Bioprinting Soft 3D Models of Hematopoiesis using Natural Silk Fibroin-Based Bioink Efficiently Supports Platelet Differentiation.

Hematopoietic stem and progenitor cells (HSPCs) continuously generate platelets throughout one's life. Inherited Platelet Disorders affect ≈ 3 million individuals worldwide and are characterized by defects in platelet formation or function. A critical challenge in the identification of these diseases lies in the absence of models that facilitate the study of hematopoiesis ex vivo. Here, a silk fibroin-based bioink is developed and designed for 3D bioprinting. This bioink replicates a soft and biomimetic environment, enabling the controlled differentiation of HSPCs into platelets. The formulation consisting of silk fibroin, gelatin, and alginate is fine-tuned to obtain a viscoelastic, shear-thinning, thixotropic bioink with the remarkable ability to rapidly recover after bioprinting and provide structural integrity and mechanical stability over long-term culture. Optical transparency allowed for high-resolution imaging of platelet generation, while the incorporation of enzymatic sensors allowed quantitative analysis of glycolytic metabolism during differentiation that is represented through measurable color changes. Bioprinting patient samples revealed a decrease in metabolic activity and platelet production in Inherited Platelet Disorders. These discoveries are instrumental in establishing reference ranges for classification and automating the assessment of treatment responses. This model has far-reaching implications for application in the research of blood-related diseases, prioritizing drug development strategies, and tailoring personalized therapies.

The Acceptability of a Psychoeducation and Skill-Based Training for Carers and Teachers to Cope with Risky Behaviours in Adolescence.

Childhood and adolescence psychopathology is associated with an increased risk of psychological difficulties in adulthood. Early interventions for youth should provide carers and teachers with knowledge and skills to respond to adolescents' risky behaviours. This study evaluated the acceptability and effectiveness of a single 3-h workshop, combining psychoeducation and skills training to promote knowledge about, and confidence to address, adolescents' risky behaviours in carers and teachers of adolescents aged 10-14. Demographics and perceived self-efficacy in the parental or teaching role were collected at baseline using self-report questionnaires. Motivation and confidence to respond to adolescents' risky behaviours were measured before and after the workshop using motivational rulers. Participants provided written feedback about their experience about the workshop. Twenty-seven carers and 27 teachers attended the workshops. Teachers reported a significant increase in both importance (p = 0.021) and confidence (p < 0.001) to respond to risky behaviours following the workshop. This change was associated with baseline self-efficacy levels (importance: p = 0.011; confidence: p = 0.002). Carers also reported greater confidence to address risky behaviours following the workshop (p = 0.002). Participants found the contents and methods of the workshop highly acceptable. Online and multiple-session workshops might increase reach and effectiveness.

Abnormal visual attention to simple social stimuli in 4-month-old infants at high risk for Autism.

Despite an increasing interest in detecting early signs of Autism Spectrum Disorders (ASD), the pathogenesis of the social impairments characterizing ASD is still largely unknown. Atypical visual attention to social stimuli is a potential early marker of the social and communicative deficits of ASD. Some authors hypothesized that such impairments are present from birth, leading to a decline in the subsequent typical functioning of the learning-mechanisms. Others suggested that these early deficits emerge during the transition from subcortically to cortically mediated mechanisms, happening around 2-3 months of age. The present study aimed to provide additional evidence on the origin of the early visual attention disturbance that seems to characterize infants at high risk (HR) for ASD. Four visual preference tasks were used to investigate social attention in 4-month-old HR, compared to low-risk (LR) infants of the same age. Visual attention differences between HR and LR infants emerged only for stimuli depicting a direct eye-gaze, compared to an adverted eye-gaze. Specifically, HR infants showed a significant visual preference for the direct eye-gaze stimulus compared to LR infants, which may indicate a delayed development of the visual preferences normally observed at birth in typically developing infants. No other differences were found between groups. Results are discussed in the light of the hypotheses on the origins of early social visual attention impairments in infants at risk for ASD.

Impact of the COVID-19 Italian Lockdown on the Physiological and Psychological Well-Being of Children with Fragile X Syndrome and Their Families.

On 10 March 2020, in Italy, a total lockdown was put in place to limit viral transmission of COVID-19 infection as much as possible. Research on the psychological impact of the COVID-19 pandemic highlighted detrimental effects in children and their parents. However, little is known about such effects in children with neurodevelopment disorders and their caregivers. The present study investigated how the lockdown has impacted the physiological and psychological well-being of children with Fragile X-Syndrome (FXS), aged from 2 to 16 years, and their mothers. In an online survey, 48 mothers of FXS children reported their perception of self-efficacy as caregivers and, at the same time, their children's sleep habits, behavioral and emotional difficulties during, and retrospectively, before the lockdown. Results showed a general worsening of sleep quality, and increasing behavioral problems. Although mothers reported a reduction in external support, their perception of self-efficacy as caregivers did not change during the home confinement compared to the period before. Overall, the present study suggested that specific interventions to manage sleep problems, as well as specific therapeutic and social support for increasing children and mother psychological well-being, need to be in place to mitigate the long-term effects of a lockdown.

Newborns' sensitivity to speed changes as a building block for animacy perception.

The human visual system can discriminate between animate beings vs. inanimate objects on the basis of some kinematic cues, such as starting from rest and speed changes by self-propulsion. The ontogenetic origin of such capability is still under debate. Here we investigate for the first time whether newborns manifest an attentional bias toward objects that abruptly change their speed along a trajectory as contrasted with objects that move at a constant speed. To this end, we systematically manipulated the motion speed of two objects. An object that moves with a constant speed was contrasted with an object that suddenly increases (Experiment 1) or with one that suddenly decreases its speed (Experiment 2). When presented with a single speed change, newborns did not show any visual preference. However, newborns preferred an object that abruptly increases and then decreases its speed (Experiment 3), but they did not show any visual preference for the reverse sequence pattern (Experiment 4). Overall, results are discussed in line with the hypothesis of the existence of attentional biases in newborns that trigger their attention towards some visual cues of motion that characterized animate perception in adults.

Covert orienting of attention in 3-month-old infants: The case of biological motion.

Humans attend to different positions in the space either by moving their eyes or by moving covertly their attention. The development of covert attention occurs during the first year of life. According to Colombo's model of attention (2001), within the first years there is a significant change in infants' visuo-spatial orienting mechanisms, from a predominantly overt form to a covert orienting starting from 4 to 5 months of life. The use of non-invasive brain imaging techniques can shed light on the origin of such mechanisms. In particular, EEG and ERP studies can directly investigate the neural correlates of covert attention in young infants. The present study investigated the neural correlates of covert attention employing a visuo-spatial cueing paradigm in 3-month-old infants. Infants were presented with a central point-light walker (PLD) followed by a single peripheral target. The target appeared randomly at a position either congruent or incongruent with the walking direction of the cue. We examined infants' target-locked P1 component and the saccade latencies toward the peripheral target. Results showed that the P1 component was larger in response to congruent than to incongruent targets and saccade latencies were faster for congruent rather than incongruent trials. Moreover, the facilitation in processing sensory information (priming effects) presented at the cued spatial location occurs even before the onset of the oculomotor response, suggesting that covert attention is present before 4 months of age. Overall, this study highlights how ERPs method could help researchers at investigating the neural basis of attentional mechanisms in infants.

Two-day-old newborns learn to discriminate accelerated-decelerated biological kinematics from constant velocity motion.

Already in uterus the hand moves with the typical accelerated-decelerated kinematics of goal-directed actions and, from the twenty-second week of pregnancy, the unborn shows the ability to modulate the velocity of the movement depending on the nature of the target. According to the direct matching hypothesis, this motor knowledge may be sufficient to attune neonates' motion perception-like adults'-to biological kinematics. Using dots configuration motions which varied with respect to the kinematics of goal-directed actions, we observed that two-day-old human newborns did not show any spontaneous preference for either biological accelerated-decelerated motion or non-biological constant velocity motion when these were simultaneously presented in a standard preferential looking paradigm. In contrast, newborns preferred the biological kinematics after the repeated visual presentation of the different motions in a standard infant-control visual habituation paradigm. We propose that present results indicate that the relationship between perception and action does not require only action development but also the accumulation of sufficient perceptual experience. They also suggest a fast plasticity of the sensorimotor system in linking an already acquired motor knowledge with a newly experienced congruent visual stimulation.

The neural correlates of orienting to walking direction in 6-month-old infants: An ERP study.

The ability to detect social signals represents a first step to enter our social world. Behavioral evidence has demonstrated that 6-month-old infants are able to orient their attention toward the position indicated by walking direction, showing faster orienting responses toward stimuli cued by the direction of motion than toward uncued stimuli. The present study investigated the neural mechanisms underpinning this attentional priming effect by using a spatial cueing paradigm and recording EEG (Geodesic System 128 channels) from 6-month-old infants. Infants were presented with a central point-light walker followed by a single peripheral target. The target appeared randomly at a position either congruent or incongruent with the walking direction of the cue. We examined infants' target-locked event-related potential (ERP) responses and we used cortical source analysis to explore which brain regions gave rise to the ERP responses. The P1 component and saccade latencies toward the peripheral target were modulated by the congruency between the walking direction of the cue and the position of the target. Infants' saccade latencies were faster in response to targets appearing at congruent spatial locations. The P1 component was larger in response to congruent than to incongruent targets and a similar congruency effect was found with cortical source analysis in the parahippocampal gyrus and the anterior fusiform gyrus. Overall, these findings suggest that a type of biological motion like the one of a vertebrate walking on the legs can trigger covert orienting of attention in 6-month-old infants, enabling enhancement of neural activity related to visual processing of potentially relevant information as well as a facilitation of oculomotor responses to stimuli appearing at the attended location.

A mental number line in human newborns.

Humans represent numbers on a mental number line with smaller numbers on the left and larger numbers on the right side. A left-to-right oriented spatial-numerical association, (SNA), has been demonstrated in animals and infants. However, the possibility that SNA is learnt by early exposure to caregivers' directional biases is still open. We conducted two experiments: in Experiment 1, we tested whether SNA is present at birth and in Experiment 2, we studied whether it depends on the relative rather than the absolute magnitude of numerousness. Fifty-five-hour-old newborns, once habituated to a number (12), spontaneously associated a smaller number (4) with the left and a larger number (36) with the right side (Experiment 1). SNA in neonates is not absolute but relative. The same number (12) was associated with the left side rather than the right side whenever the previously experienced number was larger (36) rather than smaller (4) (Experiment 2). Control on continuous physical variables showed that the effect is specific of discrete magnitudes. These results constitute strong evidence that in our species SNA originates from pre-linguistic and biological precursors in the brain.

Newborns are sensitive to the correspondence between auditory pitch and visuospatial elevation.

Amodal (redundant) and arbitrary cross-sensory feature associations involve the context-insensitive mapping of absolute feature values across sensory domains. Cross-sensory associations of a different kind, known as correspondences, involve the context-sensitive mapping of relative feature values. Are such correspondences in place at birth (like amodal associations), or are they learned from subsequently experiencing relevant feature co-occurrences in the world (like arbitrary associations)? To decide between these two possibilities, human newborns (median age = 44 hr) watched animations in which two balls alternately rose and fell together in space. The pitch of an accompanying sound rose and fell either congruently with this visual change (pitch rising and falling as the balls moved up and down), or incongruently (pitch rising and falling as the balls moved down and up). Newborns' looking behavior was sensitive to this congruence, providing the strongest indication to date that cross-sensory correspondences can be in place at birth.

Visual cues of motion that trigger animacy perception at birth: the case of self-propulsion.

Self-propelled motion is a powerful cue that conveys information that an object is animate. In this case, animate refers to an entity's capacity to initiate motion without an applied external force. Sensitivity to this motion cue is present in infants that are a few months old, but whether this sensitivity is experience-dependent or is already present at birth is unknown. Here, we tested newborns to examine whether predispositions to process self-produced motion cues underlying animacy perception were present soon after birth. We systematically manipulated the onset of motion by self-propulsion (Experiment 1) and the change in trajectory direction in the presence or absence of direct contact with an external object (Experiments 2 and 3) to investigate how these motion cues determine preference in newborns. Overall, data demonstrated that, at least at birth, the self-propelled onset of motion is a crucial visual cue that allowed newborns to differentiate between self- and non-self-propelled objects (Experiment 1) because when this cue was removed, newborns did not manifest any visual preference (Experiment 2), even if they were able to discriminate between the stimuli (Experiment 3). To our knowledge, this is the first study aimed at identifying sensitivity in human newborns to the most basic and rudimentary motion cues that reliably trigger perceptions of animacy in adults. Our findings are compatible with the hypothesis of the existence of inborn predispositions to visual cues of motion that trigger animacy perception in adults.

Walking direction triggers visuo-spatial orienting in 6-month-old infants and adults: An eye tracking study.

The present study investigates whether the walking direction of a biological motion point-light display can trigger visuo-spatial attention in 6-month-old infants. A cueing paradigm and the recording of eye movements in a free viewing condition were employed. A control group of adults took part in the experiment. Participants were presented with a central point-light display depicting a walking human, followed by a single peripheral target. In experiment 1, the central biological motion stimulus depicting a walking human could be upright or upside-down and was facing either left or right. Results revealed that the latency of saccades toward the peripheral target was modulated by the congruency between the facing direction of the cue and the position of the target. In infants, as well as in adults, saccade latencies were shorter when the target appeared in the position signalled by the facing direction of the point-light walker (congruent trials) than when the target appeared in the contralateral position (incongruent trials). This cueing effect was present only when the biological motion cue was presented in the upright condition and not when the display was inverted. In experiment 2, a rolling point-light circle with unambiguous direction was adopted. Here, adults were influenced by the direction of the central cue. However no effect of congruency was found in infants. This result suggests that biological motion has a priority as a cue for spatial attention during development.