What makes dietary restraint problematic? Development and validation of the Inflexible Eating Questionnaire.

This study presents the Inflexible Eating Questionnaire (IEQ), which measures the inflexible adherence to subjective eating rules. The scale's structure and psychometric properties were examined in distinct samples from the general population comprising both men and women. IEQ presented an 11-item one-dimensional structure, revealed high internal consistency, construct and temporal stability, and discriminated eating psychopathology cases from non-cases. The IEQ presented significant associations with dietary restraint, eating psychopathology, body image inflexibility, general psychopathology symptoms, and decreased intuitive eating. IEQ was a significant moderator on the association between dietary restraint and eating psychopathology symptoms. Findings suggested that the IEQ is a valid and useful instrument with potential implications for research on psychological inflexibility in disordered eating.

Using multiple regression, Bayesian networks and artificial neural networks for prediction of total egg production in European quails based on earlier expressed phenotypes.

The prediction of total egg production (TEP) potential in poultry is an important task to aid optimized management decisions in commercial enterprises. The objective of the present study was to compare different modeling approaches for prediction of TEP in meat type quails (Coturnix coturnix coturnix) using phenotypes such as weight, weight gain, egg production and egg quality measurements. Phenotypic data on 30 traits from two lines (L1, n=180; and L2, n=205) of quail were modeled to predict TEP. Prediction models included multiple linear regression and artificial neural network (ANN). Moreover, Bayesian network (BN) and a stepwise approach were used as variable selection methods. BN results showed that TEP is independent from other earlier expressed traits when conditioned on egg production from 35 to 80 days of age (EP1). In addition, the prediction accuracy was much lower when EP1 was not included in the model. The best predictive model was ANN, after feature selection, showing prediction correlations of r=0.792 and r=0.714 for L1 and L2, respectively. In conclusion, machine learning methods may be useful, but reasonable prediction accuracies are obtained only when partial egg production measurements are included in the model.

Effect of genotype imputation on genome-enabled prediction of complex traits: an empirical study with mice data.

BACKGROUND: Genotype imputation is an important tool for whole-genome prediction as it allows cost reduction of individual genotyping. However, benefits of genotype imputation have been evaluated mostly for linear additive genetic models. In this study we investigated the impact of employing imputed genotypes when using more elaborated models of phenotype prediction. Our hypothesis was that such models would be able to track genetic signals using the observed genotypes only, with no additional information to be gained from imputed genotypes. RESULTS: For the present study, an outbred mice population containing 1,904 individuals and genotypes for 1,809 pre-selected markers was used. The effect of imputation was evaluated for a linear model (the Bayesian LASSO - BL) and for semi and non-parametric models (Reproducing Kernel Hilbert spaces regressions - RKHS, and Bayesian Regularized Artificial Neural Networks - BRANN, respectively). The RKHS method had the best predictive accuracy. Genotype imputation had a similar impact on the effectiveness of BL and RKHS. BRANN predictions were, apparently, more sensitive to imputation errors. In scenarios where the masking rates were 75% and 50%, the genotype imputation was not beneficial. However, genotype imputation incorporated information about important markers and improved predictive ability, especially for body mass index (BMI), when genotype information was sparse (90% masking), and for body weight (BW) when the reference sample for imputation was weakly related to the target population. CONCLUSIONS: In conclusion, genotype imputation is not always helpful for phenotype prediction, and so it should be considered in a case-by-case basis. In summary, factors that can affect the usefulness of genotype imputation for prediction of yet-to-be observed traits are: the imputation accuracy itself, the structure of the population, the genetic architecture of the target trait and also the model used for phenotype prediction.

Dependence of optical attenuation coefficient and mechanical tension of irradiated human cartilage measured by optical coherence tomography.

As banked human tissues are not widely available, the development of new non-destructive and contactless techniques to evaluate the quality of allografts before distribution for transplantation is very important. Also, tissues will be processed accordingly to standard procedures and to minimize disease transmission most tissue banks will include a decontamination or sterilization step such as ionizing radiation. In this work, we present a new method to evaluate the internal structure of frozen or glycerol processed human cartilages, submitted to various dosis of irradiation, using the total optical attenuation coefficient retrieved from optical coherence tomography (OCT) images. Our results show a close relationship between tensile properties and the total optical attenuation coefficient of cartilages. Therefore, OCT associated with the total optical attenuation coefficient open a new window to evaluate quantitatively biological changes in processed tissues.

Assessment of recent to medium-term impacts of bench terrace construction on forest ground cover and selected soil physical and fertility properties along a chrono-sequence in north-central Portugal.

Mankind has built terraces on sloping terrain since pre-historic times, especially for expanding croplands. Widespread terracing for forestry purposes is comparatively recent, presumably linked to the advent of fast-growing tree plantations together with technological advances in heavy forestry machinery. Perhaps not surprisingly therefore, the impacts of terracing on soil properties are poorly studied for forest stands. The present investigation addressed this knowledge gap using eucalypt plantations in north-central Portugal as study case and using a space-for-time approach. In total, 12 pairs of neighbouring, terraced (T) versus non-terraced (NT) plantations were studied, with the terraced plantations equally divided over four time-since-terracing periods: <1 year (recently terraced); 5 years; 10 years; 17 years. As such, the studied chrono sequence covered roughly half of a full eucalypt rotation cycle in the region. All field data and all litter and topsoil (0-5 cm depth) samples were gathered during an 2-weekly campaign, at 5 equidistant transect points per plantation. Terracing changed all four cover categories most strongly and markedly during the initial time-since-terracing period, while its effects on the averages of vegetation cover (T/NT: 19/37 %) and litter cover (T/NT: 47/62 %) contrasted with those of stone cover (T/NT: 26/1 %) and bare soil cover (T/NT: 8/1 %). Terracing increased dry bulk density across the entire chrono sequence (overall averages T/NT: 1.17/0.84 g cm-3), while it greatly decreased resistance to shear stress but only for the initial post-terracing period (T/NT: 0.8/ 3.2 kg cm-2) and not towards the middle and end of the first rotation cycle (five and ten years after terracing). Total carbon content in soils was significantly affected by terracing, while total nitrogen content not. Both properties revealed similar temporal patterns, with a marked initial decrease (TC: -32 mg C g-1 soil; TN: -0.73 mg N g-1 soil) and a gradual recovery during the first rotation cycle.

HLA-B*58:01 is a risk factor for allopurinol-induced DRESS and Stevens-Johnson syndrome/toxic epidermal necrolysis in a Portuguese population.

BACKGROUND: HLA-B*58:01 is associated with allopurinol-induced severe cutaneous adverse drug reactions (sCADR) particularly in Han Chinese, but the risk in European populations has seldom been studied. OBJECTIVE: To study the association of HLA-B*58:01 with allopurinol-induced sCADR in a Portuguese population. METHODS: We studied 25 patients (11 male/14 female, mean age 67·4 years) with sCARD from allopurinol: 19 DRESS (drug reaction eosinophilia and systemic symptoms) and six Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). HLA was genotyped by reverse sequence-specific oligonucleotide-polymerase chain reaction and results compared statistically with a control group of 23 allopurinol-tolerant individuals and the control population. RESULTS: HLA-B*58:01 was present in 16 patients with sCADR (64%) [12 DRESS (63%), four SJS/TEN (67%)], one allopurinol-tolerant individual (4%) and 63 normal controls (1·96%), with a statistically significant difference between sCADR and the two control groups. When compared with the normal population, HLA-B*58:01 was associated with a higher risk of sCADR, both DRESS [odds ratio (OR) 85·36, 95% confidence interval (CI) 32·52-224·04] and SJS/TEN (OR 99·59, 95% CI 17·91-553·72). There was no statistically different risk between these two types of CADR. CONCLUSIONS: Portuguese patients with sCADR from allopurinol, both DRESS and SJS/TEN, have a high frequency of HLA-B*58:01, with an OR similar to European patients with SJS/TEN. This study also extends this association to DRESS in Europeans. The recommendation to genotype systematically before therapy is controversial, particularly when HLA-B*58:01 prevalence in the normal population is low, as in Europe. However it could be an option for patients with other risks factors.

Glucocorticoids regulate metallothionein-1/2 expression in rat choroid plexus: effects on apoptosis.

The choroid plexus (CP) participates in the synthesis, secretion and regulation of the cerebrospinal fluid, in the removal of its toxic compounds and in the regulation of the availability of essential metal ions to the brain. It expresses and secretes metallothioneins 1/2 (MT-1/2) which are key components in the maintenance of the central nervous system metal homeostasis and have anti-apoptotic properties, thereby protecting the brain. Glucocorticoids regulate MT-1/2 expression in several brain regions, but within the choroid plexuses (CPs) it remains unknown. Glucocorticoid levels increase in response to stress with implications in apoptosis. Further, CP expresses glucocorticoid (GR) and mineralocorticoid receptors (MR) turning it into likely glucocorticoid responsive structure. Data prompted us to study the regulation of MT-1/2 expression in response to glucocorticoids in the rat CP, and to investigate its implications in apoptosis. MT-1/2 protein and mRNA expression analysis showed that hydrocortisone up-regulates MT-1/2 expression in rat choroid plexus (RCP) cell line and in primary cultures of choroid plexus epithelial cells (CPEC) cultures via GR and MR. Also, incubation of RCP cells with hydrocortisone significantly diminished apoptosis, an effect eliminated by the addition of a MT-1/2 antibody. Moreover, induction of psychosocial stress, with concomitant rise of corticosterone levels, increased MT-1/2 expression in liver and in CP of male and female rats, with an exception observed in CP from males subjected to acute stress in which down-regulation in MT-1/2 expression occurred. Altogether, the results obtained demonstrated that stress/glucocorticoids regulate MT-1/2 expression in rat CP, with implications on apoptosis.

Effects of ionizing radiation and preservation on biomechanical properties of human costal cartilage.

Tissue banks around the world store human cartilage obtained from cadaveric donors for use in diverse reconstructive surgical procedures. To ensure this tissue is sterile at the time of distribution, tissues may be sterilized by ionizing radiation. In this work, we evaluate the physical changes in deep frozen costal cartilage (-70 °C) or costal cartilage preserved in high concentrations of glycerol (>98 %) followed by a terminal sterilization process using ionizing radiation, at 3 different doses (15, 25 and 50 kGy). Tension and compression tests were carried out to determine the mechanical changes related both to the different preservation methods and irradiation doses. For both methods of preservation, tension strength was increased by about 24 %, when cartilage tissue was irradiated with 15 kGy. Deep frozen samples, when irradiated with 25 or 50 kGy, had a decrease in their mechanical performance, albeit to a lesser extent than when tissues were preserved in high concentration of glycerol and equally irradiated. In conclusion, processing in high concentration of glycerol did not increase tissue protection against radiation damage; while cartilage preserved in high concentrations of glycerol withstands radiation up to 25 kGy, deep frozen human costal cartilage may be sterilized with a doses up to 50 kGy without significant mechanical impact.

T cell receptor excision circles (TREC) and recent thymic migrant cells in specific immunotherapy and respiratory allergy to Dermatophagoides pteronyssinus.

INTRODUCTION: T cell receptor excision circles (TREC) on CD31+ T cells are related to recent thymic emigrant cells (RTEs). The involvement of the functional thymic tissue occurs early in the IgE-mediated allergic reaction, and in response to specific immunotherapy (SIT). AIM: Evaluation of specific immunotherapy effects on TREC number in peripheral T cells in patients allergic to Dermatophagoides pteronyssinus (Dpt). METHOD: 85 respiratory allergic patients (both genders), 41 of them (Group II) under maintenance treatment to Dpt SIT (21 sublingual-SLIT, and 20 subcutaneous-SCIT), were selected. The allergic patients (Group I) without specific treatment were submitted to an allergen challenge test (22 nasal and 22 conjunctival). Peripheral cell analysis was performed immediately before treatment and 60 or 240 minutes after allergenic extract administration. TREC quantification was performed in CD4+CD31+ and CD8+CD31+. The results were expressed per 100.000 cells related to RTEs. Samples from 10 healthy individuals (Control - Group III) were obtained with the same method. RESULTS: The value of TRECs on RTEs was constant in control groups. For Group I patients (nasal or conjunctival test), TREC quantification in CD31+ T cells showed relevant individual changes, even in the patients tested earlier (60 minutes), and statistical significant at 240 minutes. Both SCIT and SLIT had also demonstrated enormous individual changes, particularly on TRECs/CD4+CD31+ cells assay. Basal values in Group III were significantly higher than those observed in active patients groups. CONCLUSION: Thymic functional activity is earlier involved in the allergic reaction and SIT IgE-mediated allergy is able to induce RTEs in the periphery, particularly TRECs/CD4+CD31+ cells. Both SLIT and SCIT showed reduced RETs in the periphery, probably due to maturation of regulatory T cells. Our results suggest a crucial role of the functional thymic tissue on the central mechanism of this therapy.

Searching for phenotypic causal networks involving complex traits: an application to European quail.

BACKGROUND: Structural equation models (SEM) are used to model multiple traits and the casual links among them. The number of different causal structures that can be used to fit a SEM is typically very large, even when only a few traits are studied. In recent applications of SEM in quantitative genetics mixed model settings, causal structures were pre-selected based on prior beliefs alone. Alternatively, there are algorithms that search for structures that are compatible with the joint distribution of the data. However, such a search cannot be performed directly on the joint distribution of the phenotypes since causal relationships are possibly masked by genetic covariances. In this context, the application of the Inductive Causation (IC) algorithm to the joint distribution of phenotypes conditional to unobservable genetic effects has been proposed. METHODS: Here, we applied this approach to five traits in European quail: birth weight (BW), weight at 35 days of age (W35), age at first egg (AFE), average egg weight from 77 to 110 days of age (AEW), and number of eggs laid in the same period (NE). We have focused the discussion on the challenges and difficulties resulting from applying this method to field data. Statistical decisions regarding partial correlations were based on different Highest Posterior Density (HPD) interval contents and models based on the selected causal structures were compared using the Deviance Information Criterion (DIC). In addition, we used temporal information to perform additional edge orienting, overriding the algorithm output when necessary. RESULTS: As a result, the final causal structure consisted of two separated substructures: BW→AEW and W35→AFE→NE, where an arrow represents a direct effect. Comparison between a SEM with the selected structure and a Multiple Trait Animal Model using DIC indicated that the SEM is more plausible. CONCLUSIONS: Coupling prior knowledge with the output provided by the IC algorithm allowed further learning regarding phenotypic causal structures when compared to standard mixed effects SEM applications.

Inferring causal phenotype networks using structural equation models.

Phenotypic traits may exert causal effects between them. For example, on the one hand, high yield in dairy cows may increase the liability to certain diseases and, on the other hand, the incidence of a disease may affect yield negatively. Likewise, the transcriptome may be a function of the reproductive status in mammals and the latter may depend on other physiological variables. Knowledge of phenotype networks describing such interrelationships can be used to predict the behavior of complex systems, e.g. biological pathways underlying complex traits such as diseases, growth and reproduction. Structural Equation Models (SEM) can be used to study recursive and simultaneous relationships among phenotypes in multivariate systems such as genetical genomics, system biology, and multiple trait models in quantitative genetics. Hence, SEM can produce an interpretation of relationships among traits which differs from that obtained with traditional multiple trait models, in which all relationships are represented by symmetric linear associations among random variables, such as covariances and correlations. In this review, we discuss the application of SEM and related techniques for the study of multiple phenotypes. Two basic scenarios are considered, one pertaining to genetical genomics studies, in which QTL or molecular marker information is used to facilitate causal inference, and another related to quantitative genetic analysis in livestock, in which only phenotypic and pedigree information is available. Advantages and limitations of SEM compared to traditional approaches commonly used for the analysis of multiple traits, as well as some indication of future research in this area are presented in a concluding section.

Correlation Between Anthropometric Measurements and Non-alcoholic Fatty Liver Disease in Individuals With Obesity Undergoing Bariatric Surgery: Cross-Sectional Study.

BACKGROUND: We hypothesize that non-alcoholic fatty liver disease (NAFLD) may be significantly associated with waist circumference (WC), neck circumference (NC), hip circumference (HC), and waist-to-hip ratio (WHR). OBJECTIVES: To analyze correlations between anthropometric parameters and the occurrence and intensity of NAFLD aspects assessed by histopathological examination in individuals undergoing bariatric surgery. METHODS: This is a cross-sectional study carried out in a tertiary university hospital. Demographic, clinical, anthropometric, laboratory, and histopathological variables were analyzed; uni- and multivariate analyses were performed. Histopathological variables analyzed were findings of liver biopsies collected during surgical procedures. RESULTS: Of 119 individuals, 105 (88.2%) were female. The mean age was 38.8 ± 9.3 years and the mean BMI was 37.6 ± 3.1 kg/m2. The prevalence of NAFLD histopathological aspects was: steatosis (76.5%), steatohepatitis (49.6%), and fibrosis (51.3%). WC was significantly higher in individuals with steatosis (103.5 ± 9.9 vs. 99.4 ± 8.4; p = 0.03). Individuals with steatohepatitis presented significantly higher BMI (38.2 ± 3.2 vs. 36.7 ± 2.8; p = 0.01), WC (105.3 ± 10.4 vs. 99.6 ± 8.8; p = 0.002), and WHR (1 ± 0.1 vs. 0.9 ± 0.1; p = 0.02). Age (40.6 ± 9.7 vs. 37 ± 8.5; p = 0.03) and hemoglobin A1c (6.5 ± 0.5 vs. 5.6 ± 0.5; p = 0.004) were significantly higher among individuals with fibrosis. A positive correlation was observed between the steatosis intensity and WHR (R = 0.2; p = 0.04). BMI (R = 0.2; p = 0.02) and glucose (R = 0.2; p = 0.009) were independently correlated with the steatohepatitis intensity. Age (R = 0.3; p = 0.04) was independently correlated with the fibrosis intensity. CONCLUSION: There were significant associations between anthropometric parameters and NAFLD aspects. WC and WHR were associated with steatosis; BMI, WC, and WHR were associated with steatohepatitis. WHR independently correlated with steatosis intensity.

Prevalence and Factors Associated with Hepatic Iron Overload in Obese Individuals Undergoing Bariatric Surgery: a Cross-Sectional Study.

BACKGROUND: Slight to moderate hepatic iron overload (HIO) can be found in cases of liver disease, including non-alcoholic fatty liver disease (NAFLD), but the mechanism is not completely understood, as well as its relationship with obesity. OBJECTIVE: To determine the prevalence of HIO assessed through histopathological examination in obese individuals undergoing bariatric surgery and to identify correlations between this condition and demographic, anthropometric, clinical, laboratory, and NAFLD-related aspects. METHODS: This is a cross-sectional study which enrolled individuals undergoing bariatric surgery from January 2018 to February 2019 at a tertiary university hospital. NAFLD and HIO were assessed through histological examination. RESULTS: Of 125 individuals, 87.2% were female and the average age was 38.8 ± 9.2 years. The average BMI was 37.2 ± 3.1 kg/m2. NAFLD was present in 66.4% and HIO in 17.6%, with 63.6% of patients with overload classified as mild (grade I) and 22.7% moderate (grade II). HIO was significantly more frequent in males (p = 0.003) and was significantly associated with higher levels of glucose (92.1 ± 28.4 vs. 80.7 ± 39.6; p = 0.02), ferritin (385.5 ± 290.9 vs. 131.6 ± 99.7; p < 0.0001), serum iron (82.4 ± 35.7 vs. 66.6 ± 25.1; p = 0.03), glutamic-oxaloacetic transaminase (27.3 ± 19.5 vs. 20.6 ± 8.8; p = 0.02), and glutamic-pyruvic transaminase (37.6 ± 36.4 vs. 24.6 ± 16.3; p = 0.01). Multivariate analysis showed that HIO intensity was significant and independently associated with ferritin levels (R = 0.19; p = 0.01), serum iron (R = 0.25; p < 0.0001), blood glucose (R = 0.16; p = 0.001), and total cholesterol (R = - 0.17; p < 0.0001). CONCLUSION: In obese individuals, HIO presented a high prevalence and was associated with higher levels of ferritin, serum iron, glucose, and transaminases; lower levels of total cholesterol; and male gender.

Genetic polymorphisms in CYP3A5 and MDR1 genes and their correlations with plasma levels of tacrolimus and cyclosporine in renal transplant recipients.

Immunosuppressive drugs, such as tacrolimus (FK506) and cyclosporine (CsA), play an essential role in graft survival, preventing rejection. Large interindividual differences in drug-metabolizing enzymes as well as in drug transporters make the task of reaching the optimal concentrations difficult. The bioavailability of CsA and FK506 seems to be associated with the cytocrhome P450 IIIA (CYP3A) gene. It has also been described that the Multi Drug Resistance 1 (MDR1) gene that encodes for polyglycoprotein-P (P-gp) may influence the metabolizing action of FK506 and CsA. Therefore, we sought, to correlate single nucleotide polymorphisms (SNPs) in the CYP3A and MDR1 genes with the concentrations of FK506 and CsA. For this purpose we analyzed 2 groups of renal transplant recipients by sequencing: one receiving a CsA immunosuppressive regime, and other, an FK506-immunosuppression. This study showed that subjects in the FK506 group who had encoded the 1236C>T substitution in the MDR1 gene displayed 44.4% higher drug concentrations compared with ("wild-type") individuals. Individuals carrying the 2677G>T,A mutation showed FK506 concentrations that were 44.7% higher than the wild-type individuals. Concerning the CsA group, individuals carrying the 22915A>C substitution displayed CsA concentrations 52.1% higher than wild-type individuals.

Risk factors for treatment delay in pulmonary tuberculosis in Recife, Brazil.

BACKGROUND: Tuberculosis is still a great challenge to public health in Brazil and worldwide. Early detection followed by effective therapy is extremely important in controlling the disease. Recent studies have investigated reasons for delays in treatment, but there is no agreed definition of what constitutes an "acceptable" delay. This study investigates factors associated with total delay in treatment of tuberculosis. METHODS: A cohort of adult cases of pulmonary tuberculosis diagnosed over a two-year period was studied. Patients were interviewed on entry, reporting the duration of symptoms before the start of treatment, and sputum and blood samples were collected. It was decided that sixty days was an acceptable total delay. Associations were investigated using univariable and multivariable analysis and the population attributable fraction was estimated. RESULTS: Of 1105 patients, 62% had a delay of longer than 60 days. Age, sex, alcoholism and difficulty of access were not associated with delays, but associations were found in the case of unemployment, having given up smoking, having lost weight and being treated in two of the six health districts. The proportion attributable to: not being an ex-smoker was 31%; unemployment, 18%; weight loss, 12%, and going to the two worst health districts, 25%. CONCLUSION: In this urban area, delays seem to be related to unemployment and general attitudes towards health. Although they reflect the way health services are organized, delays are not associated with access to care.

Functional aspects of cord blood lymphocytes response to polyclonal and allogeneic activation.

With the purpose of contributing to a better knowledge of the phenotypic characteristics and functional activity of umbilical cord blood (UCB) lymphocytes, we have carried out extensive immunophenotyping of these cells, evaluated their immune response to polyclonal and allogeneic activation and then compared these results with those obtained with peripheral blood lymphocytes of healthy donors (PBHD). Our results showed, in CD4+ UCB lymphocytes, an increase of CD38 and CD45RA and a decrease of CD11a (S6F1), CD54 and HLA-DR double positive cells. An increase of CD38, CD45RA and CD56, and a decrease of CD28, CD57 and HLA-DR were observed in CD8+ UCB lymphocytes. Most natural killer UCB cells are CD16+, CD56+, CD57-, and among the UCB cells there is a lower number of CD8+ and TCRgammadelta+ (either CD8- or CD8+), and higher number of CD4+ lymphocytes. After allogeneic stimulus the majority of these phenotypic differences disappeared, which seems to be in agreement with the normal allogeneic response (assessed through MLR, frequency of CTL and helper T lymphocytes precursors) presented by UCB lymphocytes. Regarding the response to polyclonal activation, among the mitogens used, only PHA induced a different result: a lower IFNgamma production by UCB cells.

Influence of skin temperature on latency and amplitude of skin potential responses in the cat.

The effect of skin temperature changes on skin potential response (SPR) amplitude and latency was examined in the cat. SPRs were elicited either by stimulating the reticular formation or the distal end of the median nerve. At room temperature, the latency due to the neuroglandular transmission and to the peripheral effector accounts for about half of the total latency of SPR evoked by reticular stimulation. This latency increases to several seconds at low skin temperatures (approximately 10 degrees C), decreases with temperature, and is minimal (300 msec) at high temperatures (over 40 degrees C). SPR amplitude increases with skin temperature, reaches a maximal value (usually around 30 degrees C) and then decreases at higher temperatures. The decrease of latency at higher temperatures confirms results previously obtained in humans. However, the mechanisms of amplitude decrease for high temperatures remain unclear.