Intellectual Disability and Brain Creatine Deficit: Phenotyping of the Genetic Mouse Model for GAMT Deficiency

none9noGuanidinoacetate methyltransferase deficiency (GAMT-D) is one of three cerebral creatine (Cr) deficiency syndromes due to pathogenic variants in the GAMT gene (19p13.3). GAMT-D is characterized by the accumulation of guanidinoacetic acid (GAA) and the depletion of Cr, which result in severe global developmental delay (and intellectual disability), movement disorder, and epilepsy. The GAMT knockout (KO) mouse model presents biochemical alterations in bodily fluids, the brain, and muscles, including increased GAA and decreased Cr and creatinine (Crn) levels, which are similar to those observed in humans. At the behavioral level, only limited and mild alterations have been reported, with a large part of analyzed behaviors being unaffected in GAMT KO as compared with wild-type mice. At the cerebral level, decreased Cr and Crn and increased GAA and other guanidine compound levels have been observed. Nevertheless, the effects of Cr deficiency and GAA accumulation on many neurochemical, morphological, and molecular processes have not yet been explored. In this review, we summarize data regarding behavioral and cerebral GAMT KO phenotypes, and focus on uncharted behavioral alterations that are comparable with the clinical symptoms reported in GAMT-D patients, including intellectual disability, poor speech, and autistic-like behaviors, as well as unexplored Cr-induced cerebral alterations.openRossi, Luigia; Nardecchia, Francesca; Pierigè, Francesca; Ventura, Rossella; Carducci, Claudia; Leuzzi, Vincenzo; Magnani, Mauro; Cabib, Simona; Pascucci, TizianaRossi, Luigia; Nardecchia, Francesca; Pierigè, Francesca; Ventura, Rossella; Carducci, Claudia; Leuzzi, Vincenzo; Magnani, Mauro; Cabib, Simona; Pascucci, Tizian

Inside the Michelangelo effect: The role of art and aesthetic attractiveness on perceived fatigue and hand kinematics in virtual painting

It has recently been discovered that during a virtual reality task of painting, if the subjects have the illusion of recreating an artistic masterpiece, they improve their performances and perceive less fatigue compared to simply coloring a virtual canvas. This phenomenon has been called the Michelangelo effect. However, it was unclear if this effect was related to the aesthetic experience of beauty or if it was specific to artistic stimuli. To clarify this point, 26 healthy subjects performed the virtual task of erasing a blank sheet on the canvas, revealing an image that could be a painting or a photo, classified as beautiful or not. Beautiful paintings were famous artistic portraits, non-beautiful paintings were rough reproductions of them. Photos of popular people were matched with paintings according to their similarity for somatic traits, posture, and clothes. Beautiful and non-beautiful photos were classified according to whether the pictured person was famous or not for their beauty. For each stimulus the objective beauty, subjective beauty, and effort to complete the task perceived by the subject were self-assessed on a numerical rating scale, recorded and analyzed. Furthermore, the hand kinematic trajectory was instrumentally recorded and its spatiotemporal parameters were computed. Less fatigue was perceived for the paintings than for the photos (p = .020), but not for beautiful versus non-beautiful stimuli (p = .325). Only in the artistic stimuli, subjective beauty was found to be negatively correlated with perceived fatigue (p = .030) and performed errors (p = .005). The kinematic parameters were found to be affected by the interactions between the gender of the participant and that of the person in the photo. These results supported the idea that the Michelangelo effect was stronger when subjects interacted with artefacts, modulated by the perceived beauty of the artistic stimulus

Michelangelo Effect in Virtual Sculpturing: Prospective for Motor Neurorehabilitation in the Metaverse

We investigated the Michelangelo effect, i.e. the facilitatory effect of a virtual art therapy in motor rehabilitation (Iosa et al. 2021), with a novel virtual reality paradigm in which users are engaged in motor exercises with 3D sculptures. In particular, thirty young adults were immersed in a virtual environment where they could sculpt, by using the real hands, some famous sculptures in the history of art, such as the David of Michelangelo, the Venus of Milo and the statue of Laocoon and His Sons, and their control stimuli, i.e. statues in very low resolution or cubes. We recorded the kinematics (length, the time to complete each trial, mean normalized jerk) and questionnaire answers (objective and subjective beauty, User Satisfaction Evaluation Questionnaire and Nasa Task Load Index). In general, we found that the perception of subjective and objective beauty was higher when sculpting the statues than control stimuli, the judgment of usability of the system was high. The perceived fatigue was not higher when sculpting the statues despite the longer time spent in completing the task that with respect to the control stimuli. Moreover, we found that the interaction with the experimental statues affected the fluidity and symmetry of hands movements. Finally, we discuss this evidence regarding the art therapy and neuroaesthetics principles for motor rehabilitation in the Metaverse with VR, including the possible role of virtual embodiment (illusory feeling to have a virtual body) for boosting the efficacy of the clinical applications

Early life adversity affecting the attachment bond alters ventral tegmental area transcriptomic patterning and behavior almost exclusively in female mice

Early life experiences that affect the attachment bond formation can alter developmental trajectories and result in pathological outcomes in a sex-related manner. However, the molecular basis of sex differences is quite unknown. The dopaminergic system originating from the ventral tegmental area has been proposed to be a key mediator of this process.Here we exploited a murine model of early adversity (Repeated Cross Fostering, RCF) to test how interfering with the attachment bond formation affects the VTA-related functions in a sex-specific manner.Through a comprehensive behavioral screening, within the NiH RDoC framework, and by next-generation RNA-Seq experiments, we analyzed the long-lasting effect of RCF on behavioral and transcriptional profiles related to the VTA, across two different inbred strains of mouse in both sexes.We found that RCF impacted to an extremely greater extent VTA-related behaviors in females than in males and this result mirrored the transcriptional alterations in the VTA that were almost exclusively observed in females. The sexual dimorphism was conserved across two different inbred strains in spite of their divergent long lasting consequences of RCF exposure.Our data suggest that to be female primes a sub-set of genes to respond to early environmental perturbations.This is, to the best of our knowledge, the first evidence of an almost exclusive effect of early life experiences on females, thus mirroring the extremely stronger impact of precocious aversive events reported in clinical studies in women

Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model

Mesenchymal stromal cells (MSCs) are considered an important therapeutic tool in cancer therapy. They possess intrinsic therapeutic potential and can also be in vitro manipulated and engineered to produce therapeutic molecules that can be delivered to the site of diseases, through their capacity to home pathological tissues. We have recently demonstrated that MSCs, upon in vitro priming with anti-cancer drug, become drug-releasing mesenchymal cells (Dr-MCs) able to strongly inhibit cancer cells growth

Epidemiological patterns of asbestos exposure and spatial clusters of incident cases of malignant mesothelioma from the Italian national registry.

BACKGROUND: Previous ecological spatial studies of malignant mesothelioma cases, mostly based on mortality data, lack reliable data on individual exposure to asbestos, thus failing to assess the contribution of different occupational and environmental sources in the determination of risk excess in specific areas. This study aims to identify territorial clusters of malignant mesothelioma through a Bayesian spatial analysis and to characterize them by the integrated use of asbestos exposure information retrieved from the Italian national mesothelioma registry (ReNaM). METHODS: In the period 1993 to 2008, 15,322 incident cases of all-site malignant mesothelioma were recorded and 11,852 occupational, residential and familial histories were obtained by individual interviews. Observed cases were assigned to the municipality of residence at the time of diagnosis and compared to those expected based on the age-specific rates of the respective geographical area. A spatial cluster analysis was performed for each area applying a Bayesian hierarchical model. Information about modalities and economic sectors of asbestos exposure was analyzed for each cluster. RESULTS: Thirty-two clusters of malignant mesothelioma were identified and characterized using the exposure data. Asbestos cement manufacturing industries and shipbuilding and repair facilities represented the main sources of asbestos exposure, but a major contribution to asbestos exposure was also provided by sectors with no direct use of asbestos, such as non-asbestos textile industries, metal engineering and construction. A high proportion of cases with environmental exposure was found in clusters where asbestos cement plants were located or a natural source of asbestos (or asbestos-like) fibers was identifiable. Differences in type and sources of exposure can also explain the varying percentage of cases occurring in women among clusters. CONCLUSIONS: Our study demonstrates shared exposure patterns in territorial clusters of malignant mesothelioma due to single or multiple industrial sources, with major implications for public health policies, health surveillance, compensation procedures and site remediation programs

Effect of Lockdowns on Hospital Staff in a COVID Center: A Retrospective Observational Study

At the onset of the SARS-CoV-2 pandemic, individual and social measures were strengthened through restrictive non-pharmaceutical interventions, labelled with the term "lockdown". In Italy, there were two lockdowns (9 March 2020-3 May 2020 and 3 November 2020-27 March 2021). As part of preventive measures, healthcare workers and the administrative staff population of Policlinico A. Gemelli underwent nasopharyngeal swab tests from 1 March 2020 to 9 February 2022, a long time interval that includes the two aforementioned lockdowns. The population included 8958 people from 1 March 2020 to 31 December 2020; 8981 people from 1 January 2021 to 31 December 2021; and 8981 people from 1 January 2022 to 9 February 2022. We then analysed pseudo-anonymized data, using a retrospective observational approach to evaluate the impact of the lockdown on the incidence of SARS-CoV-2 infections within the population. Given the 14 day contagious period, the swab positivity rate (SPR) among the staff decreased significantly at the end of the first lockdown, every day prior to 18 May 2020, by 0.093 (p < 0.0001, CI = (-0.138--0.047)). After the fourteenth day post the end of the first lockdown (18 May 2020), the SPR increased daily at a rate of 0.024 (p < 0.0001, 95% CI = (0.013-0.034)). In addition, the SPR appeared to increase significantly every day prior to 17 November 2020 by 0.024 (p < 0.0001, CI = (0.013-0.034)). After the fourteenth day post the start of the second lockdown (17 November 2020), the SPR decreased daily at a rate of 0.039 (p < 0.0001, 95% CI = (-0.050--0.027)). These data demonstrate that, in our Institution, the lockdowns helped to both protect healthcare workers and maintain adequate standards of care for COVID and non-COVID patients for the duration of the state of emergency in Italy

Epidemiological patterns of asbestos exposure and spatial clusters of incident cases of malignant mesothelioma from the Italian national registry

Abstract BACKGROUND: Previous ecological spatial studies of malignant mesothelioma cases, mostly based on mortality data, lack reliable data on individual exposure to asbestos, thus failing to assess the contribution of different occupational and environmental sources in the determination of risk excess in specific areas. This study aims to identify territorial clusters of malignant mesothelioma through a Bayesian spatial analysis and to characterize them by the integrated use of asbestos exposure information retrieved from the Italian national mesothelioma registry (ReNaM). METHODS: In the period 1993 to 2008, 15,322 incident cases of all-site malignant mesothelioma were recorded and 11,852 occupational, residential and familial histories were obtained by individual interviews. Observed cases were assigned to the municipality of residence at the time of diagnosis and compared to those expected based on the age-specific rates of the respective geographical area. A spatial cluster analysis was performed for each area applying a Bayesian hierarchical model. Information about modalities and economic sectors of asbestos exposure was analyzed for each cluster. RESULTS: Thirty-two clusters of malignant mesothelioma were identified and characterized using the exposure data. Asbestos cement manufacturing industries and shipbuilding and repair facilities represented the main sources of asbestos exposure, but a major contribution to asbestos exposure was also provided by sectors with no direct use of asbestos, such as non-asbestos textile industries, metal engineering and construction. A high proportion of cases with environmental exposure was found in clusters where asbestos cement plants were located or a natural source of asbestos (or asbestos-like) fibers was identifiable. Differences in type and sources of exposure can also explain the varying percentage of cases occurring in women among clusters. CONCLUSIONS: Our study demonstrates shared exposure patterns in territorial clusters of malignant mesothelioma due to single or multiple industrial sources, with major implications for public health policies, health surveillance, compensation procedures and site remediation programs