Flowers of Gomphrena globosa L. as an alternatve source of betacyanins: optimization of the extraction using response surface methodology

Betacyanins are betalain pigments that display a red-violet colour which have been reported to be three times stronger than the red-violet dye produced by anthocyanins [1]. The applications of betacyanins cover a wide range of matrices, mainly as additives or ingredients in the food industry, cosmetics, pharmaceuticals and livestock feed. Although, being less commonly used than anthocyanins and carotenoids, betacyanins are stable between pH 3 to 7 and suitable for colouring in low acid matrices. In addition, betacyanins have been reported to display interesting medicinal character as powerful antioxidant and chemopreventive compounds either in vitro or in vivo models [2]. Betacyanins are obtained mainly from the red beet of Beta vulgaris plant (between I 0 to 20 mg per I 00 g pulp) but alternative primary sources are needed [3]. In addition, independently of the source used, the effect of the variables that affect the extraction of betacyanins have not been properly described and quantified. Therefore, the aim of this study was to identifY and optimize the conditions that maximize betacyanins extraction using the tepals of Gomphrena globosa L. flowers as an alternative source. Assisted by the statistical technique of response surface methodology, an experimental design was developed for testing the significant explanatory variables of the extraction (time, temperature, solid-liquid ratio and ethanolwater ratio). The identification was performed using high-performance liquid chromatography coupled with a photodiode array detector and mass spectrometry with electron spray ionization (HPLC-PDAMS/ ESI) and the response was measured by the quantification of these compounds using HPLC-PDA. Afterwards, a response surface analysis was performed to evaluate the results. The major betacyanin compounds identified were gomphrenin 11 and Ill and isogomphrenin IJ and Ill. The highest total betacyanins content was obtained by using the following conditions: 45 min of extraction. time, 35•c, 35 g/L of solid-liquid ratio and 25% of ethanol. These values would not be found without optimizing the conditions of the betacyanins extraction, which moreover showed contrary trends to what it has been described in the scientific bibliography. More specifically, concerning the time and temperature variables, an increase of both values (from the common ones used in the bibliography) showed a considerable improvement on the betacyanins extraction yield without displaying any type of degradation patterns.

Feasibility of resting-state microstates neurofeedback

Despite major progress, currently available treatment options for patients suffering from schizophrenia remain suboptimal. Antipsychotic medication is one such option, and is helpful in acute phases of the disease. However, antipsychotics cause significant side-effects that often require additional medication, and can even trigger the discontinuation of treatment. Taken together, along with the fact that 20-30% of patients are medication-resistant, it is clear that new medical care options should be developed for patients with schizophrenia. Besides medication, an emerging option to treat psychiatric symptoms is through the use of neurofeedback. This technique has proven efficacy for other disorders and, more importantly, has also proven to be feasible in patients with schizophrenia. One of the major advantages of this approach is that it allows for the influence of brain states that otherwise would be inaccessible; i.e. the physiological markers underlying psychotic symptoms. EEG resting-state microstates are a very interesting electrophysiological marker of schizophrenia symptoms. Precisely, a specific class of resting-state microstates, namely microstate class D, has consistently been found to show a temporal shortening in patients with schizophrenia compared to controls, and this shortening is correlated with the presence positive psychotic symptoms. Under the scope of biological psychiatry, appropriate treatment of psychotic symptoms can be expected to modify the underlying physiological markers accompanying behavioral manifestations of a disease. We reason that if abnormal temporal parameters of resting-state microstates seem to be related to positive symptoms in schizophrenia, regulating this EEG feature might be helpful as a treatment for patients. The goal of this thesis was to prove the feasibility of microstate class D contribution self-regulation via neurofeedback. Given that no other study has attempted to regulate microstates via neurofeedback, we first tested its feasibility in a population of healthy subjects. In the first paper we describe the methodological characteristics of the neurofeedback protocol and its implementation. Neurofeedback performance was assessed by means of linear mixed effects modeling, which provided a complete profile of the neurofeedback’s training response within and between-subjects. The protocol included 20 training sessions, and each session contained three conditions: baseline (resting-state) and two active conditions: training (auditory feedback upon self-regulation performance) and transfer (self-regulation with no feedback). With linear modeling we obtained performance indices for each of them as follows: baseline carryover (baseline increments time-dependent) and learning and aptitude for each of the active conditions. Learning refers to the increase/decrease of the microstate class D contribution, time-dependent during each active condition, and aptitude refers to the constant difference of the microstate class D contribution between each active condition and baseline independent of time. The indices provided are discussed in terms of tailoring neurofeedback treatment to individual profiles so that it can be applied in future studies or clinical practice. In our sample of participants, neurofeedback proved feasible, as all participants at least showed positive results in one of the aforementioned learning indices. Furthermore, between-subjects we observed that the contribution of microstate class D across-sessions increased by 0.42% during baseline, 1.93% during training trials, and 1.83% during transfer. This range is expected to be effective in treating psychotic symptoms in patients. In the second paper presented in this thesis, we explored the possible predictors of neurofeedback success among psychological variables measured with questionnaires. An interesting finding was the negative correlation between “motivational incongruence” and some of the neurofeedback performance indices. Even though this finding requires replication, we discuss it in terms of the interfering effects of incompatible psychological processes with neurofeedback training requirements. In the third paper, we present a meta-analysis on all available studies that have related resting-state microstate abnormalities and schizophrenia. We obtained medium effect sizes for two microstate classes, namely C and D. Combining the meta-analysis results with the fact that microstate class D abnormalities are correlated with the presence of positive symptoms in patients with schizophrenia, these results add further support for the training of this precise microstate. Overall, the results obtained in this study encourage the implementation of this protocol in a population of patients with schizophrenia. However, future studies will have to show whether patients will be able to successfully self-regulate the contribution of microstate class D and, if so, whether this regulation will have an impact on symptomatology.

Subject response rates in case-control studies of cancer : time trends, study design determinants, and quality of reporting

Objectifs: Examiner les tendances temporelles, les déterminants en lien avec le design des études et la qualité des taux de réponse rapportés dans des études cas-témoins sur le cancer publiées lors des 30 dernières années. Méthodes: Une revue des études cas-témoins sur le cancer a été menée. Les critères d'inclusion étaient la publication (i) dans l’un de 15 grands périodiques ciblés et (ii) lors de quatre périodes de publication (1984-1986, 1995, 2005 et 2013) couvrant trois décennies. 370 études ont été sélectionnées et examinées. La méthodologie en lien avec le recrutement des sujets et la collecte de données, les caractéristiques de la population, les taux de participation et les raisons de la non-participation ont été extraites de ces études. Des statistiques descriptives ont été utilisées pour résumer la qualité des taux de réponse rapportés (en fonction de la quantité d’information disponible), les tendances temporelles et les déterminants des taux de réponse; des modèles de régression linéaire ont été utilisés pour analyser les tendances temporelles et les déterminants des taux de participation. Résultats: Dans l'ensemble, les qualités des taux de réponse rapportés et des raisons de non-participation étaient très faible, particulièrement chez les témoins. La participation a diminué au cours des 30 dernières années, et cette baisse est plus marquée dans les études menées après 2000. Lorsque l'on compare les taux de réponse dans les études récentes a ceux des études menées au cours de 1971 à 1980, il y a une plus grande baisse chez les témoins sélectionnés en population générale ( -17,04%, IC 95%: -23,17%, -10,91%) que chez les cas (-5,99%, IC 95%: -11,50%, -0,48%). Les déterminants statistiquement significatifs du taux de réponse chez les cas étaient: le type de cancer examiné, la localisation géographique de la population de l'étude, et le mode de collecte des données. Le seul déterminant statistiquement significatif du taux de réponse chez les témoins hospitaliers était leur localisation géographique. Le seul déterminant statistiquement significatif du taux de participation chez les témoins sélectionnés en population générale était le type de répondant (sujet uniquement ou accompagné d’une tierce personne). Conclusion: Le taux de participation dans les études cas-témoins sur le cancer semble avoir diminué au cours des 30 dernières années et cette baisse serait plus marquée dans les études récentes. Afin d'évaluer le niveau réel de non-participation et ses déterminants, ainsi que l'impact de la non-participation sur la validité des études, il est nécessaire que les études publiées utilisent une approche normalisée pour calculer leurs taux de participation et qu’elles rapportent ceux-ci de façon transparente.

Correlates of Vitamin D Status in Healthy Older Adults Living in Miami-Dade and its Association with Non-Skeletal Outcomes: A Cross-Sectional Study

Examining factors that affect vitamin D status in the fast-growing elderly population of Miami-Dade, Florida, is needed. Vitamin D deficiency in older adults has been linked to correlates of disability, including falls and fractures, and cardiovascular disease. The purpose of this study was to determine the proportion of vitamin D insufficient individuals and their relationship with vitamin D insufficiency in older adults (n=97) living in Miami-Dade. We evaluated the association between vitamin D status and 1) dual task physical performance to understand the link between vitamin D and cognition in the context of mobility; and 2) cardiometabolic risk, measured by galvanic skin response, pulse oximetry, and blood pressure to create a composite score based on autonomic nervous system and endothelial function. Participants completed baseline assessments that included serum levels of vitamin D, anthropometrics, body composition, dual task physical performance and cardiometabolic risk. Surveys to evaluate vitamin D intake, sun exposure, physical activity, and depressive symptoms were completed. Spearman’s correlations, independent t-tests, paired t-tests, repeated measures ANOVAs, and multiple logistic and linear regressions were used to examine the relationship of vitamin D insufficiency (25(OH)D /ml) and sufficiency (25(OH)D ≥30 ng/ml) with determinants of vitamin D status, dual task physical performance variables and cardiometabolic risk scores. Although the proportion of vitamin D insufficient individuals was lower when compared to the prevalance of the general United States elderly population, it was still common in healthy community-dwelling older adults living in Miami-Dade County, especially among Hispanics. Factors that affected skin synthesis (ethnicity, and sun exposure), and bioavailability/metabolism (obesity) were significant predictors of vitamin D status. Vitamin D insufficiency was not significantly correlated with worse dual task physical performance; however, cognitive performance was worse in the vitamin D insufficient group. Our results suggest a relationship of vitamin D insufficiency with executive dysfunction, and support an association with cardiometabolic risk using an innovative electro-sensor complex, possibly by modulating autonomic nervous system activity and vascular function, thus affecting cardiac performance.

The effect of notch filtering on the waveform of the newborn auditory brainstem response

OBJECTIVE: To identify whether the use of a notch filter significantly affects the morphology or characteristics of the newborn auditory brainstem response (ABR) waveform and so inform future guidance for clinical practice. DESIGN: Waveforms with and without the application of a notch filter were recorded from babies undergoing routine ABR tests at 4000, 1000 and 500 Hz. Any change in response morphology was judged subjectively. Response latency, amplitude, and measurements of response quality and residual noise were noted. An ABR simulator was also used to assess the effect of notch filtering in conditions of low and high mains interference. RESULTS: The use of a notch filter changed waveform morphology for 500 Hz stimuli only in 15% of tests in newborns. Residual noise was lower when 4000 Hz stimuli were used. Response latency, amplitude, and quality were unaffected regardless of stimulus frequency. Tests with the ABR stimulator suggest that these findings can be extended to conditions of high level mains interference. CONCLUSIONS: A notch filter should be avoided when testing at 500 Hz, but at higher frequencies appears to carry no penalty.

Centralization of cleft care in the UK. Part 6:a tale of two studies

OBJECTIVES: We summarize and critique the methodology and outcomes from a substantial study which has investigated the impact of reconfigured cleft care in the United Kingdom (UK) 15 years after the UK government started to implement the centralization of cleft care in response to an earlier survey in 1998, the Clinical Standards Advisory Group (CSAG). SETTING AND SAMPLE POPULATION: A UK multicentre cross-sectional study of 5-year-olds born with non-syndromic unilateral cleft lip and palate. Data were collected from children born in the UK with a unilateral cleft lip and palate between 1 April 2005 and 31 March 2007. MATERIALS AND METHODS: We discuss and contextualize the outcomes from speech recordings, hearing, photographs, models, oral health and psychosocial factors in the current study. We refer to the earlier survey and other relevant studies. RESULTS: We present arguments for centralization of cleft care in healthcare systems, and we evidence this with improvements seen over a period of 15 years in the UK. We also make recommendations on how future audit and research may configure. CONCLUSIONS: Outcomes for children with a unilateral cleft lip and palate have improved after the introduction of a centralized multidisciplinary service, and other countries may benefit from this model. Predictors of early outcomes are still needed, and repeated cross-sectional studies, larger longitudinal studies and adequately powered trials are required to create a research-led evidence-based (centralized) service.

Subject response rates in case-control studies of cancer : time trends, study design determinants, and quality of reporting

Objectifs: Examiner les tendances temporelles, les déterminants en lien avec le design des études et la qualité des taux de réponse rapportés dans des études cas-témoins sur le cancer publiées lors des 30 dernières années. Méthodes: Une revue des études cas-témoins sur le cancer a été menée. Les critères d'inclusion étaient la publication (i) dans l’un de 15 grands périodiques ciblés et (ii) lors de quatre périodes de publication (1984-1986, 1995, 2005 et 2013) couvrant trois décennies. 370 études ont été sélectionnées et examinées. La méthodologie en lien avec le recrutement des sujets et la collecte de données, les caractéristiques de la population, les taux de participation et les raisons de la non-participation ont été extraites de ces études. Des statistiques descriptives ont été utilisées pour résumer la qualité des taux de réponse rapportés (en fonction de la quantité d’information disponible), les tendances temporelles et les déterminants des taux de réponse; des modèles de régression linéaire ont été utilisés pour analyser les tendances temporelles et les déterminants des taux de participation. Résultats: Dans l'ensemble, les qualités des taux de réponse rapportés et des raisons de non-participation étaient très faible, particulièrement chez les témoins. La participation a diminué au cours des 30 dernières années, et cette baisse est plus marquée dans les études menées après 2000. Lorsque l'on compare les taux de réponse dans les études récentes a ceux des études menées au cours de 1971 à 1980, il y a une plus grande baisse chez les témoins sélectionnés en population générale ( -17,04%, IC 95%: -23,17%, -10,91%) que chez les cas (-5,99%, IC 95%: -11,50%, -0,48%). Les déterminants statistiquement significatifs du taux de réponse chez les cas étaient: le type de cancer examiné, la localisation géographique de la population de l'étude, et le mode de collecte des données. Le seul déterminant statistiquement significatif du taux de réponse chez les témoins hospitaliers était leur localisation géographique. Le seul déterminant statistiquement significatif du taux de participation chez les témoins sélectionnés en population générale était le type de répondant (sujet uniquement ou accompagné d’une tierce personne). Conclusion: Le taux de participation dans les études cas-témoins sur le cancer semble avoir diminué au cours des 30 dernières années et cette baisse serait plus marquée dans les études récentes. Afin d'évaluer le niveau réel de non-participation et ses déterminants, ainsi que l'impact de la non-participation sur la validité des études, il est nécessaire que les études publiées utilisent une approche normalisée pour calculer leurs taux de participation et qu’elles rapportent ceux-ci de façon transparente.

An investigation of the relationship between the components of tumour microenvironment, signal transduction pathways and outcome in breast cancer

Breast cancer, the most commonly diagnosed type of cancer in women, is a major cause of morbidity and mortality in the western world. Well-established risk factors of breast cancer are mostly related to women’s reproductive history, such as early menarche, late first pregnancy and late menopause. Survival rates have improved due to a combination of factors, including better health education, early detection with large-scale use of screening mammogram, improved surgical techniques, as well as widespread use of adjuvant therapy. At initial presentation, clinicopathological features of breast cancer such as age, nodal status, tumour size, tumour grade, and hormonal receptor status are considered to be the standard prognostic and predictive markers of patient survival, and are used to guide appropriate treatment strategies. Lymphovascular invasion (LBVI), including lymphatic (LVI) and blood (BVI) vessel invasion, has been reported to be prognostic and merit accurate evaluation, particularly in patients with node negative tumours who might benefit from adjuvant chemotherapy. There is a lack of standard assessment and agreement on distinguishing LVI from BVI despite the major challenges in the field. A systematic review of the literatures, examining methods of detection and the prognostic significance of LBVI, LVI and BVI, was carried out. The majority of studies used haematoxylin and eosin (H&E) and classical histochemistry to identify LVI and BVI. Only few recent studies used immunohistochemistry (IHC) staining of the endothelium lining lymphatic and blood vessels, and were able to show clear differences between LVI and BVI. The prognostic significance of LBVI and LVI was well-documented and strongly associated with aggressive features of breast tumours, while the prognostic value and the optimal detection method of BVI were unclear. Assessment and prognostic value of LBVI on H&E sections (LBVIH&E) was examined and compared to that of LVI and BVI detected using IHC with D2-40 for LVI (LVID2–40) and Factor VIII for BVI (BVIFVIII) in patients with breast cancer including node negative and triple negative patients (n=360). LBVIH&E, LVID2–40 and BVIFVIII were present in 102 (28%), 127 (35%) and 59 (16%) patients respectively. In node negative patients (206), LBVIH&E, LVID2–40 and BVIFVIII were present in 41 (20%), 53 (26%) and 21 (10%) respectively. In triple negative patients (102), LBVIH&E, LVID2–40 and BVIFVIII were present in 35 (29%), 36 (35%) and 14 (14%) respectively. LBVIH&E, LVID2–40 and BVIFVIII were all significantly associated with tumour recurrence in all cohorts. On multivariate survival analysis, only LVID2–40 and BVIFVIII were independent predictors of cancer specific survival (CSS) in the whole cohort (P=0.022 and P<0.001 respectively), node negative (P=0.008 and P=0.001 respectively) and triple negative patients (P=0.014 and P<0.001 respectively). Assessment of LVI and BVI by IHC, using D2-40 and Factor VIII, improves prediction of outcome in patients with node negative and triple negative breast cancer and was superior to the conventional detection method. Breast cancer is recognised as a complex molecular disease and histologically identical tumours may have highly variable outcomes, including different responses to therapy. Therefore, there is a compelling need for new prognostic and predictive markers helpful of selecting patients at risk and patients with aggressive diseases who might benefit from adjuvant and targeted therapy. It is increasingly recognised that the development and progression of human breast cancer is not only determined by genetically abnormal cells, but also dependent on complex interactions between malignant cells and the surrounding microenvironment. This has led to reconsider the features of tumour microenvironment as potential predictive and prognostic markers. Among these markers, tumour stroma percentage (TSP) and tumour budding, as well as local tumour inflammatory infiltrate have received recent attention. In particular, the local environment of cytokines, proteases, angiogenic and growth factors secreted by inflammatory cells and stromal fibroblasts has identified crucial roles in facilitating tumour growth, and metastasis of cancer cells through lymphatic and/or blood vessel invasion. This might help understand the underlying process promoting tumour invasion into these vessels. An increase in the proportion of tumour stroma and an increase in the dissociation of tumour cells have been associated with poorer survival in a number of solid tumours, including breast cancer. However, the interrelationship between these variables and other features of the tumour microenvironment in different subgroups of breast cancer are not clear. Also, whether their prognostic values are independent of other components of the tumour microenvironment have yet to be identified. Therefore, the relationship between TSP, clinicopathological characteristics and outcome in patients with invasive ductal breast cancer, in particular node negative and triple negative disease was examined in patients with invasive ductal breast cancer (n=361). The TSP was assessed on the haematoxylin and eosin-stained tissue sections. With a cut-off value of 50% TSP, patients with ≤50% stroma were classified as the low-TSP group and those with >50% stroma were classified as the high-TSP group. A total of 109 (30%) patients had high TSP. Patients with high TSP were old age (P=0.035), had involved lymph node (P=0.049), Her-2 positive tumours (P=0.029), low-grade peri-tumoural inflammatory infiltrate (P=0.034), low CD68+ macrophage infiltrate (P<0.001), low CD4+ (P=0.023) and low CD8+ T-lymphocytes infiltrate (P=0.017), tumour recurrence (P=0.015) and shorter CSS (P<0.001). In node negative patients (n=207), high TSP was associated with low CD68+ macrophage infiltrate (P=0.001), low CD4+ (P=0.040) and low CD8+ T-lymphocytes infiltrate (P=0.016) and shorter CSS (P=0.005). In triple negative patients (n=103), high TSP was associated with increased tumour size (P=0.017) high tumour grade (P=0.014), low CD8+ T-lymphocytes infiltrate (P=0.048) and shorter CSS (P=0.041). The 15-year cancer specific survival rate was 79% vs 21% in the low-TSP group vs high-TSP group. On multivariate survival analysis, a high TSP was associated with reduced CSS in the whole cohort (P=0.007), node negative patients (P=0.005) and those who received systemic adjuvant therapy (P=0.016), independent of other pathological characteristics including local host inflammatory responses. Therefore, a high TSP in invasive ductal breast cancer was associated with recurrence and poorer long-term survival. The inverse relation with the tumour inflammatory infiltrate highlights the importance of the amount of tumour stroma on immunological response in patients with invasive ductal breast cancer. Implementing this simple and reproducible parameter in routine pathological examination may help optimise risk stratification in patients with breast cancer. Similarly, the relationship between tumour budding, clinicopathological characteristics and outcome was examined in patients with invasive ductal breast cancer (n=474), using routine pathological sections. Tumour budding was associated with several adverse pathological characteristics, including positive lymph node (P=0.009), presence of LVI (P<0.001), and high TSP (P=0.001) and low-grade general peri-tumural inflammatory infiltrative (P=0.002). In node negative patients, a high tumour budding was associated with presence of LVI (P<0.001) and low-grade general peri-tumural inflammatory infiltrative (P=0.038). On multivariate survival analysis, tumour budding was associated with reduced CSS (P=0.001), independent of nodal status, tumour necrosis, CD8+ and CD138+ inflammatory cells infiltrate, LVI, BVI and TSP. Furthermore, tumour budding was independently associated with reduced CSS in node negative patients (P=0.004) and in those who have low TSP (P=0.003) and high-grade peri-tumoural inflammatory infiltrative (P=0.012). A high tumour budding was significantly associated with shorter CSS in luminal B and triple negative breast cancer subtypes (all P<0.001). Therefore, tumour budding was a significant predictor of poor survival in patients with invasive ductal breast cancer, independent of adverse pathological characteristics and components of tumour microenvironment. These results suggest that tumour budding may promote disease progression through a direct effect on local and distant invasion into lymph nodes and lymphatic vessels. Therefore, detection of tumour buds at the stroma invasive front might therefore represent a morphologic link between tumour progression, lymphatic invasion, spread of tumour cells to regional lymph nodes, and the establishment of metastatic dissemination. Given the potential importance of the tumour microenvironment, the characterisation of intracellular signalling pathways is important in the tumour microenvironment and is of considerable interest. One plausible signalling molecule that links tumour stroma, inflammatory cell infiltrate and tumour budding is the signal transducer and activator of transcription (STAT). The relationship between total and phosphorylated STAT1 (ph-STAT1), and total and ph-STAT3 tumour cell expression, components of tumour microenvironment and survival in patients with invasive ductal breast cancer was examined. IHC of total and ph-STAT1/STAT3 was performed on tissue microarray of 384 breast cancer specimens. Cellular STAT1 and cellular STAT3 expression at both cytoplasmic and nuclear locations were combined and identified as STAT1/STAT3 tumour cell expression. These results were then related to CSS and phenotypic features of the tumour and host. A high ph-STAT1 and a high ph-STAT3 tumour cell expression was associated with increased ER (P=0.001 and P<0.001 respectively) and PR (all P<0.05), reduced tumour grade (P=0.015 and P<0.001 respectively) and necrosis (all P=0.001). Ph-STAT1 was associated with increased general peri-tumoural inflammatory infiltrate (P=0.007) and ph-STAT3 was associated with lower CD4+ T-lymphocyte infiltrate (P=0.024). On multivariate survival analysis, including both ph-STAT1 and ph-STAT3 tumour cell expression, only high ph-STAT3 tumour cell expression was significantly associated with improved CSS (P=0.010) independent of other tumour and host-based factors. In patients with high necrosis grade, high ph-STAT3 tumour cell expression was independent predictor of improved CSS (P=0.021). Ph-STAT1 and ph-STAT3 were also significantly associated with improved cancer specific survival in luminal A and B subtypes. STAT1 and STAT3 tumour cell expression appeared to be an important determinant of favourable outcome in patients with invasive ductal breast cancer. The present results suggest that STATs may affect disease outcome through direct impact on tumour cells, and the surrounding microenvironment. The above observations of the present thesis point to the importance of the tumour microenvironment in promoting tumour budding, LVI and BVI. The observations from STATs work may suggest that an important driving mechanism for the above associations is the presence of tumour necrosis, probably secondary to hypoxia. Further work is needed to examine the interaction of other molecular pathways involved in the tumour microenvironment, such as HIF and NFkB in patients with invasive ductal breast cancer.

Egfr Activating Mutations And Their Association With Response To Platinum-doublet Chemotherapy In Brazilian Non-small Cell Lung Cancer Patients.

The aim of the study was to analyze the frequency of epidermal growth factor receptor (EGFR) mutations in Brazilian non-small cell lung cancer patients and to correlate these mutations with response to benefit of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Our cohort consisted of prospective patients with NSCLCs who received chemotherapy (platinum derivates plus paclitaxel) at the [UNICAMP], Brazil. EGFR exons 18-21 were analyzed in tumor-derived DNA. Fifty patients were included in the study (25 with adenocarcinoma). EGFR mutations were identified in 6/50 (12 %) NSCLCs and in 6/25 (24 %) adenocarcinomas; representing the frequency of EGFR mutations in a mostly self-reported White (82.0 %) southeastern Brazilian population of NSCLCs. Patients with NSCLCs harboring EGFR exon 19 deletions or the exon 21 L858R mutation were found to have a higher chance of response to platinum-paclitaxel (OR 9.67 [95 % CI 1.03-90.41], p = 0.047). We report the frequency of EGFR activating mutations in a typical southeastern Brazilian population with NSCLC, which are similar to that of other countries with Western European ethnicity. EGFR mutations seem to be predictive of a response to platinum-paclitaxel, and additional studies are needed to confirm or refute this relationship.

[consensus Of The Brazilian Society Of Rheumatology For The Diagnosis, Management And Treatment Of Lupus Nephritis].

To develop recommendations for the diagnosis, management and treatment of lupus nephritis in Brazil. Extensive literature review with a selection of papers based on the strength of scientific evidence and opinion of the Commission on Systemic Lupus Erythematosus members, Brazilian Society of Rheumatology. 1) Renal biopsy should be performed whenever possible and if this procedure is indicated; and, when the procedure is not possible, the treatment should be guided with the inference of histologic class. 2) Ideally, measures and precautions should be implemented before starting treatment, with emphasis on attention to the risk of infection. 3) Risks and benefits of treatment should be shared with the patient and his/her family. 4) The use of hydroxychloroquine (preferably) or chloroquine diphosphate is recommended for all patients (unless contraindicated) during induction and maintenance phases. 5) The evaluation of the effectiveness of treatment should be made with objective criteria of response (complete remission/partial remission/refractoriness). 6) ACE inhibitors and/or ARBs are recommended as antiproteinuric agents for all patients (unless contraindicated). 7) The identification of clinical and/or laboratory signs suggestive of proliferative or membranous glomerulonephritis should indicate an immediate implementation of specific therapy, including steroids and an immunosuppressive agent, even though histological confirmation is not possible. 8) Immunosuppressives must be used during at least 36 months, but these medications can be kept for longer periods. Its discontinuation should only be done when the patient achieve and maintain a sustained and complete remission. 9) Lupus nephritis should be considered as refractory when a full or partial remission is not achieved after 12 months of an appropriate treatment, when a new renal biopsy should be considered to assist in identifying the cause of refractoriness and in the therapeutic decision.

Inequalities in the distribution of dental caries among 12-year-old Brazilian schoolchildren

We assessed the inequality in the distribution of dental caries and the association between indicators of socioeconomic status and caries experience in a representative sample of schoolchildren. This study followed a cross-sectional design, with a sample of 792 schoolchildren aged 12 years, representative of this age group in Santa Maria, RS, Brazil. Guardians answered questions on socioeconomic status and a dental examination provided information on the dental caries experience (DMF-T). Inequality in dental caries distribution was measured by the Gini coefficient and the Significant Caries Index (SiC). The assessment of association used Poisson regression models. Socioeconomic factors were associated with prevalence of dental caries for the whole sample and also for individuals with a high-caries level. Children from low-income households had the highest prevalence of dental caries. The Gini coefficient was 0.7 and the SiC Index 2.5. The percentage of caries prevalence was 39.3% (95% CI: 35.8%-42.8%) and the mean for DMF-T was 0.9 (± SD 1.5). Inequalities in the distribution of dental caries were observed and socioeconomic factors were found to be strong predictors of the prevalence of oral disease in children of this age group.

Explaining sleep duration in adolescents: the impact of socio-demographic and lifestyle factors and working status

Previous studies found students who both work and attend school undergo a partial sleep deprivation that accumulates across the week. The aim of the present study was to obtain information using a questionnaire on a number of variables (e.g., socio-demographics, lifestyle, work timing, and sleep-wake habits) considered to impact on sleep duration of working (n=51) and non-working (n=41) high-school students aged 14-21 yrs old attending evening classes (19:00-22:30 h) at a public school in the city of So Paulo, Brazil. Data were collected for working days and days off. Multiple linear regression analyses were performed to assess the factors associated with sleep duration on weekdays and weekends. Work, sex, age, smoking, consumption of alcohol and caffeine, and physical activity were considered control variables. Significant predictors of sleep duration were: work (p < 0.01), daily work duration (8-10 h/day; p < 0.01), sex (p=0.04), age 18-21 yrs (0.01), smoking (p=0.02) and drinking habits (p=0.03), irregular physical exercise (p < 0.01), ease of falling asleep (p=0.04), and the sleep-wake cycle variables of napping (p < 0.01), nocturnal awakenings (p < 0.01), and mid-sleep regularity (p < 0.01). The results confirm the hypotheses that young students who work and attend school showed a reduction in night-time sleep duration. Sleep deprivation across the week, particularly in students working 8-10 h/day, is manifested through a sleep rebound (i.e., extended sleep duration) on Saturdays. However, the different roles played by socio-demographic and lifestyle variables have proven to be factors that intervene with nocturnal sleep duration. ) The variables related to the sleep-wake cycle naps and night awakenings proved to be associated with a slight reduction in night-time sleep, while regularity in sleep and wake-up schedules was shown to be associated with more extended sleep duration, with a distinct expression along the week and the weekend. Having to attend school and work, coupled with other socio-demographic and lifestyle factors, creates an unfavorable scenario for satisfactory sleep duration

Gene expression profile of the plant pathogen Fusarium graminearum under the antagonistic effect of Pantoea agglomerans

The pathogenic fungus Fusarium graminearum is an ongoing threat to agriculture, causing losses in grain yield and quality in diverse crops. Substantial progress has been made in the identification of genes involved in the suppression of phytopathogens by antagonistic microorganisms; however, limited information regarding responses of plant pathogens to these biocontrol agents is available. Gene expression analysis was used to identify differentially expressed transcripts of the fungal plant pathogen F. graminearum under antagonistic effect of the bacterium Pantoea agglomerans. A macroarray was constructed, using 1014 transcripts from an F. graminearum cDNA library. Probes consisted of the cDNA of F. graminearum grown in the presence and in the absence of P. agglomerans. Twenty-nine genes were either up (19) or down (10) regulated during interaction with the antagonist bacterium. Genes encoding proteins associated with fungal defense and/or virulence or with nutritional and oxidative stress responses were induced. The repressed genes coded for a zinc finger protein associated with cell division, proteins containing cellular signaling domains, respiratory chain proteins, and chaperone-type proteins. These data give molecular and biochemical evidence of response of F. graminearum to an antagonist and could help develop effective biocontrol procedures for pathogenic plant fungi.

Comparison of C-reactive protein and serum amyloid A protein in septic shock patients

Septic shock is a severe inflammatory state caused by an infectious agent. Our purpose was to investigate serum amyloid A (SAA) protein and C-reactive protein (CRP) as inflammatory markers of septic shock patients. Here we evaluate 29 patients in postoperative period, with septic shock, in a prospective study developed in a surgical intensive care unit. All eligible patients were monitored over a 7-day period by sequential organ failure assessment (SOFA) score, daily CRP, SAA, and lactate measurements. CRP and SAA strongly correlated up to the fifth day of observation but were not good predictors of mortality in septic shock. Copyright (C) 2008.

An empirical evaluation of imputation accuracy for association statistics reveals increased type-I error rates in genome-wide associations

Background: Genome wide association studies (GWAS) are becoming the approach of choice to identify genetic determinants of complex phenotypes and common diseases. The astonishing amount of generated data and the use of distinct genotyping platforms with variable genomic coverage are still analytical challenges. Imputation algorithms combine directly genotyped markers information with haplotypic structure for the population of interest for the inference of a badly genotyped or missing marker and are considered a near zero cost approach to allow the comparison and combination of data generated in different studies. Several reports stated that imputed markers have an overall acceptable accuracy but no published report has performed a pair wise comparison of imputed and empiric association statistics of a complete set of GWAS markers. Results: In this report we identified a total of 73 imputed markers that yielded a nominally statistically significant association at P < 10(-5) for type 2 Diabetes Mellitus and compared them with results obtained based on empirical allelic frequencies. Interestingly, despite their overall high correlation, association statistics based on imputed frequencies were discordant in 35 of the 73 (47%) associated markers, considerably inflating the type I error rate of imputed markers. We comprehensively tested several quality thresholds, the haplotypic structure underlying imputed markers and the use of flanking markers as predictors of inaccurate association statistics derived from imputed markers. Conclusions: Our results suggest that association statistics from imputed markers showing specific MAF (Minor Allele Frequencies) range, located in weak linkage disequilibrium blocks or strongly deviating from local patterns of association are prone to have inflated false positive association signals. The present study highlights the potential of imputation procedures and proposes simple procedures for selecting the best imputed markers for follow-up genotyping studies.