Followers are not followed: observed group interactions modulate subsequent social attention

We asked whether previous observations of group interactions modulate subsequent social attention episodes. Participants first completed a learning phase with two conditions. In the ‘leader’ condition one of three identities turned her gaze first, followed by the two other faces. In the ‘follower’ condition, one of the identities turned her gaze after the two other faces had first shifted their gaze. Thus, participants observed that some individuals were consistently ‘leaders’ and others ‘followers’ of others’ attention. In the test phase, the faces of ‘leaders’ and ‘followers’ were presented in a gaze cueing paradigm. Remarkably, the ‘followers’ did not elicit gaze cueing. Our data demonstrate that individuals who do not guide group attention in exploring the environment are ineffective social attention directors in later encounters. Thus, the role played in previous group social attention interactions modulates the relative weight assigned to others’ gaze: we ignore the gaze of group followers.

Are visual threats prioritized without awareness? A critical review and meta analysis involving 3 behavioral paradigms and 2696 observers

Given capacity limits, only a subset of stimuli 1 give rise to a conscious percept. Neurocognitive models suggest that humans have evolved mechanisms that operate without awareness and prioritize threatening stimuli over neutral stimuli in subsequent perception. In this meta analysis, we review evidence for this ‘standard hypothesis’ emanating from three widely used, but rather different experimental paradigms that have been used to manipulate awareness. We found a small pooled threat-bias effect in the masked visual probe paradigm, a medium effect in the binocular rivalry paradigm and highly inconsistent effects in the breaking continuous flash suppression paradigm. Substantial heterogeneity was explained by the stimulus type: the only threat stimuli that were robustly prioritized across all three paradigms were fearful faces. Meta regression revealed that anxiety may modulate threat biases, but only under specific presentation conditions. We also found that insufficiently rigorous awareness measures, inadequate control of response biases and low level confounds may undermine claims of genuine unconscious threat processing. Considering the data together, we suggest that uncritical acceptance of the standard hypothesis is premature: current behavioral evidence for threat-sensitive visual processing that operates without awareness is weak.

The “pain matrix” in pain-free individuals

Human functional imaging provides a correlative picture of brain activity during pain. A particular set of central nervous system structures (eg, the anterior cingulate cortex, thalamus, and insula) consistently respond to transient nociceptive stimuli causing pain. Activation of this so-called pain matrix or pain signature has been related to perceived pain intensity, both within and between individuals,1,2 and is now considered a candidate biomarker for pain in medicolegal settings and a tool for drug discovery. The pain-specific interpretation of such functional magnetic resonance imaging (fMRI) responses, although logically flawed,3,4 remains pervasive. For example, a 2015 review states that “the most likely interpretation of activity in the pain matrix seems to be pain.”4 Demonstrating the nonspecificity of the pain matrix requires ruling out the presence of pain when highly salient sensory stimuli are presented. In this study, we administered noxious mechanical stimuli to individuals with congenital insensitivity to pain and sampled their brain activity with fMRI. Loss-of-function SCN9A mutations in these individuals abolishes sensory neuron sodium channel Nav1.7 activity, resulting in pain insensitivity through an impaired peripheral drive that leaves tactile percepts fully intact.5 This allows complete experimental disambiguation of sensory responses and painful sensations

Breaking the double-edged sword of effort/trying hard: developmental equilibrium and Longitudinal relations among effort, achievement, and academic self-concept

Ever since the classic research of Nicholls (1976) and others, effort has been recognized as a double-edged sword: whilst it might enhance achievement, it undermines academic self-concept (ASC). However, there has not been a thorough evaluation of the longitudinal reciprocal effects of effort, ASC and achievement,in the context of modern self-concept theory and statistical methodology. Nor have there been developmental equilibrium tests of whether these effects are consistent across the potentially volatile early-to-middle adolescence. Hence, focusing on mathematics, we evaluate reciprocal effects models over the first four years of secondary school, relating effort, achievement (test scores and school grades), ASC, and ASCxEffort interactions for a representative sample of 3,421 German students (Mn age = 11.75 years at Wave 1). ASC, effort and achievement were positively correlated at each wave, and there was a clear pattern of positive reciprocal positive effects among ASC, test scores and school grades—each contributing to the other, after controlling for the prior effects of all others. There was an asymmetrical pattern of effects for effort that is consistent with the double-edged sword premise: prior school grades had positive effects on subsequent effort, but prior effort had non-significant or negative effects on subsequent grades and ASC. However, on the basis of a synergistic application of new theory and methodology, we predicted and found a significant ASC-by-effort interaction, such that prior effort had more positive effects on subsequent ASC and school grades when prior ASC was high—thus providing a key to breaking the double-edged sword.

p22phox C242T SNP inhibits inflammatory oxidative damage to endothelial cells and vessels

Background— T NADPH oxidase, by generating reactive oxygen species, is involved in the pathophysiology of many cardiovascular diseases and represents a therapeutic target for the development of novel drugs. A single-nucleotide polymorphism (SNP) C242T of the p22phox subunit of NADPH oxidase has been reported to be negatively associated with coronary heart disease (CHD) and may predict disease prevalence. However, the underlying mechanisms remain unknown. Methods and Results— Using computer molecular modelling we discovered that C242T SNP causes significant structural changes in the extracellular loop of p22phox and reduces its interaction stability with Nox2 subunit. Gene transfection of human pulmonary microvascular endothelial cells showed that C242T p22phox reduced significantly Nox2 expression but had no significant effect on basal endothelial O2.- production or the expression of Nox1 and Nox4. When cells were stimulated with TNFα (or high glucose), C242T p22phox inhibited significantly TNFα-induced Nox2 maturation, O2.- production, MAPK and NFκB activation and inflammation (all p<0.05). These C242T effects were further confirmed using p22phox shRNA engineered HeLa cells and Nox2-/- coronary microvascular endothelial cells. Clinical significance was investigated using saphenous vein segments from non CHD subjects after phlebectomies. TT (C242T) allele was common (prevalence of ~22%) and compared to CC, veins bearing TT allele had significantly lower levels of Nox2 expression and O2.- generation in response to high glucose challenge. Conclusions— C242T SNP causes p22phox structural changes that inhibit endothelial Nox2 activation and oxidative response to TNFα or high glucose stimulation. C242T SNP may represent a natural protective mechanism against inflammatory cardiovascular diseases.

Long-term positive effects of repeating a year in school: Six-year longitudinal study of self-beliefs, anxiety, social relations, school grades, and test scores

Consistently with a priori predictions, school retention (repeating a year in school) had largely positive effects for a diverse range of 10 outcomes (e.g., math self-concept, self-efficacy, anxiety, relations with teachers, parents and peers, school grades, and standardized achievement test scores). The design, based on a large, representative sample of German students (N = 1,325, M age = 11.75 years) measured each year during the first five years of secondary school, was particularly strong. It featured four independent retention groups (different groups of students, each repeating one of the four first years of secondary school, total N = 103), with multiple post-test waves to evaluate short- and long-term effects, controlling for covariates (gender, age, SES, primary school grades, IQ) and one or more sets of 10 outcomes realised prior to retention. Tests of developmental invariance demonstrated that the effects of retention (controlling for covariates and pre-retention outcomes) were highly consistent across this potentially volatile early-to-middle adolescent period; largely positive effects in the first year following retention were maintained in subsequent school years following retention. Particularly considering that these results are contrary to at least some of the accepted wisdom about school retention, the findings have important implications for educational researchers, policymakers and parents.

Dietary Quality and Associated Factors among Factory Workers in the Metropolitan Region of Sao Paulo, Brazil

The workplace is a manageable community-based setting for ensuring proper nutrition. This study aimed to evaluate dietary quality and associated factors among adult workers at a cosmetics factory in the metropolitan area of Sao Paulo, Brazil. This factory was actively participating in the Brazilian Workers` Meal Program, which was created to ensure workers` nutritional health. In this cross-sectional study, data on 202 adult workers were assessed using questionnaires (sociodemographic, anthropometric, and lifestyle characteristics) administered during August and September 2006. Dietary intake, measured by 24-hour dietary recall, was used to calculate the modified Healthy Eating Index (HEI). A repeated administration of the 24-hour dietary recall was applied in a random subsample to calculate the modified HEI adjusted for the within-person variation in intake. Mean adjusted modified HEI scores were analyzed using multiple linear regression adjusted for energy. The mean adjusted modified HEI score was 72.3 +/- 8.0. The lowest adjusted modified HEI components scores were ""milk and dairy products"" (4.4 +/- 3.2) and ""sodium"" (3.7 +/- 3.1). Two percent of workers had ""poor diet"" (adjusted modified HEI score <51 points) and the majority (87%) had ""diet that needs modification"" (adjusted modified HEI score between 51 and 80), despite their participation in the meal program. Adjusted modified HEI scores were considerably higher for men (74.7 +/- 7.0) than for women (66.9 +/- 8.2) and for normal body mass index (calculated as kg/m(2)) (73.3 +/- 7.8) than for overweight/obese (70.9 +/- 8.1). Based on these results, the vast majority of workers were found to have diets that needed improvement. Individuals with higher-quality diets were more likely to have lower body mass index and to be male. J Am Diet Assoc. 2010;110:786-790.

Performance of the Quantitative Food Frequency Questionnaire Used in the Brazilian Center of the Prospective Study Natural History of Human Papillomavirus Infection in Men: The HIM Study

The Natural History of Human Papillomavirus (HPV) Infection in Men: The HIM Study is a prospective multi-center cohort study that, among other factors, analyzes participants` diet. A parallel cross-sectional study was designed to evaluate the validity and reproducibility of the quantitative food frequency questionnaire (QFFQ) used in the Brazilian center from the HIM Study. For this, a convenience subsample of 98 men aged 18 to 70 years from the HIM Study in Brazil answered three 54-item QFFQ and three 24-hour recall interviews, with 6-month intervals between them (data collection January to September 2007). A Bland-Altman analysis indicated that the difference between instruments was dependent on the magnitude of the intake for energy and most nutrients included in the validity analysis, with the exception of carbohydrates, fiber, polyunsaturated fat, vitamin C, and vitamin E. The correlation between the QFFQ and the 24-hour recall for the deattenuated and energy-adjusted data ranged from 0.05 (total fat) to 0.57 (calcium). For the energy and nutrients consumption included in the validity analysis, 33.5% of participants on average were correctly classified into quartiles, and the average value of 0.26 for weighted kappa shows a reasonable agreement. The intraclass correlation coefficients for all nutrients were greater than 0.40 in the reproducibility analysis. The QFFQ demonstrated good reproducibility and acceptable validity. The results support the use of this instrument in the HIM Study. J Am Diet Assoc. 2011;111:1045-1051.

Underreporting of Energy Intake in Brazilian Women Varies According to Dietary Assessment: A Cross-Sectional Study Using Doubly Labeled Water

Objective Underreporting of energy intake is prevalent in food surveys, but there is controversy about which dietary assessment method provides greater underreporting rates. Our objective is to compare validity of self-reported energy intake obtained by three dietary assessment methods with total energy expenditure (TEE) obtained by doubly labeled water (DLW) among Brazilian women. Design We used a cross-sectional study. Subjects/setting Sixty-five females aged 18 to 57 years (28 normal-weight, 10 over-weight, and 27 obese) were recruited from two universities to participate. Main outcome measures TEE determined by DLW, energy intake estimated by three 24-hour recalls, 3-day food record, and a food frequency questionnaire (FFQ). Statistical analyses performed Regression and analysis of variance with repeated measures compared TEE and energy intake values, and energy intake-to-TEE ratios and energy intake-TEE values between dietary assessment methods. Bland and Altman plots were provided for each method. chi(2) test compared proportion of underreporters between the methods. Results Mean TEE was 2,622 kcal (standard deviation [SD] =490 kcal), while mean energy intake was 2,078 kcal (SD=430 kcal) for the diet recalls; 2,044 kcal (SD=479 kcal) for the food record and 1,984 kcal (SD=832 kcal) for the FFQ (all energy intake values significantly differed from TEE; P<0.0001). Bland and Altman plots indicated great dispersion, negative mean differences between measurements, and wide limits of agreement. Obese subjects underreported more than normal-weight subjects in the diet recalls and in the food records, but not in the FFQ. Years of education, income and ethnicity were associated with reporting accuracy. Conclusions The FFQ produced greater under- and overestimation of energy intake. Underreporting of energy intake is a serious and prevalent error in dietary self-reports provided by Brazilian women, as has been described in studies conducted in developed countries.

Nox2 B-loop peptide, Nox2ds, specifically inhibits the NADPH oxidase Nox2

In recent years, reactive oxygen species (ROS) derived from the vascular isoforms of NADPH oxidase, Nox1, Nox2, and Nox4, have been implicated in many cardiovascular pathologies. As a result, the selective inhibition of these isoforms is an area of intense current investigation. In this study, we postulated that Nox2ds, a peptidic inhibitor that mimics a sequence in the cytosolic B-loop of Nox2, would inhibit ROS production by the Nox2-. but not the Noxl- and Nox4-oxidase systems. To test our hypothesis, the inhibitory activity of Nox2ds was assessed in cell-free assays using reconstituted systems expressing the Nox2-, canonical or hybrid Nox1- or Nox4-oxidase. Our findings demonstrate that Nox2ds, but not its scrambled control, potently inhibited superoxide (O(2)(center dot-)) production in the Nox2 cell-free system, as assessed by the cytochrome c assay. Electron paramagnetic resonance confirmed that Nox2ds inhibits O(2)(center dot-) production by Nox2 oxidase. In contrast, Nox2ds did not inhibit ROS production by either Nox1- or Nox4-oxidase. These findings demonstrate that Nox2ds is a selective inhibitor of Nox2-oxidase and support its utility to elucidate the role of Nox2 in organ pathophysiology and its potential as a therapeutic agent. (C) 2011 Elsevier Inc. All rights reserved.

Differential kinase requirement for enhancement of Fc gamma R-mediated phagocytosis in alveolar macrophages by leukotriene B(4) vs. D(4)

In alveolar macrophages, leukotriene (IT) B(4) and cysteinyl LTs (LTC(4), LTD(4) and LTE(4)) both enhance Fc gamma receptor (Fc gamma R)-mediated phagocytosis. In the present study we investigated the role of specific PKC isoforms (PKC-alpha and -delta), the MAP kinases p38 and ERK 1/2, and PI3K in mediating the potentiation of Fc gamma R-mediated phagocytosis induced by addition of leukotrienes to the AMs. It was found that exogenously added LTB(4) and LTD(4) both enhanced PKC-delta and -alpha phosphorylation during Fc gamma R engagement. Studies with isoform-selective inhibitors indicated that exogenous LTB(4) effects were dependent on both PKC-alpha and -delta, while LTD(4) effects were exclusively due to PKC-delta activation. Although both exogenous LTB(4) and LTD(4) enhanced p38 and ERK 1/2 activation, LTB(4) required only ERK 1/2, while LTD(4) required only p38 activation. Activation by both LTs was dependent on PI3K activation. Effects of endogenous LTs on kinase activation were also investigated using selective LT receptor antagonists. Endogenous LTB(4) contributed to Fc gamma R-mediated activation of PKC-alpha, ERK 1/2 and PI3K, while endogenous cysLTs contributes to activation of PKC-delta, p38 and PI3K. Taken together, our data show that the capacities of LTB(4) and LTD(4) to enhance Fc gamma R-mediated phagocytosis reflect their differential activation of specific kinase programs. (C) 2008 Elsevier Ltd. All rights reserved.

On the unification of long-term survival models

In this paper we extend the long-term survival model proposed by Chen et al. [Chen, M.-H., Ibrahim, J.G., Sinha, D., 1999. A new Bayesian model for survival data with a surviving fraction. journal of the American Statistical Association 94, 909-919] via the generating function of a real sequence introduced by Feller [Feller, W., 1968. An Introduction to Probability Theory and its Applications, third ed., vol. 1, Wiley, New York]. A direct consequence of this new formulation is the unification of the long-term survival models proposed by Berkson and Gage [Berkson, J., Gage, R.P., 1952. Survival cure for cancer patients following treatment. journal of the American Statistical Association 47, 501-515] and Chen et al. (see citation above). Also, we show that the long-term survival function formulated in this paper satisfies the proportional hazards property if, and only if, the number of competing causes related to the occurrence of an event of interest follows a Poisson distribution. Furthermore, a more flexible model than the one proposed by Yin and Ibrahim [Yin, G., Ibrahim, J.G., 2005. Cure rate models: A unified approach. The Canadian journal of Statistics 33, 559-570] is introduced and, motivated by Feller`s results, a very useful competing index is defined. (c) 2008 Elsevier B.V. All rights reserved.

Intermolecular Contacts Influencing the Conformational and Geometric Features of the Pharmaceutically Preferred Mebendazole Polymorph C

Mebendazole (MBZ) is a common benzimidazole anthelmintic that exists in three different polymorphic forms, A, B, and C. Polymorph C is the pharmaceutically preferred form due to its adequated aqueous solubility. No single crystal structure determinations depicting the nature of the crystal packing and molecular conformation and geometry have been performed on this compound. The crystal structure of mebendazole form C is resolved for the first time. Mebendazole form C crystallizes in the triclinic centrosymmetric space group and this drug is practically planar, since the least-squares methyl benzimidazolylcarbamate plane is much fitted on the forming atoms. However, the benzoyl group is twisted by 31(1)degrees from the benzimidazole ring, likewise the torsional angle between the benzene and carbonyl moieties is 27(1)degrees. The formerly described bends and other interesting intramolecular geometry features were viewed as consequence of the intermolecular contacts occurring within mebendazole C structure. Among these features, a conjugation decreasing through the imine nitrogen atom of the benzimidazole core and a further resonance path crossing the carbamate one were described. At last, the X-ray powder diffractogram of a form C rich mebendazole mixture was overlaid to the calculated one with the mebendazole crystal structure. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2336-2344, 2009

Synthesis and characterization of a new mebendazole salt: Mebendazole hydrochloride

Mebendazole hydrochloride [(5-benzoyl-1H-benzimidazole-2-yl)-carbamic acid methyl ester hydrochloride, MBZ.HCl], a new stable salt of mebendazole (MBZ), has been synthesized and characterized. It can easily be obtained from recrystallization of forms A, B, or C of MBZ in diverse solvents with the addition of hydrochloric acid solution. Crystallographic data reveals that the particular conformation adopted by the carbamic group contributes to the stability of the network. The crystal packing is stabilized by the presence of three N-H...Cl intermolecular interactions that form chains along the b axis. The XRD analyses of the three crystalline habits found in the crystallization process (square-based pyramids, pseudohexagonal plates, and prismatic) show equivalent diffraction patterns. The vibrational behavior is consistent with crystal structure. The most important functional groups show shifts to lower or higher frequencies in relation to the MBZ polymorphs. The thermal study on MBZ center dot HCI indicates that the compound is stable up to 160 degrees C approximately. Decomposition occurs in four steps. In the first step the HCl group is eliminated, and after that the remaining MBZ polymorph A decomposes in three steps, as happens with polymorphs B and C. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:542-552, 2008.

A non-parametric vessel detection method for complex vascular structures

Modern medical imaging techniques enable the acquisition of in vivo high resolution images of the vascular system. Most common methods for the detection of vessels in these images, such as multiscale Hessian-based operators and matched filters, rely on the assumption that at each voxel there is a single cylinder. Such an assumption is clearly violated at the multitude of branching points that are easily observed in all, but the Most focused vascular image studies. In this paper, we propose a novel method for detecting vessels in medical images that relaxes this single cylinder assumption. We directly exploit local neighborhood intensities and extract characteristics of the local intensity profile (in a spherical polar coordinate system) which we term as the polar neighborhood intensity profile. We present a new method to capture the common properties shared by polar neighborhood intensity profiles for all the types of vascular points belonging to the vascular system. The new method enables us to detect vessels even near complex extreme points, including branching points. Our method demonstrates improved performance over standard methods on both 2D synthetic images and 3D animal and clinical vascular images, particularly close to vessel branching regions. (C) 2008 Elsevier B.V. All rights reserved.