Genetic variability of the blue and red shrimp Aristeus antennatus in the Western Mediterranean Sea inferred by DNA microsatellite loci

Genetic variation at eight microsatellite loci was studied in nine populations of the blue and red shrimp Aristeus antennatus to investigate whether distinct stocks are present in the Western Mediterranean Sea. A high level of gene flow and no evidence of genetic partitioning were discovered. No significant variation was found (FST = 0.00673, P-value = 0.067) even when shrimps from exploited and those from deep-water unexploited grounds were compared. No evidence of reduction or expansion of population size in the recent past was found, as indicated by the bottleneck and interlocus g-tests. Our results are consistent with previous studies using mitochondrial gene methods and allozymes, indicating that, for this species, extensive pelagic larval dispersal and adult migration are probably responsible for the genetic homogeneity observed. In particular, due to a different bathymetric distribution of males and females, reported to be associated with different water masses and hence with possible differential dispersal capacity between sexes, the hypothesis of sex-biased dispersal was tested. Mean values of corrected assignment indices and mean relatedness values were higher for males, suggesting that females are the more widely dispersing sex. Molecular assessment of A. antennatus from the Western Mediterranean provides data of biological and evolutionary interest for the successful management of such a highly valuable fishery resource

Impaired GH Secretion in Patients with SHOX Deficiency and Efficacy of Recombinant Human GH Therapy.

Background/Aims: Mutations of the short stature homeobox-containing (SHOX) gene on the pseudoautosomal region of the sex chromosomes cause short stature. GH treatment has been recently proposed to improve height in short patients with SHOX deficiency. The aim of this study was to evaluate GH secretion and analyze growth and safety of recombinant human GH (rhGH) therapy in short children and adolescents with SHOX deficiency. Patients and Design: We studied 16 patients (10 females; 9.7 ± 2.9 years old; height -2.46 ± 0.82 standard deviation score, SDS) with SHOX deficiency. All subjects underwent auxological evaluations, biochemical investigations, and were treated with rhGH (0.273 ± 0.053 mg/kg/week). Results: Impaired GH secretion was present in 37.5% of the studied subjects. Comparing baseline data with those at the last visit, we found that rhGH treatment improved growth velocity SDS (from -1.03 ± 1.44 to 2.77 ± 1.95; p = 0.001), height SDS (from -2.41 ± 0.71 to -1.81 ± 0.87; p < 0.001), and IGF-1 values (from -0.57 ± 1.23 to 0.63 ± 1.63 SDS, p = 0.010) without affecting body mass index SDS. Height SDS measured at the last visit was significantly correlated with chronological age (r = -0.618, p = 0.032), bone age (r = -0.582, p = 0.047) and height SDS (r = 0.938, p < 0.001) at the beginning of treatment. No adverse events were reported on rhGH therapy which was never discontinued. Conclusion: These data showed that impaired GH secretion is not uncommon in SHOX deficiency subjects, and that rhGH therapy may be effective in increasing height in most of these patients independent of their GH secretory status, without causing any adverse events of concern

Nonsense-mediated decay mechanism is a possible modifying factor of clinical outcome in nonsense cd39 beta thalassemia genotype

Nonsense-mediated mRNA decay (NMD) is a surveillance system to prevent the synthesis of non-functional proteins. In β-thalassemia, NMD may have a role in clinical outcome. An example of premature translation stop codons appearing for the first time is the β-globin cd39 mutation; when homozygous, this results in a severe phenotype. The aim of this study was to determine whether the homozygous nonsense cd39 may have a milder phenotype in comparison with IVS1,nt110/cd39 genotype. Genotypes have been identified from a cohort of 568 patients affected by β-thalassemia. These genotypes were compared with those found in 577 affected fetuses detected among 2292 prenatal diagnoses. The nine most common genotypes, each with an incidence rate of 1.5% or over, and together accounting for 80% of genotype frequencies, underwent statistical analysis. Genotype prevalence was calculated within the overall group. Results are expressed as proportions with 95% confidence intervals; P≤0.05 was considered statistically significant. A binomial distribution was assumed for each group; z-tests were used to compare genotype frequencies observed in the patient group with frequencies in the affected fetus group. In the absence of selecting factors, prevalence of these two genotypes was compared between a cohort of 568 β-thalassemia patients (PTS) and 577 affected fetuses (FOET) detected during the same period. IVS1,nt110/cd39 was significantly more prevalent in FOET than PTS (P<0.0001), while there was no significant difference in prevalence of cd39/cd39 in FOET compared with PTS (P=0.524). These results suggest a cd39 genotype NMD mechanism may be associated with improved clinical outcomes in thalassemia major

Combined Therapy with Insulin and Growth Hormone in 17 Patients with Type-1 Diabetes and Growth Disorders.

Combined growth hormone (GH) and insulin therapy is rarely prescribed by pediatric endocrinologists. We investigated the attitude of Italian physicians to prescribing that therapy in the case of short stature and type-1 diabetes (T1DM). Methods: A questionnaire was sent and if a patient was identified, data on growth and diabetes management were collected. Results: Data from 42 centers (84%) were obtained. Of these, 29 centers reported that the use of combined therapy was usually avoided. A total of 17 patients were treated in 13 centers (GH was started before T1DM onset in 9 patients and after the onset of T1DM in 8). Height SDS patterns during GH therapy in the 11 patients affected by GH deficiency ranged from -0.3 to +3.1 SDS. In the 8 diabetic patients in whom GH was added subsequently, mean insulin dose increased during the first 6 months of therapy from 0.7 ± 0.2 to 1.0 ± 0.2 U/kg (p = 0.004). HbA1c was unchanged during the first 6 months of combined therapy. Conclusions: Most Italian physicians do not consider prescribing the combined GH-insulin therapy in diabetic children with growth problems. However, the results of the 17 patients identified would confirm that the combined therapy was feasible and only caused mild insulin resistance. GH therapy was effective in promoting growth in most patients and did not affect diabetes metabolic contro

Population pharmacokinetics and dosing recommendations for the use of deferiprone in children younger than 6 years

AIMS: Despite long clinical experience with deferiprone, there is limited information on its pharmacokinetics in children < 6 years of age. Here we assess the impact of developmental growth on the pharmacokinetics of deferiprone in this population using a population approach. Based on pharmacokinetic bridging concepts, we also evaluate whether the recommended doses yield appropriate systemic exposure in this group of patients. METHODS: Data from a study in which 18 paediatric patients were enrolled were available for the purposes of this analysis. Patients were randomised to three deferiprone dose levels (8.3, 16.7 and 33.3 mg/kg). Blood samples were collected according to an optimised sampling scheme in which each patient contributed to a maximum of five samples. A population pharmacokinetic model was developed using NONMEM v.7.2. Model selection criteria were based on graphical and statistical summaries. RESULTS: A one-compartment model with first-order absorption and first-order elimination best described the pharmacokinetics of deferiprone. Drug disposition parameters were affected by body weight, with both clearance and volume increasing allometrically with size. Simulation scenarios show that comparable systemic exposure (AUC) is achieved in children and adults after similar dose levels in mg/kg, with median (5-95(th) quantiles) AUC values respectively of 340.6 (223.2-520.0) and 318.5 (200.4-499.0) µmol/L*h at 75 mg/kg/day and 453.7 (297.3-693.0) and 424.2 (266.9-664.0) at 100 mg/kg/day t.i.d. doses. CONCLUSIONS: Based on the current findings, a dosing regimen of 25 mg/kg t.i.d. is recommended in children below 6 years of age, with the possibility of titration up to 33.3 mg/kg t.i.d

Pediatric Systemic Multi-Inflammatory Diseases in Italy During Sars-Cov-2 Epidemic: From Kawasaki Disease To Kawacovid

Introduction: Italy was affected by the SARS-CoV-2 epidemic after its outbreak in China. With a 4-weeks delay after the peak in adults, we observed an abnormal number of patients with characteristics of a multi-inflammatory disease and similarities with Kawasaki Disease (KD). Others reported similar cases, defined PIMS-TS or MIS-C.1,2 Objectives: To better characterize clinical features and treatment response of PIMS-TS and to explore its relationship with KD. Methods: We conducted an observational, retrospective, multicenter study. On April 24th-2020 the Rheumatology Study Group of the Italian Pediatric Society launched a national online survey, to enroll patients diagnosed with KD or with a multisystem inflammatory disease between February 1st 2020 and May 31st. The population was then divided into two different groups: 1) Classical and incomplete KD, named Kawasaki Disease Group (KDG); 2) KD-like multi-inflammatory syndrome, named KawaCOVID (KCG). An expert panel of pediatric rheumatologists re-analyzed every single patient to ensure appropriate classification. Data were collected with an online database. Results: 149 cases were studied, 96 with KDG and 53 with KCG. The two population significantly differed for clinical characteristics (see table 1). Lymphopenia, higher CRP levels, elevated Ferritin and Troponin-T characterized KCG such as lower WBC and platelets (all p values&lt;0,05). KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p=0.04 and 71,9% vs 43,4%; p=0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p&lt;0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p&lt;0.0001). Short-term follow data on KCG showed minor complications while on KDG a majority of patients had persistence of CAA. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data between the two groups Conclusion: Our study would suggest that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD, possibly triggered by SARS-CoV-2, and PIMS-TS. Older age at onset and clinical peculiarities, like the occurrence of myocarditis, characterize this multiinflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths

Obesity and disease activity in juvenile idiopathic arthritis

<p>Abstract</p> <p>Background</p> <p>Children with physical disabilities may have an increased risk for obesity and obesity might be a risk factor for inflammatory arthritis. The aims of this study were: to determine the prevalence of obesity in children and adolescents with juvenile idiopathic arthritis (JIA), and to examine the association between obesity and disease activity in this population.</p> <p>Findings</p> <p>A cross-sectional analysis of all patients with JIA attending a pediatric rheumatology clinic, between October 2009 and September 2010, was performed. A linear regression model was used to explore the association between obesity and disease activity in patients with JIA. A total of 154 subjects were included in the analysis; median age was 10.6 years, 61% were female, and 88% were white. Obesity was found in 18%, 12% were overweight, and 3% were underweight. There was no association between obesity and JADAS-27 (Juvenile Arthritis Disease Activity Score 27), physician's assessment of disease activity, parent's assessment of child's well-being, erythrocyte sedimentation rate, number of active joints, or C-reactive protein (p-value range 0.10 to 0.95).</p> <p>Conclusions</p> <p>Although 18% of patients with JIA were obese, we did not find an association between obesity and disease activity. As obesity confers an additional health risk in children with arthritis, addressing this co-morbidity should be a health priority in patients with JIA. Future studies are necessary to further explore potential associations between obesity, development of JIA, and disease activity.</p

Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS