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Growth hormone deficiency (GHD) describes the impairment of growth hormone (GH) secretion by the pituitary somatotroph cells. GHD may be congenital, with causes, including genetic alterations and structural brain malformations, or acquired, including midline tumours, cranial irradiation, traumatic brain injury, central nervous system infections and inflammatory conditions. GHD in children is characterised by short stature, delayed bone maturation and abnormalities in substrate metabolism, body composition, physical and psychosocial functioning, all of which improve with recombinant human GH (rhGH) therapy. The diagnosis of GHD is based on clinical signs and symptoms, biochemistry and imaging. Although GH stimulation tests are considered the mainstay of diagnostic investigations, the results must be interpreted with caution owing to the variability in cut-off values and reproducibility. Transition refers to the physical and psychosocial changes in adolescent patients during the mid-teens to late teens (usually 15–18 years of age) until about 6–7 years after achievement of adult height. During the transition age, only a small residual capacity of longitudinal growth is left, but body maturity is not yet complete. Discontinuation of rhGH treatment at the end of longitudinal growth in adolescents with permanent GHD is associated with decreased muscle strength and mass, increased body fat (mainly in the abdomen), the arrest or reversal of muscle mass and bone mass density (BMD) gain and lipid profile deterioration. For these reasons, patients whose GHD persists during the transition age need to continue rhGH treatment to obtain full somatic maturation and normalisation of body composition, BMD, quality of life (QoL) and lipid metabolism. There is some evidence that rhGH treatment during transition may result in improved growth and bone health, as well as a better prognosis for metabolic and cardiovascular risks in the long term. Since these patients need to continue treatment to complete their body development, a multidisciplinary approach is required to ensure continuity of care during the transfer from paediatric to adult endocrinology services. Guidelines for the diagnosis and treatment of young adults with GHD have been published by the American Association of Clinical Endocrinologists (AACE), American College of Endocrinology (ACE), Endocrine Society, European Society of Paediatric Endocrinology (ESPE), Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society and Endocrine Society of Australia. However, clinical practice lacks uniformity in terms of diagnosis and treatment of transition-age patients, the impact of GH replacement during transition has not been adequately assessed in randomised clinical trials (RCTs), validated questionnaires to assess QoL in patients on rhGH treatment in the transition period are not available and there is still uncertainty about the multidisciplinary approach during transition [8]. Hence, a structured transition protocol is essential to establish the best practice for transitioning adolescents with GHD to adult care. A study in Italy in 2015 identified a low level of awareness of these issues in clinical practice and real-world gaps in the management of GHD patients during transition. To address these gaps and assist endocrinologists (adult and paediatric) in the diagnosis and treatment of GHD in transition-age patients, a Delphi consensus process was undertaken to develop clinically relevant recommendations. The current consensus statements address the diagnosis of GHD, benefits of treatment, monitoring and management of transition-age patients with GHD, along with treatment adherence and safety concerns.

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Cardiovascular prevention represents a cornerstone of modern strategies to reduce the burden of cardiovascular disease. It is of key importance to prevent cardiovascular diseases and associated events, not only to reduce morbidity and mortality, but also to increase the years of wellness in the aging population and to make the growing socio-economic burden imposed by cardiovascular events more sustainable. The current approach to prevention is based on an integrated use of effective lifestyle measures and, whenever appropriate, of antihypertensive and antidiabetic drugs, lipid-lowering agents and antiplatelet drugs. Given that population characteristics, in terms of ethnicity, demography and lifestyle habits, and healthcare system organizations differ among countries, international guidelines are not always applicable to specific countries and, often, are difficult to translate into daily clinical practice. In order to afford the specific features of Italy, 10 Scientific Societies and Research Institutions, mostly involved in preventive strategies, contributed to the present Italian consensus document, which includes brief, practical recommendations to support the preventive actions within the physician community and the general practice setting.

SHOX haploinsufficiency causes 70–90% of Léri-Weill dyschondrosteosis (LWD) and 2–10% of idiopathic short stature (ISS). Deletions removing the entire gene or enhancers and point mutations in the coding region represent a well-established cause of haploinsufficiency. During diagnostic genetic testing on ISS/LWD patients, in addition to classic SHOX defects, five 5′UTR variants (c.-58G > T, c.-55C > T, c.-51G > A, c.-19G > A, and c.-9del), were detected whose pathogenetic role was unclear and were thus classified as VUS (Variants of Uncertain Significance). The purpose of the present study was to investigate the role of these noncoding variations in SHOX haploinsufficiency. The variants were tested for their ability to interfere with correct gene expression of a regulated reporter gene (luciferase assay). The negative effect on the mRNA splicing predicted in silico for c.-19G > A was assayed in vitro through a minigene splicing assay. The luciferase assay showed that c.-51G > A, c.-19G > A, and c.-9del significantly reduce luciferase activity by 60, 35, and 40% at the homozygous state. Quantification of the luciferase mRNA showed that c.-51G > A and c.-9del might interfere with the correct SHOX expression mainly at the post-transcriptional level. The exon trapping assay demonstrated that c.-19G > A determines the creation of a new branch site causing an aberrant mRNA splicing. In conclusion, this study allowed us to reclassify two of the 5′UTR variants identified during SHOX diagnostic screening as likely pathogenic, one remains as a VUS, and two as likely benign variants. This analysis for the first time expands the spectrum of the genetic causes of SHOX haploinsufficiency to noncoding variations in the 5′UTR.

The use of double charge exchange reactions is discussed in view of their application to extract information that may be helpful to determinate the nuclear matrix elements entering in the expression of neutrinoless double beta decay half-life. The strategy adopted in the experimental campaigns performed at INFN - Laboratori Nazionali del Sud and in the analysis methods within the NUMEN project is briefly described, emphasizing the advantages of the multi-channel approach to nuclear reaction data analysis. An overview on the research and development activities on the MAGNEX magnetic spectrometer is also given, with a focus on the chosen technological solutions for the focal plane detector which will guarantee the performances at high-rate conditions.

Background & aims: Variations in gut microbiota might impact metabolism leading to body weight excess. We assessed the impact of a probiotic supplementation in pediatric obesity on weight, metabolic alterations, selected gut microbial groups, and functionality. Methods: Cross-over, double-blind, randomized control trial (BIFI-OBESE trial; NCT03261466). 101 youths (6–18 years, Tanner stage ≥2) with obesity and insulin-resistance on diet were randomized to 2 × 109 CFU/AFU/day of Bifidobacterium breve BR03 (DSM 16604) and B. breve B632 (DSM 24706) (51) or placebo (50) for 8 weeks with a 4-weeks wash-out period. Results: All subjects (M/F 54/47) completed the first 8 weeks, and 82 (M/F 43/39) the last part without adverse events. Mixed-effects models revealed a carry-over effect on many variables in the entire study, narrowing the analysis to the first 8 weeks before the wash-out periods. All subjects improved metabolic parameters, and decreased weight and Escherichia coli counts. Probiotics improved insulin sensitivity at fasting (QUICKI, 0.013 CI95%0.0–0.03) and during OGTT (ISI, 0.654 CI95%-0.11–1.41). Cytokines, GLP1, and target microbial counts did not vary. Of 25 SCFAs, acetic acid and acetic acid pentyl-ester relative abundance remained stable in the probiotics, while increased in the placebo (p < 0.02). A signature of five butanoic esters identified three clusters, one of them had better glucose responses during probiotics. Conclusion: An 8 weeks treatment with B. breve BR03 and B632 had beneficial effects on insulin sensitivity in youths with obesity. Microbiota functionality could influence metabolic answers to probiotics. Long-term studies to confirm and enrich our findings are justified. Tailored probiotic treatments could be an additional strategy for obesity. Trial registration: NCT03261466.

The performance of a 4H-SiC Schottky diode for thermal sensing in the wide temperature range from $T=85$ up to 443 K is presented. The linear dependence on temperature of the forward voltage drop, for different bias currents, is investigated through an analytical study of the temperature-dependent physical Schottky diode parameters. A high sensitivity of 1.18 mV/K was observed for a constant bias current of $I_{D}=80 \,\,\mu \text{A}$ . The device exhibits a good degree of linearity with a calculated root mean square error, with respect to the best-linear fitting model, lower than 2.7 mV. Moreover, the proposed sensor shows a good repeatability maintaining a stable output over more cycles of measurements, from (down to) 85 up to (from) 443 K, in a long period of time.

Introduction: Silver-Russell syndrome (SRS) is an imprinting disorder primarily caused by genetic and epigenetic aberrations on chromosomes 11 and 7. SRS is a rare growth retardation disorder often misdiagnosed due to its heterogeneous and non-specific clinical features. The Netchine-Harbison clinical scoring system (NH-CSS) is the recommended tool for differentiating patients into clinical SRS or unlikely SRS. However, the clinical diagnosis is molecularly confirmed only in about 60% of patients, leaving the remaining substantial proportion of SRS patients with unknown genetic etiology. Materials and Methods: A cohort of 34 Italian patients with SRS or SRS-like features scored according to the NH-CSS and without any SRS-associated (epi)genetic alterations was analyzed by high-resolution array-based comparative genomic hybridization (CGH) in order to identify potentially pathogenic copy number variants (CNVs). Results and Discussion: In seven patients, making up 21% of the initial cohort, five pathogenic and two potentially pathogenic CNVs were found involving distinct genomic regions either previously associated with growth delay conditions (1q24.3-q25.3, 17p13.3, 17q22, and 22q11.2-q11.22) and with SRS spectrum (7p12.1 and 7p15.3-p14.3) or outlined for the first time (19q13.42), providing a better definition of reported and as yet unreported SRS overlapping syndromes. All the variants involve genes with a defined role in growth pathways, and for two genes mapping at 7p, IGF2BP3 and GRB10, the association with SRS turns out to be reinforced. The deleterious effect of the two potentially pathogenic variants, comprising GRB10 and ZNF331 genes, was explored by targeted approaches, though further studies are needed to validate their pathogenic role in the SRS etiology. In conclusion, we reconfirm the utility of performing a genome-wide scan to achieve a differential diagnosis in patients with SRS or similar features and to highlight novel chromosome alterations associated with SRS and growth retardation disorders.

Cardiovascular prevention represents a cornerstone of modern strategies to reduce the burden of cardiovascular disease. It is of key importance to prevent cardiovascular diseases and associated events, not only to reduce morbidity and mortality, but also to increase the years of wellness in the aging population and to make the growing socio-economic burden imposed by cardiovascular events more sustainable.The current approach to prevention is based on an integrated use of effective lifestyle measures and, whenever appropriate, of antihypertensive and antidiabetic drugs, lipid-lowering agents and antiplatelet drugs.Given that population characteristics, in terms of ethnicity, demography and lifestyle habits, and healthcare system organizations differ among countries, international guidelines are not always applicable to specific countries and, often, are difficult to translate into daily clinical practice.In order to afford the specific features of Italy, 10 Scientific Societies and Research Institutions, mostly involved in preventive strategies, contributed to the present Italian consensus document, which includes brief, practical recommendations to support the preventive actions within the physician community and the general practice setting.