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Abstract The conditions supporting the generation of microglia-like cells in the central nervous system (CNS) after transplantation of hematopoietic stem/progenitor cells (HSPC) have been studied to advance the treatment of neurodegenerative disorders. Here, we explored the transplantation efficacy of different cell subsets and delivery routes with the goal of favoring the establishment of a stable and exclusive engraftment of HSPCs and their progeny in the CNS of female mice. In this setting, we show that the CNS environment drives the expansion, distribution and myeloid differentiation of the locally transplanted cells towards a microglia-like phenotype. Intra-CNS transplantation of HSPCs engineered to overexpress TREM2 decreased neuroinflammation, Aβ aggregation and improved memory in 5xFAD female mice. Our proof of concept study demonstrates the therapeutic potential of HSPC gene therapy for Alzheimer’s disease.

In extreme temperature environments, a newly emerging engineering application involves both the active and passive control of structures using cryogenic shape memory alloys, which are smart materials able to recover high deformation below the freezing point. With the objective of carrying out new advances in this area, the present work aims to investigate the Cu-7.5Al-13.5Mn (wt.%) shape memory alloy. Thermal, microstructural, and thermomechanical analyses of as-cast and hot-rolled specimens were performed, taking into account the effects of annealing and solubilization. It was observed that the phase transition occurs at temperatures below 120 K and changes according to the thermo-mechanical path. Specifically, hot-rolling lowers the phase transition temperature range with respect to the as-cast condition–from 34 K to 23 K for Mf, and from 89 K to 80 K for Af. Additionally, when the annealing temperature rises, the phase transformation temperature increases as well, and the alloy loses its cryogenic features when heat treated above 473 K. Finally, loss factors of 0.06 and 0.088, which were respectively found in dynamic and static settings, validate the material’s good damping response.

Background and aim: BK virus, a member of human polyomavirus family, is a worldwide distributed virus characterized by a seroprevalence rate of 70-90% in adult population. Monitoring of viral replication is made by evaluation of BK DNA by quantitative polymerase chain reaction. Many different methods can be applied for extraction of nucleic acid from several specimens. The aim of this study was to assess the impact of two different DNA extraction procedure on BK viral load. Materials and methods: DNA extraction procedure including the Nuclisens easyMAG platform (bioMerieux, Marcy l’Etoile, France) and manual QIAGEN extraction (QIAGEN Hilden, Germany). BK DNA quantification was performed by Real Time TaqMan PCR using a commercial kit. Result and discussion: The samples capacity, cost and time spent were compared for both systems. In conclusion our results demonstrate that automated nucleic acid extraction method using Nuclisense easyMAG was superior to manual protocol (QIAGEN Blood Mini kit), for the extraction of BK virus from serum and urine specimens.

Abstract In this study we carried out a behavioral experiment comparing action language comprehension in L1 (Italian) and L2 (English). Participants were Italian native speakers who had acquired the second language late (after the age of 10). They performed semantic judgments on L1 and L2 literal, idiomatic and metaphorical action sentences after viewing a video of a hand performing an action that was related or unrelated to the verb used in the sentence. Results showed that responses to literal and metaphorical L1 sentences were faster when the action depicted was related to the verb used rather than when the action depicted was unrelated to the verb used. No differences were found for the idiomatic condition. In L2 we found that all responses to the three conditions were facilitated when the action depicted was related to the verb used. Moreover, we found that the difference between the unrelated and the related modalities was greater in L2 than in L1 for the literal and the idiomatic condition but not for the metaphorical condition. These findings are consistent with the embodied cognition hypothesis of language comprehension.

IntroductionMulibrey nanism (MUL) is a rare disorder caused by TRIM37 gene variants characterized by growth failure, dysmorphic features, congestive heart failure (CHF), and an increased risk of Wilms’ tumor. Although immune system impairment has been documented in MUL, the underlying mechanisms remain poorly understood.MethodsWe present a case of MUL with progressive lymphopenia and review similar cases from the literature.ResultsOur patient presented with prenatal onset growth restriction, characteristic dysmorphic features, and Wilms’ tumor. She developed progressive lymphopenia starting at 10 years of age, leading to the initiation of intravenous immunoglobulin (IVIG) replacement therapy and infection prophylaxis. Genetic analysis detected a likely pathogenic variant on the maternal allele and copy number loss on the paternal allele in TRIM37. Subsequently a cardiac magnetic resonance imaging was conducted revealing signs of pericardial constriction raising concerns for intestinal lymphatic losses. The cessation of IVIG therapy did not coincide with any increase in the rate of infections. The patient exhibited a distinct immunological profile, characterized by hypogammaglobulinemia, impaired antibody responses, and skewed T-cell subsets with an altered CD4+/CD8+ ratio, consistent with previous reports. Normal thymocyte development assessed by artificial thymic organoid platform ruled out an early hematopoietic intrinsic defect of T-cell development.DiscussionThe immunological profile of MUL patients reported so far shares similarities with that described in protein-losing enteropathy secondary to CHF in Fontan circulation and primary intestinal lymphangiectasia. These similarities include hypogammaglobulinemia, significant T-cell deficiency with decreased CD4+ and CD8+ counts, altered CD4+/CD8+ ratios, and significantly modified CD4+ and CD8+ T-cell phenotypes toward effector and terminal differentiated T cells, accompanied by a loss of naïve CD45RA+ T lymphocytes. In MUL, CHF is a cardinal feature, occurring in a significant proportion of patients and influencing prognosis. Signs of CHF or constrictive pericarditis have been evident in the case reported here and in all cases of MUL with documented immune dysfunction reported so far. These observations raise intriguing connections between these conditions. However, further investigation is warranted to in-depth define the immunological defect, providing valuable insights into the pathophysiology and treatment strategies for this condition.

Nowadays there is a broad consensus on the role of multimodality in the construction of an embodied aesthetic experience in adults, whereas little is known about the relationship between sensorimotor and aesthetic experience during development. To fill this gap, the present study investigated whether sensorimotor experience with sculpting natural materials (i.e., clay or sand) influences beauty judgments offered to abstract artifacts made by the same materials. Five years old children (n.47) were asked to rate tactile (How smooth is it?), visual (How dark is it?) and beauty (How much do you like it?) proprieties of two artifacts using a visual-analog measurement-tool ad hoc developed to fit children’s cognitive skills. Participants rated the artifacts before and after a free-hands manipulation with only one of the two sculpting materials, either sand or clay. Results showed that the greater the sensorimotor interaction experienced with the artifacts, the higher the increment of beauty rating offered to the artifacts made by the same material previously manipulated. No modulations were found for tactile and visual ratings. These results demonstrate that, even in pre-school children, aesthetic experience is specifically linked to its sensorimotor component, supporting, from a developmental perspective, the definition of aesthetic experience as intrinsically rooted on beholders’ bodily experience.

Abstract Background Recent evidence shows an association between coronavirus disease 2019 (COVID-19) infection and a severe inflammatory syndrome in children. Cardiovascular magnetic resonance (CMR) data about myocardial injury in children are limited to small cohorts. The aim of this multicenter, international registry is to describe clinical and cardiac characteristics of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 using CMR so as to better understand the real extent of myocardial damage in this vulnerable cohort. Methods and results Hundred-eleven patients meeting the World Health Organization criteria for MIS-C associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), having clinical cardiac involvement and having received CMR imaging scan were included from 17 centers. Median age at disease onset was 10.0 years (IQR 7.0–13.8). The majority of children had COVID-19 serology positive (98%) with 27% of children still having both, positive serology and polymerase chain reaction (PCR). CMR was performed at a median of 28 days (19–47) after onset of symptoms. Twenty out of 111 (18%) patients had CMR criteria for acute myocarditis (as defined by the Lake Louise Criteria) with 18/20 showing subepicardial late gadolinium enhancement (LGE). CMR myocarditis was significantly associated with New York Heart Association class IV (p = 0.005, OR 6.56 (95%-CI 1.87–23.00)) and the need for mechanical support (p = 0.039, OR 4.98 (95%-CI 1.18–21.02)). At discharge, 11/111 (10%) patients still had left ventricular systolic dysfunction. Conclusion No CMR evidence of myocardial damage was found in most of our MIS-C cohort. Nevertheless, acute myocarditis is a possible manifestation of MIS-C associated with SARS-CoV-2 with CMR evidence of myocardial necrosis in 18% of our cohort. CMR may be an important diagnostic tool to identify a subset of patients at risk for cardiac sequelae and more prone to myocardial damage. Clinical trial registration: The study has been registered on ClinicalTrials.gov, Identifier NCT04455347, registered on 01/07/2020, retrospectively registered.

Background: Managing repaired tetralogy of Fallot (TOF) patients is still challenging despite the fact that published studies identified prognostic clinical or imaging data with rather good negative predictive accuracy but weak positive predictive accuracy. Heterogeneity of the initial anatomy, the surgical approach, and the complexity of the mechanism leading to dilation and ventricular dysfunction explain the challenge of predicting the adverse event in this population. Therefore, risk stratification and management of this population remain poorly standardized. Design: The CMR/CT WG of the Italian Pediatric Cardiology Society set up a multicenter observational clinical database of repaired TOF evaluations. This registry will enroll patients retrospectively and prospectively assessed by CMR for clinical indication in many congenital heart diseases (CHD) Italian centers. Data collection in a dedicated platform will include surgical history, clinical data, imaging data, and adverse cardiac events at 6 years of follow-up. Summary: The multicenter repaired TOF clinical database will collect data on patients evaluated by CMR in many CHD centers in Italy. The registry has been set up to allow future research studies in this population to improve clinical/surgical management and risk stratification of this population.

Abstract The COVID-19 pandemic has dramatically changed the nature of our social interactions. In order to understand how protective equipment and distancing measures influence the ability to comprehend others’ emotions and, thus, to effectively interact with others, we carried out an online study across the Italian population during the first pandemic peak. Participants were shown static facial expressions (Angry, Happy and Neutral) covered by a sanitary mask or by a scarf. They were asked to evaluate the expressed emotions as well as to assess the degree to which one would adopt physical and social distancing measures for each stimulus. Results demonstrate that, despite the covering of the lower-face, participants correctly recognized the facial expressions of emotions with a polarizing effect on emotional valence ratings found in females. Noticeably, while females’ ratings for physical and social distancing were driven by the emotional content of the stimuli, males were influenced by the “covered” condition. The results also show the impact of the pandemic on anxiety and fear experienced by participants. Taken together, our results offer novel insights on the impact of the COVID-19 pandemic on social interactions, providing a deeper understanding of the way people react to different kinds of protective face covering.

One of the most surprising features of our brain is the fact that it is extremely plastic. Among the various plastic processes supported by our brain, there is the neural representation of the space surrounding our body, the peripersonal space (PPS). The effects of real-world tool use on the PPS are well known in cognitive neuroscience, but little is still known whether similar mechanisms also govern virtual tool use. To this purpose, the present study investigated the plasticity of the PPS before and after a real (Experiment 1) or virtual motor training with a tool (Experiment 2). The results show the expansion of the PPS only following real-world tool use but not virtual use, highlighting how the two types of training potentially rely on different processes. This study enriches the current state of the art on the plasticity of PPS in real and virtual environments. We discuss our data with respect to the relevance for the development of effective immersive environment for trainings, learning and rehabilitation.

One of the crucial features defining basic emotions and their prototypical facial expressions is their value for survival. Childhood traumatic experiences affect the effective recognition of facial expressions of negative emotions, normally allowing the recruitment of adequate behavioral responses to environmental threats. Specifically, anger becomes an extraordinarily salient stimulus unbalancing victims’ recognition of negative emotions. Despite the plethora of studies on this topic, to date, it is not clear whether this phenomenon reflects an overall response tendency toward anger recognition or a selective proneness to the salience of specific facial expressive cues of anger after trauma exposure. To address this issue, a group of underage Sierra Leonean Ebola virus disease survivors (mean age 15.40 years, SE 0.35; years of schooling 8.8 years, SE 0.46; 14 males) and a control group (mean age 14.55, SE 0.30; years of schooling 8.07 years, SE 0.30, 15 males) performed a forced-choice chimeric facial expressions recognition task. The chimeric facial expressions were obtained pairing upper and lower half faces of two different negative emotions (selected from anger, fear and sadness for a total of six different combinations). Overall, results showed that upper facial expressive cues were more salient than lower facial expressive cues. This priority was lost among Ebola virus disease survivors for the chimeric facial expressions of anger. In this case, differently from controls, Ebola virus disease survivors recognized anger regardless of the upper or lower position of the facial expressive cues of this emotion. The present results demonstrate that victims’ performance in the recognition of the facial expression of anger does not reflect an overall response tendency toward anger recognition, but rather the specific greater salience of facial expressive cues of anger. Furthermore, the present results show that traumatic experiences deeply modify the perceptual analysis of philogenetically old behavioral patterns like the facial expressions of emotions.