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

Influence of micro-notches on the fatigue strength and crack propagation of unfilled and short carbon fiber reinforced PEEK

Short carbon fiber reinforced (SCFR) PEEK is a highly attractive material for lightweight structures; improving knowledge about the influence of local imperfections on its fatigue behavior is essential for the design of real components. To this aim, fatigue strength and crack propagation of two grades of SCFR PEEK and neat matrix were investigated by testing at different stress levels specimens with a micro-notch consisting of a small blind hole (range diameter 0.1–1 mm). Overall, the presence of a micro-notch resulted in a decrease of fatigue strength compared to un-notched condition, but with different sensitivity and crack propagation patterns; while a higher fiber volume fraction enhanced fatigue strength and resistance to crack propagation, the combination of a lower fiber content and inclusion of additive particles had a negative effect. Crack propagation in the notched region was also evaluated. The average values of Paris' law exponential coefficients were similar and within the range of literature values, without apparent correlation with reinforcement type. Preliminary investigations in the presence of the smallest micro-notches seem to indicate the presence of a threshold size below which the influence of a small notch is comparable with that of material inherent defects, but further testing is necessary

How Can We Assess Positive Welfare in Ruminants?

Until now, most research has focused on the development of indicators of negative welfare, and relatively few studies provide information on valid, reliable, and feasible indicators addressing positive aspects of animal welfare. However, a lack of suffering does not guarantee that animals are experiencing a positive welfare state. The aim of the present review is to identify promising valid and reliable animal-based indicators for the assessment of positive welfare that might be included in welfare assessment protocols for ruminants, and to discuss them in the light of the five domains model, highlighting possible gaps to be filled by future research. Based on the existing literature in the main databases, each indicator was evaluated in terms of its validity, reliability, and on-farm feasibility. Some valid indicators were identified, but a lot of the validity evidence is based on their absence when a negative situation is present; furthermore, only a few indicators are available in the domains of Nutrition and Health. Reliability has been seldom addressed. On-farm feasibility could be increased by developing specific sampling strategies and/or relying on the use of video- or automatic-recording devices. In conclusion, several indicators are potentially available (e.g., synchronisation of lying and feeding, coat or fleece condition, qualitative behaviour assessment), but further research is required

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

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

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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

KNOWLEDGE-BASED MODELLING FOR AUTOMATIZING HBIM OBJECTS. THE VAULTED CEILINGS OF PALAZZO DUCALE IN URBINO

Vault modelling in HBIM poses a significant challenge due to the geometrical complexity and lack of standardization of those elements. Starting from the definition of an ontology able to describe and manage different typologies of Italian Renaissance vaults, this paper presents two methods for their representation in the context of Ducal Palace of Urbino HBIM implementation. The first method is a simplified semi-automated scan-to-BIM procedure relying on Revit adaptive families; the second is a more complex parametric scripting in Dynamo VPL. The paper proposes a library of suitable vault families for the parametric modelling of Renaissance architecture and offers a comparison between the models generated and their respective surveyed point-clouds, with the aim of assessing the procedure. Revit adaptive families appeared to be the easiest to implement and the most efficient solution, while Dynamo allowed for greatest complexity thought showing limitations and implementation difficulties