Late Effects of Disturbed IGF Signaling in Congenital Diseases.

The biologic effects of insulin-like growth factor-1 (IGF-1) are mediated by specific cell surface receptors. IGF-1 binding to the extracellular -subunits activates the tyrosine kinase intrinsic to the cytoplasmic portion of the IGF-1 receptor, leading to autophosphorylation of specific tyrosine residues in the receptor -subunit. One early molecular event that links the receptor kinase to the biologic actions of IGF-1 is tyrosine phosphorylation of the insulin receptor substrate family (IRS-1 to -4). IRS acts as a multisite ‘docking’ protein by binding to downstream signal-transducing molecules. Phosphorylation of multiple tyrosine residues results in the association of IRS-1 with the Src homology 2 (SH2) domains of other cytoplasmic signaling proteins, including phosphatidylinositol 3 kinase, Syp, Grb2 and Nck. By binding to Grb2, IRS proteins couple the IGF-1 receptor to the Ras/mitogenactivated protein kinase pathway. This pathway regulates cell growth, differentiation and proliferation. Severe pre- and postnatal growth retardation may arise from abnormalities of IGF-1 signaling such as IGF-1-binding alterations and IGF-1 receptor mutations. Knockout studies have shown severe growth impairment in mice lacking IRS family components or Akt. Finally, in human placentas from pregnancies complicated by intrauterine growth retardation, multiple alterations of IGF-1-signaling molecules have recently been described

Adiponectin levels are reduced in children born small for gestational age and are inversely related to postnatal catch-up growth

Adiponectin is an adipocytokine with insulin-sensitizing and antiatherogenic properties. Reduced concentrations of adiponectin precede the onset of type 2 diabetes and the development of atherosclerosis. Our aim was to quantify adiponectin concentrations in small for gestational age (SGA) children. Fifty-one SGA children, 24 obese, and 17 short-normal children with birth weight appropriate for gestational age (short-AGA) were studied. The statures of the SGA children were corrected for their midparental height and subdivided into two groups according to their corrected height: catch-up growth group, children with corrected height of 0 z-score or greater (n = 17); and noncatch-up growth group, subjects with corrected height less than 0 z-score (n = 34). SGA children showed adiponectin levels significantly lower than short-normal children (35.2 +/- 3.5 vs. 80.4 +/- 26.6 mug/ml; P < 0.0001) and obese children (77.5 +/- 39.4 μg/ml; P < 0.0001). Catch-up growth children showed adiponectin levels significantly lower than noncatch-up growth subjects (29.4 +/- 10.3 vs. 38.1 +/- 11.5 mug/ml; P = 0.01). Adiponectin concentrations were inversely related to height z-score, corrected stature, weight, and body mass index and were positively related to birth weight. Our results suggest that adiponectin levels are reduced in SGA children and are even lower in those with postnatal catch-up growth. Whether this finding implies a higher risk of developing type 2 diabetes and atherosclerosis remains to be established

Post-traumatic stress disorder (PTSD) in parents of children with type 1 diabetes during Covid-19 pandemic

Introduction The Post-traumatic Stress Disorder (PTSD) is a group of persistent psychological and physiological symptoms due to a traumatic, severe, event. Only few studies focused on the effects of Covid-19 on psychosocial outcomes in children with Type 1 Diabetes (T1D) and their parents. Aim of the study The aim of this study was to evaluate the presence PTSD in parents of children with T1D during COVID-19 pandemic lockdown. Patients and methods In the period between March and May 2020 we submitted the "Impact of Event Scale - Revised" (IES-R) questionnaire to the parents of 34 children with Type 1 Diabetes, asking them to express their emotions about the ongoing Covid-19 pandemic. Results A total of thirty mothers (mean age 43.0 +/- 4.2 years) and 25 fathers (mean age 45.6 +/- 5.9 years) participated in the survey and completed the questionnaires. 29.1% of parents had a score that allows to define a clinically relevant level of PTSD; ten mothers and 6 fathers had a PTSD clinically relevant score, corresponding, respectively, to 28.4 and 24% of total mothers and fathers. Finally, mothers and fathers, both express PTSD symptoms mainly in the form of intrusion and hyperarousal. Conclusions The present study confirms a high prevalence symptoms related to PTSD in mothers and fathers of children with Type 1 Diabetes. We believe that psychosocial outcomes of the COVID-19 pandemic should be taken into account in the planning of the next future assistance for children with T1D

Similarities and differences between myocarditis following COVID-19 mRNA vaccine and multiple inflammatory syndrome with cardiac involvement in children

despite the multiple benefits of vaccination, cardiac adverse events following COVID-19 immunization (c-AEFI) have been reported. these events as well as the severe cardiac involvement reported in Multisystem inflammatory syndrome in children (MIS-C) appear more frequent in young adult males. herein, we firstly report on the inflammatory profiles of patients experiencing c-AEFI in comparison with age, pubertal age and gender matched MIS-C with cardiac involvement. Proteins related to systemic inflammation were found higher in MIS-C compared to c-AEFI, whereas a higher level in proteins related to myocardial injury was found in c-AEFI. In addition, higher levels of DHEAS, DHEA, and cortisone were found in c-AEFI which persisted at follow-up. No anti-heart muscle and anti-endothelial cell antibodies have been detected. overall current comparative data showed a distinct inflammatory and androgens profile in c-AEFI patients which results to be well restricted on heart and to persist months after the acute event

Measurement of the kinematic variables of beauty particles produced in 350 GeV/c π−\pi^--Cu interactions

Using a sample of $26$ b\=b events, produced in $350\,\hbox{GeV}/c$ $\pi^-$ interactions in a copper target, which includes $13$ events where the decays of both $B$ and $\overline{B}$ are well reconstructed, we measure the differential distributions with respect to $x_F$ and $p_T^2$ as well as some two-particle kinematic variables. We also compare our results with a previous experiment and with predictions based on perturbative QCD

Azimuthal correlation between beauty particles produced in 350 GeV/c π−\pi^{-}-Cu interactions

Using a sample of $10^8$ triggered events, produced in $350\, \hbox{GeV}/c$ $\pi^-$ interactions in a copper target, we have identified $26$ b\=b events. These include $13$ events where the decays of both $B$ and $\overline{B}$ are well reconstructed. We measure the azimuthal \hbox{correlation} between beauty particles, and compare our result with predictions based on perturbative QCD

Adherence to growth hormone (GH) therapy in naïve to treatment GH-deficient children: data of the Italian Cohort from the Easypod Connect Observational Study (ECOS)

Background: With the use of non-objective measurement, adherence to growth hormone (GH) therapy has been reported suboptimal in a large proportion of patients, and poor adherence has been shown to affect short-term growth response in patients receiving GH treatment. Objective: The Easypod™ electronic device allows objective measurement of adherence. In this study, we report 3-year prospective adherence data of the Italian cohort of naïve GH deficient (GHD) children extrapolated from the Easypod Connect Observational Study (ECOS) database. Patients and methods: Seventy-three GHD children naïve to GH treatment were included in the analysis. 22 Italian centers participated in the study. Results: Mean adherence rate was consistently above 85% across the 3-year observation period. Particularly, mean adherence was 88.5%, 86.6%, and 85.7% after 1, 2 and 3 years, respectively. Mean (± SD) height-SDS increase after the first year was 0.41 (± 0.38). Conclusions: The majority of naïve GHD children starting GH treatment with Easypod maintained an adherence rate > 85% up to 3 years. Easypod is a useful tool to follow-up patients’ adherence allowing timely intervention to improve optimal treatment for these patients

Adherence to growth hormone (GH) therapy in na\uefve to treatment GH-deficient children: data of the Italian Cohort from the Easypod Connect Observational Study (ECOS)

Background: With the use of non-objective measurement, adherence to growth hormone (GH) therapy has been reported suboptimal in a large proportion of patients, and poor adherence has been shown to affect short-term growth response in patients receiving GH treatment. Objective: The Easypod\u2122 electronic device allows objective measurement of adherence. In this study, we report 3-year prospective adherence data of the Italian cohort of na\uefve GH deficient (GHD) children extrapolated from the Easypod Connect Observational Study (ECOS) database. Patients and methods: Seventy-three GHD children na\uefve to GH treatment were included in the analysis. 22 Italian centers participated in the study. Results: Mean adherence rate was consistently above 85% across the 3-year observation period. Particularly, mean adherence was 88.5%, 86.6%, and 85.7% after 1, 2 and 3\ua0years, respectively. Mean (\ub1 SD) height-SDS increase after the first year was 0.41 (\ub1 0.38). Conclusions: The majority of na\uefve GHD children starting GH treatment with Easypod maintained an adherence rate > 85% up to 3\ua0years. Easypod is a useful tool to follow-up patients\u2019 adherence allowing timely intervention to improve optimal treatment for these patients