internamento na... / In recent years the interest in the occurrence of perioperative hyperglycemia in adult and pediatric patients without prior diagnosis of diabetes is increasing. Most studies that demonstrate an association between hyperglycemia and complications in the postoperative pediatric studies in children were victims of trauma or cardiac surgery. Data regarding the association between hyperglycemia and morbidity in children undergoing resection of tumors of the central nervous system are scarce. Data were collected from medical records in a standardized form with information about the anesthetic and surgical conditions and perioperative patients. Hyperglycemia was defined as blood glucose levels ≥ 150 mg / dl. Binary multivariate analysis to identify risk factors of hyperglycemia. Effects and differences were considered statistically significant if p <0.05. 109 patients were included in the study. The incidence of hyperglycemia was 2.9% preoperative, 10,4% intraoperative, 42,4% at admission to the ICU and 52,8% taking the average of glucose in the first 24 hours. Higher levels of glucose in the ICU admission (164.2 ± 36.4 and 144.8 ± 42.7 / p = 0.004) and in the first 24 hours (145.3 ± 19.7 and 137.0 ± 25.5 / p = 0.047) were observed in patients who presented with postoperative complications. The patients who had hyperglycemia on admission ICU had a longer ICU stay and hospital. Use of intraoperative corticosteroids increased risk of hyperglycemia at admission to the ICU (OR 3.56 / IC(95%) 1,07-11,7/ p= 0,037). Perioperative higher levels of blood glucose are associated with increased postoperative morbidity of pediatric... (Complete abstract click electronic access below)

Cytoplasmic dynein is a retrograde motor protein complex that carries cargo such as organelles and growth factors along microtubules from the cell periphery towards the peri-nuclear region. The cytoplasmic dynein complex is centred around two homodimerised heavy chains, within which multiple mutations have been identified in human neurological diseases. The ‘Legs at odd angles' (Loa) mouse has a missense ‘T' to ‘A' point mutation in the cytoplasmic dynein heavy chain gene (Dync1h1), resulting in a phenylalanine to tyrosine substitution at position 580. Mice homozygous for this mutation die within 24 hours of birth whilst heterozygote's manifest an age-related and progressive neurodegeneration. Fixed and live-cell microscopy shows aberrant movement of endocytosed growth factors in Loa. Retrograde speed is reduced with a distinct lack of the fastest moving carriers. Moreover, the overall pattern of movement is altered with increased anterograde and side-steps occurring in Loa. Impaired endosomal trafficking of growth factors for degradation prolongs the activation of extracellular signal related kinases 1 and 2 (ERK 1/2) and increases the expression of the immediate early gene c-Fos in mouse embryonic fibroblasts. Motor neurons also show increased levels c-Fos however this can be induced by starvation, indicating their enhanced susceptibility to stress. The light chain (KLC) of dynein's opposing motor - kinesin is one of many genes differentially expressed in Loa compared to wild-type. In addition, associations of KLC with the dynein complex is altered in Loa. Similarities between human neurological diseases and Loa both at the organism and cellular level make Loa a valuable tool towards understanding cellular mechanisms fundamental to the process of disease. Through understanding comes advancement towards therapeutic targets to improve the lives of thousands of people worldwide.

DNA single-strand breaks (SSB) are the most commonly occurring type of DNA damage arising in a cell and they are repaired by rapid repair pathways collectively termed single-strand break repair (SSBR). Recently several rare hereditary neurodegenerative disorders with mutations in genes associated with SSBR, spinocerebellar ataxia and axonal neuropathy-1 (SCAN1), ataxia oculomotor apraxia-1 (AOA1) and microcephaly with early onset seizures and developmental delay (MCSZ), have been discovered. A striking aspect that these disorders have in common is that they are all caused by mutations in end-processing factors. The majority of SSBs that arise via endogenous damage have ‘dirty' termini and require end-processing to restore DNA ends with conventional ‘ligatable' chemistry. Another common feature of these end-processing enzymes is their association with XRCC1, a scaffolding protein that is a core component of SSBR. Complete loss of XRCC1 is embryonically lethal and the conditional deletion of XRCC1 in the developing mouse brain leads to persistent DNA damage, cerebellar interneurons loss and abnormal hippocampal function resulting in behavioural abnormalities such as seizures and episodic epilepsy. Taken together these observations suggest that neural cells are exquisitely sensitive to defects in chromosomal SSBR. In my thesis, I will describe biochemical and cellular data on lymphoblastoid and fibroblast cell lines derived from patients with mutations in the end-processing factors aprataxin (APTX is mutated in AOA1). I will include data showing that aprataxin is required for the short-patch SSBR of abortive ligation intermediates in vitro and that repair arrests in AOA1 cell lines due to insufficient levels of non-adenylated DNA ligase.

O conhecimento do tempo utilizado no cuidado ao paciente, pela equipe de enfermagem, é considerado uma ferramenta de gerenciamento da assistência e dos recursos humanos, possibilita a identificação dos parâmetros que auxiliam no dimensionamento ideal de profissionais para assistir a clientela. O presente estudo tem como objetivo identificar e analisar a distribuição do tempo de trabalho da equipe de enfermagem em uma unidade de terapia intensiva neurológica. Trata-se de um estudo de natureza quantitativa, descritivo, observacional e transversal, realizado na Unidade de Terapia Intensiva Neurológica de um hospital de grande porte e alta complexidade da cidade de São Paulo. Utilizou-se das intervenções/atividades de enfermagem identificadas para unidades de terapia intensiva no estudo de Mello (2011), categorizadas de acordo com o sistema padronizado de linguagem Classificação das Intervenções de Enfermagem (NIC) e classificadas em intervenções de cuidado direto, indireto, atividades associadas e de tempo pessoal. Os dados da pesquisa foram coletados pelo método de amostragem do trabalho, por meio de observações diretas das atividades/intervenções realizadas pelos profissionais de enfermagem, a cada 10 minutos, durante 24 horas, em janeiro de 2014. Foram obtidas 10.656 amostras de intervenções e atividades realizadas pelos profissionais de enfermagem em 96 horas de coleta de dados. As intervenções em que a equipe de enfermagem emprega maior tempo de trabalho são a Documentação (22,9%), Administração de Medicamentos (5,9%), Banho (5,4%) e Monitoração dos Sinais Vitais (4,4%). A intervenção realizada com maior frequência pelos enfermeiros é a Documentação (29,1%) e também pelos técnicos de enfermagem (21,6%). Constatou-se que a equipe de enfermagem da unidade despendeu 42,1% do seu tempo em intervenções/atividades de cuidado direto, 37,1% em intervenções de cuidado indireto, 16,6% em atividades pessoais e 4,2% em atividades associadas. Os enfermeiros despendem 55,4% do seu tempo de trabalho em intervenções de cuidados indiretos, 20,5% em intervenções de cuidados diretos, 16,4% em atividades pessoais e 7,7% em atividades associadas. Os técnicos de enfermagem empregam maior tempo de trabalho no cuidado direto (46,6%), cuidado indireto (33,2%), atividades pessoais (16,6%) e associadas (3,5%). A produtividade média da equipe de enfermagem atingiu 83,4%, considerada excelente conforme proposto na literatura. O estudo possibilitou uma compreensão mais objetiva do processo de trabalho da equipe de enfermagem da terapia intensiva neurológica e evidencia novas perspectivas de investigações que subsidiem o planejamento de recursos humanos de enfermagem em unidades de cuidados críticos. / The knowlegmemt of time spent in nurse activities in patient care makes possible to identify parameters that helps to set up a method of quantifying number of professionals required to assist a unit and is considered management tool of health assistance and human resources. The aim of the present of study is to identify and analyze nursing work time distribution of a neurological intensive care unit. It is a quantitative, descriptive, observational and cross-sectional study, developed in the neurological intensive care unit of a large high-complexity hospital in the city of São Paulo. This research considers nursing activities and interventions identified by Mello (2011) for intensive care units, in according to the standardized language system Nursing Intervention Classification NIC and classified as direct and indirect care interventions, associated activities and personal time. Data were collected using the work sampling method, by means of the direct observation of the activities and interventions performed by the nursing professionals every 10 minutes, during 24 hours, in January 2014. 96 hours data were collected , 10,656 samples of interventions and activities performed by the nursing professionals were obtained Documentation (22.9%), were the most prevalent intervention followed by Medications task (5.9%), Bath (5.4%) and Vital Signs Monitoring (4.4%).Among registered nurses and technicians Documentation is the most frequent for both of them 29,1% and 21,6%. The nursing staff spent 42.1% of their time in direct care interventions 37.1% in indirect care 16.6% in personal activities and 4.2% in associated activities. Registered Nurses spent 55.4% of their time in indirect care interventions, 20.5% in direct care. 16.4% in personal activities and 7.7% in associated activities. Nursing technicians expended more working time in direct care (46.6%), followed by indirect care (33.2%), personal activities (16.6%) and associated activities (3.5%). The mean productivity of the nursing staff reached 83.4%, which is considered excellent as per the literature The present study provides an objective understanding of the working process of the nursing staff, in neurological intensive care unit and evidences new perspectives of research that support the planning of the nursing staff in critical care units.

Orientador: Vânia Maria de Vasconcelos Machado / Resumo: A ressonância magnética é um método diagnóstico primordial na avaliação de enfermidades intracranianas na medicina e na medicina veterinária para a investigação, elaboração e realização de tratamentos, planejamento cirúrgico e controle. Por meio dessa modalidade diagnóstica pode-se pesquisar muitas enfermidades intracranianas: congênitas, malformações, inflamatórias, infecciosas, vasculares, neoplásicas dentre outras. Ressonância magnética é um exame não invasivo, baseado em princípios físicos complexos que formam imagens em múltiplos planos de uma determinada região. O objetivo deste trabalho é fornecer um estudo retrospectivo das enfermidades neurológicas presentes na rotina de exames de ressonância magnética da região crânio -encefálica e sua casuística na Faculdade de Medicina Veterinária e Zootecnia da Universidade Estadual Paulista, campus de Botucatu nos anos de 2012 a 2017. Realizou-se uma análise retrospectiva dos exames de ressonância magnética de pequenos animais da região crânio- encefálica. Os dados foram compilados e classificados segundo a região de exame, diferentes áreas de encaminhamento, casuística das enfermidades intracranianas segundo a espécie durante o período de 2012 a 2017. Dentre os 420 animais, sendo eles 340 canídeos e 80 felídeos observou-se dentre as regiões de exame o encéfalo com 95%; maioria dos encaminhamentos para a realização do exame de ressonância magnética são recebidos do serviço de neurologia veterinária 58%; a casuística das suspeita... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Magnetic resonance imaging is a primordial diagnostic method in the evaluation of intracranial diseases in medicine and veterinary medicine for investigation, elaboration and realization of treatments, surgical planning and control. By means of this diagnostic modality, one can investigate many intracranial diseases: congenital, malformations, inflammatory, infectious, vascular, and neoplastic among others. Magnetic resonance imaging is a non-invasive examination based on complex physical principles that form multi-plane imaging of a region. The goal of this work is to provide a retrospective study of the neurological diseases present in routine magnetic resonance imaging of the cranioencephalic region and its casuistry at the Faculty of Veterinary Medicine and Animal Science of the Universidade Estadual Paulista, Campus Botucatu, from 2012 to 2017. Was made a retrospective analysis of magnetic resonance imaging of small animals of the craniocephalic region. The data were compiled and classified according to the region of examination, different routing areas, and the number of intracranial diseases according to the species during the period from 2012 to 2017. Among the 420 animals, of which 340 canines and 80 felids were observed among the regions examination of the brain with 95%; most referrals for performing the MRI are received from the Veterinary Neurology Service 58%; the casuistry of the diagnostic suspicions of the diseases with 54 animals with convulsion, 49 animals ... (Complete abstract click electronic access below) / Doutor

The corpus callosum, the major interhemispheric fiber tract, mediates communication between homotopic regions within the primary somatosensory cortex (S1). Recently, in 1- to 6-day-old neonatal rats, brief bursts of high-frequency, oscillatory activity - called spindle-bursts (SBs) - were described in S1 following sensory feedback from endogenously generated sleep-related myoclonic twitch movements and exogenously generated peripheral stimulation. To determine whether interhemispheric communication via the corpus callosum modulates the expression of SBs during this early period of development and contributes to cortical organization and plasticity, we investigated the endogenous (spontaneous) expression and exogenous (evoked) activity of SBs in neonatal rats with intact or surgically severed callosal fibers (i.e., callosotomy; CCx). We used Ag/AgCl cortical surface electrodes in the S1-forelimb region of the cortex to measure neurophysiological and behavioral activity in both intact and CCx subjects across the sleep-wake cycle during the first two postnatal weeks of development. Our results demonstrate, for the first time, that the corpus callosum modulates spontaneous and evoked activity between homotopic regions in S1 as early as 24-hours after birth. In addition, CCx disinhibits cortical activity, nearly doubling the rate of spontaneous SBs through, but not after, postnatal day 6 (P6). CCx also significantly and reliably disrupts the evoked response to peripheral stimulation of the forepaw. To examine the role of sleep-related twitches and their associated sensory feedback (SBs in S1) - modulated by the corpus callosum - in cortical development and plasticity, we performed CCx or sham surgeries at P1, P6, or P8, and tested subjects the day of surgery or over the ensuing week of recovery. Regardless of age, CCx immediately disrupted SBs evoked by forepaw stimulation. The P1 and P6 CCx groups exhibited full recovery after one week; in contrast, the P8 group did not exhibit recovery of function, thus indicating an abrupt decrease in cortical plasticity between P6 and P8. Together, these results provide the first evidence that sleep-related myoclonic twitches and the associated sensory feedback in S1 (SBs) contribute to cortical development, plasticity, and recovery of function after interhemispheric communication is disrupted by callosotomy. CCx-induced disinhibition of spontaneous SBs is a transient phenomenon whose disappearance coincides with the onset of increased intrinsic connectivity, establishment of excitatory-inhibitory balance, and diminished plasticity in S1. Our findings indicate that CCx-induced disinhibition of spontaneous twitch-related SBs and disruption of evoked response to peripheral stimulation serve as a bioassay of somatosensory cortical plasticity during the early postnatal period.

Neurological disorders require varying types and degrees of treatments depending on the symptoms and underlying causes of the disease. Patients suffering from medication-refractory symptoms often undergo further treatment in the form of brain stimulation, e.g. electroconvulsive therapy (ECT), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), or transcranial magnetic stimulation (TMS). These treatments are popular and have been shown to relieve various symptoms for patients with neurological conditions. However, the underlying effects of the stimulation, and subsequently the causes of symptom-relief, are not very well understood. In particular, TMS is a non-invasive brain stimulation therapy which uses time-varying magnetic fields to induce electric fields on the conductive parts of the brain. TMS has been FDA-approved for treatment of major depressive disorder for patients refractory to medication, as well as symptoms of migraine. Studies have shown that TMS has relieved severe depressive symptoms, although researchers believe that it is the deeper regions of the brain which are responsible for symptom relief. Many experts theorize that cortical stimulation such as TMS causes brain signals to propagate from the cortex to these deep brain regions, after which the synapses of the excited neurons are changed in such a way as to cause plasticity. It has also been widely observed that stimulation of the cortex causes signal firing at the deeper regions of the brain. However, the particular mechanisms behind TMS-caused signal propagation are unknown and understudied. Due to the non-invasive nature of TMS, this is an area in which investigation can be of significant benefit to the clinical community. We posit that a deeper understanding of this phenomenon may allow clinicians to explore the use of TMS for treatment of various other neurological symptoms and conditions. This thesis project seeks to investigate the various effects of TMS in the human brain, with respect to brain tissue stimulation as well as the cellular effects at the level of neurons. We present novel models of motor neuron circuitry and fiber tracts that will aid in the development of deep brain stimulation modalities using non-invasive treatment paradigms.

<p>Fatigue är ett vanligt förekommande symtom vid multipel skleros (MS). Denna ihållande och svåra trötthet beskrivs ofta som det svåraste MS-relaterade symtomet att hantera. Symtomet har en negativ påverkan på individens funktionella status samt på livskvaliteten. Syftet med litteraturstudien var att belysa upplevelserna av MS-relaterad fatigue samt hur symtomet påverkar det dagliga livet. Som metod användes en systematisk genomgång av tidigare forskning med en induktiv ansats. Forskning visar att fatigue upplevs som en oavbruten förlamande effekt som uppfattas skilja sig mycket från tidigare upplevd trötthet. Fatigue påverkar hela kroppen och leder till att kroppen blir svårare att styra och hantera. Den begränsade förmågan att utföra önskade aktiviteter påverkar individernas liv negativt. Individer med MS blir tvungna att reglera och planera sitt dagliga liv för att undvika och minska graden av fatigue. En bibehållen självkänsla samt en positiv attityd och en acceptans för sjukdomen och symtomet upplevs minska graden av fatigue. Kommande forskning bör fokusera på individanpassade metoder eller strategier som upplevs minska graden av fatigue.</p>

<p>Wilson's disease (WD), bepatolenticular degeneration, is an autosomal recessive disorder caused by mutations in the ATP7B gene, and is characterised by abnormal metabolism and deposition of copper in the liver, brain and other organs. The main aim of this thesis was to investigate the occurrence of psychopathology, as well as personality traits and neuropsychological function in Swedish patients with treated WD. The research subjects were 29 patients with confirmed WD, investigated at the Department of Internal Medicine at Uppsala University Hospital between 1996 and 2000. </p><p>The treated WD patients showed prominent psychopathology as determined by the Comprehensive Psychopathological Rating Scale. The spectrum of psychopathological symptoms is not typical of classic psychiatric syndromes, and includes symptoms from Anxiety, Depression and Obsessive-Compulsive disorders as well as Negative Symptoms. In self-assessment, the WD patients tended to underestimate the presence of psychopathological symptoms. The treated WD patients differed in their sleep pattern from the control group, as measured with the Uppsala Sleep Inventory. The spectrum of self-reported symptoms suggests an altered REM sleep function. </p><p>The treated WD patients had significant deviations in personality traits, especially in aggressivity-hostility related scales and Psychic anxiety, compared to healthy controls, as measured with the Karolinska Scales of Personality. The deviations were not related to age, age at onset or duration of WD. The treated WD patients displayed a specific profile of moderate neuropsychological impairment, as determined by the Automated Psychological Test battery. Finally, an attempt was made to search for, possible genotype-phenotype relationships in some ATP7B mutations. </p>