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OBJECTIVE: Patients' psychological reactions to multigene cancer panel testing might differ compared with the single-gene testing reactions because of the complexity and uncertainty associated with the different possible results. Understanding patients' preferences and psychological impact of multigene panel testing is important to adapt the genetic counselling model. METHODS: One hundred eighty-seven unrelated patients with clinical suspicion of hereditary cancer undergoing a 25-gene panel test completed questionnaires after pretest genetic counselling and at 1 week, 3 months, and 12 months after results to elicit their preferences regarding results disclosure and to measure their cancer worry and testing-specific distress and uncertainty. RESULTS: A pathogenic variant was identified in 38 patients (34 high penetrance and 4 moderate penetrance variants), and 54 patients had at least one variant of uncertain significance. Overall, cancer panel testing was not associated with an increase in cancer worry after results disclosure (P value = .87). Twelve months after results, carriers of a moderate penetrance variant had higher distress and uncertainty scores compared with carriers of high penetrance variants. Cancer worry prior to genetic testing predicted genetic testing specific distress after results, especially at long term (P value <.001). Most of the patients reported the wish to know all genetic results. CONCLUSIONS: Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.
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Aconselhamento Genético/psicologia , Predisposição Genética para Doença/psicologia , Testes Genéticos/métodos , Neoplasias/psicologia , Adulto , Ansiedade/psicologia , Estudos de Coortes , Feminino , Predisposição Genética para Doença/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/prevenção & controle , EspanhaRESUMO
Nasal obstruction (NO) is defined as the subjective perception of discomfort or difficulty in the passage of air through the nostrils. It is a common reason for consultation in primary and specialized care and may affect up to 30%-40% of the population. It affects quality of life (especially sleep) and lowers work efficiency. The aim of this document is to agree on how to treat NO, establish a methodology for evaluating and diagnosing it, and define an individualized approach to its treatment. NO can be unilateral or bilateral, intermittent or persistent and may be caused by local or systemic factors, which may be anatomical, inflammatory, neurological, hormonal, functional, environmental, or pharmacological in origin. Directed study of the medical history and physical examination are key for diagnosing the specific cause. NO may be evaluated using subjective assessment tools (visual analog scale, symptom score, standardized questionnaires) or by objective estimation (active anterior rhinomanometry, acoustic rhinometry, peak nasal inspiratory flow). Although there is little correlation between the results, they may be considered complementary and not exclusive. Assessing the impact on quality of life through questionnaires standardized according to the underlying disease is also advisable. NO is treated according to its cause. Treatment is fundamentally pharmacological (topical and/or systemic) when the etiology is inflammatory or functional. Surgery may be necessary when medical treatment fails to complement or improve medical treatment or when other therapeutic approaches are not possible. Combinations of surgical techniques and medical treatment may be necessary.
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Obstrução Nasal/tratamento farmacológico , Animais , Humanos , Cavidade Nasal/efeitos dos fármacos , Qualidade de Vida , Rinomanometria/métodos , Rinometria Acústica/métodosRESUMO
Despite the chronic and increasingly prevalent nature of actinic keratosis (AK) and existing evidence supporting assessment of the entire cancerization field during clinical management, a standardized definition of the AK field to aid in the understanding and characterization of the disease is lacking. The objective of this review was to present and appraise the available evidence describing the AK cancerization field, with the aim of determining a precise definition of the AK field in terms of its molecular (including genetic and immunological), histological and clinical characteristics. Eight European dermatologists collaborated to conduct a review and expert appraisal of articles detailing the characteristics of the AK field. Articles published in English before August 2016 were identified using PubMed and independently selected for further assessment according to predefined preliminary inclusion and exclusion criteria. In addition, a retrospective audit of patients with AK was performed to define the AK field in clinical terms. A total of 32 review articles and 47 original research articles provided evidence of sun-induced molecular (including genetic and immunological) and histological skin changes in the sun-exposed area affected by AK. However, the available literature was deemed insufficient to inform a clinical definition of the AK field. During the retrospective audit, visible signs of sun damage in 40 patients with AK were assessed. Telangiectasia, atrophy and pigmentation disorders emerged as 'reliable or very reliable' indicators of AK field based on expert opinion, whereas 'sand paper' was deemed a 'moderately reliable' indicator. This literature review has revealed a significant gap of evidence to inform a clinical definition of the AK field. Therefore, the authors instead propose a clinical definition of field cancerization based on the identification of visible signs of sun damage that are reliable indicators of field cancerization based on expert opinion.
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Ceratose Actínica/patologia , Neoplasias Cutâneas/patologia , HumanosRESUMO
Bone metastases in patients with solid tumours (ST) and bone lesions in patients with haematological malignancies (HM) are common. Associated skeletal-related events (SREs) cause severe pain, reduced quality of life and place a burden on health care resources. Bone-targeted agents can reduce the risk of SREs. We evaluated the management of bone metastasis/lesions in five European countries (France, Germany, Italy, Spain and the UK) by an observational chart audit. In total, 881 physicians completed brief questionnaires on 17 193 patients during the observation period, and detailed questionnaires for a further 9303 individuals. Patient cases were weighted according to the probability of inclusion. Although a large proportion of patients with bone metastases/lesions were receiving bisphosphonates, many had their treatment stopped (ST, 19%; HM, 36%) or will never be treated (ST, 18%; HM, 13%). The results were generally similar across the countries, although German patients were more likely to have asymptomatic bone lesions detected during routine imaging. In conclusion, many patients who could benefit from bone-targeted agents do not receive bisphosphonates and many have their treatment stopped when they could benefit from continued treatment. Developing treatment guidelines, educating physicians and increasing the availability of new agents could benefit patients and reduce costs.
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Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Difosfonatos/uso terapêutico , Neoplasias , Idoso , Neoplasias Ósseas/secundário , Europa (Continente) , Feminino , Neoplasias Hematológicas , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Tempo para o Tratamento , Resultado do TratamentoRESUMO
The use of endogenous protoporphyrin IX after administration of 5-aminolaevulinic acid (ALA) has led to many applications in photodynamic therapy (PDT). We have previously reported that the conjugation of ALA dendrimers enhances porphyrin synthesis. The first aim of this work was to evaluate the ability of ALA dendrimers carrying 6 and 9 ALA residues (6m-ALA and 9m-ALA) to photosensitise cancer cells. For this aim, we employed LM3 mammary carcinoma cells. In these tumour cells, at low concentrations porphyrin synthesis from dendrimers was higher compared to ALA, whereas at high concentrations, porphyrin synthesis was similar from both compounds. Topical application of ALA dendrimers on the skin overlying a subcutaneous LM3 implanted tumour showed no diffusion of the molecules either to distant skin sites or to the adjacent tumour, suggesting a promising use of the ALA macromolecules in superficial cancer models. As a second objective, we proposed the use of ALA-dendrimers in vascular PDT for the treatment of atherosclerosis. Thus, we focused our studies on ALA-dendrimer's selectivity towards macrophages in comparison with endothelial cells. For this aim we employed Raw 264.7 macrophages and HMEC-1 microvasculature cells. Porphyrin synthesis induced in macrophages by 6m-ALA and 9m-ALA (3 h, 0.025 mM) was 6 and 4.6 times higher respectively compared to the endothelial cell line, demonstrating the high affinity of ALA dendrimers for macrophages. On the other hand, ALA employed at low concentrations was slightly selective (1.7-fold) for macrophages. Inhibition studies suggested that ALA dendrimer uptake in macrophages is mainly mediated by caveloae-mediated endocytosis. Our main conclusion is that in addition to being promising molecules in PDT of superficial cancer, ALA dendrimers may also find applications in vascular PDT, since in vitro they showed selectivity to the macrophage component of the atheromatous plaque, as compared to the vascular endothelium.
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Adenocarcinoma/tratamento farmacológico , Ácido Aminolevulínico/farmacologia , Dendrímeros/farmacologia , Neoplasias Mamárias Animais/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Ácido Aminolevulínico/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Dendrímeros/química , Endocitose/efeitos dos fármacos , Endocitose/fisiologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Neoplasias Mamárias Animais/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Estrutura Molecular , Transplante de Neoplasias , Fármacos Fotossensibilizantes/química , Porfirinas/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismoRESUMO
BACKGROUND: Although there are solid findings regarding the detrimental effect of alcohol consumption, the existing evidence on the effect of other dietary factors on breast cancer (BC) risk is inconclusive. This study aimed to evaluate the association between dietary patterns and risk of BC in Spanish women, stratifying by menopausal status and tumour subtype, and to compare the results with those of Alternate Healthy Index (AHEI) and Alternate Mediterranean Diet Score (aMED). METHODS: We recruited 1017 incident BC cases and 1017 matched healthy controls of similar age (±5 years) without a history of BC. The association between 'a priori' and 'a posteriori' developed dietary patterns and BC in general and according to menopausal status and intrinsic tumour subtypes (ER+/PR+ and HER2-; HER2+; and ER-/PR- and HER2-) was evaluated using logistic and multinomial regression models. RESULTS: Adherence to the Western dietary pattern was related to higher risk of BC (OR for the top vs the bottom quartile 1.46 (95% CI 1.06-2.01)), especially in premenopausal women (OR=1.75; 95% CI 1.14-2.67). In contrast, the Mediterranean pattern was related to a lower risk (OR for the top quartile vs the bottom quartile 0.56 (95% CI 0.40-0.79)). Although the deleterious effect of the Western pattern was similarly observed in all tumour subtypes, the protective effect of our Mediterranean pattern was stronger for triple-negative tumours (OR=0.32; 95% CI 0.15-0.66 and Pheterogeneity=0.04). No association was found between adherence to the Prudent pattern and BC risk. The associations between 'a priori' indices and BC risk were less marked (OR for the top vs the bottom quartile of AHEI=0.69; 95% CI 0.51-0.94 and aMED=0.74; 95% CI 0.46-1.18)). CONCLUSIONS: Our results confirm the harmful effect of a Western diet on BC risk, and add new evidence on the benefits of a diet rich in fruits, vegetables, legumes, oily fish and vegetable oils for preventing all BC subtypes, and particularly triple-negative tumours.
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Dieta Mediterrânea , Neoplasias de Mama Triplo Negativas/etiologia , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Risco , Espanha , Neoplasias de Mama Triplo Negativas/epidemiologiaRESUMO
Brewers' spent grain (BSG) is the main byproduct from the brewing industry, which accounts for 85 % of the total waste generated during beer production. This lignocellulosic material is traditionally used as livestock feed and sold at a low price. However, BSG can be used as a low-cost feedstock for the production of bioactive molecules and chemicals precursors, upgrading the value of this byproduct. In this context, BSG is a promising feedstock for the extraction of antioxidants like ferulic acid (FA) and p-coumaric acid (p-Cu). The effectiveness of three hydrolysis treatments were evaluated for the extraction of FA and p-Cu from BSG, namely enzymatic (based on the synergistic cooperation between a feruloyl esterase and an endo-1,4-ß-xylanase), alkaline and hydrothermal. The hydrothermal treatment produced the highest extraction yields (7.2 g/kgBSG and 1.4 g/kgBSG for FA and p-Cu, respectively) in a short extraction time (an hour). On the other hand, enzymatic hydrolysis extracted 4.3 g/kgBSG for FA and negligible yields for p-Cu in 4 h of incubation at 25 °C. Yields of 5.5 g/kgBSG for FA and 0.6 g/kgBSG for p-Cu were obtained in more than 5 h of alkaline treatment at 120 °C. The mass and energy balances revealed the high dependence of the operating costs on the concentration of BSG used during the extraction process, with costs of 34.5 , 6607 and 205.5 per kg of FA for the chemical, enzymatic and hydrothermal extraction methods at 100 kg BSG/m3.
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The anterior-to-posterior (head-to-tail) body axis is extraordinarily diverse among vertebrates but conserved within species. Body axis development requires a population of axial progenitors that resides at the posterior of the embryo to sustain elongation and is then eliminated once axis extension is complete. These progenitors occupy distinct domains in the posterior (tail-end) of the embryo and contribute to various lineages along the body axis. The subset of axial progenitors with neuromesodermal competency will generate both the neural tube (the precursor of the spinal cord), and the trunk and tail somites (producing the musculoskeleton) during embryo development. These axial progenitors are called Neuromesodermal Competent cells (NMCs) and Neuromesodermal Progenitors (NMPs). NMCs/NMPs have recently attracted interest beyond the field of developmental biology due to their clinical potential. In the mouse, the maintenance of neuromesodermal competency relies on a fine balance between a trio of known signals: Wnt/ß-catenin, FGF signalling activity and suppression of retinoic acid signalling. These signals regulate the relative expression levels of the mesodermal transcription factor Brachyury and the neural transcription factor Sox2, permitting the maintenance of progenitor identity when co-expressed, and either mesoderm or neural lineage commitment when the balance is tilted towards either Brachyury or Sox2, respectively. Despite important advances in understanding key genes and cellular behaviours involved in these fate decisions, how the balance between mesodermal and neural fates is achieved remains largely unknown. In this chapter, we provide an overview of signalling and gene regulatory networks in NMCs/NMPs. We discuss mutant phenotypes associated with axial defects, hinting at the potential significant role of lesser studied proteins in the maintenance and differentiation of the progenitors that fuel axial elongation.
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Padronização Corporal , Mesoderma , Animais , Padronização Corporal/genética , Mesoderma/metabolismo , Mesoderma/citologia , Mesoderma/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Transdução de Sinais , Proteínas com Domínio T/metabolismo , Proteínas com Domínio T/genética , Diferenciação Celular , Cabeça/embriologiaRESUMO
Vesicular trafficking, which is implicated in secretion of cytolytic molecules as well as in phagocytosis, plays an important role in the pathogenic mechanism of Entamoeba histolytica, the protozoan parasite causative of human amoebiasis. Thus, Rab GTPases, that are key regulators of vesicle trafficking, should be considered as molecules involved in the parasite virulence. EhRabB is a Rab protein located in cytoplasmic vesicles that are translocated to phagocytic mouths during ingestion of target cells, suggesting that this Rab protein is involved in phagocytosis. To prove this hypothesis, we over expressed the wild type EhrabB gene and a mutant gene encoding for a protein (RabBN118I) unable to bind guanine nucleotides and therefore constitutively inactive. The over expression of the mutated protein in E. histolytica trophozoites provoked a dominant negative effect, reflected in a significant decrease of both phagocytosis and cytopathic effect as well as in a failure to produce hepatic abscesses in hamsters. These results confirm that EhRabB is involved in phagocytosis and virulence of E. histolytica.
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Entamoeba histolytica/patogenicidade , Proteínas de Protozoários/metabolismo , Animais , Western Blotting , Cricetinae , Cães , Entamoeba histolytica/genética , Entamoeba histolytica/metabolismo , Eritrócitos/parasitologia , Imunofluorescência/métodos , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Regulação da Expressão Gênica , Humanos , Abscesso Hepático Amebiano/parasitologia , Mutagênese , Fagocitose/fisiologia , Proteínas de Protozoários/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , VirulênciaRESUMO
Despite years of encouraging translational research, ischemic stroke still remains as one of the highest unmet medical needs nowadays, causing a tremendous burden to health care systems worldwide. Following an ischemic insult, a complex signaling pathway emerges leading to highly interconnected thrombotic as well as neuroinflammatory signatures, the so-called thromboinflammatory cascade. Here, we thoroughly review the cell-specific and time-dependent role of different immune cell types, i.e., neutrophils, macrophages, T and B cells, as key thromboinflammatory mediators modulating the neuroinflammatory response upon stroke. Similarly, the relevance of platelets and their tight crosstalk with a variety of immune cells highlights the relevance of this cell-cell interaction during microvascular dysfunction, neovascularization, and cellular adhesion. Ultimately, we provide an up-to-date overview of therapeutic approaches mechanistically targeting thromboinflammation currently under clinical translation, especially focusing on phase I to III clinical trials.
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Acidente Vascular Cerebral , Trombose , Humanos , Inflamação , Trombose/etiologia , Acidente Vascular Cerebral/terapia , Plaquetas , Transdução de SinaisRESUMO
Human pre-mRNA processing protein 40 homolog A (hPrp40A) is a splicing factor that interacts with the Huntington's disease protein huntingtin (Htt). Evidence has accumulated that both Htt and hPrp40A are modulated by the intracellular Ca2+ sensor calmodulin (CaM). Here we report characterization of the interaction of human CM with the third FF domain (FF3 ) of hPrp40A using calorimetric, fluorescence and structural approaches. Homology modeling, differential scanning calorimetry and small angle X-ray scattering (SAXS) data show FF3 forms a folded globular domain. CaM was found to bind FF3 in a Ca2+ -dependent manner with a 1:1 stoichiometry and a dissociation constant (Kd ) of 25 ± 3 µM at 25°C. NMR studies showed that both domains of CaM are engaged in binding and SAXS analysis of the FF3 -CaM complex revealed CaM occupies an extended configuration. Analysis of the FF3 sequence showed that the anchors for CaM binding must be buried in its hydrophobic core, suggesting that binding to CaM requires unfolding of FF3 . Trp anchors were proposed based on sequence analysis and confirmed by intrinsic Trp fluorescence of FF3 upon binding of CaM and substantial reductions in affinity for Trp-Ala FF3 mutants. The consensus model of the complex showed that binding to CaM binding occurs to an extended, non-globular state of the FF3 , consistent with coupling to transient unfolding of the domain. The implications of these results are discussed in the context of the complex interplay of Ca2+ signaling and Ca2+ sensor proteins in modulating Prp40A-Htt function.
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Calmodulina , Simulação de Dinâmica Molecular , Humanos , Calmodulina/química , Espalhamento a Baixo Ângulo , Difração de Raios X , Ligação Proteica , Cálcio/metabolismo , Sítios de LigaçãoRESUMO
BACKGROUND: A wide variety of both surgical and nonsurgical therapies is currently available for patients with skin cancer. OBJECTIVES: This part of the EPIDERM (European Prevention Initiative for Dermatological Malignancies) project is aimed at the evaluation of the treatment preferences for skin cancer in eight countries of the European Union. METHODS: A multicentre hospital-based case-control study was carried out at dermatology departments in Finland, Germany, Greece, Italy, Malta, Poland, Scotland and Spain. Patients with skin cancer (basal cell carcinoma, actinic keratosis, squamous cell carcinoma, cutaneous malignant melanoma and Bowen disease) were consecutively enrolled between July 2008 and July 2010. Information on the study variables (sex, age, country, tumour type, anatomical location and treatment) was obtained from questionnaires designed by the EPIDERM project. RESULTS: In total, 1708 patients with skin cancer were included. Surgery was the first treatment option in 76·5% of the patients (P = 0·001). Actinic keratosis was the only tumour type in which nonsurgical treatment was more frequent than surgery (91·4%). Tumours on the head were less likely to be surgically excised than those at other locations (odds ratio 0·25, P = 0·001). Simple excision or curettage was the most common surgical procedure (65·4%), followed by graft and flaps (22·4%). Cryotherapy was the most common nonsurgical option (52·4%), followed by imiquimod (18·0%), photodynamic therapy (PDT; 12·0%), 5-fluorouracil (5-FU; 5·7%), and diclofenac with hyaluronic acid (4·0%). CONCLUSIONS: Surgery remains the first-choice treatment of skin cancer. Regarding nonsurgical treatments, the conservative treatments available (imiquimod, 5-FU, PDT and diclofenac gel) have not yet exceeded the use of ablative options such as cryotherapy despite their accepted benefit of treating field cancerization.
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Atitude do Pessoal de Saúde , Dermatologia , Neoplasias Cutâneas/terapia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Europa (Continente) , Humanos , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias Cutâneas/psicologiaRESUMO
BACKGROUND: During recent years numerous studies have suggested that personal and environmental factors might influence cancer development. OBJECTIVES: To investigate environmental and personal characteristics associated with skin cancer risk. METHODS: A multicentre hospital-based case-control study was performed in Finland, Germany, Greece, Italy, Malta, Poland, Scotland and Spain, including 409 patients with squamous cell carcinoma (SCC), 602 with basal cell carcinoma (BCC) and 360 with cutaneous malignant melanoma (CMM) and 1550 control persons. Exposures were assessed by questionnaires that were partly self-administered, partly completed by dermatologists. Unconditional logistic regression modelling was used to assess associations including the influence of certain drugs and food items on skin cancer risk. RESULTS: The usual associations were observed for sun exposure and pigmentation characteristics, with chronic sun exposure being most strongly associated with SCC risk, and naevi and atypical naevi with CMM risk. Use of ciprofloxacin was associated with a decreased risk of BCC [odds ratio (OR) 0·33] and use of thiazide diuretics was associated with an increased risk of SCC (OR 1·66). Ciprofloxacin was also associated with SCC (OR 0·34) and thiazines with BCC (OR 2·04), but these associations lost significance after correction for multiple testing. Consumption of pomegranate, rich in antioxidants, was associated with decreased BCC and SCC risk, also after correcting for multiple testing. Recent experience of stressful events was associated with increased risk, particularly of CMM. CONCLUSIONS: In this large case-control study from across Europe the expected associations were observed for known risk factors. Some new potential protective factors and potential risk factors were identified for consumption of certain food items, medication use and stress, which deserve further investigation in future studies.
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Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Melanoma/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Dieta/efeitos adversos , Toxidermias/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estresse Psicológico/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: There are limited data regarding the association of actinic keratosis (AK) and other types of nonmelanoma skin cancer (NMSC); studies investigating possible correlation of AK with melanocytic naevi are even scarcer. To our knowledge, there are no data examining the risk of AK in people using specific medications. OBJECTIVE: To investigate constitutional and exposure risk factors leading to AK and the coexistence of AK with NMSC and melanoma. METHODS: A multicentre hospital-based case-control study was performed in Finland, Germany, Greece, Italy, Malta, Poland, Scotland and Spain, including 343 patients with actinic keratosis (AK), 409 with squamous cell carcinoma (SCC), 602 with basal cell carcinoma (BCC), 360 with invasive melanoma and 119 with in situ melanoma, and 686 control subjects. Exposures were assessed by questionnaires that were partly self-administered and partly filled out by dermatologists. Unconditional logistic regression modelling was used to assess associations including the influence of phenotypic characteristics, presence of naevi, sun-exposure habits and certain drugs on AK risk. RESULTS: Differences in hair and eye coloration variably influenced the risk for AK, with red hair signifying a seven times higher risk [odds ratio (OR) 6·9, 95% confidence interval (CI) 4·34-11·00), and brown - compared with blue - eyes, about a 40% reduced risk (OR 0·61, 95% CI 0·13-0·92). The darker the skin phototype, the lower the risk for AK, with phototype IV exhibiting nine times less risk of developing AK. Some and many freckles on the arms were associated with an OR of 1·8 (95% CI 1·08-2·81) and 3·0 (95% CI 1·10-3·54), respectively, while overall number of naevi and high educational level were inversely associated with AK. Sun exposure, thiazide diuretics and cardiac drugs had a higher risk for AK. SCC was the most frequent (58%) skin neoplasm coexisting with AKs, followed by BCC (30%), melanoma in situ (12%) and invasive melanoma (6%). CONCLUSION: In this large case-control study from across Europe the expected associations were confirmed for known risk factors. Some possible new risk factors, including cardiac and diuretic drugs, were identified, creating a new field for further investigation in future studies.
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Exposição Ambiental/efeitos adversos , Ceratose Actínica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Fármacos Dermatológicos/uso terapêutico , Exposição Ambiental/análise , Europa (Continente)/epidemiologia , Feminino , Humanos , Ceratose Actínica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Raios Ultravioleta/efeitos adversosRESUMO
BACKGROUND: There are poorly documented variations in the journey a skin cancer patient will follow from diagnosis to treatment in the European Union. OBJECTIVES: To investigate the possible difficulties or obstacles that a person with a skin malignancy in the European Union may have to overcome in order to receive adequate medical screening and care for his/her condition. In addition, we wished to explore differences in European health systems, which may lead to health inequalities and health inequities within Europe. METHODS: Ten European countries took part in this investigation (in alphabetical order): Finland, Germany, Greece, Italy, Malta, Poland, Romania, Spain, the Netherlands and the U.K. The individual participants undertook local and national enquiries within their own country and completed a questionnaire. RESULTS: This exercise has identified important differences in the management of a skin cancer patient, reflecting major disparities in health care between European countries. CONCLUSIONS: Further investigation of health disparities and efforts to address health inequalities should lead to improvements in European health care quality and reduction in morbidity from skin cancer.
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Disparidades em Assistência à Saúde/estatística & dados numéricos , Neoplasias Cutâneas/terapia , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Custos e Análise de Custo , Fármacos Dermatológicos/economia , Fármacos Dermatológicos/uso terapêutico , Dermatologia , Custos de Medicamentos , União Europeia , Clínicos Gerais/provisão & distribuição , Disparidades em Assistência à Saúde/economia , Humanos , Guias de Prática Clínica como Assunto , Encaminhamento e Consulta/estatística & dados numéricos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/economia , Recursos HumanosRESUMO
Genome analysis of Entamoeba histolytica predicts the presence of acetyl-CoA carboxylase. Using Western blot, histochemistry, and confocal microscopy, we demonstrated the presence of a biotin-containing protein in the cytoplasm of E. histolytica, with a molecular weight of 136 kDa and biotin-carboxylase activity. This protein probably corresponds to a transcarboxylase that catalyzes the rate-limiting reaction leading to fatty acid elongation.
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Carboxil e Carbamoil Transferases/metabolismo , Entamoeba histolytica/enzimologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Proteínas de Protozoários/metabolismo , Animais , Carboxil e Carbamoil Transferases/genética , Entamoeba histolytica/genética , Entamoeba histolytica/metabolismo , Genoma de Protozoário , Proteínas de Protozoários/genéticaRESUMO
BACKGROUND: Pulmonary hypertension (PH) is associated with poor prognosis for patients with chronic obstructive pulmonary disease (COPD). Most of the knowledge about PH in COPD has been generated at sea level, with limited information associated with high altitude (HA). OBJECTIVES: To assess the prevalence and severity of PH in COPD patients living in a HA city (2,640 m). METHODS: Cross-sectional study in COPD patients with forced expiratory volume in the first second / forced vital capacity ratio (FEV1/FVC) post-bronchodilator <0,7. Transthoracic echocardiography (TTE), spirometry, carbon monoxide diffusing capacity, and arterial blood gasses tests were performed. Patients were classified according to the severity of airflow limitation. PH was defined by TTE as an estimated systolic pulmonary artery pressure (sPAP) > 36 mmHg or indirect PH signs; severe PH as sPAP > 60 mmHg; and disproportionate PH as an sPAP > 60 mmHg with non-severe airflow limitation (FEV1 > 50% predicted). RESULTS: We included 176 COPD patients. The overall estimated prevalence of PH was 56.3% and the likelihood of having PH increased according to airflow-limitation severity: mild (31.6%), moderate (54.9%), severe (59.6%) and very severe (77.8%) (p = 0.038). The PH was severe in 7.3% and disproportionate in 3.4% of patients. CONCLUSIONS: The estimated prevalence of PH in patients with COPD at HA is high, particularly in patients with mild to moderate airflow limitation, and greater than that described for COPD patients at low altitude. These results suggest a higher risk of developing PH for COPD patients living at HA compared to COPD patients with similar airflow limitation living at low altitude.
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The 6-min walk distance (6MWD) predicted values have been derived from small cohorts mostly from single countries. The aim of the present study was to investigate differences between countries and identify new reference values to improve 6MWD interpretation. We studied 444 subjects (238 males) from seven countries (10 centres) ranging 40-80 yrs of age. We measured 6MWD, height, weight, spirometry, heart rate (HR), maximum HR (HR(max)) during the 6-min walk test/the predicted maximum HR (HR(max) % pred), Borg dyspnoea score and oxygen saturation. The mean ± sd 6MWD was 571 ± 90 m (range 380-782 m). Males walked 30 m more than females (p < 0.001). A multiple regression model for the 6MWD included age, sex, height, weight and HR(max) % pred (adjusted r² = 0.38; p < 0.001), but there was variability across centres (adjusted r² = 0.09-0.73) and its routine use is not recommended. Age had a great impact in 6MWD independent of the centres, declining significantly in the older population (p < 0.001). Age-specific reference standards of 6MWD were constructed for male and female adults. In healthy subjects, there were geographic variations in 6MWD and caution must be taken when using existing predictive equations. The present study provides new 6MWD standard curves that could be useful in the care of adult patients with chronic diseases.
Assuntos
Caminhada/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Teste de Esforço/normas , Feminino , Geografia , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Padrões de Referência , Valores de Referência , Fatores SexuaisRESUMO
Twenty-two landrace-derived inbred lines from the Spanish Barley Core Collection (SBCC) were found to display high levels of resistance to a panel of 27 isolates of the fungus Blumeria graminis that exhibit a wide variety of virulences. Among these lines, SBCC145 showed high overall resistance and a distinctive spectrum of resistance compared with the other lines. Against this background, the main goal of the present work was to investigate the genetic basis underlying such resistance using a doubled haploid population derived from a cross between SBCC145 and the elite spring cultivar Beatrix. The population was genotyped with the 1,536-SNP Illumina GoldenGate Oligonucleotide Pool Assay (Barley OPA-1 or BOPA1 for short), whereas phenotypic analysis was performed using two B. graminis isolates. A major quantitative trait locus (QTL) for resistance to both isolates was identified on the long arm of chromosome 6H (6HL) and accounted for ca. 60% of the phenotypic variance. Depending on the B. graminis isolate tested, three other minor QTLs were detected on chromosomes 2H and 7H, which explained less than 5% of the phenotypic variation each. In all cases, the alleles for resistance derived from the Spanish parent SBCC145. The position, the magnitude of the effect observed and the proportion of phenotypic variation accounted for by the QTL on 6HL suggest this is a newly identified locus for broad-based resistance to powdery mildew.
Assuntos
Ascomicetos/patogenicidade , Hordeum/genética , Doenças das Plantas/imunologia , Locos de Características Quantitativas , Alelos , Cruzamento , Mapeamento Cromossômico , Cromossomos de Plantas , Resistência à Doença , Genes de Plantas , Ligação Genética , Marcadores Genéticos , Genótipo , Hordeum/imunologia , Hordeum/microbiologia , Imunidade Inata , Fenótipo , Doenças das Plantas/microbiologiaRESUMO
In the search for possible new anti-cancer agents, we investigated the effects of 75 aqueous and methanol extracts from 41 Argentinean plant species. The effect in cell growth was evaluated in the LM2 mammary adenocarcinoma cells. In a second stage, the highly active selected extracts were assayed in 3 other tumour cell lines: melanoma B16, bladder MB49 and lung A549; and 3 normal cell lines: mammary Hb4a and keratinocytes PAM212 and HaCat. Eight methanol extracts were found to be highly cytotoxic: Collaea argentina leaf, Iochroma australe leaf, Ipomoea bonariensis flower, Jacaranda mimosifolia flower, Solanum amygdalifolium flower, Solanum chacoense leaf, Solanum sisymbriifolium flower and Solanum verbascifolium flower. However, extract inhibition on cell growth was highly dependent on cell type. In general, except for the highly resistant cell lines, the inhibitory concentrations 50% were in the range of 10-150 µg/ml The eight extracts highly inhibited cell growth in a concentration-dependent manner, and in general the methanol extracts were always more active than the aqueous. Murine cells appear to be more sensitive than human cells to the cytotoxic action of the plant extracts. The human melanoma B16 line was the most resistant to four of the extracts. In terms of selectivity, S. verbascifolium was the species which showed most selectivity for tumour cells. Overall, this is one of the first studies focusing on southern South American native plants and their biological effects. Since some species of 5 genera analyzed have been reported to possess different degrees of alkaloid content, we examined microtubule structures after extract treatments. The eight extracts induced destabilization, condensation and aggregation of microtubules in LM2 cells, although no depolarization, typical of Vinca alkaloids damage was observed. In a near future, antitumour activity of purified fractions of the extracts administered at non-toxic doses will be assayed in transplantable murine tumour models.