Chemical composition and pharmacological activities of essential oils of Lavandula spp.

Lavandula spp. belong to the family Lamiatae and some species are often used in popular medicine and have been used for centuries in a large number of medical applications and in aromatherapy. Although similar ethnobotanical properties of Lavandula spp., its essential oils, general chemical composition and therapeutic applications differ from different species. Lavandula stoechas L. subsps. luisieri (Rozeira) Rozeira and L. viridis L’Hér are endemic to the Iberian Peninsula, widespread in the South of Portugal, namely in Southern Alentejo and Algarve. The aim of our study was evaluate the chemical composition and toxicological and pharmacological activities of leaves essential oils of spontaneous plants of L. stoechas L. subsps. luisieri (Alentejo) and L. viridis (Algarve). The essential oils of these wild plants, collected in spring, were obtained by hydrodistillation in a Clevenger-type apparatus and its chemical composition was evaluated by GC/FID. The acute toxicity of essential oils was evaluated "in vitro" using brine shrimp (LC50) and "in vivo" using Swiss mice (DL50). The analgesic and anti-inflammatory pharmacological properties of L. stoechas subsp. luisieri essential oil were evaluated in mouse or rats by the Amour-Smith and carrageen-induced paw edema tests, respectively. Results showed important differences in chemical composition of essential oils from two species analyzed either to diversity and proportion of its constituents. The essentials oils showed citotoxicity against Artemia salina and a DL50 higher than 2000 mg/kg for mice. The analgesic and anti-inflammatory activities of essential oils were exhibit for the doses of 100 and 200 mg/kg.

CHEMICAL COMPOSITION AND ANTIMICROBIAL ACTIVITY OF ESSENTIAL OILS OF LAVANDULA SPP.

Lavenders belong to the family Labiatae and represent some of the most popular medicinal plants of great economic importance. Their essential oils are important for the perfume, cosmetic, flavouring and pharmaceutical industries. However, despite its popularity, and the long tradition of use, biological properties of the various Lavandula species are not yet been well sustained by scientific or clinical studies and some available data being inconclusive and controversial [1]. Although Lavandula spp. have similar ethnobotanical properties, however, chemical composition and therapeutic uses differ from different species and main composition of essential oils showed differences with species and with the region were they grow [1,2,3]. L. stoechas L. subsps. luisieri (Rozeira) Rozeira. L. pedunculata (Mill.) Cav. and L. viridis L’Hér are endemic to the Iberian Peninsula, widespread in the South of Portugal, namely in Alentejo and Algarve. In our work, essential oils from the stems or leaves from wild grown plants of L. luisieri (Alentejo), L. pedunculata (Alentejo) and L. viridis (Algarve), were extracted by hydrodistillation and analyzed by GC-FID. Antimicrobial activity was evaluated by solid diffusion disk assay and minimal inhibitory concentration (MIC) against pathogenic Gram-positive and Gram-negative bacteria and food spoilage fungi.

“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.

Multifunctional nanoparticles for MR and fluorescence imaging

In the past few years a new generation of multifunctional nanoparticles (NPs) has been proposed for biomedical applications, whose structure is more complex than the structure of their predecessor monofunctional counterparts. The development of these novel NPs aims at enabling or improving the performance in imaging, diagnosis and therapeutic applications. The structure of such NPs comprises several components exhibiting various functionalities that enable the nanoparticles to perform multiple tasks simultaneously, such as active targeting of certain cells or compartmentalization, imaging and delivery of active drugs. This thesis presents two types of bimodal bio-imaging probes and describes their physical and chemical properties, namely their texture, structure, and 1H dynamics and relaxometry, in order to evaluate their potential as MRI contrast agents. The photoluminescence properties of these probes are studied, aiming at assessing their interest as optical contrast agents. These materials combine the properties of the trivalent lanthanide (Ln3+) complexes and nanoparticles, offering an excellent solution for bimodal imaging. The designed T1- type contrast agent are SiO2@APS/DTPA:Gd:Ln or SiO2@APS/PMN:Gd:Ln (Ln= Eu or Tb) systems, bearing the active magnetic center (Gd3+) and the optically-active ions (Eu3+ and Tb3+) on the surface of silica NPs. Concerning the relaxometry properties, moderate r1 increases and significant r2 increases are observed in the NPs presence, especially at high magnetic fields, due to susceptibility effects on r2. The Eu3+ ions reside in a single low-symmetry site, and the photoluminescence emission is not influenced by the simultaneous presence of Gd3+ and Eu3+. The presence of Tb3+, rather than Eu3+ ion, further increases r1 but decreases r2. The uptake of these NPs by living cells is fast and results in an intensity increase in the T1-weighted MRI images. The optical features of the NPs in cellular pellets are also studied and confirm the potential of these new nanoprobes as bimodal imaging agents. This thesis further reports on a T2 contrast agent consisting of core-shell NPs with a silica shell surrounding an iron oxide core. The thickness of this silica shell has a significant impact on the r2 and r2* relaxivities, and a tentative model is proposed to explain this finding. The cell viability and the mitochondrial dehydrogenase expression given by the microglial cells are also evaluated.

Synthesis and biological activities of polyphenolic hybrids - evaluation of anti-cancer, anti-inflammatory and antioxidant activities

Os compostos polifenólicos constituem uma classe de metabolitos secundários de plantas, mas existe também uma enorme quantidade de derivados sintéticos ou semi-sintéticos contendo múltiplas unidades fenólicas. Estes compostos apresentam importantes características biológicas, que dependem das suas estruturas básicas. Certos derivados desta família de compostos, tais como flavonoides, cromonas e cumarinas contribuem para os benefícios da dieta humana, e partilham o núcleo de benzopiran-(2 e 4)-ona ou benzofuran-3-ona. A presente dissertação inclui uma introdução geral e três capítulos que descrevem as novas rotas sintéticas estabelecidas para a preparação de novos híbridos de diversos compostos polifenólicos, assim como a sua elucidação estrutural e termina com a presentação dos resultados da avaliação biológica desses mesmos compostos. No segundo capítulo discute-se a preparação de híbridos de pirimidina- e imidazolidina-polifenóis, especialmente a síntese diastereoseletiva de novos híbridos benzofuran-3-ona-hidantoína e derivados de uracilo. A rota sintética envolve a ação de carbodiimidas sobre os ácidos cromona-(2- e 3)-carboxílicos num só passo ou em dois passos sequenciais, catalisada por uma base orgânica ou inorgânica. O terceiro capítulo descreve reações do tipo adições conjugadas 1,4 - hetero-ciclisações em cascata de compostos 1,3-dicarbonílicos em ácido cromona-3-carboxílico catalisadas por uma base orgânica, que originaram novas cromonas, cromanonas e flavonas polissubstituídas. As bispiranonas [bispiran-2 e 4)-onas] foram elaboradas numa reacção de acoplamento da 4-hidroxicumarina ou da lactona do ácido triacético com o ácido cromona-3-carboxílico ou precursores formil-funcionalizados (ω-formil-2’-hydroxy acetofenonas e cromona-3-carbaldeídos) utilizando organocatálise básica. Finalmente, alargou-se o estudo das adições conjugadas 1,4 para uma variedade de 4-hidroxipiran-2-onas e cetonas α,β-insaturadas para originar novos análogos de warfarina. Obteve-se uma variedade de estruturas complexas por hibridação das unidades de 4-hidroxicumarina ou da lactona do ácido triacético com os novos derivados de cromonas polissubstituídas. Todos as reações foram executadas em condições suaves e ambientalmente favoráveis, utilizando a 4-pirrolidinopiridina como organocatalisador básico. As estruturas dos novos híbridos polifenólicos foram caracterizados por técnicas espectroscópicas de alta resolução, incluindo espectroscopia de ressonância magnética nuclear (1D e 2D) e por difractometria de raios-X, que nos permitiram resolver o complexidade estrutural dos compostos sintetizados. O quarto capítulo apresenta os resultados da avaliação biológica obtidos com os híbridos polifenólicos sintetizados neste trabalho, mostrando a possibilidade de seu envolvimento na terapia do cancro. A maioria dos compostos foram avaliados quanto ao seu efeito sobre a citotoxicidade e proliferação de células leucémicas e ao seu envolvimento na regulação de via pró-inflamatória NF-kB, na qual, os híbridos de biscumarinas exibiram actividades elevadas (IC50 = 6-19 μM para inibição de NF-kB depois de 8 horas de incubação e IC50 = 15-39 μM para efeitos citotóxicos em células cancerosas, após 24 horas de incubação). Uma inibição moderada das enzimas HDAC e Cdc25 foi induzida pelos derivados de benzofuran-3-ona-hidantoína. Catorze dos novos derivados polifenólicos polissubstituídos, tendo como estrutura básica a benzopiran-4-ona, foram avaliados pela sua actividade quimiopreventiva do cancro mediada pela indução de sinalização citoprotectora Nrf2 (fator 2 relacionado com o fator nuclear da proteína E2) e capacidade para inibir a proliferação das células de cancro da mama. Os derivados da classe das cromanonas foram identificados como os indutores mais potentes da actividade Nrf2. As concentrações necessárias para aumentar a actividade de luciferase em 10 vezes (C10) foram de 2,8-21,3 μM. Todos os novos híbridos polifenólicos que apresentam atividade citotóxica e anti-proliferativa não afectam o crescimento de células saudáveis periféricas do sangue (PBMC) (IC50 > 50 μM), indicando a sua seletividade para as células cancerosas e sugerindo que alguns deles são estruturalmente interessantes para posteriores análises. A avaliação da atividade antioxidante utilizando os testes do radical livre DPPH e o poder redutor do ião férrico FRAP foram realizados em algumas estruturas híbridas polifenólicas.

Engineering new strategies to improve pharmacokinetics of therapeutic proteins

Tese de doutoramento, Farmácia (Biotecnologia Farmacêutica), Universidade de Lisboa, Faculdade de Farmácia, 2014

Solid contact PVC membrane electrodes based on neutral or charged carriers for the selective reading of anionic sulfamethoxazole and their application to the analysis of aquaculture water

Sulfamethoxazole (SMX) is among the antibiotics employed in aquaculture for prophylactic and therapeutic reasons. Environmental and food spread may be prevented by controlling its levels in several stages of fish farming. The present work proposes for this purpose new SMX selective electrodes for the potentiometric determination of this sulphonamide in water. The selective membranes were made of polyvinyl chloride (PVC) with tetraphenylporphyrin manganese (III) chloride or cyclodextrin-based acting as ionophores. 2-nitrophenyl octyl ether was employed as plasticizer and tetraoctylammonium, dimethyldioctadecylammonium bromide or potassium tetrakis (4-chlorophenyl) borate was used as anionic or cationic additive. The best analytical performance was reported for ISEs of tetraphenylporphyrin manganese (III) chloride with 50% mol of potassium tetrakis (4-chlorophenyl) borate compared to ionophore. Nersntian behaviour was observed from 4.0 × 10−5 to 1.0 × 10−2 mol/L (10.0 to 2500 µg/mL), and the limit of detection was 1.2 × 10−5 mol/L (3.0 µg/mL). In general, the electrodes displayed steady potentials in the pH range of 6 to 9. Emf equilibrium was reached before 15 s in all concentration levels. The electrodes revealed good discriminating ability in environmental samples. The analytical application to contaminated waters showed recoveries from 96 to 106%.

Women's Attachment as a Predictor of Pain During Labour and Post-Delivery: a Prospective Observational Study

INTRODUCTION: Labour is considered to be one of the most painful and significant experiences in a woman's life. The aim of this study was to examine whether women's attachment style is a predictor of the pain experienced throughout labour and post-delivery. MATERIAL AND METHODS:Thirty-two pregnant women were assessed during the third trimester of pregnancy and during labour. Adult attachment was assessed with the Adult Attachment Scale ' Revised. The perceived intensity of labour pain was measured using a visual analogue scale for pain in the early stage of labour, throughout labour and post-delivery. RESULTS:Women with an insecure attachment style reported more pain at 3 cm of cervical dilatation (p < 0.05), before the administration of analgesia (p < 0.01) and post-delivery (p < 0.05) than those securely attached. In multivariate models, attachment style was a significant predictor of labour pain at 3 cm of cervical dilatation and before the first administration of analgesia but not of the perceived pain post-delivery. DISCUSSION: These findings confirm that labour pain is influenced by relevant psychological factors and suggest that a woman's attachment style may be a risk factor for greater pain during labour. CONCLUSION:Future studies in the context of obstetric pain may consider the attachment style as an indicator of individual differences in the pain response during labour. This may have important implications in anaesthesiology and to promote a relevant shift in institutional practices and therapeutic procedures.

Assessment by doppler ultrasound of entheseal lesions in spondyloarthritis : a longitudial study to determine structural damage and disease activity lesions

RESUMO: Enthesitis is the hallmark of spondyloarthritis (SpA), and is observed in all subtypes. Wide information on SpA abnormalities, including synovitis, tendinitis and enthesitis, can be efficiently perceived by Doppler ultrasound. Furthermore, several studies on imaging of enthesis showed that imaging techniques are better than clinical examination to detect enthesis alterations; and vascularized enthesitis detected by Doppler ultrasound appears to be a valuable diagnostic tool to confirm SpA diagnosis. However, data published until now concerning entheseal elementary alterations that characterize SpA enthesitis (enthesis inflammatory activity) or enthesopathy (permanent structural changes) reflect rather the authors’ empiric opinion than a methodological validation process. In this sense it seems crucial to identify elementary entheseal lesions associated with activity or damage, in order to improve monitoring and treatment response in SpA patients. The development of better assessment tools is today a challenge and a need in SpA. The first study of this thesis focused on the analysis of the reliability of inter-lector and inter-ultrasonography equipment of Madrid sonography enthesitis index (MASEI). Fundamental data for the remaining unrolling project validity. In the second and third studies we concerned about two entheseal elemental lesions: erosions and bursa. In literature erosions represent a permanent structural damage, being useful for monitoring joint injury, disease activity and therapeutic response in many rheumatic diseases; and to date, this concept has been mostly applied in rheumatoid arthritis (RA). Unquestionably, erosion is a tissue-related damage and a structural change. However, the hypothesis that we decided to test was if erosions represent a permanent structural change that can only grow and worsen over time, as occurs in RA, or a transitory alteration. A longitudinal study of early SpA patients was undertaken, and the Achilles enthesis was used as a model. Our results strongly suggested that previously detected erosions could disappear during the course of the disease, being consistent with the dynamic behavior of erosion over time. Based on these striking results it seems reasonable to suggest that the new-bone formation process in SpA could be associated with the resolution of cortical entheseal erosion over time. These results could also be in agreement with the apparent failure of anti-tumor necrosis factor (TNF) therapies to control bone proliferation in SpA; and with the relation of TNF-α, Dickkopf-related protein 1 (Dkk-1) and the regulatory molecule of the Wnt signaling pathway in the bone proliferation in SpA. In the same model, we then proceeded to study the enthesis bursa. Interestingly, the Outcome Measures in Rheumatology Clinical Trials (OMERACT) enthesopathy definition does not include bursa as an elementary entheseal lesion. Nonetheless, bursa was included in 46% of the enthesis studies in a recently systematic literature review, being in agreement with the concept of “synovio-entheseal complex” that includes the link between enthesitis and osteitis in SpA. It has been clarified in recent data that there is not only a close functional integration of the enthesis with the neighboring bone, but also a connection between enthesitis and synovitis. Therefore, we tried to assess the prevalence and relevance of the bursa-synovial lesion in SpA. Our findings showed a significant increase of Achilles bursa presence and thickness in SpA patients compared to controls (healthy/mechanical controls and RA controls). These results raise awareness to the need to improve the enthesopathy ultrasonographic definition. In the final work of this thesis, we have explored new perspectives, not previously reported, about construct validity of enthesis ultrasound as a possible activity outcome in SpA. We performed a longitudinal Achilles enthesis ultrasound study in patients with early SpA. Achilles ultrasound examinations were performed at baseline, six- and twelve-month time periods and compared with clinical outcome measures collected at basal visit. Our results showed that basal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are higher in patients with Doppler signal in enthesis, and even that higher basal ESR, CRP and Ankylosing Spondylitis Disease Activity Score (ASDAS) predicted a higher Doppler signal (an ultrasound alteration accepted as representative of inflammation) six months later. Patients with very high disease activity assessed by ASDAS (>3.5) at baseline had significantly higher Achilles total ultrasound score verified at the same time; and ASDAS <1.3 predicted no Doppler signal at six and twelve months. This seems to represent a connection between classical biomarkers and clinical outcomes associated with SpA activity and Doppler signal, not only at the same time, but also for the following months. Remarkably, patients with inactive disease (ASDAS < 1.3) at baseline had no Doppler signal at six and twelve months. These findings reinforce the potential use of ultrasound related techniques for disease progression assessment and prognosis purposes. Intriguingly, Ankylosing Spondylitis Disease Activity Index (BASDAI) didn’t show significant differences between different cut-offs concerning ultrasound lesions or Doppler signal, while verified with ASDAS. These results seem to indicate that ASDAS reflects better than BASDAI what happens in the enthesis. The work herein discussed clearly shows the potential utility of ultrasound in enthesis assessment in SpA patients, and can be important for the development of ultrasound activity and structural damage scores for diagnosis and monitoring purposes. Therefore, local promotion of this technique constitutes a medical intervention that is worth being tested in SpA patients for diagnosis, monitoring and prognosis purposes.

Effects of motive-oriented therapeutic relationship in a ten-session general psychiatric treatment of borderline personality disorder: a randomized controlled trial.

Background: Motive-oriented therapeutic relationship (MOTR) was postulated to be a particularly helpful therapeutic ingredient in the early treatment phase of patients with personality disorders, in particular with borderline personality disorder (BPD). The present randomized controlled study using an add-on design is the first study to test this assumption in a 10-session general psychiatric treatment with patients presenting with BPD on symptom reduction and therapeutic alliance. Methods: A total of 85 patients were randomized. They were either allocated to a manual-based short variant of the general psychiatric management (GPM) treatment (in 10 sessions) or to the same treatment where MOTR was deliberately added to the treatment. Treatment attrition and integrity analyses yielded satisfactory results. Results: The results of the intent-to-treat analyses suggested a global efficacy of MOTR, in the sense of an additional reduction of general problems, i.e. symptoms, interpersonal and social problems (F1, 73 = 7.25, p < 0.05). However, they also showed that MOTR did not yield an additional reduction of specific borderline symptoms. It was also shown that a stronger therapeutic alliance, as assessed by the therapist, developed in MOTR treatments compared to GPM (Z55 = 0.99, p < 0.04). Conclusions: These results suggest that adding MOTR to psychiatric and psychotherapeutic treatments of BPD is promising. Moreover, the findings shed additional light on the perspective of shortening treatments for patients presenting with BPD. © 2014 S. Karger AG, Basel.

Relationships between imatinib plasma levels and efficacy

Purpose: While imatinib has revolutionized the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumors (GIST), its pharmacokinetic-pharmacodynamic relationships have been poorly studied. This study aimed to explore the issue in oncologic patients, and to evaluate the specific influence of the target genotype in a GIST subpopulation. Patients and methods: Data from 59 patients (321 plasma samples) were collected during a previous pharmacokinetic study. Based on a population model purposely developed, individual post-hoc Bayesian estimates of pharmacokinetic parameters were derived, and used to estimate drug exposure (AUC; area under curve). Free fraction parameters were deduced from a model incorporating plasma alpha1-acid glycoprotein levels. Associations between AUC (or clearance) and therapeutic response (coded on a 3-point scale), or tolerability (4-point scale), were explored by ordered logistic regression. Influence of KIT genotype on response was also assessed in GIST patients. Results: Total and free drug exposure correlated with the number of side effects (p < 0.005). A relationship with response was not evident in the whole patient set (with good-responders tending to receive lower doses and bad-responders higher doses). In GIST patients however, higher free drug exposure predicted better responses. A strong association was notably observed in patients harboring an exon 9 mutation or a wild type KIT, known to decrease tumor sensitivity towards imatinib (p < 0.005). Conclusions: Our results are arguments to further evaluate the potential benefit of a therapeutic monitoring program for imatinib. Our data also suggest that stratification by genotype will be important in future trials.

Genetics of calcium homeostasis in humans: continuum between monogenic diseases and continuous phenotypes

Extracellular calcium participates in several key physiological functions, such as control of blood coagulation, bone calcification or muscle contraction. Calcium homeostasis in humans is regulated in part by genetic factors, as illustrated by rare monogenic diseases characterized by hypo or hypercalcaemia. Both serum calcium and urinary calcium excretion are heritable continuous traits in humans. Serum calcium levels are tightly regulated by two main hormonal systems, i.e. parathyroid hormone and vitamin D, which are themselves also influenced by genetic factors. Recent technological advances in molecular biology allow for the screening of the human genome at an unprecedented level of detail and using hypothesis-free approaches, such as genome-wide association studies (GWAS). GWAS identified novel loci for calcium-related phenotypes (i.e. serum calcium and 25-OH vitamin D) that shed new light on the biology of calcium in humans. The substantial overlap (i.e. CYP24A1, CASR, GATA3; CYP2R1) between genes involved in rare monogenic diseases and genes located within loci identified in GWAS suggests a genetic and phenotypic continuum between monogenic diseases of calcium homeostasis and slight disturbances of calcium homeostasis in the general population. Future studies using whole-exome and whole-genome sequencing will further advance our understanding of the genetic architecture of calcium homeostasis in humans. These findings will likely provide new insight into the complex mechanisms involved in calcium homeostasis and hopefully lead to novel preventive and therapeutic approaches. Keyword: calcium, monogenic, genome-wide association studies, genetics.

Interstitial pregnancies' diagnosis and management: an eleven cases series.

PRINCIPLES: Interstitial pregnancy represents 2% of ectopic pregnancies, but it is a highly morbid condition with a 2.5% of maternal mortality. Its diagnostic and therapeutic management remains controversial. The aim of this review is to describe the management of interstitial pregnancy in our institution between 2001 and 2011 and to define some general rules for the clinical practice. METHODS: Single institution retrospective study. RESULTS: Eleven women were treated for interstitial pregnancy. The median age was 33 years and the median gestity was 4. Seven patients had a history of gynaecological surgery and four interstitial pregnancies followed in vitro fertilisation. The diagnosis was made at a median gestational age of seven weeks with a median beta-HCG level of 5,838 U/l. Six of the eleven patients received an initial treatment with intracornual methotrexate, three with intramuscular methotrexate and two with surgery. The median time to beta-HCG resolution was 58 days. Three of the eleven patients needed a second line treatment: two after intramuscular methotrexate and one after intracornual methotrexate. Six patients had further pregnancies and delivered by caesarean section. CONCLUSIONS: A high prevalence of previous ectopic pregnancies, gynaecological surgery and of pregnancies resulting from in vitro fertilisation was observed. The earliness of the diagnosis was the factor that allowed a conservative treatment in most cases. Beta-HCG level follow up was fundamental in allowing a second line therapy but beta-HCG can persist over a long period of time and this must be taken into account due to its possible psychological impact. Intracornual methotrexate seems to be more efficacious than intramuscular methotrexate in our series.

Anxiety-Related Disorders in Primary-Junior Grades (K-3): Teacher Perceptions and Knowledge

This study used a descriptive case study design to analyze teachers’ experiences of anxiety-related conditions and emotions in the primary-junior grades (K-3). The study sought to examine (a) educators’ perceptions of anxiety conditions and how such interpretations influence their teaching practice; (b) teachers’ knowledge of the diagnostic processes, symptomology, and emotions related to anxiety disorders; (c) primary teachers’ knowledge of and experience with emotional regulation strategies and therapeutic approaches for anxiety; and (d) additional strategies and knowledge that should be available to help students. The study adopted Bronfenbrenner’s (1986) Ecological Model to frame participants’ experiences and perspectives, as well as the impact of several factors (e.g., school, home) and individuals (e.g. teachers, parents, students) on students’ anxiety and the participants’ perspectives. Through in-person interviews, participants shared their experiences with and knowledge about students in their teaching practice who had experienced anxiety-related conditions and emotions. Four major themes emerged from the data: symptoms and situational contexts; knowledge of strategies and interventions; understanding and perspectives of students; anxious emotional responses; and challenges. The study contributes to the literature by providing the real-life perspectives and experiences of primary-junior teachers (K-3) related to students experiencing anxiety. The study provides further information for educators, administrators, and research regarding any additional support and knowledge that should be implemented to further assist educators and students in regards to anxiety.

A Narrative Study of Patient Encounter Accounts of Physicians, Nurses, and Medical Receptionists after Two Decades of a Paradigm of Patient-Centered Care

Despite recent well-known advancements in patient care in the medical fields, such as patient-centeredness and evidence-based medicine and practice, there is rather less known about their effects on the particulars of clinician-patient encounters. The emphasis in clinical encounters remains mostly on treatment and diagnosis and less on communicative competency or engagement for medical professionals. The purpose of this narrative study was to explore interactive competencies in diagnostic and therapeutic encounters and intake protocols within the context of the physicians’, nurses’, and medical receptionists’ perspectives and experiences. Literature on narrative medicine, phenomenology and medicine, therapeutic relationships, cultural and communication competency, and non-Western perspectives on human communication provided the guiding theoretical frameworks for the study. Three data sets including 13 participant interviews (5 physicians, 4 nurses, and 4 medical receptionists), policy documents (physicians, nurses, and medical receptionists) and a website (Communication and Cultural Competency) were used. The researcher then engaged in triangulated analyses, including N-Vivo, manifest and latent, Mishler’s (1984, 1995) narrative elements and Charon’s (2005, 2006a, 2006b, 2013) narrative themes, in recursive, overlapping, comparative and intersected analysis strategies. A common factor affecting physicians’ relationships with their clients was limitation of time, including limited time (a) to listen, (b) to come up with a proper diagnosis, and (c) to engage in decision making in critical conditions and limited time for patients’ visits. For almost all nurse participants in the study establishing therapeutic relationships meant being compassionate and empathetic. The goals of intake protocols for the medical receptionists were about being empathetic to patients, being an attentive listener, developing rapport, and being conventionally polite to patients. Participants with the least iv amount of training and preparation (medical receptionists) appeared to be more committed to working narratively in connecting with patients and establishing human relationships as well as in listening to patients’ stories and providing support to narrow down the reason for their visit. The diagnostic and intake “success stories” regarding patient clinical encounters for other study participants were focused on a timely securing of patient information, with some acknowledgement of rapport and emapathy. Patient-centeredness emerged as a discourse practice, with ambiguous or nebulous enactment of its premises in most clinical settings.