Changes in [18F]Fluoro-2-deoxy-D-glucose incorporation induced by doxorubicin and anti-HER antibodies by breast cancer cells modulated by co-treatment with metformin and its effects on intracellular signalling

Peer reviewed

Changes in [18F]Fluoro-2-deoxy-D-glucose incorporation induced by doxorubicin and anti-HER antibodies by breast cancer cells modulated by co-treatment with metformin and its effects on intracellular signalling

Peer reviewed

Changes in [18F]Fluoro-2-deoxy-D-glucose incorporation induced by doxorubicin and anti-HER antibodies by breast cancer cells modulated by co-treatment with metformin and its effects on intracellular signalling

Peer reviewed

From labelling to social aid for immigrants in the 21st Century

Migration is as old as humanity, but since the 1990s migration flows in Western Europe have led to societies that are not just multicultural but so-called «super-diverse». As a result, Western towns now have very complex social structures, with amongst others large amounts of small immigrant communities that are in constant change. In this paper we argue that for social workers to be able to offer adequate professional help to non-native residents in town, they will need balanced view of ‘culture’ and of the role culture plays in social aid. Culture is never static, but is continually changing. By teaching social workers about how to look at cultural backgrounds of immigrant groups and about the limitations of then role that culture plays in communication, they will be better equipped to provide adequate aid and will contribute to making various groups grow towards each other and to avoid people thinking in terms of ‘out-group-homogeneity’. Nowadays, inclusion is a priority in social work that almost every social worker supports. Social workers should have an open attitude to allow them to approach every individual as a unique person. They will see the other person as the person they are, and not as a part of a specific cultural group. Knowledge about the others makes them see the cultural heterogeneity in every group. The social sector, though, must be aware not to fall into the trap of the ‘inclusion mania’! This will cause the social deprivation of a particular group to be forgotten. An inclusive policy requires an inclusive society. Otherwise, this could result in even more deprivation of other groups, already discriminated against. Emancipation of deprived people demands a certain target-group policymaking. Categorized aid will raise efficiency of working with immigrants and of acknowledging the cultural identity of the non-natives group. It will also create the possibility to work on fighting social deprivation, in which most immigrants can be found.

Chinese Men and "Leftover Women" : How do Chinese Men Position Themselves in Relation to the Concept of Labelling Women as "Leftover"?

In recent years there has been a resurgence of gender inequality in China. Today, women are pressured to get married by the state and their social surroundings, as they told if they remain unmarried and have the "three highs"; high age, education and salary, they will become leftovers on the marriage market. Previous research on the concept of labelling women as "leftover" has 4 shown that labelling women as "leftover" can have several different negative impacts. In this thesis, both the theory of masculine hegemony and the theory of symbolic interaction have been used. The concept creates a hegemonic masculinity as it is a normative practice that promotes the subordination of women. However, as the concept is based on the notion that all Chinese men, or at least those of relevant social standing, would find the "three highs" undesirable, it is relevant to see how Chinese men in fact do position themselves in relation to the hegemonic masculinity on an individual level. In symbolic interaction, the concept of gender is created through social construction when people attach special meanings to the sex of a person, a process which is called "doing gender". Therefore symbolic interaction is used to see what special meaning Chinese men attach to women having the "three highs" and masculine hegemony to put their answers into a larger context. If it could be shown that Chinese men do not comply with the hegemonic masculinity, Chinese women would not have to feel obliged to adjust to the hegemonic masculinity and thereby making it easier for them to pursue higher education, high paying jobs and marrying at a later age. However, as this thesis is a qualitative study, and therefore a limited number of data subjects, the generalizability of the result should not be exaggerated. The interviews that were conducted for this thesis showed that the data subjects were familiar with the concept and that they considered it to be natural for there to be women China labelled as "leftover". Nevertheless, in relation to their own marital choices, the data subjects did not attach the negative meaning as set out by the hegemonic masculinity, a result which to some extent was confirmed by the data subjects’ experiences and other control questions. The result is interesting, and enforces Connell and MesserSchmidt’s theory, that even though a hegemonic masculinity is normative, not everyone has to comply with it. As the cornerstone of the concept is that Chinese men find women with the "three highs" undesirable, the result of the study shows that there is a need for the concept to be further examined and questioned.

Assessment of the quality of sample labelling for clinical research

Objective: To assess the quality of the labels for clinical trial samples through current regulations, and to analyze its potential correlation with the specific characteristics of each sample. Method: A transversal multicenter study where the clinical trial samples from two third level hospitals were analyzed. The eleven items from Directive 2003/94/EC, as well as the name of the clinical trial and the dose on the label cover, were considered variables for labelling quality. The influence of the characteristics of each sample on labelling quality was also analyzed. Outcome: The study included 503 samples from 220 clinical trials. The mean quality of labelling, understood as the proportion of items from Appendix 13, was of 91.9%. Out of these, 6.6% did not include the name of the sample in the outer face of the label, while in 9.7% the dose was missing. The samples with clinical trial-type samples presented a higher quality (p < 0.049), blinding reduced their quality (p = 0.017), and identification by kit number or by patient increased it (p < 0.01). The promoter was the variable which introduced the highest variability into the analysis. Conclusions: The mean quality of labelling is adequate in the majority of clinical trial samples. The lack of essential information in some samples, such as the clinical trial code and the period of validity, is alarming and might be the potential source for dispensing or administration errors.

Cerebrotendinous xanthomatosis with bradyphrenia and psychiatric disorders: a case with 18F-FDG PET imaging and a literature review

Background and Objectives: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid-storage disease caused by mutations in the CYP27A1. The purpose of this study is to determine the clinical characteristics, neuroimaging and mutation detect in a family with CTX systematically. Methods: Collecting history materials and detecting the routine clinical biochemical tests and imaging examination, and for the first time taking the whole body positron emission tomography (PET)-CT examination for probed in the world to research abnormal metabolism activities in CTX. To observe the effect of treatment with chenodeoxycholic acid (CDCA) and stains before and after the intervention, using serum lipid level detection and neuropsychological evaluation. Genetic testing was carried out to screen the nine exons and exon-intron boundaries about 200-300bq of CYP27A1. Results: A 37-year-old woman with typical clinical characteristics of CTX. Magnetic resonance imaging (MRI) of brain showed bilateral lesions in the dentate nucleus of the cerebellum, then, PET images revealed multiple abnormal hypermetabolism areas at distal tendon, and multifocal areas of hypometabolism in bilateral sides of cerebellar hemispheres, the frontal lobe and temporal lobe. Histopathology reveals accumulation of xanthoma cells and dispersed lipid crystal clefts in xanthomas. In genetic analysis, it shown an insertion of cytosine (77-78insC) located in the first exon of CYP27A1 in the proband. Conclusions: We found that a Chinese patient presented a typical clinical feature of CTX along with clear correlation on both structural and functional imaging had a novel mutation in the CYP27A1 gene.

16α-[18F]-fluoro-17ß-oestradiol ([18F]FES): A biomarker for imaging oestrogen receptor expression with positron emission tomography (PET)

International audience

Estudo combinado de PET com [11C]PiB e [18F]FDG na avaliação de doença de Alzheimer

A doença de Alzheimer (DA) têm-se constituído, nos últimos anos, num sério problema de saúde pública nas sociedades ocidentais, um reflexo de uma população cada vez mais envelhecida fruto da melhoria geral da assistência médica e das mudanças demográficas daí decorrentes. Tratando-se uma doença neurodegenerativa a DA conduz à perda de diversas faculdades cognitivas e carateriza-se pela redução progressiva de tamanho e número das células cerebrais, a par da formação de emaranhados neurofibrilares (NFTs) no seu interior e placas de β-amilóide (Aβ) no espaço exterior. Na última década, o diagnóstico da DA ganhou um importante aliado com a possibilidade de realização de Tomografia por Emissão de Positrões (PET) com o radiofármaco [11C]PiB que apresenta afinidade pelas placas de Aβ. Recentemente, foi também possível aumentar a confiança deste diagnóstico complementando-o com a avaliação do metabolismo cerebral da glicose através da sua conjugação, no mesmo protocolo PET com a [18F]FDG. No que concerne à realidade portuguesa, o ICNAS, uma unidade orgânica de investigação da Universidade de Coimbra focada na Utilização Biomédica das Ciências Nucleares, que inclui na sua estrutura uma unidade de produção radiofarmacêutica com ciclotrão, é um local privilegiado para a realização de PET cerebral com [11C]PiB. Desde Abril de 2012 até Julho de 2014 foram já realizados 107 estudos com [11C]PiB, dos quais 37 fizeram parte de estudos sequenciais onde o mesmo doente realizou o estudo combinado com [11C]PiB e [18F]FDG.

Exposição à radiação em exames de corpo inteiro de 18F-FDG PET-TC

O sistema de PET-TC resulta da combinação de duas modalidades de imagem médica: a Tomografia Computorizada (TC), que permite obter imagens anatómicas precisas, e a Tomografia por Emissão de Positrões (PET), que oferece imagens moleculares do corpo humano. Num exame hibrido de PET-TC, para além da exposição interna, o doente é também submetido a uma exposição externa devida à irradiação do mesmo por uma fonte externa, referente à aquisição dos dados de TC. Como tal, o exame de PET-TC tem associado um aumento da exposição para o doente [Huang, 2009], pelo que normalmente os scans de TC são adquiridos com baixa dose [Nunes,2011]. Pretende-se com este trabalho, estabelecer um método capaz de estimar a dose efetiva em exames de corpo inteiro de 18F-FDG PET-TC, uma vez que existem diversos métodos para realizar análise dosimétrica dos exames individuais de PET e de TC, e comparar os valores obtidos com os valores utilizados em outros países. Foram recolhidos dados de 24 pacientes que efetuaram exames de corpo inteiro de PET-TC com 18F-FDG no ICNAS, por questões de saúde e por necessidade própria, com o intuito de estimar a dose efetiva associada a esses exames. Para estimar a dose efetiva referente ao exame de TC recorreu-se ao valor de DLP, fornecido pelo equipamento de TC com controlo de qualidade em dia, e ao método dos coeficicientes de dose efetiva normalizados, proposto pela CE, obtendo-se um valor de dose de 4.75 mSv. A dose efetiva do exame de PET foi calculada com base nos valores da atividade no momento de aquisição das imagens e em coeficientes de dose para a PET, obtendo-se um valor de dose de 4.77 mSv. Concluiu-se que para os pacientes sujeitos ao exame de corpo inteiro de 18F-FDG PET-TC, foi registado um valor de dose de 9.47 mSv de dose efetiva. Este valor de dose efetiva para os exames de PET-TC é significativamente mais baixo comparativamente aos valores registados em vários estudos internacionais (13.65 mSv, 14.3 mSv, 18.85 mSv, 24.8 mSv, 25 mSv, 32.18 mSv), dos quais apenas no estudo de Brix um dos hospitais estudados regista um valor ligeiramente inferior, de 8.5 mSv. Com este estudo foi possível determinar o valor de exposição à radiação a que os pacientes do ICNAS se encontram sujeitos em exames de corpo inteiro de 18F-FDG PET-TC considerando as duas modalidades de imagem médica.

From ‘Bad’ to ‘Mad’: Labelling and Behaviour in Peter Shaffer’s Equus

The process of ‘labelling’ (whereby labels are socially imposed on a given behaviour by a given person) is an extensive and recurrent one in our society, as proved by the labelling of behaviours and people even into the literary text. In our analysis, we will try to show how applying one of two most different labels (psychopathic or psychotic) greatly influences our understanding of the existence of ‘evil’ or moral responsibility in the deeds of a person. To such end, we will use Peter Shaffer’s play Equus (1973), which requires both the characters in the play and the spectators to decide whether Alan Strang’s terrible crime is a result of evil or of insane behaviour: whether he is ‘mad’ or simply ‘bad’. We will try to evince the current social and cultural confusion between madness and evil, and how processes of medicalization or criminalization affect our understanding of those around us and those living in the books we read.

Evaluation of tumor recurrences after radical prostatectomy using 18F-Choline PET/CT and 3T multiparametric MRI without endorectal coil: a single center experience

The aim os this study is to evaluate and compare the utility of 18F-fluorocholine (18F-CH) PET/CT versus 3-Tesla multiparametric MRI (mpMRI) without endorectal coil to detect tumor recurrences in patients with biochemical relapse following radical prostatectomy (RP). Secondarily, to identify possible prognostic variables associated with mpMRI and 18F-CH PET/CT findings. Retrospective study of 38 patients who developed biochemical recurrence after RP between the years 2011 and 2015 at our institution. PET/CT and mpMRI were both performed within 30 days of each other in all patients. The PET/CT was reviewed by a nuclear medicine specialist while the mpMRI was assessed by a radiologist, both of whom were blinded to outcomes. The median prostate-specific antigen (PSA) value pre-MRI/PET-CT was 0.9 ng/mL (interquartile range 0.4–2.2 ng/mL). There were no differences in the detection rate between 18F-CH PET/CT and mpMRI for local recurrence (LR), lymph node recurrence (LNR) and bone metastases (BM). Separately, mpMRI and 18F-CH PET/CT were positive for recurrence in 55.2% and 52.6% of cases, respectively, and in 65.7% of cases when findings from both modalities were considered together. The detection of LR was better with combined mpMRI and choline PET/CT versus choline PET/CT alone (34.2% vs 18.4%, p = 0.04). Salvage treatment was modified in 22 patients (57.8%) based on the imaging findings. PSA values on the day of biochemical failure were significantly associated with mpMRI positivity (adjusted odds ratio (OR): 30.9; 95% confidence interval (CI): 1.5–635.8). Gleason score > 7 was significantly associated with PET/CT positivity (OR: 13.9; 95% CI: 1.5–125.6). A significant association was found between PSA doubling time (PSADT) (OR: 1.3; 95% CI: 1.0–1.7), T stage (OR: 21.1; 95% CI: 1.6–272.1), and LR. Multiparametric MRI and 18F-CH PET/CT yield similar detection rates for LR, LNR and pelvic BM. The combination of both imaging techniques provides a better LR detection versus choline PET/CT alone. The initially planned salvage treatment was modified in 57.8% of patients due to imaging findings. In addition to PSA values, Gleason score, T stage, and PSADT may provide valuable data to identify those patients that are most likely to benefit from undergoing both imaging procedures.

Diversity of accuracy profiles for absolute pitch recognition

Most advanced musicians are able to identify and label a heard pitch if given an opportunity to compare it to a known reference note. This is called ‘relative pitch’ (RP). A much rarer skill is the ability to identify and label a heard pitch without the need for a reference. This is colloquially referred to as ‘perfect pitch’, but appears in the academic literature as ‘absolute pitch’ (AP). AP is considered by many as a remarkable skill. As people do not seem able to develop it intentionally, it is generally regarded as innate. It is often seen as a unitary skill and that a set of identifiable criteria can distinguish those who possess the skill from those who do not. However, few studies have interrogated these notions. The present study developed and applied an interactive computer program to map pitch-labelling responses to various tonal stimuli without a known reference tone available to participants. This approach enabled the identification of the elements of sound that impacted on AP. Pitch-labelling responses of 14 participants with AP were recorded for their accuracy. Each participant’s response to the stimuli was unique. Their accuracy of labelling varied across dimensions such as timbre, range and tonality. The diversity of performance between individuals appeared to reflect their personal musical experience histories.

The manipulation of apoptosis-related genes to generate resistance to Fusarium wilt and water stress in banana

Bananas are susceptible to a diverse range of biotic and abiotic stresses, many of which cause serious production constraints worldwide. One of the most destructive banana diseases is Fusarium wilt caused by the soil-borne fungus, Fusarium oxysporum f. sp. cubense (Foc). No effective control strategy currently exists for this disease which threatens global banana production. Although disease resistance exists in some wild bananas, attempts to introduce resistance into commercially acceptable bananas by conventional breeding have been hampered by low fertility, long generation times and association of poor agronomical traits with resistance genes. With the advent of reliable banana transformation protocols, molecular breeding is now regarded as a viable alternative strategy to generate disease-resistant banana plants. Recently, a novel strategy involving the expression of anti-apoptosis genes in plants was shown to result in resistance against several necrotrophic fungi. Further, the transgenic plants showed increased resistance to a range of abiotic stresses. In this thesis, the use of anti-apoptosis genes to generate transgenic banana plants with resistance to Fusarium wilt was investigated. Since water stress is an important abiotic constraint to banana production, the resistance of the transgenic plants to water stress was also examined. Embryogenic cell suspensions (ECS) of two commercially important banana cultivars, Grand Naine (GN) and Lady Finger (LF), were transformed using Agrobacterium with the anti-apoptosis genes, Bcl-xL, Bcl-xL G138A, Ced-9 and Bcl- 2 3’ UTR. An interesting, and potentially important, outcome was that the use of anti-apoptosis genes resulted in up to a 50-fold increase in Agrobacterium-mediated transformation efficiency of both LF and GN cells over vector controls. Regenerated plants were subjected to a complete molecular characterisation in order to detect the presence of the transgene (PCR), transcript (RT-PCR) and gene product (Western blot) and to determine the gene copy number (Southern blot). A total of 36 independently-transformed GN lines (8 x Bcl-xL, 5 x Bcl-xL G138A, 15 x Ced-9 and 8 x Bcl-2 3’ UTR) and 41 independently-transformed LF lines (8 x Bcl-xL, 7 x BclxL G138A, 13 x Ced-9 and 13 x Bcl-2 3’ UTR) were identified. The 41 transgenic LF lines were multiplied and clones from each line were acclimatised and grown under glasshouse conditions for 8 weeks to allow monitoring for phenotypic abnormalities. Plants derived from 3 x Bcl-xL, 2 x Ced-9 and 5 x Bcl-2 3’ UTR lines displayed a variety of aberrant phenotypes. However, all but one of these abnormalities were off-types commonly observed in tissue-cultured, non-transgenic banana plants and were therefore unlikely to be transgene-related. Prior to determining the resistance of the transgenic plants to Foc race 1, the apoptotic effects of the fungus on both wild-type and Bcl-2 3’ UTR-transgenic LF banana cells were investigated using rapid in vitro root assays. The results from these assays showed that apoptotic-like cell death was elicited in wild-type banana root cells as early as 6 hours post-exposure to fungal spores. In contrast, these effects were attenuated in the root cells of Bcl-2 3’ UTR-transgenic lines that were exposed to fungal spores. Thirty eight of the 41 transgenic LF lines were subsequently assessed for resistance to Foc race 1 in small-plant glasshouse bioassays. To overcome inconsistencies in rating the internal (vascular discolouration) disease symptoms, a MatLab-based computer program was developed to accurately and reliably assess the level of vascular discolouration in banana corms. Of the transgenic LF banana lines challenged with Foc race 1, 2 x Bcl-xL, 3 x Ced-9, 2 x Bcl-2 3’ UTR and 1 x Bcl-xL G138A-transgenic line were found to show significantly less external and internal symptoms than wild-type LF banana plants used as susceptible controls at 12 weeks post-inoculation. Of these lines, Bcl-2 3’ UTR-transgenic line #6 appeared most resistant, displaying very mild symptoms similar to the wild-type Cavendish banana plants that were included as resistant controls. This line remained resistant for up to 23 weeks post-inoculation. Since anti-apoptosis genes have been shown to confer resistance to various abiotic stresses in other crops, the ability of these genes to confer resistance against water stress in banana was also investigated. Clonal plants derived from each of the 38 transgenic LF banana plants were subjected to water stress for a total of 32 days. Several different lines of transgenic plants transformed with either Bcl-xL, Bcl-xL G138A, Ced-9 or Bcl-2 3’ UTR showed a delay in visual water stress symptoms compared with the wild-type control plants. These plants all began producing new growth from the pseudostem following daily rewatering for one month. In an attempt to determine whether the protective effect of anti-apoptosis genes in transgenic banana plants was linked with reactive oxygen species (ROS)-associated programmed cell death (PCD), the effect of the chloroplast-targeting, ROS-inducing herbicide, Paraquat, on wild-type and transgenic LF was investigated. When leaf discs from wild-type LF banana plants were exposed to 10 ìM Paraquat, complete decolourisation occurred after 48 hours which was confirmed to be associated with cell death and ROS production by trypan blue and 3,3-diaminobenzidine (DAB) staining, respectively. When leaf discs from the transgenic lines were exposed to Paraquat, those derived from some lines showed a delay in decolourisation, suggesting only a weak protective effect from the transgenes. Finally, the protective effect of anti-apoptosis genes against juglone, a ROS-inducing phytotoxin produced by the causal agent of black Sigatoka, Mycosphaerella fijiensis, was investigated. When leaf discs from wild-type LF banana plants were exposed to 25 ppm juglone, complete decolourisation occurred after 48 hours which was again confirmed to be associated with cell death and ROS production by trypan blue and DAB staining, respectively. Further, TdT-mediated dUTP nick-end labelling (TUNEL) assays on these discs suggested that the cell death was apoptotic. When leaf discs from the transgenic lines were exposed to juglone, discs from some lines showed a clear delay in decolourisation, suggesting a protective effect. Whether these plants are resistant to black Sigatoka is unknown and will require future glasshouse and field trials. The work presented in this thesis provides the first report of the use of anti-apoptosis genes as a strategy to confer resistance to Fusarium wilt and water stress in a nongraminaceous monocot, banana. Such a strategy may be exploited to generate resistance to necrotrophic pathogens and abiotic stresses in other economically important crop plants.