In the processing of emotions, the brain prepares and reacts in distinctive manners depending upon the negative or positive nuance of the emotion elicitors. Previous investigations showed that ...negative elicitors generally evoke more intense neural activities than positive and neutral ones, as reflected in the augmented amplitude of all sub-components of the event-related potentials (ERP) late posterior positivity (LPP) complex, while less is known about the emotion of disgust. The present study aimed to examine whether the LPP complex during the processing of disgust stimuli showed greater amplitude than other emotion elicitors with negative or positive valences, thus confirming it as a neural marker of disgust-related negativity bias at earlier or later stages. Thus, in the present study, we leveraged the ERP technique during the execution of an affective self-administered visual stimuli task to disentangle the neural contributions associated with images of positive, negative, disgust, or neutral emotions. Crucially, we showed that handling with disgust elicitors prompted the greatest neural activity and the highest delay during self-administration. Overall, we demonstrated progressive neural activities associated with the unpleasantness of the emotion elicitors and peculiar processing for disgust compared with all other emotions.
The present study aimed at investigating the relationship between Emotional Susceptibility (ES), an aspect of the personality trait Neuroticism, and individual differences in the neural responses in ...anterior insula to primary sensory stimuli colored by affective valence, i.e., distasting or pleasantly tasting oral stimuli. In addition, it was studied whether intrinsic functional connectivity patterns of brain regions characterized by such differential responses could be related to ES. To this purpose 25 female participants underwent functional magnetic resonance imaging scanning, while being involved in a flavor experiment. During the experiment, flavor stimuli were administered consisting of small amounts of liquid with a different affective valence: neutral, pleasant, unpleasant. The results showed that individual differences in ES trait predicted distinct neural activity patterns to the different stimulus conditions in a region of left anterior insula that a previous meta-analysis revealed to be linked with olfacto-gustatory processing. Specifically, low ES was associated with enhanced neural responses to both pleasant and unpleasant stimuli, compared to neutral stimuli. By contrast, high ES participants showed equally strong neural responses to all types of stimuli without differentiating between the neutral and affective stimuli. Finally, during a task-free state, high ES trait appeared also to be related to decreased intrinsic functional connectivity between left anterior insula and left cerebellum. Our findings show that individual differences in ES are associated with differential anterior insula responses to primary sensory (flavor) stimuli as well as to intrinsic functional cortico-cerebellar connectivity, the latter suggesting a basis in the brain intrinsic functional architecture of the regulation of emotional experiences.
Emotional perception has been extensively studied, but only a few studies have investigated the brain activity preceding exposure to emotional stimuli, especially when they are triggered by the ...subject himself. Here, we sought to investigate the emotional expectancy by means of movement related cortical potentials (MRCPs) in a self-paced task, in which the subjects begin the affective experience by pressing a key. In this experiment, participants had to alternatively press two keys to concomitantly display positive, negative, neutral, and scrambled images extracted from the International Affective Pictures System (IAPS). Each key press corresponded to a specific emotional category, and the experimenter communicated the coupling before each trial so that the subjects always knew the valence of the forthcoming picture. The main results of the present study included a bilateral positive activity in prefrontal areas during expectancy of more arousing pictures (positive and negative) and an early and sustained positivity over occipital areas, especially during negative expectancy. In addition, we observed more pronounced and anteriorly distributed Late Positive Potential (LPPs) components in the emotional conditions. In conclusion, these results show that emotional expectancy can influence brain activity in both motor preparation and stimulus perception, suggesting enhanced pre-processing in the to-be-stimulated areas. We propose that before a predictable emotional stimulus, both appetitive and defensive motivational systems act to facilitate the forthcoming processing of survival-relevant contents by means of an enhancement of attention toward more arousing pictures.
Purpose: Wide interindividual variability characterizes language development in the general and at-risk populations of up to 3 years of age. We adopted a complex approach that considers multiple ...aspects of lexical and grammatical skills to identify language profiles in low-risk preterm and full-term children. We also investigated biological and environmental predictors and relations between language profiles and cognitive and motor skills. Method: We enrolled 200 thirty-month-old Italian-speaking children--consisting of 100 low-risk preterm and 100 comparable full-term children. Parents filled out the Italian version of the MacArthur--Bates Communicative Development Inventories Infant and Toddler Short Forms (word comprehension, word production, and incomplete and complete sentence production), Parent Report of Children's Abilities--Revised (cognitive score), and Early Motor Questionnaire (fine motor, gross motor, perception-action, and total motor scores) questionnaires. Results: A latent profile analysis identified four profiles: poor (21%), with lowest receptive and expressive vocabulary and absent or limited word combination and phonological accuracy; weak (22.5%), with average receptive but limited expressive vocabulary, incomplete sentences, and absent or limited phonological accuracy; average (25%), with average receptive and expressive vocabulary, use of incomplete and complete sentences, and partial phonological accuracy; and "advanced" (31.5%), with highest expressive vocabulary, complete sentence production, and phonological accuracy. Lower cognitive and motor scores characterized the poor profile, and lower cognitive and perception-action scores characterized the weak profile. Having a nonworking mother and a father with lower education increased the probability of a child's assignment to the poor profile, whereas being small for gestational age at birth increased it for the "weak" profile. Conclusions: These findings suggest a need for a person-centered and cross-domain approach to identifying children with language weaknesses and implementing timely interventions. An online procedure for data collection and data-driven analyses based on multiple lexical and grammatical skills appear to be promising methodological innovations.
•RRT activity on the bond behavior of FRCM composites.•Evaluation of the influence of different set-up parameters.•Estimation of the expected experimental scattering.•Recommendations for set-up ...standardization.•Contribution to the improvement of test procedures included in current guidelines.
Fabric Reinforced Cementitious Matrix (FRCM) composites represent an innovative and effective retrofitting solution for masonry structures. The use of FRCMs as an external retrofitting technique requires an insight knowledge of their mechanical behavior, failure modes and masonry-to-FRCM bond properties. A Round Robin Test (RRT) programme was launched by twelve Italian Universities, aimed at evaluating the effect of the shear test set-up parameters and at assessing the test variability. The experimental tests were performed on systems made of glass and steel fibers/cords applied onto masonry substrates. The results were carefully analyzed discussing failure modes, bond capacity, and slip statistical dispersion. Differences in the set-up, including the clamping method, textile impregnation, and instrumentation used for measuring the slip during the tests, were discussed in detail providing useful considerations and suggestions for reducing experimental scattering and obtaining reliable results.
LSD1 is a lysine demethylase highly involved in initiation and development of cancer. To design highly effective covalent inhibitors, a strategy is to fill its large catalytic cleft by designing ...tranylcypromine (TCP) analogs decorated with long, hindered substituents. We prepared three series of TCP analogs, carrying aroyl- and arylacetylamino (1 a-h), Z-amino acylamino (2 a-o), or double-substituted benzamide (3 a-n) residues at the C4 or C3 position of the phenyl ring. Further fragments obtained by chemical manipulation applied on the TCP scaffold (compounds 4 a-i) were also prepared. When tested against LSD1, most of 1 and 3 exhibited IC
values in the low nanomolar range, with 1 e and 3 a,d,f,g being also the most selective respect to monoamine oxidases. In MV4-11 AML and NB4 APL cells compounds 3 were the most potent, displaying up to sub-micromolar cell growth inhibition against both cell lines (3 a) or against NB4 cells (3 c). The most potent compounds in cellular assays were also able to induce the expression of LSD1 target genes, such as GFI-1b, ITGAM, and KCTD12, as functional read-out for LSD1 inhibition. Mouse and human intrinsic clearance data highlighted the high metabolic stability of compounds 3 a, 3 d and 3 g. Further studies will be performed on the new compounds 3 a and 3 c to assess their anticancer potential in different cancer contexts.
Role of interim-PET (I-PET) in diffuse large B-cell Lymphoma (DLBCL) is controversial. To determine predictive value of I-PET on progression-free survival (PFS), we enrolled 88 first-line DLBCL ...patients treated with 6-8 R-CHOP courses regardless of I-PET. PET/CT were performed at diagnosis, after 2 to 4 courses and at the end of therapy with central reviewing according to visual dichotomous criteria. Results are as follows: I-PET, 72% negative, 28% positive; final-PET (F-PET), 88% negative, 12% positive; clinical complete response 90%. Concordance between clinical response and F-PET negativity was 97% because of 2 false positive. With a median follow-up of 26.2 months, 2-year overall survival and PFS were 91% and 77%, respectively. Two-year PFS for I-PET and F-PET negative versus positive were as follows: I-PET 85% versus 72% (P = .0475); F-PET 83% versus 64% (P < .001). Because of a small number of events, 2 independent bivariate Cox models were tested for PFS. In model 1, F-PET contradicted I-PET (hazard ratio HR = 5.03, P = .015 vs 1.27, P = 691); in model 2, F-PET (HR = 4.54) and International propnostic Index score (HR = 5.36, P = .001) remained independent prognostic factors. In conclusion, positive I-PET is not predictive of a worse outcome in DLBCL; larger prospective studies and harmonization of I-PET reading criteria are needed.
Bis-(3-bromo-4-hydroxy)benzylidene cyclic compounds have been reported by us as epigenetic multiple ligands, but different substitutions at the two wings provided analogues with selective inhibition. ...Since the 1-benzyl-3,5-bis((
)-3-bromobenzylidene)piperidin-4-one
displayed dual p300/EZH2 inhibition joined to cancer-selective cell death in a panel of tumor cells and in in vivo xenograft models, we prepared a series of bis((
)-2-bromobenzylidene) cyclic compounds
-
to test in biochemical (p300, PCAF, SIRT1/2, EZH2, and CARM1) and cellular (NB4, U937, MCF-7, SH-SY5Y) assays. The majority of
-
exhibited potent dual p300 and CARM1 inhibition, sometimes reaching the submicromolar level, and induction of apoptosis mainly in the tested leukemia cell lines. The most effective compounds in both enzyme and cellular assays carried a 4-piperidone moiety and a methyl (
), benzyl (
), or acyl (
-
) substituent at N1 position. Elongation of the benzyl portion to 2-phenylethyl (
) and 3-phenylpropyl (
) decreased the potency of compounds at both the enzymatic and cellular levels, but the activity was promptly restored by introduction of a ketone group into the phenylalkyl substituent (
-
). Western blot analyses performed in NB4 and MCF-7 cells on selected compounds confirmed their inhibition of p300 and CARM1 through decrease of the levels of acetyl-H3 and acetyl-H4, marks for p300 inhibition, and of H3R17me2, mark for CARM1 inhibition.
Studies on late talkers (LTs) highlighted their heterogeneity and the relevance of describing different communicative profiles.
To examine lexical skills and gesture use in expressive (E-LTs) vs. ...receptive-expressive (R/E-LTs) LTs through a structured task.
Forty-six 30-month-old screened LTs were distinguished into E-LTs (n= 35) and R/E-LTs (n= 11) according to their receptive skills. Lexical skills and gesture use were assessed with a Picture Naming Game by coding answer accuracy (correct, incorrect, no response), modality of expression (spoken, spoken-gestural, gestural), type of gestures (deictic, representational), and spoken-gestural answers’ semantic relationship (complementary, equivalent, supplementary).
R/E-LTs showed lower scores than E-LTs for noun and predicate comprehension with fewer correct answers, and production with fewer correct and incorrect answers, and more no responses. R/E-LTs also exhibited lower scores in spoken answers, representational gestures, and equivalent spoken-gestural answers for noun production and in all spoken and gestural answers for predicate production.
Findings highlighted more impaired receptive and expressive lexical skills and lower gesture use in R/E-LTs compared to E-LTs, underlying the relevance of assessing both lexical and gestural skills through a structured task, besides parental questionnaires and developmental scales, to describe LTs’ communicative profiles.
•Receptive/expressive and expressive late talkers differ in lexicon and gesture use.•Receptive/expressive late talkers show lower receptive and expressive lexical skills.•Receptive/expressive late talkers show lower gesture use.•Receptive/expressive, gesture, and cognitive assessment is needed in language delay.
•A cluster analysis identified three distinct profiles among late talkers.•Severe late talkers showed limited communicative, receptive/expressive and cognitive skills.•Moderate late talkers showed ...limited expressive and cognitive skills.•Mild late talkers showed partially limited expressive skills.•Male gender was significantly more represented in the severe late talkers.
Late talkers represent a heterogeneous population. We aimed to describe communication profiles of low-risk preterm and full-term late talkers according to their receptive and expressive vocabulary size, considering communicative, linguistic, cognitive, and motor skills, as well as biological and environmental risk factors.
Sixty-eight late talkers (33 born low-risk preterm and 35 full-term) were identified through a language screening at 30 months. Parents filled out the Italian Short Forms of the MacArthur Bates Communicative Development Inventories and the Socio Conversational Skills Rating Scales. Children were assessed with the Picture Naming Game test and the Bayley Scales of Infant and Toddler Development.
A two-step cluster analysis identified three distinct profiles among late talkers according to their receptive and expressive vocabulary size. Severe late talkers (25%) showed less frequent use of pointing, limited verbal imitation, receptive vocabulary size, lexical and sentence production, responsiveness and assertiveness, and lower cognitive scores than mild late talkers (40%). Moderate late talkers (35%) showed less frequent verbal imitation, limited lexical and sentence production and lower cognitive scores than mild late talkers. Male gender was significantly more represented in the severe late profile, whereas other biological and environmental factors did not differ among the three profiles.
Findings highlighted the relevance of assessing communicative, lexical, grammar, pragmatic, and cognitive skills to describe late talkers’ profiles. A deeper investigation of phonological skills might also contribute to a further understanding of interindividual variability in this population.
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