Lysosomal storage disorders: molecular basis andlaboratory testing.

Lysosomal storage disorders (LSDs) are a large group of more than 50 different inherited metabolic diseases which, in the great majority of cases, result from the defective function of specific lysosomal enzymes and, in cases, of non-enzymatic lysosomal proteins or non-lysosomal proteins involved in lysosomal biogenesis. The progressive lysosomal accumulation of undegraded metabolites results in generalised cell and tissue dysfunction, and, therefore, multi-systemic pathology. Storage may begin during early embryonic development, and the clinical presentation for LSDs can vary from an early and severe phenotype to late-onset mild disease. The diagnosis of most LSDs--after accurate clinical/paraclinical evaluation, including the analysis of some urinary metabolites--is based mainly on the detection of a specific enzymatic deficiency. In these cases, molecular genetic testing (MGT) can refine the enzymatic diagnosis. Once the genotype of an individual LSD patient has been ascertained, genetic counselling should include prediction of the possible phenotype and the identification of carriers in the family at risk. MGT is essential for the identification of genetic disorders resulting from non-enzymatic lysosomal protein defects and is complementary to biochemical genetic testing (BGT) in complex situations, such as in cases of enzymatic pseudodeficiencies. Prenatal diagnosis is performed on the most appropriate samples, which include fresh or cultured chorionic villus sampling or cultured amniotic fluid. The choice of the test--enzymatic and/or molecular--is based on the characteristics of the defect to be investigated. For prenatal MGT, the genotype of the family index case must be known. The availability of both tests, enzymatic and molecular, enormously increases the reliability of the entire prenatal diagnostic procedure. To conclude, BGT and MGT are mostly complementary for post- and prenatal diagnosis of LSDs. Whenever genotype/phenotype correlations are available, they can be helpful in predicting prognosis and in making decisions about therapy

Quaternary evolution of the lower calore and middle volturno valleys (Southern Italy)

The lower Calore and middle Volturno valleys preserve stratigraphical and morphological evidence and tephrostratigraphic markers particularly suitable for reconstructing the long-term geomorphological evolution of the central-southern Apennines. Aim of our study is to identify the main steps of the Quaternary landscape evolution of these valley systems and to improve knowledge about the relationships between fluvial processes and tectonics, volcanic activity, climatic and human influences. To this purpose, we carried out an integrated geomorphological and chronostratigraphical analysis of identified fluvial landforms and related deposits, integrated by230Th/234U datings on travertines from the Telese Plain area. The study highlighted in particular: (1) fluvial sedimentation started in the Middle Pleistocene (~650 ka) within valleys that originated in the lower Pleistocene under the control of high-angle faults; (2) extensional tectonics acted during the Middle and Upper Pleistocene, driving the formation of the oldest fluvial terraces and alluvial fans, and persisted beyond the emplacement of the Campanian Ignimbrite pyroclastic deposits (~39 ka); and (3) from the late Upper Pleistocene onwards (<15 ka), the role of tectonics appears negligible, while climatic changes played a key role in the formation of three orders of valley floor terraces and the youngest alluvial fans

Serious Games for Wrist Rehabilitation in Juvenile Idiopathic Arthritis

Rehabilitation is a painful and tiring process involving series of exercises that patients must repeat over a long period. Unfortunately, patients often grow bored, frustrated, and lose motivation making rehabilitation less effective. In the recent years video games have been widely used to implement rehabilitation protocols so as to make the process more entertaining, engaging and to keep patients motivated. In this paper, we present an integrated framework we developed for the wrist rehabilitation of patients affected by Juvenile Idiopathic Arthritis (JIA) following a therapeutic protocol at the Clinica Pediatrica G. e D. De Marchi. The framework comprises four video games and a set modules that let the therapists tune and control the exercises the games implemented, record all the patients actions, replay and analyze the sessions. We present the result of a preliminary validation we performed with four poliarticular JIA patients at the clinic under the supervision of the therapists. Overall, we received good feedback both from the young patients, who enjoyed performing known rehabilitation exercises using video games, and therapists who were satisfied with the framework and its potentials for engaging and motivating the patients

Hospital clinical pathways for children affected by juvenile idiopathic arthritis

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common pediatric chronic rheumatic disease, which requires constant follow-up over the years, due to relapses during its progression. To maintain a good quality of life, it is important to limit admissions as far as possible. With the development of a Diagnostic Therapeutic Assistance Pathway (DTAP), we aim to select patients with suitable clinical conditions to be moved from routine hospital management to day care or outpatient treatment, evaluating the number of patients to whom this would apply. METHODS: Monocentric study regarding admissions for JIA between 2014 and 2016 in a Pediatric Unit of a university hospital in Milan. Through an analysis of the medical records, relevant information was extracted and collected in a Microsoft™ Excel database; starting from the data collected during the first year, a DTAP was prepared for patients with active arthritis and appropriate clinical conditions. RESULTS: The study includes data from 223 JIA hospitalization cases involving 127 patients. Applying DTAP criteria, 32% patients would have avoided admissions and 23% would have been admitted less frequently. The data concerning the activities of the Unit for JIA patients showed a relevant drop in the number of hospitalizations since 2015, from 89 in 2014 to 66 and 68 in 2015 and 2016 respectively. CONCLUSION: The opportunity offered by DTAP, has suggested feasible changes in hospitalization management and it's use would promote the possibility of treating the children without hospitalization, or minimizing it. In conclusion DTAP application is a priority for the continuous improvement of clinical practice and quality of life for patients and their families

Hospital clinical pathways for children affected by juvenile idiopathic arthritis

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common pediatric chronic rheumatic disease, which requires constant follow-up over the years, due to relapses during its progression. To maintain a good quality of life, it is important to limit admissions as far as possible. With the development of a Diagnostic Therapeutic Assistance Pathway (DTAP), we aim to select patients with suitable clinical conditions to be moved from routine hospital management to day care or outpatient treatment, evaluating the number of patients to whom this would apply. METHODS: Monocentric study regarding admissions for JIA between 2014 and 2016 in a Pediatric Unit of a university hospital in Milan. Through an analysis of the medical records, relevant information was extracted and collected in a Microsoft\u2122 Excel database; starting from the data collected during the first year, a DTAP was prepared for patients with active arthritis and appropriate clinical conditions. RESULTS: The study includes data from 223 JIA hospitalization cases involving 127 patients. Applying DTAP criteria, 32% patients would have avoided admissions and 23% would have been admitted less frequently. The data concerning the activities of the Unit for JIA patients showed a relevant drop in the number of hospitalizations since 2015, from 89 in 2014 to 66 and 68 in 2015 and 2016 respectively. CONCLUSION: The opportunity offered by DTAP, has suggested feasible changes in hospitalization management and it's use would promote the possibility of treating the children without hospitalization, or minimizing it. In conclusion DTAP application is a priority for the continuous improvement of clinical practice and quality of life for patients and their families