New steroidal aromatase inhibitors: biological effects in hormone-dependent breast cancer cell models

Aromatase inhibitors (AIs) are currently used as a first-line therapeutic approach for hormone-dependent (ER+) breast tumors in postmenopausal women, the most common type of cancer diagnosed among women, in which estrogen plays a key role. Aromatase is the enzyme responsible for estrogen biosynthesis, so its inhibition results in estrogen suppression, avoiding tumor growth. However, the existence of side-effects with the current AIs used in clinic, such as development of therapy resistance and bone loss, justifies the search for new AIs. In the past few years, several steroidal compounds have been synthesized with structural modifications in androstenedione, the aromatase substrate, in order to achieve maximum inhibitory effects on aromatase. The present work aims to continue this research line, so newly synthesized steroidal compounds (49, 50, 51 and 52) with structural modifications on A-, B- and D-rings are under biological evaluation, using different human breast cancer cell lines, an ER+ aromatase overexpressing breast cancer cell line (MCF-7aro), an ER- breast cancer cell line (SK-BR-3) and a late stage of acquired endocrine resistance cell line (LTEDaro). [...

Detection of anti-infliximab antibodies is impacted by antibody titer, infliximab level and IgG4 antibodies: a systematic comparison of three different assays

Background: There is scant information on the accuracy of different assays used to measure anti-infliximab antibodies (ADAs), especially in the presence of detectable infliximab (IFX). We thus aimed to evaluate and compare three different assays for the detection of IFX and ADAs and to clarify the impact of the presence of circulating IFX on the accuracy of the ADA assays.Methods: Blood samples from 79 ulcerative colitis (UC) patients treated with infliximab were assessed for IFX levels and ADAs using three different assays: an in-house assay and two commercial kits, Immundiagnostik and Theradiag. Sera samples with ADAs and undetectable levels of IFX were spiked with exogenous IFX and analyzed for ADAs.Results: The three assays showed 81-96% agreement for the measured IFX level. However, the in-house assay and Immundiagnostik assays detected ADAs in 34 out of 79 samples, whereas Theradiag only detected ADAs in 24 samples. Samples negative for ADAs with Theradiag, but ADA-positive in both the in-house and Immundiagnostik assays, were positive for IFX or IgG4 ADAs. In spiking experiments, a low concentration of exogenous IFX (5 mu g/ml) hampered ADA detection with Theradiag in sera samples with ADA levels of between 3 and 10 mu g/ml. In the Immundiagnostik assay detection interference was only observed at concentrations of exogenous IFX higher than 30 mu g/ml. However, in samples with high levels of ADAs (> 25 mu g/ml) interference was only observed at IFX concentrations higher than 100 mu g/ml in all three assays. Binary (IFX/ADA) stratification of the results showed that IFX+/ADA and IFX-/ADAs + were less influenced by the assay results than the double-positive (IFX+/ADAs+) and double-negative (IFX-/ADAs-) combination.Conclusions: All three methodologies are equally suitable for measuring IFX levels. However, erroneous therapeutic decisions may occur when patients show double-negative (IFX-/ADAs) or double-positive (IFX+/ADAs+) status, since agreement between assays is significantly lower in these circumstances

a detailed view of the methodology

Rheumatic and musculoskeletal diseases (RMD) are prevalent and leading causes of disability and consumption of healthcare and social resources. EpiReumaPt is a national population-based survey developed by the Portuguese Society of Rheumatology that aimed to estimate the prevalence of RMDs and determine their impact on function, quality of life, mental health and use of healthcare resources. This article describes in detail the design, methodology and planned analyses of EpiReumaPt. Recruitment started in September 2011 and finished in December 2013. This study involved a three-stage approach. The first step was a face-to-face survey performed by trained interviewers at the household of 10,661 subjects who where randomly selected by a stratified multistage sampling. A highly sensitive screening questionnaire for RMDs was used. Secondly, participants who screened positive (64%) for at least one RMD as well as 20% of individuals with a negative screening were invited for assessment by a rheumatologist. In total, 3,877 subjects participated in this second phase, where they were also invited to donate a blood sample to be stored at the Biobanco-IMM. History and physical examination, followed by appropriate laboratory and imaging tests were performed. At the end of the visit, the rheumatologist established a diagnosis. Finally, a team of three experienced rheumatologists reviewed all the clinical data and defined the diagnoses according to previously validated criteria. The EpiReumaPt dataset, containing data from several questionnaires, various clinical measurements and information from laboratory and imaging tests, comprises an invaluable asset for research. The large amount of information collected from each participant and the large number of participants, with a wide age range covering and being representative of the adults from the entire country, makes EpiReumaPt the largest study of RMDs performed in Portugal.publishersversionpublishe

Promoção do Sucesso e Redução do Abandono Académico: Plano de Ação

Projeto financiado: POCH-02-53I2-FSE-000030 - Skills 4 Pós-COVID - Competências para o futuro no Ensino Superior.De forma de criar e potenciar, no Instituto Politécnico de Leiria, um trabalho colaborativo a partir da identificação e utilização de uma metodologia integrada de promoção do sucesso escolar, que permita identificar, no contexto académico, todas as dimensões do problema e um roteiro de intervenção futuro que inclua a identificação de estratégias para promoção do sucesso académico em Instituições de Ensino Superior nacionais e internacionais, foi desenvolvido o “Laboratório da Mudança”. Através de um método sistémico, participativo e criativo para enfrentar, gerir e mitigar problemas sociais complexos, como são o insucesso e abandono escolar, foi desenvolvido um trabalho em conjunto com os diferentes intervenientes da comunidade académica do Instituto Politécnico de Leiria, no qual foi utilizada a ferramenta Teoria da Mudança para a criação de um plano de ação face a problemas sociais complexos. No Laboratório da Mudança foram convidados a participar vários atores da comunidade académica do IP Leiria, desde direções e escolas, coordenações pedagógicas e demais serviços, bem como docentes e estudantes. A equipa multidisciplinar constituída para o desenvolvimento do Laboratório trouxe contributos variados relevantes e inovadores no desenho de uma estratégia colaborativa e na construção do presente plano de ação. Aquando da identificação do problema, e após o término do projeto, estes atores contribuirão na promoção de outras estratégias, além das propostas em desenvolvimento neste projeto, que possam ser concebidas no futuro visando a resolução dos problemas identificados do insucesso e abandono escolar.N/

Assessment and prediction of tablet properties using transmission and backscattering Raman spectroscopy and transmission NIR spectroscopy

AbstractThis study investigated whether Raman and Near Infrared (NIR) spectroscopy could predict tablet properties. Granules were produced on a continuous line by varying granulation parameters. Tableting process parameters were adjusted to obtain uniform tablet weight and thickness. Spectra were collected offline and tablet properties determined with traditional analyzing methods. Partial Least Squares (PLS) regression was used to correlate spectral information to tablet properties, but predictive models couldn't be established. Principal component analysis (PCA) was effectively used to distinguish theophylline concentrations and hydration levels and multiple linear regression (MLR) analysis allowed insight on how granulation parameters affect granule and tablet properties

Visceral Dissemination of Mucocutaneous Leishmaniasis in a Kidney Transplant Recipient

Intracellular protozoan of the genus Leishmania, endemic in the Mediterranean basin, are the cause of cutaneous (CL), mucocutaneous (MCL), and visceral leishmaniasis (VL). A 75-year-old woman was admitted nine years after a second kidney transplant (KT), due to persistent pancytopenia and fever. She presented edema and erythema of the nose in the last two years and an exophytic nodular lesion located on the left arm, with areas of peripheral necrosis and central ulceration in the last 18 months. A bone marrow biopsy revealed features compatible with Leishmania amastigotes, and polymerase chain reaction test (PCR) for Leishmania infantum was positive. Moreover, biopsy and PCR for L. infantum of the cutaneous lesion on the patient’s left arm and nose and PCR from peripheral blood were positive. Thus, a diagnosis of CL, MCL, and VL was made, and liposomal amphotericin B was initiated, but the patient had an unfavorable outcome and died. This is the first report of a KT recipient presenting with the entire spectrum of leishmaniasis. In Portugal, this infection is rare—so a high degree of clinical suspicion is required for its diagnosis, especially in endemic regions, as visceral leishmaniasis is a potentially life-threatening infection