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1.
Plant Dis ; 106(4): 1238-1243, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34818914

ABSTRACT

Sweetpotato is a staple crop in Brazil presenting a smaller number of pathogens and diseases in comparison with other root and tuberous crops. Root-knot nematodes are among the most serious sweetpotato root pathogens. The impact of these pathogens also extends to succeeding crops. Because in Brazil, it is common to cultivate more than one crop per season, this problem is rapidly disseminated. The aim of this study was to assess the resistance of two sweetpotato clones and four commercial sweetpotato genotypes to three different Meloidogyne species. Assays were performed under greenhouse and field conditions. 'CIP BRS Nuti' and 'Canadense' were resistant to Meloidogyne incognita, M. javanica, and M. enterolobii under greenhouse conditions. This finding was obtained based on the reproduction factor < 0.2, meaning that the initial population of 5,000 nematodes was reduced to <1,000 individuals after 90 days of inoculation. Tomato and sweetpotato cultivar Beauregard, known to be susceptible to the three nematode species, were highly damaged by the pathogens. Similar results were also observed under field conditions. To our knowledge, 'CIP BRS Nuti' and 'Canadense' are the first South American commercial cultivars with triple nematode resistance.


Subject(s)
Ipomoea batatas , Solanum lycopersicum , Tylenchoidea , Animals , Genotype , Ipomoea batatas/genetics , Plant Diseases/genetics , Tylenchoidea/genetics
2.
Int J Biometeorol ; 61(2): 325-333, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27459867

ABSTRACT

The aim of this paper is to analyze the relationship between North Atlantic Oscillation (NAO), meteorological variables, air pollutants, and hospital admissions due to diseases of circulatory systems in Lisbon (Portugal) during winter months (2003-2012). This paper is one of the few studies analyzing the impact of NAO on health through its influence on thermal stress and air pollution and is the first to be conducted in Lisbon. This study uses meteorological data (synthetized into a thermal comfort index), air pollutant metrics, and the NAO index (all clustered in 10-day cycles to overcome daily variability of the NAO index). The relationship between morbidity, thermal comfort index, NAO index, and air pollutants was explored through several linear models adjusted to seasonality through a periodic function. The possible indirect effect between the NAO index and hospital admissions was tested, assuming that NAO (independent variable) is affecting hospital admissions (outcome variable) through thermal discomfort and/or pollution levels (tested as individual mediators). This test was conducted through causal mediation analysis and adjusted for seasonal variation. The results from this study suggest a possible indirect relationship between NAO index and hospital admissions. Although NAO is not significantly associated with hospital admissions, it is significantly associated with CO, PM2.5, NO, and SO2 levels, which in turn increase the probability of hospitalization. The discomfort index (built with temperature and relative humidity) is significantly associated with hospital admissions, but its variability is not explained by the NAO index. This study highlights the impacts of the atmospheric circulation patterns on health. Furthermore, understanding the influence of the atmospheric circulation patterns can support the improvement of the existing contingency plans.


Subject(s)
Cardiovascular Diseases/epidemiology , Hospitalization/statistics & numerical data , Weather , Air Pollutants/analysis , Carbon Monoxide/analysis , Cities/epidemiology , Humans , Linear Models , Nitric Oxide/analysis , Particulate Matter/analysis , Portugal/epidemiology , Seasons , Sulfur Dioxide/analysis
3.
Biom J ; 59(6): 1166-1183, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28464317

ABSTRACT

A typical survival analysis with time-dependent covariates usually does not take into account the possible random fluctuations or the contamination by measurement errors of the variables. Ignoring these sources of randomness may cause bias in the estimates of the model parameters. One possible way for overcoming that limitation is to consider a longitudinal model for the time-varying covariates jointly with a survival model for the time to the event of interest, thereby taking advantage of the complementary information flowing between these two-model outcomes. We employ here a Bayesian hierarchical approach to jointly model spatial-clustered survival data with a fraction of long-term survivors along with the repeated measurements of CD4+ T lymphocyte counts for a random sample of 500 HIV/AIDS individuals collected in all the 27 states of Brazil during the period 2002-2006. The proposed Bayesian joint model comprises two parts: on the one hand, a flexible model using Penalized Splines to better capture the nonlinear behavior of the different CD4 profiles over time; on the other hand, a spatial cure model to cope with the set of long-term survivor individuals. Our findings show that joint models considering this set of patients were the ones with the best performance comparatively to the more traditional survival approach. Moreover, the use of spatial frailties allowed us to map the heterogeneity in the disease risk among the Brazilian states.


Subject(s)
Acquired Immunodeficiency Syndrome/immunology , Biometry/methods , Survivors/statistics & numerical data , Bayes Theorem , CD4 Lymphocyte Count , Databases, Factual , Humans , Longitudinal Studies
4.
Stat Med ; 35(19): 3368-84, 2016 08 30.
Article in English | MEDLINE | ID: mdl-26990773

ABSTRACT

Joint analysis of longitudinal and survival data has received increasing attention in the recent years, especially for analyzing cancer and AIDS data. As both repeated measurements (longitudinal) and time-to-event (survival) outcomes are observed in an individual, a joint modeling is more appropriate because it takes into account the dependence between the two types of responses, which are often analyzed separately. We propose a Bayesian hierarchical model for jointly modeling longitudinal and survival data considering functional time and spatial frailty effects, respectively. That is, the proposed model deals with non-linear longitudinal effects and spatial survival effects accounting for the unobserved heterogeneity among individuals living in the same region. This joint approach is applied to a cohort study of patients with HIV/AIDS in Brazil during the years 2002-2006. Our Bayesian joint model presents considerable improvements in the estimation of survival times of the Brazilian HIV/AIDS patients when compared with those obtained through a separate survival model and shows that the spatial risk of death is the same across the different Brazilian states. Copyright © 2016 John Wiley & Sons, Ltd.


Subject(s)
Acquired Immunodeficiency Syndrome/mortality , Bayes Theorem , Models, Statistical , Brazil/epidemiology , Humans , Longitudinal Studies
5.
Plants (Basel) ; 13(11)2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38891354

ABSTRACT

Lettuce is an important cool-temperature crop, and its principal abiotic stress is low heat tolerance. Lettuce production has become more challenging in the context of global warming changes. Hence, the main objective of this research was to investigate the relationship between stability and lettuce heat tolerance. Field and greenhouse trials were run in 2015 (summer) and 2016 (fall and spring). The environments were composed of a combination of season and place (field, glass, and plastic greenhouse), and the assessed genotypes were BRS Leila and Mediterrânea, Elisa, Everglades, Simpson, and Vanda. Statistical analysis showed a significant effect (p < 0.05) of environments (E), genotypes (G), and the GEI. BRS Leila, Elisa, and BRS Mediterrânea showed the greatest means to the first anthesis in suitable environments (milder temperatures). Among these cultivars, BRS Mediterrânea was the most stable and adapted to hot environments. The environmental conditions studied in this research, mainly high temperatures, could become a reality in many lettuce-producing areas. Therefore, the results can help indicate and develop lettuce varieties with greater heat tolerance.

6.
Ann Surg Oncol ; 20(5): 1530-7, 2013 May.
Article in English | MEDLINE | ID: mdl-23250736

ABSTRACT

PURPOSE: To evaluate "classic" prognostic parameters, as well as DNA ploidy and S-phase fraction (SPF), in relation to disease-free (DFS) and disease-specific (DSS) survival in breast invasive ductal carcinoma (IDC) with long-term follow-up study. METHODS: The study involved 393 patients with IDC and median follow-up of 134 months (50-240). Histological grading, tumor size, axillary nodal involvement, pathological staging and hormone receptor status were considered as established prognostic markers. Ploidy and SPF were determined prospectively by DNA flow cytometry using fresh/frozen tissue. A Cox regression model was used for statistical analysis of the prognostic variables. RESULTS: There were 105 (26.7 %) deaths and 140 (35.6 %) disease recurrences during follow-up. Two hundred thirty-one (58.8 %) tumors were aneuploid. High SPF and aneuploidy were associated with tumors with higher grade of differentiation, greater size and negative hormone receptors. Higher SPF and advanced disease stage are correlated. In univariate analysis, all the clinicopathological and cytometric features, including patients <40 years and a subgroup presenting hypertetraploid/multiploid tumors, are significantly correlated with clinical outcome, apart from SPF and estrogen receptors for DFS. In multivariate analysis, nodal involvement, DNA aneuploidy and lack of progesterone receptors (for DSS) retained statistically significant association with shorter survival. In node-negative patients, ploidy (for DFS) and estrogen receptors (for DSS) significantly predicted survival. In both subgroups of node-positive patients and those (n = 195) with intermediate differentiation tumors (G2), aneuploidy was an indicator of worse prognosis. CONCLUSIONS: Along with nodal status and hormone receptor expression, DNA ploidy is an independent predictor of long-term survival in IDC.


Subject(s)
Aneuploidy , Breast Neoplasms/genetics , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/pathology , S Phase , Adult , Aged , Aged, 80 and over , Breast Neoplasms/secondary , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Disease-Free Survival , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Proportional Hazards Models , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Time Factors , Young Adult
7.
Pathol Res Pract ; 246: 154513, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37167811

ABSTRACT

AIM: In breast carcinoma (BC), the relationship between the ploidy pattern and molecular subtyping is still unknown. We aim to investigate the prognostic impact of DNA ploidy within molecular subtypes of a large cohort of BC patients. METHODS: The series involved 520 BC patients with no neoadjuvant therapy and a median follow-up of 115.5 months. Immunohistochemical assessment of hormonal receptors, ERBB2 (HER2) status and Ki67 proliferative activity was the basis of the surrogate molecular subtyping. Ploidy was evaluated by DNA flow cytometry in fresh/frozen tumour samples. Kaplan-Meier (K-M) survival estimation was used for prognostic statistical analysis. RESULTS: Luminal A subtype had the lowest prevalence of disease recurrences (23.6 %) and deaths from disease (18.3 %), while Luminal B (42.2 %/37.9 %), Triple-negative (46.4 %/40.6 %), and HER2-positive (55.9 %/50.0 %) subtypes had the highest. The Triple-positive subtype shows an intermediate/low frequency of adverse events (29.4 % of disease recurrences and 17.6 % of deaths from disease). Luminal A tumours were mostly diploid (55.3 %), while Triple-negative and HER2-positive tumours showed a high incidence of aneuploidy (82.6 % and 88.2 %, respectively). Luminal B and Triple-positive tumours had an intermediate percentage of aneuploidy (63.8 % and 70.6 %, respectively). K-M survival curves showed that DNA aneuploidy is significantly associated with shorter disease-free survival and overall survival in Luminal A and Luminal B molecular subtypes. CONCLUSION: DNA aneuploidy identifies a subset of Luminal BC patients with worse clinical outcome, potentially eligible for more aggressive adjuvant therapy.


Subject(s)
Breast Neoplasms , Receptor, ErbB-2 , Humans , Female , Receptor, ErbB-2/analysis , Neoplasm Recurrence, Local , Breast Neoplasms/pathology , Prognosis , Disease-Free Survival , Aneuploidy , DNA , Receptors, Progesterone/analysis , Biomarkers, Tumor/analysis
8.
PLoS One ; 18(8): e0289365, 2023.
Article in English | MEDLINE | ID: mdl-37535564

ABSTRACT

BACKGROUND: Breast cancer therapy improved significantly, allowing for different surgical approaches for the same disease stage, therefore offering patients different aesthetic outcomes with similar locoregional control. The purpose of the CINDERELLA trial is to evaluate an artificial-intelligence (AI) cloud-based platform (CINDERELLA platform) vs the standard approach for patient education prior to therapy. METHODS: A prospective randomized international multicentre trial comparing two methods for patient education prior to therapy. After institutional ethics approval and a written informed consent, patients planned for locoregional treatment will be randomized to the intervention (CINDERELLA platform) or controls. The patients in the intervention arm will use the newly designed web-application (CINDERELLA platform, CINDERELLA APProach) to access the information related to surgery and/or radiotherapy. Using an AI system, the platform will provide the patient with a picture of her own aesthetic outcome resulting from the surgical procedure she chooses, and an objective evaluation of this aesthetic outcome (e.g., good/fair). The control group will have access to the standard approach. The primary objectives of the trial will be i) to examine the differences between the treatment arms with regards to patients' pre-treatment expectations and the final aesthetic outcomes and ii) in the experimental arm only, the agreement of the pre-treatment AI-evaluation (output) and patient's post-therapy self-evaluation. DISCUSSION: The project aims to develop an easy-to-use cost-effective AI-powered tool that improves shared decision-making processes. We assume that the CINDERELLA APProach will lead to higher satisfaction, better psychosocial status, and wellbeing of breast cancer patients, and reduce the need for additional surgeries to improve aesthetic outcome.


Subject(s)
Artificial Intelligence , Breast Neoplasms , Female , Humans , Breast Neoplasms/surgery , Cloud Computing , Intelligence , Patient Satisfaction , Prospective Studies
9.
Clin Endocrinol (Oxf) ; 77(2): 302-9, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22329804

ABSTRACT

OBJECTIVE: To investigate the prognostic influence of DNA ploidy and S-phase fraction (SPF) on disease-free (DFS) and overall survival (OS) of patients with primary disease and loco-regional lymph node recurrence of papillary thyroid carcinoma (PTC). DESIGN: A large prospective study with long-term follow-up (median, 117 months). PATIENTS: Two series of patients with primary PTC (n = 305) and lymph node recurrence metastasis (LNM) (n = 39) were involved in the study. MEASUREMENTS: Patient's age and gender, histological variant, pathological tumour-node-metastasis (pTNM) staging, extrathyroidal extension, vascular and lymphatic invasion and tumour bilateral growth were the clinical and pathological characteristics evaluated. DNA flow cytometry was performed on fresh/frozen surgical tumour samples. Cox regression models were estimated for prognostic analyses. RESULTS: Seventeen (5·6%) primary tumours and five (12·8%) LNMs were aneuploid, while mean SPF was 2·7% and 3·7%, respectively (P = 0·022). High SPF was significantly associated with lymphatic invasion and tall cell and diffuse sclerosing variants. In univariate analysis, all the clinico-pathological variables, but tumour bilateral growth and gender, were significantly correlated with survival. SPF showed borderline significance (P = 0·051) in relation to OS. In multivariate analysis, older age (≥48 years), lymph node spread and high SPF were significantly adverse prognostic factors. Extrathyroidal extension and distant metastasis for OS, as well as tumour size for DFS, were also found as unfavourable prognostic features. In LNM, the Kaplan-Meier curves showed significant differences for older age and DNA aneuploidy (recurrence; P = 0·011). CONCLUSION: The results indicate that SPF and ploidy can provide additional predictive information in patients with PTC.


Subject(s)
Ploidies , S Phase , Thyroid Neoplasms/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma , Carcinoma, Papillary , Child , Child, Preschool , Disease-Free Survival , Female , Flow Cytometry , Humans , Male , Middle Aged , Prospective Studies , Thyroid Cancer, Papillary , Thyroid Neoplasms/mortality , Young Adult
10.
Nutrients ; 14(11)2022 May 24.
Article in English | MEDLINE | ID: mdl-35683985

ABSTRACT

Undernutrition, anemia, and intestinal parasitic infections are public health problems in Angola, especially in pre-school children. We analyzed binary data from a longitudinal four-arm randomized parallel trial conducted in Bengo Province, northern Angola, over the course of two years, with seven follow-up assessments to explore the effects of four interventions (deworming and a test-and-treat approach for intestinal parasites, at both the individual and household levels) on wasting and stunting, and to understand their indirect benefits for anemia, malaria, diarrhea, and vomiting. A total of 121 children with intestinal parasitic infections received baseline treatment, and were allocated to the four arms (1:1:1:1). Using continuous outcome variables of height-for-age (HAZ) and weight-for-height (WHZ) statistical approaches did not reveal a clear benefit of any particular arm (Pathogens 2021, 10, 309). Next, HAZ and WHZ were transformed into binary variables of stunting and wasting, respectively, considering their mild-to-severe (Z-score < −1) and moderate-to-severe degrees (Z-score < −2). Original clinical data (on anemia, diarrhea, vomiting, and malaria) were also analyzed. From a binary longitudinal analysis with different dependence structures, using the R package bild, fitted models revealed the potential benefit of a test-and-treat approach at the individual level for wasting compared with annual albendazole at the individual level, especially considering mild-to-severe forms (ORadj = 0.27; p = 0.007). All arms showed similar effects on stunting, compared with annual albendazole, at a 5% significance level. Time and age at baseline presented favorable effects in the percentage of stunting using both severity degrees. Results showed a decreased chance of having anemia and diarrhea over time, although with no significant differences between arms. Data from longitudinal studies are essential to study the direct and indirect effects of interventions, such as deworming, and to explore additional approaches aiming at better understanding the temporal structure of nutrition and health outcomes in children.


Subject(s)
Anemia , Intestinal Diseases, Parasitic , Malaria , Parasites , Albendazole/therapeutic use , Anemia/diagnosis , Anemia/drug therapy , Anemia/etiology , Animals , Cachexia , Child , Child, Preschool , Diarrhea/drug therapy , Growth Disorders/drug therapy , Humans , Infant , Intestinal Diseases, Parasitic/diagnosis , Intestinal Diseases, Parasitic/drug therapy , Malaria/complications , Malaria/drug therapy , Prevalence , Vomiting
11.
Oncol Lett ; 24(4): 329, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36039057

ABSTRACT

The influence of age on the outcome of patients with invasive breast carcinoma (IBC) has not yet been fully established. The present study investigated two subgroups of patients either side of the age spectrum, and evaluated cytometric, histopathological and molecular characteristics. The series involved 219 patients with IBC that had long-term follow-up, which were divided into two subgroups: Young (≤45 years; n=103) and old patients (≥75 years; n=116). Immunohistochemical evaluation of hormonal receptors, Ki67 index and HER2 status (plus HER2 silver in situ hybridization in equivocal cases) were used as the basis for surrogate molecular subtyping. Ploidy and S-phase fraction (SPF) were analysed by DNA flow cytometry. Differences between the subgroups' characteristics were assessed by the two proportion Z test. Kaplan-Meier estimation and log-rank test were applied for survival analyses. The median age in the subgroups were 40 years (range, 19-45 years) in the young group and 78 years (range, 75-91 years) in the older subgroup. Young patients exhibited higher lymph node involvement, more advanced disease staging, higher SPF tumour proliferative activity, and a trend of lower incidence of Luminal A and higher incidence of Luminal B tumours. The median SPF value was significantly higher in young patients [7.1% (range, 1.5-23.7%) vs. 4.5% (range, 0.7-26.4%)], whereas the ploidy pattern showed no significant difference. In the whole series, as within IBC of no special type, young patients had a higher rate of recurrence (46.6 vs. 22.4%; P<0.001) and deaths from disease (35.9 vs. 20.7%; P=0.030), with a statistically significant difference for disease-free survival. In conclusion, the present study indicated that young patients with IBC exhibited more aggressive disease, with an increased risk of recurrence and shorter disease-free survival. SPF, lymph node status and staging appeared to be the main prognostic factors to differentiate young from older patients with IBC.

12.
Breast Cancer (Auckl) ; 15: 11782234211002496, 2021.
Article in English | MEDLINE | ID: mdl-33888988

ABSTRACT

BACKGROUND: Male breast carcinoma (male BC) is an uncommon neoplasia without individualized strategies for diagnosis and therapeutics. Low overall survival (OS) rates have been reported, mostly associated with patients' advanced stage and older age. Intratumoral heterogeneity versus homogeneity of malignant epithelial cells seems to be an important factor to consider for the development of combination therapies with curative intention. OBJECTIVE: In this preliminary study, we aim to provide valuable insight into the distinct clinicopathologic features of male BC. MATERIAL AND METHODS: In a series of 40 male BC patients, we evaluated by immunohistochemistry androgen receptor; activating transcription factor 3 (ATF3); p16; cyclin D1; fatty acid synthase (FASN); fatty acid transport protein 1 (FATP1); ß1, ß3, ß4, and ß6 integrins; collagen I and collagen IV; and their interactions. Kaplan-Meier survival curves and log-rank tests were assessed for statistical analysis. RESULTS: Homogeneous epithelial staining of p16, ATF3, ß6 integrin, FASN, and FATP1 was found to be significantly intercorrelated, and associated with high Ki67. These markers also stained tumor stromal fibroblasts. The prognostic analysis showed statistically significant associations of FASN with disease-free survival (DFS) and OS, as well as of ATF3 with OS and collagen IV with DFS. CONCLUSIONS: This study highlights, as a novel finding, the relevance of FASN, ATF3, and collagen IV immunophenotypes, which may have innovative application in the clinical management of male BC.

13.
Stat Methods Med Res ; 30(3): 643-654, 2021 03.
Article in English | MEDLINE | ID: mdl-33146585

ABSTRACT

We consider random changepoint segmented regression models to analyse data from a study conducted to verify whether treatment with stem cells may delay the onset of a symptom of amyotrophic lateral sclerosis in genetically modified mice. The proposed models capture the biological aspects of the data, accommodating a smooth transition between the periods with and without symptoms. An additional changepoint is considered to avoid negative predicted responses. Given the nonlinear nature of the model, we propose an algorithm to estimate the fixed parameters and to predict the random effects by fitting linear mixed models iteratively via standard software. We compare the variances obtained in the final step with bootstrapped and robust ones.


Subject(s)
Algorithms , Software , Animals , Linear Models , Mice
14.
Soc Sci Med ; 265: 113411, 2020 11.
Article in English | MEDLINE | ID: mdl-33045652

ABSTRACT

Different authors have identified geographic variations in the rates of suicide. This study aims to discuss the limitations of the officially recorded suicide data and to evaluate the statistical relationship between a biometeorological index, Apparent Temperature (AT), and suicide in Madrid and Lisbon. We performed a time-series study. The association was analyzed using a quasi-Poisson regression model. To assess potential delayed and non-linear effects of AT on suicides, a lag non-linear model was fitted in a generalized additive model. There was an average rate of 3.30 suicides/100,000 inhabitants in Madrid and of 7.92 suicides/100,000 inhabitants in Lisbon, and a downward trend was found throughout the period. In Madrid, there is no statistically significant association between AT and suicide. However, in Lisbon, under higher AT, there was a higher risk of suicide. The highest accumulated statistically significant Relative Risk (RR) of suicide was detected at 7 days after the exposure, when at 38 °C, the risk of suicide is 2.7 times that existing at the median AT, 20.62°. The average mortality rate recorded in Lisbon was 41.6% higher than that registered in Madrid. However, the limitations of suicide record databases in Spain and Portugal have to be taken into account when analyzing incidence and especially when comparing data from different countries. It is necessary to improve the filing systems of violent deaths in order to perform reliable epidemiological studies.


Subject(s)
Suicide , Cities/epidemiology , Humans , Portugal/epidemiology , Spain/epidemiology , Temperature
15.
J Inorg Biochem ; 205: 111002, 2020 04.
Article in English | MEDLINE | ID: mdl-32007697

ABSTRACT

Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania, which has very limited treatment options and affects poor and underdeveloped populations. The current treatment is plagued by many complications, such as high toxicity, high cost and resistance to parasites; therefore, novel therapeutic agents are urgently needed. Herein, the synthesis, characterization and in vitro leishmanicidal potential of new complexes with the general formula [RuCl3(TMP)(dppb)] (1), [PtCl(TMP)(PPh3)2]PF6 (2) and [Cu(CH3COO)2(TMP)2]·DMF (3) (dppb = 1,4-bis(diphenylphosphino)butane, PPH3 = triphenylphosphine and TMP = trimethoprim) were evaluated. The complexes were characterized by infrared, UV-vis, cyclic voltammetry, molar conductance measurements, elemental analysis and NMR experiments. Also, the geometry of (2) and (3) were determined by single crystal X-ray diffraction. Despite being less potent against promastigote L. amazonensis proliferation than amphotericin B reference drug (IC50 = 0.09 ± 0.02 µM), complex (2) (IC50 = 3.6 ± 1.5 µM) was several times less cytotoxic (CC50 = 17.8 µM, SI = 4.9) in comparison with amphotericin B (CC50 = 3.3 µM, SI = 36.6) and gentian violet control (CC50 = 0.8 µM). Additionally, complex (2) inhibited J774 macrophage infection and amastigote number by macrophages (IC50 = 6.6 and SI = 2.7). Outstandingly, complex (2) was shown to be a promising candidate for a new leishmanicidal therapeutic agent, considering its biological power combined with low toxicity.


Subject(s)
Antiprotozoal Agents , Coordination Complexes , Copper , Leishmania/growth & development , Leishmaniasis/drug therapy , Platinum , Rubidium , Trimethoprim , Animals , Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacology , Cell Line , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Copper/chemistry , Copper/pharmacology , Crystallography, X-Ray , Leishmaniasis/metabolism , Leishmaniasis/pathology , Mice , Molecular Structure , Platinum/chemistry , Platinum/pharmacology , Rubidium/chemistry , Rubidium/pharmacology , Trimethoprim/chemistry , Trimethoprim/pharmacology
16.
Pathobiology ; 76(5): 235-42, 2009.
Article in English | MEDLINE | ID: mdl-19816083

ABSTRACT

OBJECTIVE: To investigate the biological role of BCL-6 oncoprotein in breast cancer disease progression (recurrence and metastasis). METHODS: The series consisted of 93 consecutive female patients with primary breast cancer and median follow-up of 10 years. BCL-6 expression was assessed in vivo by immunohistochemistry and real-time PCR. Breast cancer cell lines and some metastasis-related genes (CXCR4, Itgbeta-3 and FLT-1) were also analysed by molecular techniques. Prognostic evaluation was performed by fitting a multivariate Cox regression model. RESULTS: BCL-6 immunoexpression was positive in 22 (23.7%) tumours and negative in 71 (76.3%). All axillary lymph node metastases of 47 node-positive patients were negative, including 12 cases showing BCL-6-positive primary tumours. Likewise, in 9 recurrence cases, BCL-6 expression was similar or decreased compared with primary tumours. No correlation between immunoexpression and gene expression of BCL-6 was observed. BCL-6 was significantly reduced both in derived metastases of a breast cancer cell line (M435) and when the latter was treated with a demethylation agent (5-azacytidine). However, BCL-6-transfected breast cancer cell lines expressed significantly higher levels of CXCR4, Itgbeta-3 and FLT-1. Co-expression of the 4 genes was found in 4 of 17 tumours evaluated, but lacking prognostic significance. BCL-6 oncoprotein revealed no significant influence on outcome. CONCLUSION: The results strongly suggest the loss of BCL-6 expression in breast cancer progression, which might be related with methylation status alterations of still unknown partner gene(s).


Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , DNA-Binding Proteins/biosynthesis , Adult , Aged , Aged, 80 and over , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/pathology , Cell Line, Tumor , DNA Methylation , DNA-Binding Proteins/genetics , Disease Progression , Female , Flow Cytometry , Gene Expression , Humans , Immunohistochemistry , Integrin beta3/biosynthesis , Integrin beta3/genetics , Lymphatic Metastasis/genetics , Lymphatic Metastasis/pathology , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Prognosis , Proto-Oncogene Proteins c-bcl-6 , Receptors, CXCR4/biosynthesis , Receptors, CXCR4/genetics , Reverse Transcriptase Polymerase Chain Reaction , Transfection , Vascular Endothelial Growth Factor Receptor-1/biosynthesis , Vascular Endothelial Growth Factor Receptor-1/genetics
17.
Sci Total Environ ; 647: 127-133, 2019 Jan 10.
Article in English | MEDLINE | ID: mdl-30077842

ABSTRACT

BACKGROUND: Individuals with mental disorders are often susceptible to the effects of extreme ambient temperatures. The aim of this study is to assess the short-term impacts of daily mean temperature on hospitalizations for mental disorders in the Lisbon Metropolitan Area, Portugal. METHODS: To assess the short-term impacts of daily mean temperature on hospitalizations for mental disorders (2008-2014), a quasi-Poisson generalized additive model combined with a distributed lag non-linear model was applied. The model was adjusted for day of the week, air pollution, relative humidity, time and seasonality. RESULTS: The number of hospital admissions for mental disorder during the study period was 30,139. Hospital admissions increase significantly with high temperatures on day of exposure, at lag 0-1 and at lag 0-2. Women are more vulnerable than men, and there was no difference between the age groups studied. CONCLUSIONS: The exposure to high temperatures should be considered a significant risk factor for mental disorders; therefore, patient management services may need to be strengthened when extreme high temperature alerts are given.


Subject(s)
Environmental Exposure/statistics & numerical data , Mental Disorders/epidemiology , Temperature , Air Pollutants , Air Pollution , Female , Hospitalization , Humans , Male , Portugal
18.
Esc. Anna Nery Rev. Enferm ; 28: e20220419, 2024. tab, graf
Article in Portuguese | LILACS, BDENF - nursing (Brazil) | ID: biblio-1534451

ABSTRACT

Resumo Introdução O câncer tem impacto na vida das crianças e seus familiares. As Histórias em Quadrinhos podem ser uma estratégia de fortalecer o vínculo e a comunicação entre profissional/paciente/família. Objetivo Desenvolver e validar um material instrucional/educativo, no formato de Histórias em Quadrinhos, voltada para crianças hospitalizadas com leucemia linfóide aguda. Metodologia Estudo metodológico desenvolvido em nove etapas: elaboração do projeto de pesquisa; definição e seleção do conteúdo; adaptação da linguagem; inclusão de ilustrações; construção de um material piloto; validação do material; layout; impressão final e disponibilização. A validação ocorreu com 10 especialistas entre março e maio de 2022, utilizando-se o Instrumento de Validação de Conteúdo Educativo em Saúde. Resultados Foram elaboradas 5 Histórias em Quadrinhos, com 6 personagens principais, sendo necessárias 63 horas de trabalho. Elas foram divididas por temáticas (distúrbios gastrointestinais; cistite hemorrágica; problemas relacionados a autoestima e autoimagem; risco de infecção e dor óssea) que obtiveram Índice de Validade de Conteúdo global satisfatório entre 0,78 e 0,87. Conclusões e implicações para a prática As histórias em quadrinhos podem ser utilizadas como fonte atrativa e confiável de informações sobre a doença, servindo como apoio às informações durante a internação hospitalar e o preparo para alta.


Resumen Introducción El cáncer tiene un impacto en la vida de los niños y sus familias. Los cómics pueden ser una estrategia para fortalecer el vínculo y la comunicación entre profesional/paciente/familia. Objetivo Desarrollar y validar un material didáctico/educativo, en formato de Historietas, dirigido a niños hospitalizados con leucemia linfocítica aguda. Metodología Estudio metodológico desarrollado en nueve etapas: elaboración del proyecto de investigación; definición y selección de contenidos; adaptación lingüística; inclusión de ilustraciones; construcción de un material piloto; validación del material; disposición; impresión final y disponibilidad. La validación se realizó con 10 especialistas entre marzo y mayo de 2022, utilizando el Instrumento de Validación de Contenido de Educación en Salud. Resultados Se crearon 5 Comics, con 6 personajes principales, requiriendo 63 horas de trabajo. Fueron divididos por temas (trastornos gastrointestinales; cistitis hemorrágica; problemas relacionados con la autoestima y la autoimagen; riesgo de infección y dolor óseo) que obtuvieron un Índice de Validez de Contenido global satisfactorio entre 0,78 y 0,87. Conclusiones e implicaciones para la práctica Los cómics pueden ser utilizados como una fuente atractiva y confiable de información sobre la enfermedad, apoyando información durante la hospitalización y preparación para el alta.


Abstract Introduction Cancer has an impact on the lives of children and their families. Comics can be a strategy to strengthen the bond and communication between professional/patient/family. Objective To develop and validate an instructional/educational material, in the format of Comics, aimed at children hospitalized with acute lymphocytic leukemia. Methodology Methodological study developed in nine stages: preparation of the research project; content definition and selection; language adaptation; inclusion of illustrations; construction of a pilot material; validation of the material; layout; final printing and availability. Validation took place with 10 specialists between March and May 2022, using the Health Education Content Validation Instrument. Results 5 Comics were created, with 6 main characters, requiring 63 hours of work. They were divided by themes (gastrointestinal disorders; hemorrhagic cystitis; problems related to self-esteem and self-image; risk of infection and bone pain) that obtained a satisfactory global Content Validity Index between 0.78 and 0.87. Conclusions and implications for practice Comics can be used as an attractive and reliable source of information about the disease, supporting information during hospitalization and preparation for discharge.


Subject(s)
Humans , Male , Female , Child , Adult , Middle Aged , Child Health , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Graphic Novels as Topic , Play and Playthings , Nausea
19.
Mol Clin Oncol ; 10(6): 644-654, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31031981

ABSTRACT

Male breast cancer (BC) represents an individual subtype of BC, with therapeutic procedures based on female BC therapy results. The present study evaluated the parameters currently used for the characterization and therapy of male BC, and their association with disease-free (DFS) and overall survival (OS), aiming to obtain a comprehensive basis to improve the personalized care of male BC. A total of 196 patients from March 1970 to March 2018 (mean follow-up, 84.9 months) were profiled, using clinicopathological review, molecular assessment [BRCA1/2, DNA repair associated (BRCA1/2) status, immunohistochemistry, fluorescence in situ hybridization and DNA flow cytometry] and Cox regression statistical analysis. The median age of patients was 66.5 years. At presentation, 39.2% of patients with invasive carcinomas were in anatomic stage (AS) I. Patients exhibited primarily invasive carcinomas of no special type, histological grade 2, estrogen receptor α-(ERα) and progesterone receptor (PR)-positive, receptor tyrosine kinase erbB-2-negative, high Ki-67, Luminal B-like and aneuploid tumors. A total of 13 of the 44 (29.5%) BRCA-evaluated patients exhibited BRCA2 mutations, significantly associated with family history (FH), bilaterality, high Ki-67 expression, absence of PR and Luminal B-like tumors. Bilaterality was associated with the occurrence of non-breast primary neoplasms (NBPN). The 5 and 10-year DFS rates, excluding patients with distant metastasis, NBPN and in situ carcinomas (n=145) were 65.9 and 58.2%, respectively, and the 5 and 10-year OS rates were 77.5 and 59.2%, respectively. In the univariate analysis, Luminal B-like subtype, BRCA2 mutations, high Ki-67 expression, and AS II and III were significantly associated with shorter DFS and OS. In addition, age >70 years was associated with low OS. In the multivariate analysis, FH, AS II and III, and Luminal B-like subtypes were associated with poorer OS. In conclusion, the data from the present study emphasize the high incidence of BRCA2 mutation in male BC, and its association with FH, bilaterality, high Ki-67 expression, negative PR expression and Luminal B-like subtypes, and with shorter DFS and OS in univariate analysis.

20.
Oncol Rep ; 20(4): 913-9, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18813835

ABSTRACT

This study aimed to investigate the prognostic influence of DNA flow cytometry and RAS gene mutations in patients with poorly differentiated (PDTC) and anaplastic thyroid carcinoma (ATC). The series consisted of 26 patients with PDTC and ATC, and a median follow-up of 10 months (range 1-138). DNA ploidy and S-phase fraction (SPF) were assessed by flow cytometry on frozen samples. RAS point mutations were detected using PCR techniques. Disease staging and tumour angioinvasion were included as prognostic parameters for survival analysis. Nineteen patients (73.1%) succumbed to the disease (median time 5 months; range 1-45). Eighteen tumours (69.2%) were classified as DNA aneuploid. Median SPF was 5.6% (range 1.9-23.1), which was used as a cut-off value to distinguish between low versus high cell proliferation. Three of 20 (15%) patients presented N-RAS gene mutations in codon 61. DNA aneuploidy was most frequently found in female patients (p=0.034). Kaplan-Meier and Cox regression analyses showed that only DNA aneuploidy (p=0.044 and p=0.055, respectively) and high SPF (p=0.001 and p=0.006, respectively) significantly correlated with worse survival. The results indicate that aneuploidy and high SPF are biomarkers of poor clinical outcome in PDTC and ATC, which may provide useful prognostic information with a potentially therapeutic impact in patient management.


Subject(s)
Aneuploidy , Carcinoma/mortality , S Phase , Thyroid Neoplasms/mortality , Adult , Aged , Biomarkers , Biomarkers, Tumor , Carcinoma/genetics , Carcinoma/pathology , Female , Flow Cytometry , Genes, ras , Humans , Male , Middle Aged , Mutation , Prognosis , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology
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