Olive Oil Components as Novel Antioxidants in Neuroblastoma Treatment: Exploring the Therapeutic Potential of Oleuropein and Hydroxytyrosol.

In this review, we explored the therapeutic potential of oleuropein (OLE) and hydroxytyrosol (HT) in the treatment of neuroblastoma (NB). NB is an extracranial tumour that predominantly affects children aged between 17 and 18 months. Recurrence and drug resistance have emerged as the biggest challenges when treating NB, leading to a crucial need for new therapeutic approaches. Food of the Mediterranean Diet (MD) presents several health benefits, including that of cancer treatment. In this review, we emphasised olive oil since it is one of the main liquid ingredients of the MD. OLE is the principal phenolic compound that constitutes olive oil and is hydrolysed to produce HT. Considering that tumour cells produce increased amounts of reactive oxygen species, this review highlights the antioxidant properties of OLE and HT and how they could result in increased cellular antioxidant defences and reduced oxidative damage in NB cells. Moreover, we highlight that these phenolic compounds lead to apoptosis and cell cycle arrest, reduce the side effects caused by conventional treatments, and activate tumours that become dormant as a resistance mechanism. Future research should explore the effects of these compounds and other antioxidants on the treatment of NB in vivo.

Correction to: Reliability and validity of the Pittsburgh Sleep Quality Index in breast cancer patients.

There is a typo in the Funding reference cited in the paper. This alteration is fundamental to justify the funding of the project.

The impact of breast cancer treatments on sleep quality 1 year after cancer diagnosis.

PURPOSE: The increasing number of women living longer with potential side effects of breast cancer treatment highlights the need of a comprehensive assessment of its burden. Therefore, we aimed to quantify the relation between different breast cancer treatments and sleep quality 1 year after diagnosis. METHODS: A cohort of 502 newly diagnosed breast cancer patients was prospectively followed. Sleep quality was evaluated with the Pittsburgh Sleep Quality Index (PSQI), at baseline and at the 1-year follow-up. Odds ratios (OR) were computed to quantify the association between patient characteristics and poor sleep quality (PSQI score >5) at baseline, and relative risks (RR) were computed for the association between treatments and the occurrence of poor sleep quality at 1 year. RESULTS: A total of 60.2% of the patients had poor sleep quality before breast cancer treatments, especially those with anxiety [OR = 2.86, 95% confidence interval (95%CI) 1.92 to 4.27] or depression (OR = 5.25, 95%CI 2.01 to 13.67). Radiotherapy increased the risk of poor sleep quality at 1 year (RR = 3.71, 95%CI 1.15 to 11.96, for a cumulative dose >50 Gy) and there was a tendency for a higher risk in those submitted to chemotherapy, although not statistically significant. CONCLUSIONS: Our study shows that sleep disturbances are frequent before cancer treatment and confirms their co-occurrence with other medical conditions, such as anxiety and depression. Different breast cancer treatments increase the risk of impaired sleep quality, therefore contributing to the global disability associated with cancer treatments.

Trajectories of sleep quality during the first three years after breast cancer diagnosis.

OBJECTIVE: To identify trajectories of sleep quality up to three years after breast cancer diagnosis and to assess differences in characteristics of patients across distinct trajectories. METHODS: A total of 458 breast cancer patients underwent a neurological evaluation before treatment and at one and three years after diagnosis. Clinical data were obtained throughout the follow-up. Anxiety and depression were evaluated at baseline, using the Hospital Anxiety and Depression Scale. In all sessions of follow-up, sleep quality was assessed using the Pittsburgh Sleep Quality Index. Model-based clustering was used to identify groups of patients with homogeneous variation in sleep quality. RESULTS: We identified three trajectories of variation in sleep quality, named "low" (LSQ), "medium" (MSQ), and "high sleep quality" (HSQ). Women in the HSQ trajectory presented good sleep quality during the three years. LSQ and MSQ trajectories were characterized by poor sleep quality during the whole period, although during the first year the latter depicted a significant deterioration of sleep quality and the former a significant improvement. Patients included in the LSQ trajectory were more likely to have clinically significant anxiety and depression at baseline. The two trajectories with worse sleep quality were associated with neuropathic pain three years after cancer diagnosis. CONCLUSIONS: This study provides a model for describing the variation in sleep quality during the first three years after breast cancer diagnosis, based on three main trajectories. Further studies are needed understanding the heterogeneity of the individual trajectories within each of these major patterns of variation.

Neuropathic pain after breast cancer treatment and its impact on sleep quality one year after cancer diagnosis.

OBJECTIVES: Data regarding the impact of breast cancer treatment-related neuropathic pain (NP) on sleep quality are scarce. Therefore, we aimed to assess the impact of breast cancer treatment-related NP on patients' sleep quality, during the first year after cancer diagnosis. MATERIALS AND METHODS: A total of 501 breast cancer patients were followed prospectively. Incident NP was identified through systematic evaluations after treatments and one year after enrolment. NP severity was quantified using the Brief Pain Inventory severity subscale and sleep quality was evaluated through the Pittsburgh Sleep Quality Index (PSQI), at baseline and after one year. Adjusted regression coefficients (ß) and 95% confidence intervals (95%CI) were used to quantify the relation between NP and the variation in the PSQI z-scores. RESULTS: The occurrence of NP was associated with a deterioration in sleep quality during the first year of follow-up, more pronounced among those with good sleep quality (PSQI≤5) than those with poor sleep quality at baseline (PSQI>5) (ß = 0.44, 95%CI: 0.11 to 0.77 versus ß = 0.33, 95%CI: 0.08 to 0.59). These differences were accentuated when only the cases of NP with greater severity were considered (ß = 0.86, 95%CI: 0.37 to 1.35 versus ß = 0.31, 95%CI: -0.08 to 0.64). Within the PSQI components, daytime dysfunction and sleep duration were the most impaired by NP. CONCLUSION: Our findings highlight the importance of the promotion of sleep hygiene among breast cancer patients diagnosed with NP, especially among those with good sleep quality before treatments.

Reliability and validity of the Pittsburgh Sleep Quality Index in breast cancer patients.

PURPOSE: We aimed to assess the factor structure, internal consistency, test-retest reliability, and construct validity of the European Portuguese version of the Pittsburgh Sleep Quality Index (PSQI) in breast cancer patients. METHODS: This study was based on a cohort of breast cancer patients, among whom the PSQI was used to measure sleep quality three years after cancer diagnosis (N = 474). A sample of 62 participants underwent additional PSQI testing, wore a wrist actigraph for five consecutive days, and was reevaluated with the PSQI after one month. A confirmatory factor analysis, considering the components suggested by the principal component analysis (PCA), was performed to determine model fit. To evaluate internal consistency and test-retest reliability, Cronbach's alpha and intraclass correlation coefficient (ICC) were calculated, respectively. To assess construct validity, Spearman's correlation coefficients were computed between PSQI scores and actigraphy measures and other theoretical related constructs. RESULTS: PCA suggested one or two components. The latter showed better fit to the data, though the two factors were strongly correlated (r = 0.76) and internal consistency was not satisfactory for one of the factors. Regarding the one-factor model, internal consistency (Cronbach's alpha = 0.70) and test-retest reliability (ICC = 0.76) were adequate. Sleep duration, habitual sleep efficiency, and sleep disturbance dimensions were significantly correlated with the corresponding actigraphy measures; the PSQI global score derived from the one-factor model was more strongly correlated with subjective sleep complaints (r ≥ 0.60). CONCLUSIONS: The unidimensional construct of the European Portuguese version of the PSQI showed adequate reliability and validity among breast cancer patients.

Interpreting WAIS-III performance after primary brain tumor surgery.

The literature lacks information on the performance of patients with brain tumors on the Wechsler Intelligence Scales. This study aimed to explore the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) performance profile of 23 consecutive patients with brain tumors and 23 matched controls selected from the Portuguese WAIS-III standardization sample, using the technical manual steps recommended for score interpretation. The control group was demographically matched to the tumor group regarding gender, age, education, profession, and geographic region. The technical manual steps recommended for score interpretation were applied. Patients with brain tumors had significantly lower performances on the Performance IQ, Full-Scale IQ, Perceptual Organization Index, Working Memory Index, Processing Speed Index, Arithmetic, Object Assembly, and Picture Arrangement, though all scaled scores were within the normal range according to the manual tables. Only Vocabulary and Comprehension scatter scores were statistically different between groups. No strengths or weaknesses were found for either group. The mean discrepancy scores do not appear to have clinical value for this population. In conclusion, the study results did not reveal a specific profile for patients with brain tumors on the WAIS-III.

Impaired T-cell differentiation in diabetic foot ulceration.

Foot ulceration is one of the most debilitating complications associated with diabetes, but its cause remains poorly understood. Several studies have been undertaken to understand healing kinetics or find possible therapies to enhance healing. However, few studies have been directed at understanding the immunological alterations that could influence wound healing in diabetes. In this study, we analysed the T-cell receptor (TCR) repertoire diversity in TCR-αß+ T cells. We also analysed the distribution and phenotype of T cells obtained from the peripheral blood of healthy controls and diabetic individuals with or without foot ulcers. Our results showed that diabetic individuals, especially those with foot ulcers, have a significantly lower naive T-cell number and a poorer TCR-Vß repertoire diversity. We also showed that the reduced TCR-Vß repertoire diversity in diabetic individuals was mainly owing to the accumulation of effector T cells, the major source of tumour necrosis factor-α production, which was even more pronounced in patients with acute foot ulceration. Moreover, the expression of several inflammatory chemokine receptors was significantly reduced in diabetic patients. In conclusion, effector T-cell accumulation and TCR repertoire diversity reduction appear to precede the development of foot ulcers. This finding may open new immunological therapeutic possibilities and provide a new prognostic tool in diabetic wound care.

Searching for a neurologic injury's Wechsler Adult Intelligence Scale-Third Edition profile.

This study aimed to investigate the presence of a Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) cognitive profile in a Portuguese neurologic injured sample. The Portuguese WAIS-III was administered to 81 mixed neurologic patients and 81 healthy matched controls selected from the Portuguese standardization sample. Although the mixed neurologic injury group performed significantly lower than the healthy controls for the majority of the WAIS-III scores (i.e., composite measures, discrepancies, and subtests), the mean scores were within the normal range and, therefore, at risk of being unobserved in a clinical evaluation. ROC curves analysis showed poor to acceptable diagnostic accuracy for the WAIS-III composite measures and subtests (Working Memory Index and Digit Span revealed the highest accuracy for discriminating between participants, respectively). Multiple regression analysis showed that both literacy and the presence of brain injury were significant predictors for all of the composite measures. In addition, multiple regression analysis also showed that literacy, age of injury onset, and years of survival predicted all seven composite measures for the mixed neurologic injured group. Despite the failure to find a WAIS-III cognitive profile for mixed neurologic patients, the results showed a significant influence of brain lesion and literacy in the performance of the WAIS-III.

IPSF: análise da estrutura interna em uma amostra de jovens adultos portugueses / IPSF: analysis of internal structure in a sample of portuguese young adults / IPSF: análisis de la estructura interna en una muestra de adultos jóvenes portugueses

A avaliação da percepção que se tem da família é fundamental para saber quanto os jovens estão satisfeitos com essa instituição social, sendo que em Portugal não existe uma escala com essa função. O objetivo deste estudo foi avaliar as semelhanças psicométricas do conjunto inicial de 136 itens que foi utilizado na construção do Inventário de Percepção do Suporte Familiar (IPSF) no Brasil, tendo sua versão final com 42 itens e comparar os resultados em uma amostra portuguesa de jovens adultos (N=248). Para o tratamento dos dados, recorreu-se à mesma análise realizada no Brasil, de componentes principais com rotação Oblimin. Os resultados demonstraram um número de itens e distribuição nas três categorias iniciais (afetivo-consistente, adaptação e autonomia) muito próximos aos encontrados na amostra de normatização brasileira, o que sugere semelhança tanto no número quanto na constituição dos componentes nas duas culturas.

The evaluation of the people’s perception of family is fundamental to understanding the degree to which young people are satisfied with this social institution, and in Portugal there is no scale with this function. The objective of this study was to evaluate the psychometric similarities of the initial set of 136 items that was used in the construction of Family Support Perception Inventory (IPSF) in Brazil, having a final version with 42 items, and compare the results to a Portuguese sample of young adults (N=248). For the data processing, we used the same analysis as in Brazil, of the principal components with oblimin rotation. Results showed a number of items and distribution in the three initial categories (affective-consistent, adaptation and autonomy) very close to those found on the Brazilian standardization sample, suggesting similarity both in number and in the constitution of the components in the two cultures.

La evaluación de la percepción que se tiene sobre la familia es fundamental para saber en qué medida los jóvenes están satisfechos con esta institución social; en Portugal no existe una escala con esta función. El objetivo de este estudio fue evaluar las semejanzas psicométricas del conjunto inicial de 136 ítems que se utilizan en la construcción del Inventario de Percepción de Soporte Familiar (IPSF) en Brasil, teniendo su versión final con 42 ítems, y comparar los resultados en una muestra portuguesa de jóvenes adultos (N=248). Para el tratamiento de los datos se recurrió al mismo análisis realizado en Brasil, de componentes principales con rotación oblimin. Los resultados mostraron una serie de ítems y distribución en las tres categorías iniciales (afectivo-consistente, adaptación y autonomía) muy cercanos a los encontrados en la muestra brasileña de normalización, lo que sugiere semejanzas tanto en número como en la constitución de los componentes en las dos culturas.

Aggressive mature natural killer cell neoplasms: report on a series of 12 European patients with emphasis on flow cytometry based immunophenotype and DNA content of neoplastic natural killer cells.

We report 12 cases of aggressive natural killer (NK) cell neoplasms diagnosed in Portugal, with emphasis on flow cytometry. Ten patients had extranodal NK/T cell lymphoma, nasal type and two had aggressive NK cell leukemia, and seven were men and five were women, with a median age of 50 years. NK cells brightly expressed the CD56 adhesion molecule and CD94 lectin type killer receptor and had an activation-related HLA-DR+ CD45RA+ CD45RO+ immunophenotype, in most cases. In contrast, dim CD16 expression was found in a minor proportion of cases, whereas CD57 and the CD158a and CD158e1 killer immunoglobulin-like receptors were negative. One-third of cases showed a hyperploid DNA content and nearly all had a very high S-phase proliferative rate. The phenotypic features of the neoplastic NK cells would suggest that they represent the transformed counterpart of the CD56 + bright NK cells that circulate in normal blood.

Impact of breast cancer treatments on sleep disturbances - A systematic review.

Sleep disturbances are highly prevalent in women with breast cancer; side effects of cancer treatment may worsen pre-existing sleep problems and have been pointed to as important determinants of their incidence. Therefore, we aimed to assess the association between different types of breast cancer treatment and sleep disturbances, through a systematic review. Medline (using PubMed), CINAHL Plus with full text, PsycINFO and Cochrane Central Register of Controlled Trials (Central) were searched from inception to January 2014. Studies that evaluated samples of women with breast cancer, assessed sleep disturbances with standardized sleep-specific measures, and provided data for different cancer treatments were eligible. A total of 12 studies met the inclusion criteria. Three studies evaluated insomnia, five studies assessed sleep quality, two provide data on general sleep disturbances and two analysed specific sleep parameters. Women submitted to chemotherapy, or radiotherapy, tended to report higher levels of sleep disturbances. More heterogeneous findings were observed regarding the effect of surgical treatment and hormonal therapy. However, a sound assessment of the impact of these treatments was hampered by differences across studies regarding the outcomes assessed, reporting bias and the fact that most studies did not control for the effect of potential confounders. The present review highlights the potential relation between breast cancer treatments and sleep disturbances, particularly of chemotherapy, though more robust evidence is needed for a proper understanding of these associations.

H3N2 homeopathic influenza virus solution modifies cellular and biochemical aspects of MDCK and J774G8 cell lines.

BACKGROUND: Influenza viruses cause highly contagious acute respiratory illnesses with significant mortality, especially among young children, elderly people, and individuals with serious medical conditions. This encourages the development of new treatments for human flu. Biotherapies are diluted solutions prepared from biological products compounded following homeopathic procedures. OBJECTIVES: To develop a biotherapy prepared from the infectious influenza A virus (A/Aichi/2/68 H3N2) and to verify its in vitro response. METHODS: The ultradiluted influenza virus solution was prepared in the homeopathic dilution 30dH, it was termed Influenzinum RC. The cellular alterations induced by this preparation were analyzed by optical and electron microscopy, MTT and neutral red assays. Glycolytic metabolism (PFK-1) was studied by spectrophotometric assay. Additionally, the production of tumor necrosis factor-α (TNF-α) by J774.G8 macrophage cells was quantified by ELISA before and after infection with H3N2 influenza virus and treatment. RESULTS: Influenzinum RC did not cause cytotoxic effects but induced morphological alterations in Madin-Darby canine kidney (MDCK) cells. After 30 days, a significant increase (p < 0.05) in mitosis rate was detected compared to control. MDCK mitochondrial activity was changed after treatment for 10 and 30 days. Treatment significantly diminished (p < 0.05) PFK-1 activity. TNF-α in biotherapy-stimulated J774.G8 macrophages indicated a significant (p < 0.05) increase in this cytokine when the cell supernatant was analyzed. CONCLUSION: Influenzinum RC altered cellular and biochemical features of MDCK and J774G8 cells.

EFEITO DO SORO DO LEITE E GOMA GUAR NOS TEORES DE LACTOSE, ÁCIDO LÁTICO E TEMPO DE FERMENTAÇÃO DE BEBIDAS LÁCTEAS / EFFECT OF WHEY AND GUAR GUM IN THE LEVELS OF LACTOSE, LACTIC ACID AND FERMENTATION TIME OF MILK BEVERAGE

Visando melhor aproveitamento do soro de queijo estudou-se a influência da proporção de soro e da concentração de hidrocoloide nos teores de lactose, ácido lático e tempo de fermentação de bebidas lácteas. Utilizou-se planejamento composto central rotacional com 3 pontos centrais, totalizando 11 experimentos. Empregaram-se as proporções soro/leite de 51, 55, 65, 75 e 79%, e as concentrações de hidrocoloide de 0,03; 0,04; 0,07; 0,10 e 0,11%. Os resultados foram tratados por análise de variância ao nível de significância de 5%. A proporção de soro influenciou significativamente (p<0,05) as variáveis resposta tempo de fermentação, lactose, sólidos totais e acidez titulável, porém não houve influência significativa (p<0,05) para a concentração de hidrocoloide. Menores tempos de fermentação foram atingidos quando se utilizou até 65% de soro. Os maiores teores de lactose foram obtidos nos experimentos com maior proporção de soro, enquanto que as bebidas com menor proporção de soro apresentaram maior teor de sólidos totais e acidez titulável.

Cell alterations induced by a biotherapic for influenza / Cell alterations induced by a biotherapic for influenza

Introduction: Influenza viruses have been responsible for highly contagious acute respiratory illnesses with high mortality, mainly in the elderly, which encourages the development of new drugs for the treatment of human flu. The biotherapics are medicines prepared from biological products, which are not chemically defined. They are compounded following the homeopathic procedures indicated for infectious diseases with known etiology [1]. Aim: The purpose of the present study is to verify cellular alterations induced by a biotherapic prepared from the infectious influenza A virus. Methodology: This biotherapic was prepared for this study in the homeopathic potency of 30X according to the Brazilian Homeopathic Pharmacopeia [2]. The concentration of 10% was not cytotoxic to cells, as verified by neutral red assay. The cellular alterations observed in MDCK cells were analyzed by optical microscopy for the quantification of mitosis, nucleoli and lipid bodies. The mitochondrial activity was assessed by MTT assay and the phosphosfructokinase-1 (PFK-1) enzyme activity was analyzed on the MDCK cells treated for 5, 10 and 30 days. Macrophages J778.G8 were treated with this biotherapic to evaluate the immunostimulatory cytokine release. Results: The cellular alterations observed in MDCK cells were verified by optical microscopy. The number of lipid bodies present in MDCK cells stimulated for 10 days was significantly lower (p <0.05) when compared to controls. The biotherapic significantly increased (p <0.05) the number of mitosis and the mitochondrial activity of MDCK cells stimulated for 10 and 30 days. These changes were confirmed by a significant reduction (p <0.05) on the PFK-1 activity. These results suggest that the biotherapic was able to activate the Krebs cycle and pentosephosphate metabolism to the generation of amino acids and nucleotides, situations common to cells whose rate of mitosis is increased. The quantification of immunostimulatory cytokines by macrophages J774.G8 indicated that the tumor necrosis factor (TNF-?) production was higher (p <0.05) in the supernatant of the macrophages pre-treated with this biotherapic and infected with influenza virus, suggesting an activation of the macrophages by this biotherapic. Conclusion: This biotherapic is able to induce some cellular alterations, which show strong evidence that it might be a promising option for the human flu. New experiments are being developed to understand the mechanisms of action of this biotherapic.

Chemokine receptor repertoire reflects mature T-cell lymphoproliferative disorder clinical presentation.

The World Health Organization classification of mature T-cell lymphoproliferative disorders, combines clinical, morphological and immunophenotypic data. The latter is a major contributor to the classification, as well as to the understanding of the malignant T-cell behavior. The fact that T-cell migration is regulated by chemokines should, in theory, enable us to identify tissue tropism and organ involvement by neoplastic T-cells by monitoring chemokine receptor surface expression. To address this issue we compared the expression of several early and late inflammatory, homeostatic, and organ specific chemokine receptors on blood T-cells from normal individuals and patients with T-cell large granular lymphocytic leukemia and peripheral T-cell lymphoma. T-cell large granular lymphocytic leukemia cells mainly express late inflammatory chemokine receptors (CXCR1 and CXCR2), whereas peripheral T-cell lymphoma cells usually express one or more organ homing receptors (CCR4, CCR6 and CCR7). Nevertheless, no clear correlation was found between CCR4 and CCR7 expression and skin and lymph node involvement, respectively. Compared to their normal counterparts, lymphoma T-cells displayed an exaggerated CCR4 expression, whereas leukemic T-cells had abnormally high CXCR1 and CXCR2 expression. Further analysis revealed that, in leukemia patients, the percentage of neoplastic cells expressing CCR5 correlates directly with lymphocytosis. In addition, in the case of CD8 T-cell leukemia patients, an inverse correlation with neutropenia was found. In lymphoma patients, higher CCR4 and CCR7 expression is accompanied by lower to absent CCR5 expression.

Citologia endocervical (CE) e curetagem endocervical (CEE) como métodos preditivos da presença de lesöes de alto grau residuais nas margens de conizaçöes por cirurgia de alta frequência (CAF) / Endocervical cytology (EC) and curettage (ECC) as prediction methods of high-grade lesions marginal extension on loop electrosurgical excision procedures (LEEP) results

Objetivo: este estudo objetiva avaliar a eficácia da CE e da CEE após o cone-CAF como preditores do compromentimento lesional das margens do cone. Métodos: O CAF foi realizado sob anestesia local e visäo colposcópia dirta em 35 pacientes encaminhadas por resultados alterados na citologia e/ou biópsia. As CE/CEE foram coletadas imediatamente após o CAF, utilizando-se Cytobrush e cureta de Novak, respectivamente. Resultados: foram observadas lesöes de alto grau em 25/35 (71,43porcento) dos cones-CAF, todos compatíveis com os resultados citoistológicos prévios. Ocorreu comprometimento das margens em 14/35 (40porcento) dos cones. O material coletado por CEE foi insuficiente em 6/14 (42,86porcento) e positivo em 3/14 (21,43porcento) dos restantes. A CE se apresentou inconclusiva em 5/14 (35,72porcento) dos casos e positiva em 3/14 (21,43porcento). Os limites das lesöes colposcópicas näo foram visibilizados em 12/35 (34,29porcento)pacientes e, deste total, 3/12 (25porcento) das lesöes endocervicais foram detectadas através do material coletado pelas CE/CEE. Cnclusöes: considerando a alta incidência de comprometimento das margens do cone pós-CAF, ambos os métodos CE e CEE se mostraram úteis como instrumentos primários de detecçäo em um terço dos casos estudados. Estes resultados prliminares devem ser melhor avaliados com a sua inclusäo no protocolo de rotina, especialmente indicado em pacientes apresentando lesöes colposcópias de limites endocervicais näo visiveis. O acompanhamento a longo-prazo maiores reduzirá o número de coletas insuficientes/inconclusivas, possibilitando melhores conclusöes sobre ambos os métodos e permitindo, inclusive, prevenir as indicaçöes de histerectomia devido a lesöes residuais pós-cone (au)