Identification and validation of the dopamine agonist bromocriptine as a novel therapy for high-risk myelodysplastic syndromes and secondary acute myeloid leukemia

Myelodysplastic syndromes (MDS) represent a broad spectrum of diseases characterized by their clinical manifestation as one or more cytopenias, or a reduction in circulating blood cells. MDS is predominantly a disease of the elderly, with a median age in the UK of around 75. Approximately one third of MDS patients will develop secondary acute myeloid leukemia (sAML) that has a very poor prognosis. Unfortunately, most standard cytotoxic agents are often too toxic for older patients. This means there is a pressing unmet need for novel therapies that have fewer side effects to assist this vulnerable group. This challenge was tackled using bioinformatic analysis of available transcriptomic data to establish a gene-based signature of the development and progression of MDS. This signature was then used to identify novel therapeutic compounds via statistically-significant connectivity mapping. This approach suggested re-purposing an existing and widely-prescribed drug, bromocriptine as a novel potential therapy in these disease settings. This drug has shown selectivity for leukemic cells as well as synergy with current therapies.

Pulpal Neuropeptide Y levels in relation to pain experience

Neuropeptide Y is a 36 amino acid peptide that belongs to the pancreatic polypeptide family. It co-localises with adrenaline in sympathetic nerves and is released upon sympathetic activation resulting in vasoconstriction. In addition to its vascular effects NPY is also thought to have a role in pain modulation, angiogenesis and immunomodulation. Objectives: The aim of this study was to quantify the levels of NPY in human dental pulp tissue from intact and grossly carious teeth and to relate these results to pain experience. Methods: A total of 48 permanent teeth [mean age 32.1(+/- 11.2 years)] were included in the study, of these 22 were intact and 26 were grossly carious. In the grossly carious group, 17 teeth were reported painful prior to extraction and the remainder were reported non-painful. NPY was measured using a sensitive and specific radioimmunoassay which has been previously described. Pain was scored as either present or absent in all the teeth studied. Results: Of particular interest in this study was the finding that NPY levels were significantly higher in dental pulp tissue from non-painful grossly carious teeth (p= 0.006) compared with painful grossly carious teeth. Conclusions: The increased levels of NPY reported in non-painful grossly carious teeth may suggest a role for NPY in pain modulation in human dental pulp.

Supporting an ethnic minority woman's choice for pain relief in labour: a reflection

Despite professional expectations for midwives to provide care to women that is founded in equality and recognises diversity (Nursing and Midwifery Council, 2015), women from ethnic minority populations consistently suggest that they are not heard (Briscoe and Lavender, 2009; Tobin et al, 2014). This article reflects upon a situation where a Portuguese woman with limited English speaking ability was denied access to epidural anaesthesia as the midwife felt that she could not give valid consent to the procedure without the presence of an interpreter. The midwife’s role within this situation will be reflected upon and implications for midwifery practice identified.

“CAPACITAR O DOENTE ONCOLÓGICO COM DOENÇA AVANÇADA E/OU O CUIDADOR PARA A GESTÃO DA DOR EM DOMICÍLIO” “EMPOWER THE ONCOLOGIC PATIENT WITH ADVANCED DISEASE AT HOME AND/OR THE CAREGIVER FOR THE MANAGEMENT OF PAIN”

RESUMO ABSTRACT Comunicações orais e Posters Oral communications and posters Este formulário, após preenchido, e aceites as condições descritas no regulamento das Comunicações orais e Posters deve ser enviado para isnr@porto.ucp.pt After complete this form and accept the conditions described in the oral communications and posters regulation, please sent to isnr@porto.ucp.pt Tipo de comunicação (comunicação oral ou poster): Comunicação oral Type of communication: (oral communication or poster): Oral comunication Título (Title): “CAPACITAR O DOENTE ONCOLÓGICO COM DOENÇA AVANÇADA E/OU O CUIDADOR PARA A GESTÃO DA DOR EM DOMICÍLIO” “EMPOWER THE ONCOLOGIC PATIENT WITH ADVANCED DISEASE AT HOME AND/OR THE CAREGIVER FOR THE MANAGEMENT OF PAIN” Autoria (Authors): CORREIA, Isabel* (doutoranda em Enfermagem na Universidade de Lisboa) LOPES, Manuel (orientador do projeto) Afiliação dos autores (Authors affiliation): – Professora adjunta na Universidade de Évora, Escola Superior de Enfermagem de São João de Deus de Évora, doutoranda em enfermagem Universidade de Lisboa - – Professor Doutor em Enfermagem, Diretor da Escola Superior de Enfermagem de São João de Deus de Évora, Universidade de Évora E-mail: icorreia@uevora.pt - 964078445 mjl@uevora.pt Resumo (3000 caracteres com espaços) INTRODUÇÃO Um dos sintomas mais frequentes no doente oncológico com doença avançada é a dor. Segundo Palliative Care in European, a dor oncológica, tem uma importância especial porque o cancro é a segunda causa de morte em Portugal e por existir dor moderada a intensa em mais de 90% dos doentes em situação oncológica terminal. O desenvolvimento de um programa estruturado de intervenção de enfermagem que vá de encontro às necessidades do doente oncológico com doença avançada e/ou cuidador, relativamente à gestão da dor, poderá ter um impacto muito significativo no controlo da dor e de outros sintomas. OBJETIVOS Avaliar o efeito de um programa de Intervenção de Enfermagem na capacidade de gestão da dor por parte do doente oncológico com doença avançada e/ou o cuidador em domicílio. MATERIAIS E MÉTODOS A implementação do programa tem a duração prevista para 6 semanas. Compreende duas sessões educativas, três telefonemas e uma sessão de avaliação final. O programa foi elaborado, após uma Revisão sistemática de Literatura, com base no programa “ THE PRO-SELF”, nas Orientações Genéricas preconizadas pelo Plano Nacional de Luta Contra a dor e na Intervenção de enfermagem “Controle da Dor” da Nursing Intervention Classification (NIC). RESULTADOS O projeto encontra-se na fase de implementação e avaliação do programa educativo. No início os doentes não apresentam informação relativamente à gestão da dor, no final demonstram capacidade para a monitorização da dor e de outros sintomas e para a gestão da terapêutica, realizando os registos num diário de bordo. A literacia, a situação clínica e a disponibilidade interferem na capacidade de gestão. A proximidade da morte e a alteração do estado de consciência interferem na autonomia e na tomada de decisão. CONCLUSÃO Em fase de colheita e análise de dados. REFERÊNCIAS BIBLIOGRÁFICAS 1. FREIXO, Manuel. Metodologia Cientifica - Fundamentos, Metodos e Tecnicas. s.l. : Piaget, 2011. 2. Bulechek, Gloria M. e etal. Classificaçaõ das Intervenções de Enfermagem (NIC). Rio de Janeiro : elsevier, 2010. 3. Tsigaroppoulos, T. e etal. Problems faced by relatives caring for cancer patients at home. International Journal Of Nursing Practice. 15, 2009, Vol. 1, Nursing Pratice. 4. west, C.:Dodd,M., et al. Pain Control Program-an effective approach for cancer pain management. Oncology Nursing Forum. 1, 2003, Vol. 30, Oncology Nursing. 5. NR/rdonlyres/6861126B-C57A-46E1-B065-316C0CF8DACD/0/ControlodaDor.pdf, . (2008). . Consultado em 30 de Novembro de 2012 a partir de. Direcção-Geral da Saúde . http://www.portaldasaude.pt. [Online] 2008. [Citação: 30 de Novembro de 2012.] http://www.portaldasaude.pt/NR/rdonlyres/6861126B-C57A-46E1-B065-316COCF8DACD/0/Controlodador.pdf . Abstract (3000 characters with spaces) INTRODUCTION One of the most frequent symptoms in oncological patient with advanced disease is pain. According to Palliative Care in European, oncological pain, has a special importance because the cancer is the second most common cause of death in Portugal and there is moderate to severe pain in more than 90 % of patients in oncological terminal situation. The development of a structured program of nursing intervention that will meet the needs of the oncological patient with advanced disease and/or caregiver at home on pain management, will be able to provide for the management of pain, increasing knowledge for the control of pain while minimizing the associated symptoms that influence the quality of life of the patient and the caregiver's anxiety. PURPOSE/GOAL/AIM To evaluate the effect of an educational program of Nursing Intervention on pain management by the oncological patient with advanced disease and/or caregiver. RESEARCH/PROBLEM What is the effect of a structured program of nursing intervention directed to the patient and/or oncological patient caregiver with advanced disease at home, in the management of pain? METHODOLOGY Almost experimental study, with assessment of the management capacity of the oncological patient pain with advanced disease at home and/or informal caregiver, before and after the intervention of nursing (educational program) and transverse evaluation throughout the study. Population: oncological patients with advanced disease at home, with more than 18 years, and or family caregiver, attending an Oncology Unit – Hospital during the day. RESULTS Made an application in an Oncology service in oncological patients with advanced disease at home, it was found that at the beginning the patients did not present information regarding pain management, at the end demonstrated capacity for monitoring of pain and other symptoms and therapeutic management, performing a logbook records. CONCLUSION In the process of collection and analysis of data. KEYWORDS Educational Program; oncological patient; oncological pain.

Does this case hold the answer to one of the worse types of pain in medicine--that of loin pain haematuria syndrome (LPHS)

A patient with loin pain haematuria syndrome suffering chronic throbbing pulsing pain overlaid with prolonged periods of incapacitating colic and overnight vomiting was presented 10 months following diagnosis. Ultrasound was normal. No renal or ureteral stones, or filling defects were seen on CT. At cytoscopy, bladder and urethra were normal, and bloody urine effluxed from the left ureteric orifice. The ureters were normal at diagnosis, and developed new abutting non‐penetrating calcifications by 8 months. Pain episodes of complete incapacitating intensity of 2–4 h duration were reduced to 10 min with 5 mg crushed tadalafil administered at onset. If tadalafil was delayed to after onset, the original course of agony resulted. Daily tadalafil reduced loin pain intensity, but not the exacerbations. Tadalafil efficacy may indicate that the pain exacerbations are due to spasm of ureter smooth muscle. 5 mg tadalafil taken at onset alleviated severe loin pain exacerbations in this case of loin pain haematuria syndrome.

Modulation of pain threshold by virtual body ownership

Background Appropriate sensorimotor correlations can result in the illusion of ownership of exogenous body parts. Nevertheless, whether and how the illusion of owning a new body part affects human perception, and in particular pain detection, is still poorly investigated. Recent findings have shown that seeing one’s own body is analgesic, but it is not known whether this effect is transferable to newly embodied, but exogenous, body parts. In recent years, results from our laboratory have demonstrated that a virtual body can be felt as one’s own, provided realistic multisensory correlations. Methods The current work aimed at investigating the impact of virtual body ownership on pain threshold. An immersive virtual environment allowed a first-person perspective of a virtual body that replaced the own. Passive movement of the index finger congruent with the movement of the virtual index finger was used in the “synchronous” condition to induce ownership of the virtual arm. The pain threshold was tested by thermal stimulation under four conditions: 1) synchronous movements of the real and virtual fingers, 2) asynchronous movements, 3) seeing a virtual object instead of an arm, and 4) not seeing any limb in real world. Results Our results show that, independently of attentional and stimulus adaptation processes, the ownership of a virtual arm per se can significantly increase the thermal pain threshold. Conclusions This finding may be relevant for the development and improvement of digital solutions for rehabilitation and pain treatment.

Pain expressiveness and altruistic behavior

Predictions which invoke evolutionary mechanisms ar e hard to test. Agent-based modeling in artificial life offers a way to simulate behaviors and interac tions in specific physical or social environments o ver many generations. The outcomes have implications fo r understanding adaptive value of behaviors in context. Pain-related behavior in animals is communicated to other animals that might protect or help, or might exploit or predate. An agent-based model simulated the effects of displaying or not displaying pain (expresser/non-expresser strategies) when injured, and of helping, ignoring or exploiting another in pain (altruistic/non-altruistic/selfish strategies) . Agents modeled in MATLAB interacted at random while foraging (gaining energy); random injury inte rrupted foraging for a fixed time unless help from an altruistic agent, who paid an energy cost, speeded recovery. Environmental and social conditions also varied, and each model ran for 10,000 iterations. Findings were meaningful in that, in general, conti ngencies evident from experimental work with a variety of mammals, over a few interactions, were r eplicated in the agent-based model after selection pressure over many generations. More energy-demandi ng expression of pain reduced its frequency in successive generations, and increasing injury frequ ency resulted in fewer expressers and altruists. Allowing exploitation of injured agents decreased e xpression of pain to near zero, but altruists remained. Decreasing costs or increasing benefits o f helping hardly changed its frequency, while increasing interaction rate between injured agents and helpers diminished the benefits to both. Agent- based modeling allows simulation of complex behavio urs and environmental pressures over evolutionary time.

Tradução científica de The thalassaemia syndromes: reflexões sobre questões terminológicas e estratégias de tradução

Trabalho de projecto de mestrado, Tradução, Universidade de Lisboa, Faculdade de Letras, 2012

Managing Stress and Pain to Prevent Patient Discomfort, Distress and Delayed Wound Healing.

Evidence suggests stress slows the healing of wounds but pain may also play a part. Regular assessment could improve patients' quality of life and recovery time.

Exercise Prescription for Patients with Non-specific Chronic Low Back Pain: a Qualitative Exploration of Decision Making in Physiotherapy Practice

Background: Providing an effective exercise prescription process for patients with non-specific chronic low back pain (NSCLBP) is a challenging task. Emerging research has indicated that partnership in care and shared decision making are important for people with NSCLBP and calls for further investigation into the approaches used to prescribe exercise. Objective: To explore how shared decision making and patient partnership are addressed by physiotherapists in the process of exercise prescription for patients with NSCLBP. Design: A qualitative study using a philosophical hermeneutic approach. Methods: Eight physiotherapists were each observed on three occasions undertaking their usual clinical activities (total n=24 observations). They conducted brief interviews after each observation and a later in depth semi-structured interview. Iterative hermeneutic strategies were used to interpret the texts and identify the characteristics and processes of exercise prescription for patients with NSCLBP. Findings: The findings revealed how physiotherapy practice often resulted in unequal possibilities for patient participation which were in turn linked to the physiotherapists? assumptions about the patients, clinical orientation, cognitive and decision making processes. Three linked themes emerged: (1) I want them to exercise, (2) Which exercise? - the tension between evidence and everyday practice and (3) Compliance-orientated more than concordance based. Conclusions: This research, by focusing on a patient-centred approach, makes an important contribution to the body of evidence relating to the management of NSCLBP. It challenges physiotherapists to critically appraise their approaches to the prescription of exercise therapy in order to improve outcomes for these patients.

Teaching Toward Utopia: Promise, Provocation, and Pain in Pedagogies of Radical Imagination

Thesis (Ph.D.)--University of Washington, 2014