Hereditary spastic paraplegia is a common phenotypic finding in ARG1 deficiency, P5CS deficiency and HHH syndrome: Three inborn errors of metabolism caused by alteration of an interconnected pathway of glutamate and urea cycle metabolism

Hereditary Spastic Paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by a progressive rigidity and weakness of the lower limbs, caused by pyramidal tract lesions. As of today, 80 different forms of HSP have been mapped, 64 genes have been cloned, and new forms are constantly being described. HSPs represent an intensively studied field, and the functional understanding of the biochemical and molecular pathogenetic pathways are starting to be elucidated. Recently, dominant and recessive mutations in the ALDH18A1 gene resulting in the deficiency of the encoded enzyme (delta-1-pyrroline-5-carboxylate synthase, P5CS) have been pathogenetically linked to HSP. P5CS is a critical enzyme in the conversion of glutamate to pyrroline-5-carboxylate, an intermediate that enters in the proline biosynthesis and that is connected with the urea cycle. Interestingly, two urea cycle disorders, Argininemia and Hyperornithinemia-Hyperammonemia-Homocitrullinuria syndrome, are clinically characterized by highly penetrant spastic paraplegia. These three diseases represent a peculiar group of HSPs caused by Inborn Errors of Metabolism. Here we comment on these forms, on the common features among them and on the hypotheses for possible shared pathogenetic mechanisms causing the HSP phenotype

Tumor derived Microvesicles enhance cross-processing ability of clinical grade Dendritic Cells

Tumor cells release extracellular microvesicles (MVs) in the microenvironment to deliver biological signals to neighbouring cells as well as to cells in distant tissues. Tumor-derived MVs appear to play contradictory role promoting both immunosuppression and tumor growth and both evoking tumor specific immune response. Recent evidences indicate that tumor-derived MVs can positively impact Dendritic Cells (DCs) immunogenicity by reprogramming DC antigen processing machinery and intracellular signaling pathways, thus promoting anti-tumor response. DCs are considered pivot cells of the immune system due to their exclusive ability to coordinate the innate and acquired immune responses, cross-present exogenous antigens and prime naïve T cells. DCs are required for the induction and maintenance of long-lasting anti-tumor immunity and their exploitation has been extensively investigated for the design of anti-tumor vaccines. However, the clinical grade culture conditions that are required to generate DCs for therapeutic use can strongly affect their functions. Here, we investigated the immunomodulatory impact of MVs carrying the MUC1 tumor glycoantigen (MVsMUC1) as immunogen formulation on clinical grade DCs grown in X-VIVO 15 (X-DCs). Results indicated that X-DCs displayed reduced performance of the antigen processing machinery in term of diminished phagocytosis and acidification of the phagosomal compartment suggesting an altered immunogenicity of clinical grade DCs. Pulsing DCs with MVsMUC1 restored phagosomal alkalinization, triggering ROS increase. This was not observed when a soluble MUC1 protein was employed (rMUC1). Concurrently, MVsMUC1 internalization by X-DCs allowed MUC1 cross-processing. Most importantly, MVsMUC1 pulsed DCs activated IFNγ response mediated by MUC1 specific CD8+ T cells. These results strongly support the employment of tumor-derived MVs as immunogen platforms for the implementation of DC-based vaccine

In-water lidar simulations: the ALADIN ADM-Aeolus backscattered signal at 355 nm

The Lidar Ocean Color (LiOC) Monte Carlo code has been developed to simulate the in-water propagation of the lidar beam emitted by the ALADIN ADM-Aeolus instrument in the ultraviolet (UV) spectral region (∼ 355 nm). To this end, LiOC accounts for reflection/transmission processes at the sea surface, absorption and multiple scattering in the water volume, and reflection from the sea bottom. The water volume components included in the model are pure seawater, Chlorophyll-a concentration (Chl-a), Colored Dissolved Organic Matter (CDOM), and/or a generic absorbing species. By considering the transmission/reception measurement geometry of ALADIN ADM-Aeolus, the study documents the variability of the normalized backscattered signal in different bio-optical conditions. The potential for data product retrieval based on information at 355 nm is considered by developing a demonstrative lookup table to estimate the absorption budget exceeding that explained by Chl-a. Results acknowledge the interest of space programs in exploiting UV bands for ocean color remote sensing, as, for instance, addressed by the PACE mission of NASA

Nursing students’ experience of risk assessment, prevention and management: a systematic review

Introduction:  As a fundamental dimension of quality, the patient safety and healthcare workers safety in the healthcare environment depend on the ability of each healthcare workers (whether administrators or technicians) to reduce the probability of error. This review focused on nursing students. The aim was to assess level and determinants of knowledge about risk assessment, risk prevention and risk management of nursing students. Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Two reviewers searched the bibliographic databases Pubmed, Scopus and Cinahl to collect all the available articles in English and Italian issued between 2015 and August 2019. To obtain an exhaustive string search, the following keywords were combined through Boolean operators AND and OR: Clinical Risk Assessment, Nursing Education, Nursing Student*, Patient Safety. The authors assessed the quality of the evidence by using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method.  Results: Twelve papers are included. Although the literature on the nursing student's error is limited, their frequencies are worrying. Some authors have created a model of prevention of clinical error based on three level. However, the majority of nursing students don’t felt confident with a patient safety. Many authors shown that patient safety education was delivery by lecture, laboratory or simulation sessions. Conclusions: This review underlines the need to revise the nursing curriculum on patient safety and the need to think what educational methodology is the better for the student to create a safe care. &nbsp

A novel mutation in NDUFB11 unveils a new clinical phenotype associated with lactic acidosis and sideroblastic anemia

NDUFB11, a component of mitochondrial complex I, is a relatively small integral membrane protein, belonging to the 'supernumerary' group of subunits, but proved to be absolutely essential for the assembly of an active complex I. Mutations in in the X-linked nuclear encoded NDUFB11 gene have recently been discovered in association with two distinct phenotypes, i.e. microphthalmia with linear skin defects and histiocytoid cardiomyopathy. We report on a male with complex I deficiency, caused by a de novo mutation in NDUFB11 and displaying early onset sideroblastic anemia as the unique feature. This is the third report that describes a mutation in NDUFB11 but all are associated to a different phenotype. Our results further expand the molecular spectrum and associated clinical phenotype of NDUFB11 defects