ACE2 acts as a novel regulator of TMPRSS2-catalyzed proteolytic activation of influenza A virus in airway cells.

The transmembrane serine protease 2 (TMPRSS2) activates the outer structural proteins of a number of respiratory viruses including influenza A virus (IAV), parainfluenza viruses, and various coronaviruses for membrane fusion. Previous studies showed that TMPRSS2 interacts with the carboxypeptidase angiotensin-converting enzyme 2 (ACE2), a cell surface protein that serves as an entry receptor for some coronaviruses. Here, by using protease activity assays, we determine that ACE2 increases the enzymatic activity of TMPRSS2 in a non-catalytic manner. Furthermore, we demonstrate that ACE2 knockdown inhibits TMPRSS2-mediated cleavage of IAV hemagglutinin (HA) in Calu-3 human airway cells and suppresses virus titers 100- to 1.000-fold. Transient expression of ACE2 in ACE2-deficient cells increased TMPRSS2-mediated HA cleavage and IAV replication. ACE2 knockdown also reduced titers of MERS-CoV and prevented S cleavage by TMPRSS2 in Calu-3 cells. By contrast, proteolytic activation and multicycle replication of IAV with multibasic HA cleavage site typically cleaved by furin were not affected by ACE2 knockdown. Co-immunoprecipitation analysis revealed that ACE2-TMPRSS2 interaction requires the enzymatic activity of TMPRSS2 and the carboxypeptidase domain of ACE2. Together, our data identify ACE2 as a new co-factor or stabilizer of TMPRSS2 activity and as a novel host cell factor involved in proteolytic activation and spread of IAV in human airway cells. Furthermore, our data indicate that ACE2 is involved in the TMPRSS2-catalyzed activation of additional respiratory viruses including MERS-CoV.IMPORTANCEProteolytic cleavage of viral envelope proteins by host cell proteases is essential for the infectivity of many viruses and relevant proteases provide promising drug targets. The transmembrane serine protease 2 (TMPRSS2) has been identified as a major activating protease of several respiratory viruses, including influenza A virus. TMPRSS2 was previously shown to interact with angiotensin-converting enzyme 2 (ACE2). Here, we report the mechanistic details of this interaction. We demonstrate that ACE2 increases or stabilizes the enzymatic activity of TMPRSS2. Furthermore, we describe ACE2 involvement in TMPRSS2-catalyzed cleavage of the influenza A virus hemagglutinin and MERS-CoV spike protein in human airway cells. These findings expand our knowledge of the activation of respiratory viruses by TMPRSS2 and the host cell factors involved. In addition, our results could help to elucidate a physiological role for TMPRSS2.

Synthesis and structural characterization of new macrocyclic inhibitors of the Zika virus NS2B-NS3 protease.

Three new series of macrocyclic active site-directed inhibitors of the Zika virus (ZIKV) NS2B-NS3 protease were synthesized. First, attempts were made to replace the basic P3 lysine residue of our previously described inhibitors with uncharged and more hydrophobic residues. This provided numerous compounds with inhibition constants between 30 and 50 nM. A stronger reduction of the inhibitory potency was observed when the P2 lysine was replaced by neutral residues, all of these inhibitors possess Ki values >1 µM. However, it is possible to replace the P2 lysine with the less basic 3-aminomethylphenylalanine, which provides a similarly potent inhibitor of the ZIKV protease (Ki = 2.69 nM). Crystal structure investigations showed that the P2 benzylamine structure forms comparable interactions with the protease as lysine. Twelve additional structures of these inhibitors in complex with the protease were determined, which explain many, but not all, SAR data obtained in this study. All individual modifications in the P2 or P3 position resulted in inhibitors with low antiviral efficacy in cell culture. Therefore, a third inhibitor series with combined modifications was synthesized; all of them contain a more hydrophobic  d-cyclohexylalanine in the linker segment. At a concentration of 40 µM, two of these compounds possess similar antiviral potency as ribavirin at 100 µM. Due to their reliable crystallization in complex with the ZIKV protease, these cyclic compounds are very well suited for a rational structure-based development of improved inhibitors.

Memory support training and lifestyle modifications to promote healthy aging in persons at risk for Alzheimer's disease: a digital application supported intervention (Brain Boosters).

BACKGROUND: Evidence-based interventions to protect against cognitive decline among older adults at risk for Alzheimer's disease and related dementias (ADRD) are urgently needed. Rehabilitation approaches to support memory and behavioral/lifestyle interventions are recognized as promising strategies for preserving or improving cognitive health, although few previous interventions have combined both approaches. This paper describes the protocol of the Brain Boosters intervention, which synergistically combines training in compensatory and healthy lifestyle behaviors and supports implementation and tracking of new behaviors with a digital application. METHODS: The study utilizes a single-site, single-blinded, randomized controlled design to compare a structured lifestyle and compensatory aid intervention to an education-only self-guided intervention. We plan to enroll 225 community-dwelling adults (25% from underrepresented groups) aged 65 + who endorse subjective cognitive decline (SCD) and low baseline levels of healthy lifestyle behaviors. Both interventions will be administered in group format, consisting of 15 two-hour classes that occur weekly for ten weeks and taper to bi-monthly and monthly, for an intervention duration of 6 months. Participants in both interventions will receive education about a variety of memory support strategies and healthy lifestyle behaviors, focusing on physical and cognitive activity and stress management. The structured intervention will also receive support in adopting new behaviors and tracking set goals aided by the Electronic Memory and Management Aid (EMMA) digital application. Primary outcomes include global cognition (composite of memory, attention, and executive function tests) and everyday function (Everyday Cognition Questionnaire). Data will be collected at baseline and outcome visits, at approximately 6, 12, and 18 months. Qualitative interviews, self-report surveys (e.g., indicators of self-determination, health literacy) and EMMA data metrics will also be used to identify what components of the intervention are most effective and for whom they work. DISCUSSION: Successful project completion will provide valuable information about how individuals with SCD respond to a compensation and preventative lifestyle intervention assisted by a digital application, including an understanding of factors that may impact outcomes, treatment uptake, and adherence. The work will also inform development, scaling, and personalization of future interventions that can delay disability in individuals at risk for ADRD. TRIAL REGISTRATION: ClinicalTrials.gov. (NCT05027789, posted 8/30/2021).

Borderline Personality Traits and Emotion Regulation Strategies in Adolescents: The Role of Implicit Theories.

Borderline Personality Disorder (BPD) is associated with emotion dysregulation. The emotion regulation strategies people adopt may depend on one's belief about emotion as either fixed or changeable (termed "implicit theory"). We test this experimentally by modifying beliefs about emotions using virtual reality (VR). A sample of 29 adolescents (ages 14-17 years) were recruited from two adolescent inpatient units for an uncontrolled pilot trial of a new brief intervention. We measured BPD traits, beliefs about emotion, treatment preference, cognitive reappraisal and rumination, before the VR game and 14-31 days later. Adolescents with higher levels of BPD traits endorsed fixed beliefs of emotion and reported higher levels of rumination and lower levels of cognitive reappraisal. After a one-time message delivered via VR, adolescents evidenced an increase in belief that their emotions were changeable. These findings suggest beliefs about emotions may have an important role in interventions for adolescents with BPD traits.

Developing a consensus definition of psychosocial complexity in cancer patients using Delphi methods.

OBJECTIVE: Cancer is one of the biggest health challenges of our times, affecting all the personal areas of a patient. The interrelationships between these areas and the need for multidisciplinary care require the assessment of psychosocial complexity in cancer patients. The main aim of this study was to reach a consensus on the general definition of psychosocial complexity in cancer and its main elements according to the experts in the field. METHOD: A Delphi study was performed, which first involved a comprehensive review of the literature to create a questionnaire that was validated by two expert panels. The first panel consisted of intra-institutional experts, while the second included extra-institutional experts in the field. The study included three more rounds: (1) validation of the questionnaire by the internal panel, (2) discussion of the results and resolving discrepancies, and (3) validation of the questionnaire by the external panel. RESULTS: After the four-round Delphi process, we obtained a consensus definition of psychosocial complexity in cancer patients, as well as of its main factors: medical-physical, social-family, psychological, and spiritual. A 21-indicators list and its 8-indicators brief version were also proposed as indicators of psychosocial complexity. SIGNIFICANCE OF RESULTS: We present a definition of psychosocial complexity in cancer patients that has been agreed by experts, also establishing its four factors: medical-physical, social-family, psychological, and spiritual. This has led to the development of a list of indicators (and its brief version) that, after a validation process, could help health professionals to identify patients with high psychosocial complexity to provide them an optimal care.

Mind-mindedness versus mentalistic interpretations of behavior: Is mind-mindedness a relational construct?

Mind-mindedness is a measure of the tendency to represent significant others in internal state terms and is central to supportive parent-infant relationships. The two studies reported here explored whether mind-mindedness generalizes to representations of unknown individuals, using a novel task that assessed individual differences in adults' tendency to interpret others' behavior with reference to their internal states: the Unknown Mother-Infant Interaction Task (UMIIT). We compared UMIIT performance with measures of mind-mindedness from (a) adults' descriptions of close friends and partners (Study 1, N = 96) and (b) mothers' appropriate versus nonattuned comments on their infants' internal states (Study 2, N = 56). In line with the proposal that mind-mindedness is a relational construct, UMIIT performance was unrelated to mind-mindedness in both studies.

La consciente mentalidad es una medida que tiende a representar a quienes nos son importantes en términos de un estado interno y es esencial para las relaciones de mucho apoyo entre progenitores e infantes. Los dos estudios que se reportan aquí exploraron si la mentalidad consciente generaliza al punto de representar a individuos desconocidos, usando una novedosa tarea que evalúa las diferencias individuales en la tendencia de los adultos a interpretar la conducta de otros en función de sus estados mentales: El Trabajo de la Interacción Madre Desconocida-Infante (UMIIT). Comparamos la actuación de UMIIT con las medidas de mentalidad consciente de (a) descripciones de adultos sobre amigos cercanos y parejas (Estudio 1, N = 96), y (b) los comentarios apropiados de las madres versus sus no armonizados comentarios con respecto a los estados internos de sus infantes (Estudio 2, N = 56). Alineado con la propuesta de que la mentalidad consciente es un concepto de la relación, la actuación de UMIIT no estuvo relacionada con la mentalidad consciente en ninguno de los estudios.

L'esprit-qualité mentale (en anglais mind-mindedness) est une mesure de la tendance à représenter les personnes qui nous sont chères en des termes d'état interne. Elle est centrale aux relations parent-enfant positives. Les deux études dont on fait état ici ont exploré si l'esprit-qualité mentale généralise les représentations d'individus inconnus, en utilisant une tâche nouvelle qui a évalué les différences individuelles dans la tendance des adultes à interpréter le comportement des autres en référence à leurs états internes: la Tâche de Mère Inconnue-Interaction du Nourrisson (UMIIT en anglais, soit Unknown Mother-Infant Interaction Task). Nous avons comparé la performance UMIIT aux mesures de l'esprit-qualité mentale de (a) descriptions d'adultes de leurs amis proches et de leurs partenaires (Etude 1, N = 96) et (b) de commentaires appropriés par rapport à pas trop appropriés des mères sur les états internes de leurs nourrissons (Etude 2, N = 56). Conformément à la proposition selon laquelle l'esprit-qualité mentale est une construction relationnelle, la performance de l'UMIIT n'était pas liée à l'esprit-qualité mentale dans les deux études.

Callous-unemotional traits and fearlessness: A cardiovascular psychophysiological perspective in two adolescent samples using virtual reality.

There has been a longstanding debate about the link between callous-unemotional traits and fearlessness. However, biological evidence for a relationship in adolescents is lacking. Using two adolescent samples, we measured emotional reactivity and cardiac measures of sympathetic (pre-ejection period) and parasympathetic (respiratory sinus arrhythmia) reactivity during 3D TV and virtual reality fear induction. Study 1 included 62 community adolescents from a stratified sample. Study 2 included 60 adolescents from Emotional and Behavioral Difficulties schools. Results were consistent across both studies. Adolescents with high callous-unemotional traits showed coactivation of the sympathetic and parasympathetic nervous system. Consistent with these results, youths with callous-unemotional traits self-reported that they felt more in control after the fear induction. Thus, in both samples, youth with callous-unemotional traits displayed a physiological and emotional profile suggesting they maintained control during fear induction. Therefore, it is proposed here that a shift in thinking of youth with callous-unemotional traits as fearless to youth with callous-unemotional traits are better able to manage fearful situations, may be more appropriate.

Parental Adjustment following Pediatric Burn Injury: The Role of Guilt, Shame, and Self-Compassion.

Objective: The purpose of this study was to examine the association between factors: guilt, shame, self-compassion, and parents' psychological adjustment to their child's burn injury. Methods: Participants were 91 parents and primary caregivers (63 mothers, 25 fathers, 3 other) of 71 children recruited on the ward or at outpatient clinics during the first 8 weeks following their child's burn injury. In 20 cases, both parents participated, while for 51 children only one parent participated. Participants completed questionnaires which assessed adjustment (symptoms of depression, anxiety, and posttraumatic stress syndrome [PTSS]) as well as guilt, shame, and self-compassion. Results: Multilevel analysis indicated that feelings of guilt and shame were associated with poorer adjustment in parents, while parents who rated high in self-compassion reported fewer symptoms of depression and PTSS. Guilt and shame showed a differing pattern of effects with shame explaining more variance for anxiety and depression. Length of hospitalization predicted PTSS; however, the remaining injury factors (size of burn, requiring a skin graft) were unrelated to parental adjustment. Conclusions: Health-care professionals should pay close attention to families' subjective injury experiences. Screening for psychological distress should be offered to all families regardless of the size and severity of the burn injury.

Mothers' Early Mind-Mindedness Predicts Educational Attainment in Socially and Economically Disadvantaged British Children.

Relations between mothers' mind-mindedness (appropriate and nonattuned mind-related comments) at 8 months (N = 206), and children's educational attainment at ages 7 (n = 158) and 11 (n = 156) were investigated in a British sample. Appropriate mind-related comments were positively correlated with reading and mathematics performance at both ages but only in the low-socioeconomic status (SES) group. Path analyses showed that in the low-SES group, appropriate mind-related comments directly predicted age-11 reading performance, with age-4 verbal ability mediating the relation between appropriate mind-related comments and age-7 reading. In contrast, maternal sensitivity and infant-mother attachment security did not predict children's educational attainment. These findings are discussed in terms of genetic and environmental contributions to reading and mathematics performance.

Metagenomic Analysis of the Whole Gut Microbiota in Brazilian Termitidae Termites Cornitermes cumulans, Cyrilliotermes strictinasus, Syntermes dirus, Nasutitermes jaraguae, Nasutitermes aquilinus, Grigiotermes bequaerti, and Orthognathotermes mirim.

Although some previous studies have described the microbial diversity of termite in Brazil, the lack of studies about this subject is still evident. In the present study, we described by whole genome sequencing, the gut microbiota of seven species of termites (Termitidae) with different feeding habits from four Brazilian locations. For the litter species, the most abundant bacterial phylum was Firmicutes, where Cornitermes cumulans and Syntermes dirus (Syntermitinae) were identified. For the humus species, the most abundant bacterial phylum was Proteobacteria where three species were studied: Cyrilliotermes strictinasus (Syntermitinae), Grigiotermes bequaerti (Apicotermitinae), and Orthognathotermes mirim (Termitinae). For the wood termites, Firmicutes and Spirochaetes were the most abundant phyla, respectively, where two species were identified: Nasutitermes aquilinus and Nasutitermes jaraguae (Nasutitermitinae). The gut microbiota of all four examined subfamilies shared a conserved functional and carbohydrate-active enzyme profile and specialized in cellulose and chitin degradation. Taken together, these results provide insight into the partnerships between termite and microbes that permit the use of refractory energy sources.

Antioxidant and pro-oxidant actions of resveratrol on human serum albumin in the presence of toxic diabetes metabolites: Glyoxal and methyl-glyoxal.

Methylglyoxal (MGO) and glyoxal (GO) are attracting considerable attention because of their role in the onset of diabetes symptoms. Therefore, to comprehend the molecular fundamentals of their pathological actions is of the utmost importance. In this study, the molecular interactions between resveratrol (RES) and human serum albumin (HSA) and the ability of the stilbene to counteract the oxidative damage caused by pathological concentrations of MGO and GO to the human plasma protein, was assessed. The oxidation of Cys34 in HSA as well as the formation of specific protein semialdehydes AAS (α-aminoadipic), GGS (γ-glutamic) and the accumulation of Advanced Glycation End-products (AGEs) was investigated. Resveratrol was found to neutralize both α-dicarbonyls by forming adducts detected by HESI-Orbitrap-MS. This antioxidant action was manifested in a significant reduction of AGEs. However, RES-α-dicarbonyl conjugates oxidized Cys34 and lysine, arginine and/or proline by a nucleophilic attack on SH and ε-NH groups in HSA. The formation of specific semialdehydes in HSA after incubation with GO and MGO at pathological concentrations was reported for the first time in this study, and may be used as early and specific biomarkers of the oxidative stress undergone by diabetic patients. The pro-oxidative role of the RES-α-dicarbonyl conjugates should be further investigated to clarify whether this action leads to positive or harmful clinical consequences. The biological relevance of human protein carbonylation as a redox signaling mechanism and/or as a reflection of oxidative damage and disease should also be studied in future works.

Pubertal timing and callous-unemotional traits in girls: Associations across two samples from the UK and Cyprus.

INTRODUCTION: Girls remain an understudied group when examining delinquency. Callous-unemotional traits are chief among personality traits that relate to delinquency. Some suggest, however, that girls who evince callous-unemotional traits delay their delinquent behavior until adolescence. This transitional period encompasses physical factors that relate to engagement in risky decision making, but we don't know how these factors relate to callous-unemotional traits. Early pubertal timing shows positive associations with delinquency; we tested if this was also the case for callous-unemotional traits. METHODS: We tested associations among pubertal timing (i.e., maturity and menarche age), delinquency, and callous-unemotional traits within girls (ages 11-18 years) sampled from two European countries (UK and Cyprus). We also tested the interaction between callous-unemotional traits and pubertal timing in statistically predicting delinquency to test if associations between early puberty and delinquency were moderated by callous-unemotional traits. RESULTS: Greater callous-unemotional traits were surprisingly negatively related to early pubertal timing. Those girls in the delayed menarche group had the highest level of callous-unemotional traits, higher than the typical and early menarche groups. Only callous-unemotional traits statistically predicted variance in delinquency and no moderation was evident. CONCLUSIONS: The implications are that callous-unemotional traits and the transition to puberty may be particularly important for girls' adjustment in adolescence, particularly if menarche is delayed allowing girls to avoid punishment by capitalizing on their immaturity.

Proactive and Reactive Aggression Subgroups in Typically Developing Children: The Role of Executive Functioning, Psychophysiology, and Psychopathy.

This study aimed to assess whether groups of aggressive children differed on psychopathic traits, and neuropsychological and neurobiological measures of prefrontal functioning consistent with the objectives of their aggression-reactive or proactive. Including 110 typically developing children (9-11 years), a latent class analysis identified a low aggression group, a high reactive aggression group, and a mixed (high reactive and proactive) aggression group. Results show high callous-unemotional traits and low resting respiratory sinus arrhythmia increased the likelihood of children being in the mixed aggression group, when compared to the reactive and low aggression groups. However, deficits in planning and inhibitory control increased the likelihood of children being in the reactive aggression group, when compared to the mixed and low aggression groups. Executive functioning deficits did not differentiate the mixed group from the low aggression group. These findings highlight psychobiological and executive functioning differences that may explain heterogeneity in childhood aggression.

A quick and robust MHC typing method for free-ranging and captive primate species.

Gene products of the major histocompatibility complex (MHC) of human and non-human primates play a crucial role in adaptive immunity, and most of the relevant genes not only show a high degree of variability (polymorphism) but also copy number variation (CNV) is observed. Due to this diversity, MHC proteins influence the capability of individuals to cope with various pathogens. MHC and/or MHC-linked gene products such as odorant receptor genes are thought to influence mate choice and reproductive success. Therefore, MHC typing of wild and captive primate populations is considered to be useful in conservation biology, which is, however, often hampered by the need of invasive and time-consuming methods. All intact Mhc-DRB genes in primates appear to possess a complex and highly divergent microsatellite, DRB-STR. A panel of 154 pedigreed olive baboons (Papio anubis) was examined for their DRB content by DRB-STR analysis of genomic DNA. Using the same methodology on DNA of feces samples, DRB variability of a silvery gibbon population (Hylobates moloch) (N = 24), an endangered species, could successfully be studied. In both species, length determination of the DRB-STR resulted in the definition of unique genotyping patterns that appeared to be specific for a certain chromosome. Moreover, the different STR lengths were shown to segregate with the allelic variation of the respective gene. The results obtained expand data gained previously on DRB-STR typing in macaques, great apes, and humans and strengthen the conclusion that this protocol is applicable in molecular ecology, conservation biology, and colony management, especially of endangered primate species.

Dietary protein oxidation: A silent threat to human health?

Protein oxidation has become a topic of great scientific interest in the field of food science and nutrition. Food proteins are known to be preferential targets of radical species, and protein oxidation has relevant consequences on protein functionality and food quality. Current trends in this field call attention to the nutritional and health dimensions of oxidized foods. Both lipid and protein oxidation products are accumulated in food during processing and storage and also upon food intake during the subsequent digestion phases. The gastrointestinal tract and internal organs are exposed to the cytotoxic and mutagenic potential of these species. While the molecular basis of the pathogenesis of particular dietary lipid oxidation products is well known, the impact of dietary oxidized proteins on human health has been largely ignored. The well-established association between in vivo protein oxidation and aging and age-related diseases urges scientists to investigate the contribution of dietary protein oxidation to particular pathological conditions. Recent reports indicate the involvement of dietary protein oxidation species on particular health disorders, which emphasizes the link between dietary and in vivo protein oxidation.

How does restricted and repetitive behavior relate to language and cognition in typical development?

Relations between restricted and repetitive behavior at age 26 months and children's concurrent (N = 203) and later (n = 161) social cognition and language development were investigated. Restricted and repetitive behavior was assessed using two scales: sensory and motor repetitive behaviors and rigidity/routines/restricted interests. Language was assessed at ages 26 and 51 months; social cognition was assessed at ages 26 (symbolic play) and 51 and 61 months (theory of mind). Sensory and motor repetitive behavior was negatively related to children's (a) language performance at 26 and 51 months, (b) instructed symbolic play at 26 months, and (c) theory of mind performance at 51 and 61 months. Path analyses showed that children's sensory and motor repetitive behavior at age 26 months was related to lower receptive verbal ability and theory of mind at 51 months, which led to lower theory of mind at 61 months. Rigidity/routines/restricted interests at 26 months were unrelated to concurrent and later social cognition and language. These results are discussed in terms of the pathways via which sensory and motor repetitive behavior might impact negatively on development.

Proof of concept of a mind-mindedness intervention for mothers hospitalized for severe mental illness.

Studies 1 and 2 investigated how maternal severe mental illness (SMI) related to mothers' mind-mindedness (appropriate and nonattuned mind-related comments). Study 1 showed that mothers with SMI (n = 50) scored lower than psychologically well mothers for both appropriate and nonattuned comments, whereas mothers with SMI in Study 2 (n = 22) had elevated levels of nonattuned comments. Study 2 also tested the efficacy of a single-session video-feedback intervention to facilitate mind-mindedness in mothers with SMI. The intervention was associated with a decrease in nonattuned comments, such that on discharge, mothers did not differ from psychologically well controls. Study 3 assessed infant-mother attachment security in a small subset of intervention-group mothers from Study 2 (n = 9) and a separate group of standard care mothers (n = 30) at infant mean age 17.1 months (SD = 2.1). Infants whose mothers completed the intervention were more likely to be securely attached and less likely to be classified as insecure-disorganized than those of mothers who received standard care. We conclude that a single session of video-feedback to facilitate mind-mindedness in mothers with SMI may have benefits for mother-infant interaction into the second year of life.

Vulvar and gastric involvement in plasmablastic lymphoma.

Plasmablastic lymphoma is highly malignant and invasive. It is most commonly found in gastrointestinal tract and is strongly asso- ciated with human immunodeficiency virus (HIV). The authors report a case of a 37-year-old HIV-positive African American woman with a vulvar mass diagnosed as plasmablastic lymphoma. Involvement of the upper gastrointestinal tract had been detected by endoscopic biopsy, suggesting that any patient diagnosed with plasmablastic lymphoma in unusual locations should be investigated for primary lesions in the gastrointestinal tract.

Callous-Unemotional Traits Moderate the Relation Between Prenatal Testosterone (2D:4D) and Externalising Behaviours in Children.

Children who exhibit callous-unemotional (CU) traits are identified as developing particularly severe forms of externalising behaviours (EB). A number of risk factors have been identified in the development of CU traits, including biological, physiological, and genetic factors. However, prenatal testosterone (PT) remains un-investigated, yet could signal fetal programming of a combination of CU/EB. Using the 2D:4D digit ratio, the current study examined whether CU traits moderated the relationship between PT and EB. Hand scans were obtained from 79 children aged between 5 and 6 years old whose parents completed the parent report ICU (Inventory of Callous Unemotional Traits) and SDQ (Strengths and Difficulties Questionnaire). CU traits were found to moderate the relationship between PT and EB so that children who were exposed to increased PT and were higher in CU traits exhibited more EB. Findings emphasize the importance of recognising that vulnerability for EB that is accompanied by callousness may arise before birth.

Callous-unemotional traits and impulsivity: distinct longitudinal relations with mind-mindedness and understanding of others.

BACKGROUND: Problems in understanding other people's mental states may relate to distinct personality traits that are associated with early externalizing behavior. A distinction between theory of mind (ToM) and empathy has proven important in shedding light on the problems in understanding other minds encountered by children high on callous-unemotional (CU) traits and exhibiting impulsivity. The aim of this study was to investigate whether children's early ToM and emotion understanding abilities predicted CU traits and impulsivity at age 10. A further aim was to explore whether the quality of the parent-child relationship very early in the development indirectly or directly predicted the children's CU traits and impulsivity. METHOD: We examined whether ToM and empathy skills might differentially relate to personality traits associated with externalizing behaviors (i.e., impulsivity and CU traits). We examined these relations over time in a longitudinal cohort of 96 boys and girls using follow-back analyses, incorporating measures of maternal mind-mindedness (appropriate mind-related talk) to examine the possible role of parent-child interaction quality. RESULTS: Appropriate mind-related talk indirectly predicted CU traits (at age 10 years) via its effect on children's emotion understanding. ToM predicted impulsive/irresponsible traits, but ceased to be significant when controlling for externalizing behaviors. CONCLUSION: The present findings demonstrate that parents who remark appropriately on their infant's mental states may help the child to understand emotions and may mold an empathic understanding of others, thereby preventing CU traits.