Construct validity of a continuous metabolic syndrome score in children

<p>Abstract</p> <p>Objective</p> <p>The primary purpose of this study was to examine the construct validity of a continuous metabolic syndrome score (cMetS) in children. The secondary purpose was to identify a cutpoint value(s) for an adverse cMetS based on receiver operating characteristic (ROC) curve analysis.</p> <p>Methods</p> <p>378 children aged 7 to 9 years were assessed for the metabolic syndrome which was determined by age-modified cutpoints. High-density-lipoprotein cholesterol, triglycerides, the homeostasis assessment model of insulin resistance, mean arterial pressure, and waist circumference were used to create a cMetS for each subject.</p> <p>Results</p> <p>About half of the subjects did not possess any risk factors while about 5% possessed the metabolic syndrome. There was a graded relationship between the cMetS and the number of adverse risk factors. The cMetS was lowest in the group with no adverse risk factors (-1.59 ± 1.76) and highest in those possessing the metabolic syndrome (≥3 risk factors) (7.05 ± 2.73). The cutoff level yielding the maximal sensitivity and specificity for predicting the presence of the metabolic syndrome was a cMetS of 3.72 (sensitivity = 100%, specificity = 93.9%, and the area of the curve = 0.978 (0.957-0.990, 95% confidence intervals).</p> <p>Conclusion</p> <p>The results demonstrate the construct validity for the cMetS in children. Since there are several drawbacks to identifying a single cut-point value for the cMetS based on this sample, we urge researchers to use the approach herein to validate and create a cMetS that is specific to their study population.</p

Disassembly and reassembly of human papillomavirus virus-like particles produces more virion-like antibody reactivity

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus (HPV) vaccines based on major capsid protein L1 are licensed in over 100 countries to prevent HPV infections. The yeast-derived recombinant quadrivalent HPV L1 vaccine, GARDASIL(R), has played an important role in reducing cancer and genital warts since its introduction in 2006. The L1 proteins self-assemble into virus-like particles (VLPs).</p> <p>Results</p> <p>VLPs were subjected to post-purification disassembly and reassembly (D/R) treatment during bioprocessing to improve VLP immunoreactivity and stability. The post-D/R HPV16 VLPs and their complex with H16.V5 neutralizing antibody Fab fragments were visualized by cryo electron microscopy, showing VLPs densely decorated with antibody. Along with structural improvements, post-D/R VLPs showed markedly higher antigenicity to conformational and neutralizing monoclonal antibodies (mAbs) H16.V5, H16.E70 and H263.A2, whereas binding to mAbs recognizing linear epitopes (H16.J4, H16.O7, and H16.H5) was greatly reduced.</p> <p>Strikingly, post-D/R VLPs showed no detectable binding to H16.H5, indicating that the H16.H5 epitope is not accessible in fully assembled VLPs. An atomic homology model of the entire</p> <p>HPV16 VLP was generated based on previously determined high-resolution structures of bovine papillomavirus and HPV16 L1 pentameric capsomeres.</p> <p>Conclusions</p> <p>D/R treatment of HPV16 L1 VLPs produces more homogeneous VLPs with more virion-like antibody reactivity. These effects can be attributed to a combination of more complete and regular assembly of the VLPs, better folding of L1, reduced non-specific disulfide-mediated aggregation and increased stability of the VLPs. Markedly different antigenicity of HPV16 VLPs was observed upon D/R treatment with a panel of monoclonal antibodies targeting neutralization sensitive epitopes. Multiple epitope-specific assays with a panel of mAbs with different properties and epitopes are required to gain a better understanding of the immunochemical properties of VLPs and to correlate the observed changes at the molecular level. Mapping of known antibody epitopes to the homology model explains the changes in antibody reactivity upon D/R. In particular, the H16.H5 epitope is partially occluded by intercapsomeric interactions involving the L1 C-terminal arm. The homology model allows a more precise mapping of antibody epitopes. This work provides a better understanding of VLPs in current vaccines and could guide the design of improved vaccines or therapeutics.</p

Dyslipidemia Patterns among Hispanics/Latinos of Diverse Background in the United States

BACKGROUND: The prevalence and determinants of dyslipidemia patterns among Hispanics/Latinos are not well known. METHODS: Lipid and lipoprotein data were used from the Hispanic Community Health Study / Study of Latinos -- a population-based cohort of 16,415 US Hispanic/Latinos ages 18–74. National Cholesterol Education Program cutoffs were employed. Differences in demographics, lifestyle factors, biological and acculturation characteristics were compared among those with and without dyslipidemia. RESULTS: Mean age was 41.1 years and 47.9% were male. The overall prevalence of any dyslipidemia was 65.0%. The prevalence of elevated LDL-C was 36.0% and highest among Cubans (44.5%; p<0.001). Low HDL-C was present in 41.4% and did not significantly differ across Hispanic background groups (p=0.09). High triglycerides were seen in 14.8% of Hispanics/Latinos, most commonly among Central Americans (18.3%; p<0.001). Elevated non-HDL-C was seen in 34.7% with the highest prevalence among Cubans (43.3%; p<0.001). Dominicans consistently had a lower prevalence of most types of dyslipidemia. In multivariate analyses, the presence of any dyslipidemia was associated with increasing age, body mass index and low physical activity. Older age, female gender, diabetes, low physical activity, and alcohol use were associated with specific dyslipidemia types. Spanish-language preference and lower educational status were associated with higher dyslipidemia prevalence. CONCLUSION: Dyslipidemia is highly prevalent among US Hispanics/Latinos; Cubans seem particularly at risk. Determinants of dyslipidemia varied across Hispanic backgrounds with socioeconomic status and acculturation having a significant effect on dyslipidemia prevalence. This information can help guide public health measures to prevent disparities among the US Hispanic/Latino population