Variance-Preserving Estimation of Intensity Values Obtained From Omics Experiments.

Faced with the lack of reliability and reproducibility in omics studies, more careful and robust methods are needed to overcome the existing challenges in the multi-omics analysis. In conventional omics data analysis, signal intensity values (denoted by M and values) are estimated neglecting pixel-level uncertainties, which may reflect noise and systematic artifacts. For example, intensity values from two-color microarray data are estimated by taking the mean or median of the pixel intensities within the spot and then subjected to a within-slide normalization by LOWESS. Thus, focusing on estimation and normalization of gene expression profiles, we propose a spot quantification method that takes into account pixel-level variability. Also, to preserve relevant variation that may be removed in LOWESS normalization with poorly chosen parameters, we propose a parameter selection method that is parsimonious and considers intrinsic characteristics of microarray data, such as heteroskedasticity. The usefulness of the proposed methods is illustrated by an application to real intestinal metaplasia data. Compared with the conventional approaches, the analysis is more robust and conservative, identifying fewer but more reliable differentially expressed genes. Also, the variability preservation allowed the identification of new differentially expressed genes. Using the proposed approach, we have identified differentially expressed genes involved in pathways in cancer and confirmed some molecular markers already reported in the literature.

Heritability and Sex-Specific Genetic Effects of Self-Reported Physical Activity in a Brazilian Highly Admixed Population.

INTRODUCTION: The engagement in sports or habitual physical activity (PA) has shown an extensive protective role against multiple diseases such as cancer, obesity, and many others. Additionally, PA has also a significant impact on life quality, since it aids with managing stress, preserving cognitive function and memory, and preventing fractures in the elderly. OBJECTIVE: Considering there has been multiple evidence showing that genetic variation underpins variation of PA-related traits, we aimed to estimate the heritability (h2) of these phenotypes in a sample from the Brazilian population and assess whether males and females differ in relation to those estimates. METHODS: 2,027 participants from a highly admixed population from Baependi, MG, Brazil, had information regarding their PA and sedentary behavior (SB) phenotypes collected through a questionnaire (IPAQ-SF). After data cleaning and transformation procedures, we obtained four variables to be evaluated: total PA (TPA MET), walking time, (WK MET), moderate-vigorous PA (MVPA MET), and SB. A model selection procedure was performed using a single-step covariate inclusion approach. We tested for BMI, waist, hip and neck circumferences, smoking, and depression separately, and performed correlation tests among covariates. Linear mixed models, selection procedure, and the variance components approach to estimate h2 were implemented using SOLAR-Eclipse 8.3.1. RESULTS: We obtained estimates of 0.221, 0.109, 0.226, and 0 for TPA MET, WK MET, MVPA MET, and SB, respectively. We found evidence for gene-sex interactions, with males having higher sex-specific heritabilities than females for TPA MET and MVPA MET. In addition, we found higher estimates of the genetic variance component in males than females for most phenotypes. DISCUSSION/CONCLUSION: The heritability estimates presented in this work show a moderate heritable set of genetic factors affecting PA in a sample from the Brazilian population. The evaluation of the genetic variance component suggests segregating genetic factors in male individuals are more heterogeneous, which can explain why men globally tend to need to practice more intense PA than women to achieve similar health benefits. Hence, these findings have significant implications for the understanding of the genetic architecture of PA and might aid to promote health in the future.

Assessing functional status after intensive care unit stay: the Barthel Index and the Katz Index.

OBJECTIVE: To assess the functional status of post-ICU patients using the Barthel Index (BI) and the Katz Index (KI) and to assess which is more suitable for this population. DESIGN: Retrospective longitudinal study. SETTING: Public tertiary hospital in São Paulo (Brazil). PARTICIPANTS: Patients aged ≥18 years old, admitted to ICU, who were treated with mechanical ventilation (MV) ≥ 24 h and were discharged to ward. EXCLUSION CRITERIA: Inability to answer the BI and the KI; limiting neurological or orthopaedic conditions; ICU stay ≥90 days. Patients transferred to or from other hospitals or who died in the wards were not analysed. INTERVENTION: BI and KI were scored pre-ICU and post-ICU and the variation was calculated. MAIN OUTCOME MEASURES: BI and KI scores were compared using analysis based on item response theory (IRT), using degree of difficulty and discriminating items as parameters. RESULTS: Median age was 52 years old, median APACHE II score was 15. Median ICU stay was 11 days and median MV duration was 4 days. BI variation was 44% and KI variation was 55%. In IRT analysis, BI considered a larger number of items with different levels of difficulty. CONCLUSION: Both the BI and the KI revealed significant deterioration of functional status after ICU discharge. The IRT analysis suggested that the Barthel Index might be a better scale than the Katz Index for the assessment of functional status of patients discharged from ICU, since it presented better discrimination of the ability to carry out the tasks.

Degradação dos materiais restauradores utilizados em lesões cervicais não cariosas / Degradation of the restorative materials used in non-carious cervical lesions

OBJETIVO: Avaliar o efeito de bebidas ácidas e da escovação em materiais utilizados em lesões cervicais não cariosas. MÉTODOS: Três resinas compostas, um compômero e um cimento de ionômero resino-modificado foram testados. Para cada material, cinco espécimes foram imersos em uma das soluções teste (suco de laranja, coca-cola, uísque ou água destilada) por 10 dias a 37ºC. Em seguida, os espécimes foram submetidos à escovação (20000 ciclos, 200g de carga). O peso e a rugosidade superficial foram avaliados antes e após a imersão nas soluções e escovação. Os dados foram analisados pela ANOVA/Teste Tukey (p<0,05). RESULTADOS: As imersões em suco de laranja e coca-cola seguida de escovação causaram significativamente maior perda de peso para o compômero e cimento de ionômero de vidro resino-modificado comparado às resinas compostas. O maior aumento de rugosidade superficial foi observado no cimento de ionômero de vidro resino-modificado após imersão em suco de laranja seguida de escovação. CONCLUSÃO: A imersão em bebidas ácidas seguida de escovação causou degradação nos materiais restauradores avaliados, com perda de material e aumento na rugosidade superficial.

OBJECTIVE: Evaluate the effect of acidic beverages and brushing on the restorative materials used in non-carious cervical lesions. METHODS: Three composite resins, one compomer and one resin-modified glass ionomer were tested. Five specimens of each material were immersed in each of the test solutions (orange juice, Coca-Cola, whisky and distilled water) for a 10-day period at 37ºC. Next, the specimens were brushed (20000 cycles with a load of 200g). Weight and surface roughness were measured before and after immersion and brushing. The data were analyzed by ANOVA/Tukey Test (p<0.05). RESULTS: The compomer and resin-modified glass ionomer lost significantly more weight after immersion in orange juice and Coca-Cola followed by brushing than the composite resins. The resin-modified glass-ionomer presented the highest increase in surface roughness after orange juice immersion and brushing. CONCLUSION: Immersion in acidic beverages followed by brushing degraded the restorative materials tested, causing loss of material and increased surface roughness.

Genetic analysis of age-at-onset for cardiovascular risk factors in a Brazilian family study.

BACKGROUND/AIMS: Statistical analysis of age-at-onset involving family data is particularly complicated because there is a correlation pattern that needs to be modeled and also because there are measurements that are censored. In this paper, our main purpose was to evaluate the effect of genetic and shared family environmental factors on age-at-onset of three cardiovascular risk factors: hypertension, diabetes and high cholesterol. METHODS: The mixed-effects Cox model proposed by Pankratz et al. [2005] was used to analyze the data from 81 families, involving 1,675 individuals from the village of Baependi, in the state of Minas Gerais, Brazil. RESULTS: The analyses performed showed that the polygenic effect plays a greater role than the shared family environmental effect in explaining the variability of the age-at-onset of hypertension, diabetes and high cholesterol. The model which simultaneously evaluated both effects indicated that there are individuals which may have risk of hypertension due to polygenic effects 130% higher than the overall average risk for the entire sample. For diabetes and high cholesterol the risks of some individuals were 115 and 45%, respectively, higher than the overall average risk for the entire population. CONCLUSIONS: Results showed evidence of significant polygenic effects indicating that age-at-onset is a useful trait for gene mapping of the common complex diseases analyzed. In addition, we found that the polygenic random component might absorb the effects of some covariates usually considered in the risk evaluation, such as gender, age and BMI.

Erbium, chromium:yttrium scandium gallium garnet laser for caries removal: influence on bonding of a self-etching adhesive system.

This study evaluated the influence of the dental substrates obtained after the use of different caries removal techniques on bonding of a self-etching system. Forty, extracted, carious, human molars were ground to expose flat surfaces containing caries-infected dentine surrounded by sound dentine. The caries lesions of the specimens were removed or not (control--G1) either by round steel burs and water-cooled, low speed, handpiece (G2), or by irradiation with an erbium, chromium:yttrium scandium gallium garnet (Er,Cr:YSGG) laser (2W, 20 Hz, 35.38 J/cm(2), fiber G4 handpiece with 0.2826 mm(2), non-contact mode at a 2 mm distance, 70% air/20% water--G3) or using a chemo-mechanical method (Carisolv--G4). Caries-infected, caries-affected and sound dentines were submitted to a bonding system followed by construction of a resin-based composite crown. Hour-glass shaped samples were obtained and submitted to a micro-tensile bond test. The bond strength data were compared by analysis of variance (ANOVA), complemented by Tukey's test (P