A new class of survival regression models with heavy-tailed errors: robustness and diagnostics

Birnbaum-Saunders models have largely been applied in material fatigue studies and reliability analyses to relate the total time until failure with some type of cumulative damage. In many problems related to the medical field, such as chronic cardiac diseases and different types of cancer, a cumulative damage caused by several risk factors might cause some degradation that leads to a fatigue process. In these cases, BS models can be suitable for describing the propagation lifetime. However, since the cumulative damage is assumed to be normally distributed in the BS distribution, the parameter estimates from this model can be sensitive to outlying observations. In order to attenuate this influence, we present in this paper BS models, in which a Student-t distribution is assumed to explain the cumulative damage. In particular, we show that the maximum likelihood estimates of the Student-t log-BS models attribute smaller weights to outlying observations, which produce robust parameter estimates. Also, some inferential results are presented. In addition, based on local influence and deviance component and martingale-type residuals, a diagnostics analysis is derived. Finally, a motivating example from the medical field is analyzed using log-BS regression models. Since the parameter estimates appear to be very sensitive to outlying and influential observations, the Student-t log-BS regression model should attenuate such influences. The model checking methodologies developed in this paper are used to compare the fitted models.

Ultrasensitive Simultaneous Quantification of 1,N(2)-Etheno-2 `-deoxyguanosine and 1,N(2-)Propano-2 `-deoxyguanosine in DNA by an Online Liquid Chromatography-Electrospray Tandem Mass Spectrometry Assay

Exocyclic DNA adducts produced by exogenous and endogenous compounds are emerging as potential tools to study a variety of human diseases and air pollution exposure. A highly sensitive method involving online reverse-phase high performance liquid chromatography with electrospray tandem mass spectrometry detection in the multiple reaction monitoring mode and employing stable isotope-labeled internal standards was developed for the simultaneous quantification of 1,N(2)-etheno-2`-deoxyguanosine (1,N(2)-epsilon dGuo) and 1,N(2)-propano-2`-deoxyguanosine (1,N(2)-propanodGuo) in DNA. This methodology permits direct online quantification of 2`-deoxyguanosine and ca. 500 amol of adducts in 100 mu g of hydrolyzed DNA M the same analysis. Using the newly developed technique, accurate determinations of 1,N(2)-etheno-2`-deoxyguanosine and 1,N2-propano-2`-deoxyguanosine levels in DNA extracts of human cultured cells (4.01 +/- 0.32 1,N(2)-epsilon dGuo/10(8) dGuo and 3.43 +/- 0.33 1,N(2)-propanodGuo/10(8) dGuo) and rat tissue (liver, 2.47 +/- 0.61 1,N(2)-epsilon dGuo/10(8) dGuo and 4.61 +/- 0.69 1,N(2)-propanodGuo/108 dGuo; brain, 2.96 +/- 1.43,N(2)-epsilon dGuo/10(8) dGuo and 5.66 +/- 3.70 1,N(2)-propanoclGuo/10(8) dGuo; and lung, 0,87 +/- 0.34 1,N(2)-edGuo/ 10(8) dGuo and 2.25 +/- 1.72 1,N(2)-propanodGuo/10(8) dGuo) were performed. The method described herein can be used to study the biological significance of exocyclic DNA adducts through the quantification of different adducts in humans and experimental an with pathological conditions and after air pollution exposure.

Determination of lipophilic and hydrophilic antioxidants in Solanum Lycopersicum L. tomato from Gordal variety by LL-USAE combined with UHPLC-PDA/FLR

Tomato (Lycopersicon esculentum L.) is one of the main constituents of the Mediterranean diet. Its consumption has been proposed to reduce the risk of cardiovascular diseases and certain types of cancer. It is therefore one of the most popular and extensively consumed vegetable crop worldwide. To gain insights on the potential of Lycopersicon esculentum L. as bioactive food, two analytical methodologies were developed to determine the levels of the lipophilic -tocopherol, α-tocopherol, β-carotene, lycopene; and hydrophilic antioxidants ascorbic acid. The quantification of total carotenoids (β-carotene and lycopene) was assessed through a liquid–liquid ultrasound assisted extraction (LL-USAE) in combination with ultraviolet-visible spectroscopy (UV-Vis), according to method of mean, for total carotenoids (λmáx = 450 nm. The ultra-high performance liquid chromatographic using both photodiode array and fluorescence detection (UHPLC-PDA/FLR), allows the identification and quantification of the target lipophilic and hydrophilic antioxidants. This methodology UHPLC-PDA/FLR is fast, simple and revealed a high sensitivity for the compounds under study. The limits of detection (LODs) and quantification (LOQs) obtained were much lower (about 10 times) than the reported in literature. The method LL-USAE/UV-Vis was validated and applied to different tomato foodstuffs. The results reveal a small increase of carotenoids content during maturation, reaching the maximum level when ripe. These results complement those obtained by the ORAC and TBARS assays that show an increase of antioxidant capacity during maturation. The LODs ans LOQs obtained were also about 10 times lower than reported in literature. The carotenoid content was also evaluated by LL-USAE/UV-Vis in different tomatoes varieties. Regional variety present the high carotenoid level, followed by campari and gordal, and at last grape. This methodology was also applied to different processed food samples containing tomatoes derivatives. Highest carotenoids content were obtained in concentrated tomato foodstuffs.

PEGylated polyethyleneimine-entrapped gold nanoparticles for enhanced and targeted gene delivery applications

Gene therapy, which involves the transfer of nucleic acid into target cells in patients, has become one of the most important and widely explored strategies to treat a variety of diseases, such as cancer, infectious diseases and genetic disorders. Relative to viral vectors that have high immunogenicity, toxicity and oncogenicity, non-viral vectors have gained a lot of interest in recent years. This is largely due to their ability to mimic viral vector features including the capacity to overcome extra- and intra-cellular barriers and to enhance transfection efficiency. Polyethyleneimine (PEI) has been extensively investigated as a non-viral vector. This cationic polymer, which is able to compact nucleic acid through electrostatic interactions and to transport it across the negatively charged cell membranes, has been shown to effectively transfect nucleic acid into different cell lines. Moreover, entrapment of gold nanoparticles (Au NPs) into such an amine-terminated polymer template has been shown to significantly enhance gene transfection efficiency. In this work, a novel non-viral nucleic acid vector system for enhanced and targeted nucleic acid delivery applications was developed. The system was based on the functionalization of PEI with folic acid (FA; for targeted delivery to cancer cells overexpressing FA receptors on their surface) using polyethylene glycol (PEG) as a linker molecule. This was followed by the preparation of PEI-entrapped Au NPs (Au PENPs; for enhancement of transfection efficiency). In the synthesis process, the primary amines of PEI were first partially modified with fluorescein isothiocyanate (FI) using a molar ratio of 1:7. The formed PEI-FI conjugate was then further modified with either PEG or PEGylated FA using a molar ratio of 1:1. This process was finally followed by entrapment of Au NPs into the modified polymers. The resulting conjugates and Au PENPs were characterized by several techniques, namely Nuclear Magnetic Resonance, Dynamic Light Scattering and Ultraviolet-Visible Spectroscopy, to assess their physicochemical properties. In the cell biology studies, the synthesized conjugates and their respective Au PENPs were shown to be non-toxic towards A2780 human ovarian carcinoma cells. The role of these materials as gene delivery agents was lastly evaluated. In the gene delivery studies, the A2780 cells were successfully transfected with plasmid DNA using the different vector systems. However, FA-modification and Au NPs entrapment were not determinant factors for improved transfection efficiency. In the gene silencing studies, on the other hand, the Au PENPs were shown to effectively deliver small interfering RNA, thereby reducing the expression of the B-cell lymphoma 2 protein. Based on these results, we can say that the systems synthesized in this work show potential for enhanced and targeted gene therapy applications.

The effectiveness of community-based interventions to improve maternal and infant health in the Northeast of Brazil

EMOND, Alan et al. The effectiveness of community-based interventions to improve maternal and infant health in the Northeast of Brazil. Revista Panamericana de Salud Pública/ Pan American Journal of Public Health , v.12, n.2, p.101-110, 2002

Dinâmica populacional de ovos e lagartas e parasitismo de ovos de Curuquerê-do-algodoeiro por Trichogramma pretiosum em cultivares convencionais e transgênica de algodoeiro

The introduction of new cotton cultivars in the Midwest region of Brazil resulted in a significant increase in productivity, but the use of inappropriate farming techniques brought many problems to field, as the higher incidence of pests, diseases and weeds. The aim of this work was to study the population dynamics of eggs and larvae of cotton leafworm and natural egg parasitism of the pest by Trichogramma pretiosum Riley (Hymenoptera: Trichogrammatidae) at different phenological stages of conventional and transgenic cultivars (Bollgard I) of cotton was carried out this experiment from December 2007 to April 2008 in Ipameri, Goias State, Brazil. The experimental design was a randomized blocks with five trataments and four replications. The treatments consisting of the conventional cotton cultivars DeltaOPAL, FMX 966, FMX 993, FMX 910 and the cultivar transgenic NuOPAL. Allabama argillacea Hubner (Lepidoptera: Noctuidae) oviposited on all cultivars, not presented differences in relation to oviposition preference. Compared to the average number of eggs of A. argillacea parasitized by T. pretiosum, there were no differences between cultivars. In conventional cultivars, small, medium and large larvae occurred from 34 days after plant emergence until the end of the cycle, while in the transgenic cultivar were found only small caterpillars. Cultivar NuOPAL control cotton leafworm since the first larval stage, and does not interfere in egg parasitism by T. pretiosum compared with other cultivars.

Association between MUC1 gene polymorphism and expected progeny differences in Nelore cattle (Bos primigenius indicus)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efficiency of intermittent exercise on adiposity and fatty liver in rats fed with high-fat diet

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genotoxicity of polar and apolar extracts obtained from Qualea multiflora and Qualea grandiflora

Ethnopharmacological relevance: The species Qualea grandiflora and Qualea multiflora, which belong to the Vochysiaceae family, are common in the Brazilian savannah (Cerrado biome), and the local inhabitants use these species to treat external ulcers and gastric diseases and as an anti-inflammatory agent. Studies have demonstrated that these plants contain compounds that exhibit pharmacological activities; however, the risks associated with their consumption are not known.Material and methods: In the present study, the mutagenicity of polar and apolar extracts from Qualea grandiflora and Qualea multiflora were assessed by employing the Ames assay with and without metabolic activation. Additionally, phytochemical analyses (HPLC-ESI-IT-MS, HPLC-UV-PDA and GC-IT-MS) were performed to identify the chemical constituents present in these species, including the evaluation of physico-chemical properties, such as polarity or apolarity of the organic compounds, which are related to each fraction obtained. These studies provide important information regarding the biochemical behaviour of these compounds.Results: All extracts exhibited mutagenicity, inducing frameshift mutations and base substitutions in DNA. Phytochemical analysis identified terpenes, ellagic acid derivatives and phytosteroids.Conclusions: The mutagenicity observed might be due to the presence of pentacyclic triterpenes and polyphenols, which are able to generate reactive oxygen species (ROS) and result in the potential to cause DNA damage. The genetic risk identified in this present work shows that special attention should be considered for the use of compounds obtained from these plant species in medicinal treatments. Further studies must be conducted to identify safe therapeutic doses. (C) 2011 Elsevier B.V. All rights reserved.

Relationship among oxidative DNA damage, gastric mucosal density and the relevance of cagA, vacA and iceA genotypes of Helicobacter pylori

The aim of this study was to evaluate the relationship among oxidative DNA damage, density of Helicobacter pylori and the relevance of cagA, vacA and iceA genotypes of H. pylori. Gastric epithelial cells were isolated from 24 uninfected patients, 42 H. pylori infected patients with gastritis, and 61 patients with gastric cancer. Oxidative DNA damage was analyzed by the Comet assay, the density of H. pylori was measured by real-time polymerase chain reaction (PCR), and allelic variants of cagA, vacA and iceA were identified using the PCR. Infected patients by Helicobacter pylori cagA(+), vacAs1 m1 and iceA1 genotype showed higher levels of oxidative DNA damage than infected patients with H. pylori cagA(-), vacAs2 m2 and iceA2 genotypes and uninfected patients. Density of H. pylori did not influence oxidative DNA damage. Our results indicate that H. pylori genotype is more relevant than density for oxidative DNA damage.

Effects of Helicobacter pylori Infection on the Expressions of Bax and Bcl-2 in Patients with Chronic Gastritis and Gastric Cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country

Myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED). We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome). Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

Acquired hepatocerebral degeneration and hepatic encephalopathy: correlations and variety of clinical presentations in overt and subclinical liver disease

A degeneração hepatocerebral adquirida (AHD) e a degeneração hepatolenticular podem ter apresentações clínicas semelhantes, mas quando uma doença hepática crônica e achados motores atípicos coexistem, a distinção entre AHD e encefalopatia hepática (HE) pode ser ainda mais complicada. Descrevemos três casos de AHD (dois tendo HE) com diferentes achados em neuroimagem, doenças hepáticas distintas e apresentações motoras semelhantes, todos com hipertensão arterial e perda de peso antes das manifestações motoras. O diagnóstico e a fisiopatologia são comentados e comparados com relatos prévios. Concluímos que existem muitas correlações entre HE, degeneração hepatolenticular e AHD, mas a sobreposição de HE e AHD pode ser mais comum dependendo do conhecimento clínico e da acurácia dos critérios diagnósticos adotados para cada enfermidade. Como a AHD não é considerada prioridade na lista de transplante hepático, o prognóstico dos pacientes com AHD permanece ruim, e a interrupção do fluxo nos shunts portossistêmicos deve ser sempre considerada.

Occurrence of pneumocystis pneumonia in HIV-infected patients and the interference of the highly active antiretroviral therapy

From the beginning of the AIDS epidemic, pneumocystis pneumonia ( PCP) has been distinguished as one of the most frequent opportunistic diseases with high morbid-mortality. As from 1996, the advent of the highly active antiretroviral therapy ( HAART) has changed the characteristics of such epidemic by reducing its related diseases and, as a result, AIDS-related mortality. With the purpose to estimate PCP occurrence and HAART interference, 376 HIV-infected or AIDS patients were studied from January 1992 to December 2002. Among them, 58 ( 15.5%) PCP cases were found. There was a higher occurrence of PCP in the group of patients in which HAART was not used, with 40 ( 69.0%) of the episodes. As regards the studied period, a tendency to a linear reduction in annual PCP incidence was observed. The mean of T CD4+ lymphocytes in the patients with PCP ( 117 cells/mm(3)) was significantly lower when compared to that of the other individuals ( 325 cells/mm(3)). Therefore, this study suggests a temporal reduction in PCP occurrence related to HAART use with higher T CD4+ lymphocyte counts. Nevertheless, this opportunistic infection still shows significant incidence in AIDS patients. ( NCT00516581).

Clinical presentation and salivary gland histopathology of paediatric primary Sjogren's syndrome

ObjectiveExplore the presentation, diagnostic criteria and exocrine gland histopathology of paediatric primary Sjogren's syndrome (PPSjS).MethodsA case series of 8 children is reported and American-European Consensus Group (AECG-2002) criteria were examined, as well as minor labial salivary and lachrymal gland biopsies, which were scored by a pathologist blinded to outcome. For all cases, connective tissue diseases and parotid-related infectious disease were excluded.ResultsAge at onset varied from 5-13 years old; 6 were females, all followed from diagnosis up to the last visit (1-10 years). The main features at presentation were recurrent tender parotid swelling and sialectasis imaging, with decreased salivary function assessed by Tc-99 scintigraphy. Mild sicca symptoms were observed in 4/8 cases. Systemic features, including fatigue, myalgia, arthritis, tenosynovitis, joint contractures, transient Raynaud's and high ESR, were recorded at onset. Autoantibody profile was unremarkable for diagnosis, while lymphocytic infiltration of labial salivary glands and sialectasis were observed in all biopsies (8/8). In lachrymal glands, massive lymphocytic infiltration and lymphocytic gastritis were observed during complementary assessment. Flares were treated with low dose steroids and long-term use of hydroxychloroquine (5/8), although only 318 fulfilled AECG-2002 diagnostic criteria, throughout the disease course.ConclusionPPSjS is rare, slowly progressive and its early presentation is variable. Standardised diagnostic algorithms should include recurrent parotid swelling and early diagnosis should rely mostly on salivary and lachrymal gland histopathology in this age group.