SURVEY AND RESTORATION: NEW WAYS OF INTERACTION

The present paper analyses two cases exemplifying a possible use of survey and its elaborations in the field of conservation: the bell tower of the Basilica Santa Maria delle Vigne and the Chiesa di San Matteo, both situated in Genoa. In the first case, the threedimensional survey was used as a basis to build a model for the structural analysis. The need for an accurate database created with the three-dimensional survey allowed the research team to determine and highlight the critical points of the structure as the thickness of vaults and floors, the location of loads and the inclination of the walls. The data collected was used to create an accurate 3D model to be tested with simulations, in order to verify the stability of the bell tower when applying stress and limitations. In the second case, the three-dimensional survey was used as the basis for the collection, management and representation of the data derived from the survey on rising damp. The purpose was to test a dynamic data processing system that could be used as a tool to collect data on site as well as to access data remotely. By using software for three-dimensional representation and a node programming language, it was possible to define a system that offered dynamic viewing and was easy to use, through the use of chromatic scales and level curves, which can be generated starting from tables containing numerical data. Surveying, diagnostics, modelling and representation allow one to experiment with new ways of interaction within the common goal of conservation

HBIM TO VR. SEMANTIC AWARENESS AND DATA ENRICHMENT INTEROPERABILITY FOR PARAMETRIC LIBRARIES OF HISTORICAL ARCHITECTURE

Recently we assist to an increasing availability of HBIM models rich in geometric and informative terms. Instead, there is still a lack of researches implementing dedicated libraries, based on parametric intelligence and semantically aware, related to the architectural heritage. Additional challenges became from their portability in non-desktop environment (such as VR). The research article demonstrates the validity of a workflow applied to the architectural heritage, which starting from the semantic modeling reaches the visualization in a virtual reality environment, passing through the necessary phases of export, data migration and management. The three-dimensional modeling of the classical Doric order takes place in the BIM work environment and is configured as a necessary starting point for the implementation of data, parametric intelligences and definition of ontologies that exclusively qualify the model. The study also enables an effective method for data migration from the BIM model to databases integrated into VR technologies for AH. Furthermore, the process intends to propose a methodology, applicable in a return path, suited to the achievement of an appropriate data enrichment of each model and to the possibility of interaction in VR environment with the model

De novo 1q21.3q22 duplication revaluation in a “cold” complex neuropsychiatric case with syndromic intellectual disability

Syndromic intellectual disability often obtains a genetic diagnosis due to the combination of first and next generation sequencing techniques, although their interpretation may require revaluation over the years. Here we report on a composite neuropsychiatric case whose phenotype includes moderate intellectual disability, spastic paraparesis, movement disorder, and bipolar disorder, harboring a 1.802 Mb de novo 1q21.3q22 duplication. The role of this duplication has been reconsidered in the light of negativity of many other genetic exams, and of the possible pathogenic role of many genes included in this duplication, potentially configuring a contiguous gene-duplication syndrome

Increased creatine demand during pregnancy in Arginine: Glycine Amidino-Transferase deficiency: A case report

Background: Creatine (Cr), an amino acid derivative, is one of the most important sources of energy acting as both a spatial and temporal energy buffer through its phosphorylated analogue phosphocreatine (PCr) and creatine kinase (CK). Maternal Cr biosynthesis and metabolism seem to play an important role in pregnancy, as shown in preclinical and in healthy human pregnancy studies. Patients with Arginine:Glycine Amidino-Transferase deficiency (AGAT-d), due to the deficit of the first enzyme involved in Cr synthesis, are at a disadvantage due to their failure to synthesize Cr and their dependence on external intake, in contrast to normal subjects, where changes in Cr biosynthesis supply their needs. We report the outcomes of a pregnancy in an AGAT-d woman, and the challenge we faced in managing her treatment with oral Cr to ensure optimal conditions for her fetus. Case presentation: A 22-year-old AGAT-d woman referred to our Institute for the management of her first conception at 11 weeks of fetal gestational age. Sonographic monitoring at 20 w GA indicated a reduction of fetal growth, in particular of the head circumference that was below the 3rd centile. Biochemical monitoring of Cr in biological fluids of the mother revealed a decline of the Cr concentrations, in particular in the urine sample, requiring prompt correction of the Cr dose. At 35 weeks of gestation the patient delivered a male infant, heterozygous for GATM mutation, with normal brain Cr levels; at one year the baby achieved typical developmental milestones. Conclusions: This rare pregnancy demonstrates that Cr levels in the blood and urine of the mother with AGAT-d decreased since the first months of gestation. The increase of the Cr daily dose administered to the mother seems to have produced beneficial effects also on the fetus

Effect of slow-moving landslides on a vaulted masonry building: The case of San Carlo Borromeo church in Cassingheno (Genova)

This paper presents the structural analysis of San Carlo Borromeo church, a masonry building located in Cassingheno (Genoa, Italy) in an area affected by a slow-moving landslide. A deep knowledge of the building in terms of geometry, structural configuration, history and construction phases was acquired by means of on-site surveys and archival research. The crack patterns were surveyed in detail and the deformations were studied through a point cloud obtained from a LIDAR survey. The comparison between the landslide direction and the damage observed showed discrepancies and suggested the presence of foundation settlements due to other phenomena. To identify the actual causes of damage, a finite element model (FEM) of the building in its hypothetical undeformed configuration was created. The geometry of such configuration was reconstructed starting from the point cloud obtained from the LIDAR survey and removing geometrical defects such as leaning of walls, deformation of vaults and inclination of tie-rods. To simulate the effects produced by the landslide and the foundation settlements on the building over time, nonlinear analyses were performed by imposing different displacement fields at the foundation plane in multiple steps. The damage predicted numerically was then compared with the one experienced by the building, showing good agreement

Focusing on autism spectrum disorder in xia–gibbs syndrome: Description of a female with high functioning autism and literature review

Background: Xia–Gibbs syndrome (XGS) is a rare disorder caused by de novo mutations in the AT-Hook DNA binding motif Containing 1 (AHDC1) gene, which is characterised by a wide spectrum of clinical manifestations, including global developmental delay, intellectual disability, structural abnormalities of the brain, global hypotonia, feeding problems, sleep difficulties and apnoea, facial dysmorphisms, and short stature. Methods: Here, we report on a girl patient who shows a peculiar cognitive and behavioural profile including high-functioning autism spectrum disorder (ASD) without intellectual disability and provide information on her developmental trajectory with the aim of expanding knowledge of the XGS clinical spectrum. On the basis of the current clinical case and the literature review, we also attempt to deepen understanding of behavioural and psychiatric manifestations associated with XGS. Results: In addition to the patient we described, a considerable rate of individuals with XGS display autistic symptoms or have been diagnosed with an autistic spectrum disorder. Moreover, the analysis of the few psychopathological profiles of patients with XGS described in the literature shows a frequent presence of aggressive and self-injurious behaviours that could be either an expression of autistic functioning or an additional symptom of the ASD evolution. A careful investigation of the abovementioned symptoms is therefore required, since they could represent a “red flag” for ASD

Muscle MRI in <i>TRPV4-</i> related congenital distal SMA

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Clinical, molecular and glycophenotype insights in SLC39A8-CDG

Background: SLC39A8, a gene located on chromosome 4q24, encodes for the manganese (Mn) transporter ZIP8 and its detrimental variants cause a type 2 congenital disorder of glycosylation (CDG). The common SLC39A8 missense variant A391T is associated with increased risk for multiple neurological and systemic disorders and with decreased serum Mn. Patients with SLC39A8-CDG present with different clinical and neuroradiological features linked to variable transferrin glycosylation profile. Galactose and Mn supplementation therapy results in the biochemical and clinical amelioration of treated patients. Results: Here, we report clinical&nbsp;manifestations, neuroradiological features and glycophenotypes associated with novel SLC39A8 variants (c.1048G &gt; A; p.Gly350Arg and c.131C &gt; G; p.Ser44Trp) in two siblings of the same Italian family. Furthermore, we describe a third patient with overlapping clinical features harbouring the homozygous missense variant A391T. The clinical phenotype of the three patients was characterized by severe developmental disability, dystonic postural pattern and dyskinesia with a more severe progression of the disease in the two affected siblings. Neuroimaging showed a Leigh syndrome-like pattern involving the basal ganglia, thalami and white matter. In the two siblings, atrophic cerebral and cerebellum changes consistent with SLC39A8-CDG were detected as well. Serum transferrin isoelectric focusing (IEF) yielded variable results with slight increase of trisialotransferrin isoforms or even normal pattern. MALDI-MS showed the presence of hypogalactosylated transferrin N-glycans, spontaneously decreasing during the disease course, only in one affected sibling. Total serum N-glycome depicted a distinct pattern for the three patients, with increased levels of undergalactosylated and undersialylated precursors of fully sialylated biantennary glycans, including the monosialo-monogalacto-biantennary species A2G1S1. Conclusions: Clinical, MRI and glycosylation features of patients are consistent with SLC39A8-CDG. We document two novel variants associated with Leigh syndrome-like disease presentation of SLC39A8-CDG. We show, for the first time, a severe neurological phenotype overlapping with that described for SLC39A8-CDG in association with the homozygous A391T missense variant. We observed a spontaneous amelioration of transferrin N-glycome, highlighting the efficacy of MS-based serum glycomics as auxiliary tool for the diagnosis and clinical management of therapy response in patients with SLC39A8-CDG. Further studies are needed to analyse more in depth the influence of SLC39A8 variants, including the common missense variant, on the expression and function of ZIP8 protein, and their impact on clinical, biochemical and neuroradiological features

Phenotypic definition and genotype-phenotype correlates in pmpca-related disease

Background: Peptidase mitochondrial processing alpha (PMPCA) biallelic mutations cause a spectrum of disorders ranging from severe progressive multisystemic mitochondrial encephalopathy to a milder non-progressive cerebellar ataxia with or without intellectual disability. Recently, we and others described an intermediate phenotype in two unrelated patients. Methods: We report a second Italian patient carrying novel PMPCA variants (p.Trp278Leu; p.Arg362Gly). Molecular modeling, dynamics simulation, RT-qPCR, and Western blotting were performed to predict the pathogenic impact of variants in the two Italian patients and attempt genotype-phenotype correlates. Results: In line with the two patients with intermediate phenotypes, our case presented global psychomotor delay with regression, intellectual disability, spastic-ataxic gait, and hyperkinetic movements, with cerebellar atrophy and bilateral striatal hyperintensities. However, blood lactate, muscle biopsy, and MRI spectroscopy were normal. PMPCA protein levels were significantly higher than controls despite normal cDNA levels. Dynamics simulation of several PMPCA missense variants showed a variable impact on the flexibility of the glycine rich loop and, for some cases, on the overall protein stability, without clear genotype-phenotype correlates. Conclusion: We confirm the expansion of PMPCA phenotypic spectrum including an intermediate phenotype of progressive encephalopathy without systemic involvement. The association of cerebellar atrophy with “Leigh-like” striatal hyperintensities may represent a “red flag” for this condition

The role of preclinical models in creatine transporter deficiency: Neurobiological mechanisms, biomarkers and therapeutic development

Creatine (Cr) Transporter Deficiency (CTD) is an X-linked metabolic disorder, mostly caused by missense mutations in the SLC6A8 gene and presenting with intellectual disability, autistic behavior, and epilepsy. There is no effective treatment for CTD and patients need lifelong assistance. Thus, the research of novel intervention strategies is a major scientific challenge. Animal models are an excellent tool to dissect the disease pathogenetic mechanisms and drive the preclinical development of therapeutics. This review illustrates the current knowledge about Cr metabolism and CTD clinical aspects, with a focus on mainstay diagnostic and therapeutic options. Then, we discuss the rodent models of CTD characterized in the last decade, comparing the phenotypes expressed within clinically relevant domains and the timeline of symptom development. This analysis highlights that animals with the ubiquitous deletion/mutation of SLC6A8 genes well recapitulate the early onset and the complex pathological phenotype of the human condition. Thus, they should represent the preferred model for preclinical efficacy studies. On the other hand, brain-and cell-specific conditional mutants are ideal for understanding the basis of CTD at a cellular and molecular level. Finally, we explain how CTD models might provide novel insight about the pathogenesis of other disorders, including cancer