Association of Adiponectin, Resistin and High Sensitive CRP Level with the Metabolic Syndrome in Childhood and Adolescence

Early markers are required in pathophysiological process of obesity, MS and type 2 diabetes. We aimed to clarify the usefulness of serum adipokines (adiponectin, AD and resistin) and inflammatory markers to identify obese and overweight children with MS. Three hundred and seven of 2491 subjects aged 11-19 with BMI >= 85 centile selected with a multistage, stratified sampling were included. Their height, weight and waist circumference were measured, all subjects underwent physical examination and standard OGTT. AD, resistin and hs-CRP were measured from baseline blood sample. The mean age of subjects was 14.2 +/- 1.8, 57.7% was girl (n=177) and 42.3% (n=130) boy. Of the 307 subjects 40 (13%) were classified as having MS. Serum AD levels were significantly lower in boys (p = 0.02), and decreased while BMI increased, but this trend was not significant (p>0.05). Although median resistin values were higher in obese than others (20, 18.5, 17ng/ml, respectively) it was not significant (p>0.05). In obese subjects, hs-CRP levels were significantly high (0.21 mg/L)(p=0.000). All three markers in obese and overweight children with and without MS were not significant (p>0.05). Girls with MS had lower adiponectin levels than those without MS. Waist circumference had the highest sensitivity and specificity for predicting MS in ROC analysis. The area under the curve (AUC) was 0.831 for WC standard error (SE) 0.033; 95% CI 0.767-0.896; p<0.0001. But the AUCs for the adiponectin, resistin, hs-CRP were not significant. In this study, we observed that adipokines or inflammatory markers have no predictive value in the diagnosis of MS. We concluded that the best marker for MS diagnosis is the measurement of waist circumference

Evaluation and Treatment Results of Ovarian Cysts in Childhood and Adolescence: A Multicenter, Retrospective Study of 100 Patients

PMID = 2816713

53BP1 and USP28 mediate p53 activation and G1 arrest after centrosome loss or extended mitotic duration

In normal human cells, centrosome loss induced by centrinone—a specific centrosome duplication inhibitor—leads to irreversible, p53-dependent G1 arrest by an unknown mechanism. A genome-wide CRISPR/Cas9 screen for centrinone resistance identified genes encoding the p53-binding protein 53BP1, the deubiquitinase USP28, and the ubiquitin ligase TRIM37. Deletion of TP53BP1, USP28, or TRIM37 prevented p53 elevation in response to centrosome loss but did not affect cytokinesis failure–induced arrest or p53 elevation after doxorubicin-induced DNA damage. Deletion of TP53BP1 and USP28, but not TRIM37, prevented growth arrest in response to prolonged mitotic duration. TRIM37 knockout cells formed ectopic centrosomal-component foci that suppressed mitotic defects associated with centrosome loss. TP53BP1 and USP28 knockouts exhibited compromised proliferation after centrosome removal, suggesting that centrosome-independent proliferation is not conferred solely by the inability to sense centrosome loss. Thus, analysis of centrinone resistance identified a 53BP1-USP28 module as critical for communicating mitotic challenges to the p53 circuit and TRIM37 as an enforcer of the singularity of centrosome assembly

Analysis of Centrosome and Dna Damage Response In Plk4 Associated Seckel Syndrome

Microcephalic primordial dwarfism (MPD) is a group of autosomal recessive inherited single-gene disorders with intrauterine and postnatal global growth failure. Seckel syndrome is the most common form of the MPD. Ten genes are known with Seckel syndrome. Using genome-wide SNP genotyping and homozygosity mapping we mapped a Seckel syndrome gene to chromosomal region 4q28.1-q28.3 in a Turkish family. Direct sequencing of PLK4 (polo-like kinase 4) revealed a homozygous splicing acceptor site transition (c.31-3 A>G) that results in a premature translation termination (p.[=,Asp11Profs*14]) causing deletion of all known functional domains of the protein. PLK4 is a master regulator of centriole biogenesis and its deficiency has recently been associated with Seckel syndrome. However, the role of PLK4 in genomic stability and the DNA damage response is unclear. Evaluation of the PLK4-Seckel fibroblasts obtained from patient revealed the expected impaired centriole biogenesis, disrupted mitotic morphology, G2/M delay, and extended cell doubling time. Analysis of the PLK4-Seckel cells indicated that PLK4 is also essential for genomic stability and DNA damage response. These findings provide mechanistic insight into the pathogenesis of the severe growth failure associated with PLK4-deficiency.WoSScopu