More favorable metabolic impact of three-times-weekly versus daily growth hormone (GH) treatment in na\uefve GH-deficient children

OBJECTIVE: Growth hormone treatment (GHT) is commonly administered daily, although pulsatile GH secretion is unlikely to be achieved. The auxological effect of a three-injections-per-week (TIW) regimen is controversial, while the metabolic effects have been never evaluated in children. The objective was to evaluate whether two different regimens of weekly injections could lead to similar auxological and metabolic effects in children with GH deficiency (GHD). DESIGN: 32 GHD children (25 males, mean age 10.5 \ub1 2.2 yr) were randomly assigned to receive daily (group A, No 16) or TIW (group B, No 16) GHT for 12 months. METHODS: Auxological parameters, insulin-like growth factor-I (IGF-I), glucose and insulin during OGTT, glycosylated hemoglobin (HbA1c), lipid profile, the oral disposition index (DIo), the homeostasis model assessment estimate of insulin resistance (Homa-IR) and the insulin sensitivity index (ISI). RESULTS: After 12 months, both groups showed a significant and comparable improvement in height (p<0.001) and IGF-I (p<0.001). As regards the metabolic parameters, in both groups we found a significant increase in fasting insulin (p<0.001 and p=0.026) and Homa-IR (p<0.001 and p=0.019). A significant increase in fasting glucose (p=0.001) and a decrease in ISI (p<0.001) and DIo (p=0.002) were only found in group A. CONCLUSIONS: The TIW regimen is effective and comparable with the daily regimen in improving auxological parameters and has a more favorable metabolic impact in GHD children (www.ClinicalTrials.gov. NCT03033121)

Accuracy of a Wrist-Worn Heart Rate Sensing Device during Elective Pediatric Surgical Procedures

The reliability of wearable photoplethysmography (PPG) sensors to measure heart rate (HR) in hospitalized patients has only been demonstrated in adults. We evaluated the accuracy of HR monitoring with a personal fitness tracker (PFT) in children undergoing surgery. HR monitoring was performed using a wrist-worn PFT (Fitbit Charge HR) in 30 children (8.21 \ub1 3.09 years) undergoing laparoscopy (n = 8) or open surgery (n = 22). HR values were analyzed preoperatively and during surgery. The accuracy of HR recordings was compared with measurements recorded during continuous electrocardiographic (cECG) monitoring; HRs derived from continuous monitoring with pulse oximetry (SpO2R) were used as a positive control. PFT-derived HR values were in agreement with those recorded during cECG (r = 0.99) and SpO2R (r = 0.99) monitoring. PFT performance remained high in children &lt; 8 years (r = 0.99), with a weight &lt; 30 kg (r = 0.99) and when the HR was &lt; 70 beats per minute (bpm) (r = 0.91) or &gt; 140 bpm (r = 0.99). PFT accuracy was similar during laparoscopy and open surgery, as well as preoperatively and during the intervention (r &gt; 0.9). PFT-derived HR showed excellent accuracy compared with HRs measured by cECG and SpO2R during pediatric surgical procedures. Further clinical evaluation is needed to define whether PFTs can be used in different health care settings

Chirality effects on the IRMPD spectra of basket resorcinarene/nucleoside complexes

The IRMPD spectra of the ESI-formed proton-bound complexes of the R,R,R,R- and S,S,S,S-enantiomers of a bis(diamido)-bridged basket resorcin[4]arene (R and S) with cytosine (1), cytidine (2), and cytarabine (3) were measured in the region 2800– 3600 cm1. Comparison of the IRMPD spectra with the corresponding ONIOM (B3LYP/6-31(d):UFF)-calculated absorption frequencies allowed the assessment of the vibrational modes that are responsible for the observed spectroscopic features. All of the complexes investigated, apart from [R·H·3]+, showed similar IRMPD spectra, which points to similar structural and conformational landscapes. Their IRMPD spectra agree with the formation of several isomeric structures in the ESI source, wherein the N(3)-protonated guest establishes noncovalent interactions with the host amidocarbonyl groups that are either oriented inside the host cavity or outside it between one of the bridged side-chains and the upper aromatic nucleus. The IRMPD spectrum of the [R·H·3]+ complex was clearly different from the others. This difference is attributed to the effect of intramolecular hydrogen bonding interactions between the C(2’)-OH group and the aglycone oxygen atom of the nucleosidic guest upon repulsive interactions between the same oxygen atom and the aromatic rings of the host

High-resolution tracking in a GEM-Emulsion detector

SHiP (Search for Hidden Particles) is a beam dump experiment proposed at the CERN SPS aiming at the observation of long lived particles very weakly coupled with ordinary matter mostly produced in the decay of charmed hadrons. The beam dump facility of SHiP is also a copious factory of neutrinos of all three kinds and therefore a dedicated neutrino detector is foreseen in the SHiP apparatus. The neutrino detector exploits the Emulsion Cloud Chamber technique with a modular structure, alternating walls of target units and planes of electronic detectors providing the time stamp to the event. GEM detectors are one of the possible choices for this task. This paper reports the results of the first exposure to a muon beam at CERN of a new hybrid chamber, obtained by coupling a GEM chamber and an emulsion detector. Thanks to the micrometric accuracy of the emulsion detector, the position resolution of the GEM chamber as a function of the particle inclination was evaluated in two configurations, with and without the magnetic fiel

Predictive ability of the estimate of fat mass to detect early-onset metabolic syndrome in prepubertal children with obesity

Body mass index (BMI), usually used as a body fatness marker, does not accurately dis-criminate between amounts of lean and fat mass, crucial factors in determining metabolic syndrome (MS) risk. We assessed the predictive ability of the estimate of FM (eFM) calculated using the following formula: FM = weight − exp(0.3073 × height2 −10.0155×d-growth-standards/standards/body-mass-index-for-age-bmi-for-age weight−1 +0.004571×weight− 0.9180×ln(age) + 0.6488×age0.5 + 0.04723×male + 2.8055) (exp = exponential function, score 1 if child was of black (BA), south Asian (SA), other Asian (AO), or other (other) ethnic origin and score 0 if not, ln = natural logarithmic transformation, male = 1, female = 0), to detect MS in 185 prepubertal obese children compared to other adiposity parameters. The eFM, BMI, waist circumference (WC), body shape index (ABSI), tri-ponderal mass index, and conicity index (C-Index) were calculated. Patients were classified as hav-ing MS if they met ≥ 3/5 of the following criteria: WC ≥ 95th percentile; triglycerides ≥ 95th percen-tile; HDL-cholesterol ≤ 5th percentile; blood pressure ≥ 95th percentile; fasting blood glucose ≥ 100 mg/dL; and/or HOMA-IR ≥ 97.5th percentile. MS occurred in 18.9% of obese subjects (p < 0.001), with a higher prevalence in females vs. males (p = 0.005). The eFM was correlated with BMI, WC, ABSI, and Con-I (p < 0.001). Higher eFM values were present in the MS vs. non-MS group (p < 0.001); the eFM was higher in patients with hypertension and insulin resistance (p <0.01). The eFM shows a good predictive ability for MS. Additional to BMI, the identification of new parameters determi-nable with simple anthropometric measures and with a good ability for the early detection of MS, such as the eFM, may be useful in clinical practice, particularly when instrumentation to estimate the body composition is not available

Gender-based differences in the clustering of metabolic syndrome factors in children and adolescents

We depicted gender-differences in metabolic syndrome (MS) clustering before and after puberty in pediatrics, in order to develop gender specific preventive strategies for childhood obesity. We considered 1079 children and adolescents (529 females and 550 males; mean age 11.5 \ub1 2.8 year). According to body mass index (BMI) percentiles the subjects were classified as normal weight BMI &lt;75th, overweight BMI 75-95th and with obesity BMI &gt;95th. MS was diagnosed when three of the following criteria for age and sex percentiles were met: BMI &gt;95th, triglycerides (TGs) level &gt;95th, high-density lipoprotein-cholesterol (HDL-c) level &lt;5th, blood pressure (blood pressure) &gt;95th percentile, fasting blood glucose (FBG) &gt;100 mg/dL and/or homeostatic model assessment-insulin resistance (HOMA-IR) &gt;97.5th percentile. The prevalence of dismetabolic factors was similar in both genders, except for pathological BP, which was higher in males (p = 0.02). MS was detected only in patients with obesity, with a higher prevalence in pubertal than late/post-pubertal subjects (p &lt; 0.001), without any significant difference between gender. In pre-puberty, the most common MS combination was obesity (HBMI) + hypertension (HBP) + hyperglycemia/insulin resistance (HGLY/IR) followed by HBMI + low HDL-levels (LHDL) + HGLY/IR versus HBMI + HBP + HGLY/IR followed by HBMI + HBP + LHDL, respectively, in females and males. In the early and late/post-pubertal periods, the most prevalent combination remained similar to pre-puberty, additionally in both sexes other combinations, such as HBMI + HTG + HBP + HGLY/IR, HBMI + HBP + LHDL + HGLY/IR, HBMI + HTG + LHDL + HGLY/IR and HBMI + HTG + LHDL + HBP + HGLY/IR were also detected, differently distributed in males and females. We confirm that MS is an important consequence related to obesity, particularly in the post-puberty stage. Some gender-based differences should be considered early in order to identify specific preventive and treatment strategies

MKRN3 and KISS1R mutations in precocious and early puberty

Background Pubertal timing is known to be influenced by interactions among various genetic, nutritional, environmental and socio-economic factors, although the ultimate mechanisms underlying the increase in pulsatile GnRH secretion at puberty have yet to be fully elucidated. The aim of our research was to verify the role of KISSR1 (previously named GPR54) and MKRN3 genes on pubertal timing. Methods We analyzed the DNA sequence of these genes in 13 girls affected by central precocious puberty (CPP) who showed onset of puberty before 8 years of age, and in 6 girls affected by early puberty (EP) between 8 and 10 years of age. Results Direct sequencing of the KISS1R (GPR54) gene revealed two SNPs. One SNP is a missense variant (rs 350,132) that has been previously reported in connection to CPP in Korean girls. The other variant that we found in the GPR54 gene (rs764046557) was a missense SNP located in exon 5 at position 209 of the aminoacid. We identified this variant in only one CPP patient. Automatic sequencing of MKRN3 in all patients revealed three variants in eight subjects. In 6 out of 19 (31.5%) patients (3/13 CPP patients and 3/6 EP patients) we found the synonymous variant c.663C &gt; T (rs2239669). Another synonymous variant (rs140467331) was found in one of our CPP patients, as well as one missense variant (rs760981395) in another CPP patient. Conclusion In conclusion, we identified sequence variations of the KISS1R and MKRN3 genes, two of the most frequent genetic causes of ICPP. Our results suggest that these variants might be inducible factors in the pathogenesis of CPP

Multiscenario flood hazard assessment using probabilistic runoff hydrograph estimation and 2D hydrodynamic modelling

In this paper, we aim to define a procedure of flood hazard assessment applicable to large river basins in which flood events can be induced/sustained by the full basin area or by fractions of the total area as functions of the extent of the triggering precipitation event. The proposed procedure is based on a combined approach accounting for (1) the reconstruction of intensity–duration–frequency curves expressing the magnitude in terms of intensity for multiple return periods; (2) the application of the soil conservation service method for runoff estimation from a selected rainfall scenario considering some characteristics of the basin (i.e. soil type, land use/treatment, surface condition, and antecedent moisture conditions); (3) 2D hydrodynamic modelling conducted by the HEC-RAS model using runoff hydrographs as hydrological input data; (4) the reconstruction of flood hazard maps by overlaying multiple inundation maps depicting flood extent for different return periods. To account for the variability in the extent of the triggering precipitation event and the resulting input hydrograph, multiple contributing areas are considered. The procedure is tested at the archaeological site of Sybaris in southern Italy, which is periodically involved in flood events of variable magnitude. The obtained results highlight that the variable extent of the floodable area is strongly conditioned by the extent of the contributing area and return period, as expected. The archaeological site is always involved in the simulated flooding process, except for the smallest contributing area for which only a 300-year event involves this part of the site. Our findings may be useful for developing and supporting flood risk management plans in the area. The developed procedure might be easily exported and tested in other fluvial contexts in which evaluations of multiple flood hazard scenarios, due to the basin geometry and extent, are needed

Subcutaneous Adipose Tissue Transcriptome Highlights Specific Expression Profiles in Severe Pediatric Obesity: A Pilot Study

The prevalence of pediatric obesity is rising rapidly worldwide, and "omic" approaches are helpful in investigating the molecular pathophysiology of obesity. This work aims to identify transcriptional differences in the subcutaneous adipose tissue (scAT) of children with overweight (OW), obesity (OB), or severe obesity (SV) compared with those of normal weight (NW). Periumbilical scAT biopsies were collected from 20 male children aged 1-12 years. The children were stratified into the following four groups according to their BMI z-scores: SV, OB, OW, and NW. scAT RNA-Seq analyses were performed, and a differential expression analysis was conducted using the DESeq2 R package. A pathways analysis was performed to gain biological insights into gene expression. Our data highlight the significant deregulation in both coding and non-coding transcripts in the SV group when compared with the NW, OW, and OB groups. A KEGG pathway analysis showed that coding transcripts were mainly involved in lipid metabolism. A GSEA analysis revealed the upregulation of lipid degradation and metabolism in SV vs. OB and SV vs. OW. Bioenergetic processes and the catabolism of branched-chain amino acids were upregulated in SV compared with OB, OW, and NW. In conclusion, we report for the first time that a significant transcriptional deregulation occurs in the periumbilical scAT of children with severe obesity compared with those of normal weight or those with overweight or mild obesity

Neurological manifestations of Kawasaki disease and multisystem inflammatory syndrome in children associated with COVID-19: A comparison of two different clinical entities

Kawasaki disease (KD) is one of the most frequent idiopathic vasculitis in children, affecting medium- and small-sized vessels. Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 has recently emerged as a new systemic hyperinflammatory condition affecting children some weeks after an acute COVID-19 infection. KD and MIS-C share different aspects and differ in many others: patients affected by MIS-C are usually older, with prominent gastrointestinal manifestations, diffuse adenopathy, extensive conjunctivitis, myocardial damage, leukopenia, and thrombocytopenia at the laboratory exams. Both conditions can present neurological complications. The aim of this manuscript is to provide a narrative review of neurological involvement in KD and MIS-C. A comprehensive review literature has been performed, and the main clinical features have been analyzed, contributing to neurological differential diagnosi