Insulin resistance plays a central role in the development of the metabolic syndrome, but how it relates to cardiovascular disease remains controversial. Liver insulin receptor knockout (LIRKO) mice have pure hepatic insulin resistance. On a standard chow diet, LIRKO mice have a proatherogenic lipoprotein profile with reduced high-density lipoprotein (HDL) cholesterol and very low-density lipoprotein (VLDL) particles that are markedly enriched in cholesterol. This is due to increased secretion and decreased clearance of apolipoprotein B-containing lipoproteins, coupled with decreased triglyceride secretion secondary to increased expression of Pgc-1 beta (Ppargc-1b), which promotes VLDL secretion, but decreased expression of Srebp-1c (Srebf1), Srebp-2 (Srebf2), and their targets, the lipogenic enzymes and the LDL receptor. Within 12 weeks on an atherogenic diet, LIRKO mice show marked hypercholesterolemia, and 100% of LIRKO mice, but 0% of controls, develop severe atherosclerosis. Thus, insulin resistance at the level of the liver is sufficient to produce the dyslipidemia and increased risk of atherosclerosis associated with the metabolic syndrome.

Objective To compare the polysomnography findings and cardiometabolic function among adolescent girls with PCOS and matched female and male controls. Method Retrospective chart review of electronic medical records of 28 girls with PCOS (age: 16.8±1.9 yrs, BMI Z-score 2.4±0.4), 28 control females (age: 17.1±1.8, BMI Z-score 2.4±0.3) and 28 control males (age: 16.6±1.6, BMI Z-score 2.5±0.5) in a tertiary care center. Results The prevalence of obstructive sleep apnea (OSA) was higher in girls with PCOS compared to control females (16/28 (57%) vs. 4/28(14.3%), p<0.01), however, was comparable to that of the control males (16/28(57%) vs. 21/28(75%), p=0.4). Girls with PCOS had a significantly higher prevalence of insulin resistance compared to control females and control males (20/28 (71.4%) vs. 9/22 (41.0%) (p=0.04) vs. 8/23 (34.8%) (p=0.01). Among girls with PCOS, those with OSA had significantly higher proportions of metabolic syndrome (9/16 (56.3% ) vs. 1/12 (8.3%) p=0.03), higher insulin resistance (13/16 (81.3%) vs. 5/12 (41.6%), p=0.03), elevated daytime systolic blood pressure (128.4±12.8 vs. 115.6±11.4, p<0.01), lower HDL (38.6±8.7 vs. 49±10.9, p=0.01) and elevated triglycerides (149.7±87.7 vs. 93.3±25.8, p=0.03) compared to those without OSA. Conclusions We report a higher prevalence of OSA and metabolic dysfunction in a selected group of obese girls with PCOS referred with sleep related complaints compared to BMI matched control girls without PCOS. We also report higher prevalence of cardiometabolic dysfunction in girls with PCOS and OSA compared to girls with PCOS without OSA.

Pseudohypoparathyoridism type Ib (PHP-Ib) typically defines the presence of end-organ resistance to parathyroid hormone in the absence of Albright's hereditary osteodystrophy. Patients affected by this disorder present with imprinting defects in the complex GNAS locus. Microdeletions within STX16 or GNAS have been identified in familial cases with PHP-Ib, but the molecular cause of the GNAS imprinting defects in sporadic PHP-Ib cases remains poorly defined. We now report a case with sporadic PHP-Ib for whom a SNPlex analysis revealed loss of the maternal GNAS allele. Further analysis of the entire genome with a 100K SNP chip identified a paternal uniparental isodisomy affecting the entire chromosome 20 without evidence for another chromosomal abnormality. Our findings explain the observed GNAS methylation changes and the patient's hormone resistance, and furthermore suggest that chromosome 20 harbors, besides GNAS, no additional imprinted region that contributes to the clinical and laboratory phenotype.

The self-diffusion coefficients (SDCs) of Na(+), Cs(+), and Ba(2+) have been determined in Nafion-117 membrane having mixed cationic compositions. Membranes with different proportions of Na(+)-Cs(+), Cs(+)-Ba(2+), Na(+)-Ba(2+), and Ag(+)-Ba(2+) cations have been prepared by equilibrating with solutions containing different ratios of these cations. The SDCs of the cations (D(Na), D(Cs), D(Ba)) and the ionic compositions of the membrane have been determined using a radiotracer method. For the Na-Cs and Cs-Ba systems, the SDCs of the cations have been found to be independent of the ionic compositions of the membrane. In the case of the Na-Ba system, D(Na) does not change with ionic composition, while D(Ba) has been found to be strongly dependent on the ionic composition of the membrane and decreases continuously with increasing Na(+) content in the membrane. Similar results have also been obtained for D(Ba) in the case of the Ag-Ba system. The specific conductivities (κ(imp)) of the membrane in mixed cationic forms have also been obtained from ac impedance measurement and compared with that (κ(cal)) calculated from the SDC data. For the Na-Ba system, the increment of κ(imp) with increase in the Na(+) content of the membrane has been found to be parabolic, whereas for the Na-Cs system the increment is linear. The reason behind the different behaviors for different types of ionic systems has been qualitatively explained based on different transport pathways of the cations in the membrane.

Nutritional rickets and osteomalacia are reemerging in Western societies, particularly in young children and in adolescents of African or Asian descent. Hypocalcemic seizures resulting from vitamin D deficiency are rare in adolescents, whereas fractures caused by seizures without evidence of direct trauma have not yet been reported in this population. We present an unusual case of secondary bilateral femoral fractures caused by hypocalcemic seizures in a 17-year-old boy with primary vitamin D deficiency. We examine the epidemiology and the clinical presentation of rickets and osteomalacia in the adolescent population, the risk of secondary injuries in patients with seizures, and the evaluation and management of hypocalcemic seizures and primary vitamin D deficiency.

Objectives Evaluate ovarian morphology using 3-dimensional MRI in adolescent girls with and without PCOS. Compare the utility of MRI versus ultrasonography (US) for diagnosis of PCOS Design Cross-sectional Setting Urban academic tertiary-care children’s hospital Patients Thirty-nine adolescent girls with untreated PCOS and 22 age/BMI-matched controls. Intervention MRI and/or transvaginal/transabdominal US Main Outcome Measure Ovarian volume (OV); follicle number per section (FNPS); correlation between OV on MRI and US; proportion of subjects with features of polycystic ovaries on MRI and US. Results MRI demonstrated larger OV and higher FNPS in subjects with PCOS compared to controls. Within the PCOS group, median OV was 11.9 (7.7) cm3 by MRI, compared with 8.8 (7.8) cm3 by US. Correlation coefficient between OV by MRI and US was 0.701. Due to poor resolution, FNPS could not be determined by US or compared with MRI. ROC curve analysis for MRI demonstrated that increasing volume cut-offs for polycystic ovaries from 10cm3 to 14cm3, increased specificity from 77% to 95%. For FNPS on MRI, specificity increased from 82% to 98% by increasing cut-offs from ≥12 to ≥17. Using Rotterdam cut-offs, 91% of subjects with PCOS met polycystic ovary criteria on MRI, while only 52% met criteria by US. Conclusions US measures smaller OV than MRI, cannot accurately detect follicle number, and is a poor imaging modality for characterizing polycystic ovaries in adolescents with suspected PCOS. For adolescents in whom diagnosis of PCOS remains uncertain after clinical and laboratory evaluation, MRI should be considered as a diagnostic imaging modality.

Objective To determine the prevalence and clinical and metabolic correlates of sleep disordered breathing (SDB) and excessive daytime sleepiness (EDS) in adolescent girls with polycystic ovarian syndrome (PCOS). Study design Standardized questionnaires were administered to subjects with PCOS and age-, sex-, ethnicity-, and BMI Z-score-matched controls. Medical records were reviewed for anthropometric and metabolic data. Results We studied 103 subjects with PCOS (16.9±1.5 years) and 90 controls (16.8±1.7 years). Compared with controls, girls with PCOS had a higher prevalence of SDB (45.6% vs. 27.8%, p=0.01) and EDS (54.4% vs.35.6%, p<0.01). Within PCOS, those with SDB had higher BMI Z-score (2.1±0.5 vs.1.7±0.6, p< 0.01), higher homeostatic model assessment (HOMA) (5.1±2.3 vs. 4.1±3.5, p<0.01), and higher prevalence of the metabolic syndrome (MetS) (42.6% vs. 16.1%, p=0.003), compared with those without SDB. Similarly, subjects with PCOS and EDS had higher BMI-Z score (2.0±0.6 vs.1.7±0.6, p=0.03), higher HOMA (5.1±2.9 vs.3.8±3.1, p=0.01), and higher rate of MetS (39.3% vs. 14.9% p<0.01), compared with those without EDS. MetS was independently associated with SDB (OR 3.2, CI-1.0–10.1) and EDS (OR 4.5, CI-1.2–16). Conclusions SDB and EDS are highly prevalent in adolescent girls with PCOS compared with matched controls. The MetS is independently associated with SDB and EDS in this group.

The transport characteristics of multivalent cations like Ba(2+) and Eu(3+) have been studied in bi-ionic form of the Nafion-117 membrane. The membranes have been prepared by loading different proportions of H(+)-Ba(2+)/Mg(2+)-Ba(2+)/Ba(2+)-Eu(3+)/H(+)-Eu(3+)/Na(+)-Eu(3+). The cationic compositions of the membranes have been determined from the measured ion exchange isotherms. Results show that the self-diffusion coefficient of Ba(2+) (D(Ba)) in H-Ba/Mg-Ba systems as well as the self-diffusion coefficient of Eu(3+) (D(Eu)) in H-Eu/Na-Eu systems are strongly dependent on the membrane ionic compositions and decreased continuously with increasing concentration of the highly hydrated ions (H(+)/Na(+)/Mg(2+)) in the membrane. Increase in the proportion of H(+)/Na(+)/Mg(2+) ions in the membrane increases the effective charge on the membrane matrix. This causes stronger electrostatic interaction of the less hydrated multivalent ions (Ba(2+)/Eu(3+)) with the membrane matrix charges, which ultimately results in their slower self-diffusion coefficients. The higher the valence, the stronger the electrostatic interaction is with the fixed ionic charges; hence, in general, D(Eu) is affected more as compared to D(Ba). On the basis of the free-volume theory for polymers, the effective interaction potential (Φ) of the Ba(2+) with the fixed ionic sites in the membrane has been calculated and found to be on the order of approximately millivolts. The higher the proportion of hydrated ion in the membrane, the higher the Φ is and the stronger the ion pair formation is with the fixed ionic sites in the membrane. However, in the Ba-Eu system, as the electrostatic interactions of the two ions with the membrane matrix are close, D(Ba) and D(Eu) are independent of the membrane ionic composition. The ionic composition dependence of D(Ba) in the H-Ba system is reflected in the transport rate of Ba(2+), showing the importance of such measurements in understanding the transport characteristics of the membrane.