Indirect method for validating transference of reference intervals

Abstract Background: Transference of reference intervals (RIs) from multicentre studies are often verified by use of a small number of samples from reference individuals or by the use of one serum sample (Serum X for NORIP RI). Despite recommended and appropriate methods, both have inconveniencies and drawbacks. Several attempts have been made to develop an indirect method, which uses historical data from the laboratory. These methods are retrospective relying on older test results. A near prospective method would be preferable for the laboratories introducing new methods or changing analytical platforms. Methods: We performed a data mining experiment using results from our laboratory information system covering patients from a large geographic area. Request patterns for patients with assumed healthy characteristics were identified and used to extract laboratory results for calculation of new RI by an indirect method. Calculated RI and confidence intervals (CIs) were compared to transferred NORIP RI verified by NFKK Reference Serum X. Results: We found that our indirect method and NFKK Reference Serum X in general produced similar results when verifying transference of RI. The method produces results for all stratifications. Only single stratifications and one analyte showed unexplained incongruences to the NORIP RI. Conclusions: Our results suggest using request patterns as a surrogate measure for good health status. This allows for a data mining method for validation of RI or validating their transference, which is likely to be applicable in countries with similar healthcare and laboratory information system. </jats:sec

Multilingual signs for Latin American residents in a local town in Japan : Findings based on fieldwork in Minokamo city

Analysis of a Selected Set of Antimicrobial Peptides The rapid emergence of resistance to classical antibiotics has increased the interest in novel antimicrobial compounds. Antimicrobial peptides (AMPs) represent an attractive alter-native to classical antibiotics and a number of different studies have reported antimicrobial activity data of various AMPs, but there is only limited comparative data available. The mode of action for many AMPs is largely unknown even though several models have sug-gested that the lipopolysaccharides (LPS) play a crucial role in the attraction and attach-ment of the AMP to the bacterial membrane in Gram-negative bacteria. We compared th

Duplication and Diversification of the Hypoxia-Inducible IGFBP-1 Gene in Zebrafish

Gene duplication is the primary force of new gene evolution. Deciphering whether a pair of duplicated genes has evolved divergent functions is often challenging. The zebrafish is uniquely positioned to provide insight into the process of functional gene evolution due to its amenability to genetic and experimental manipulation and because it possess a large number of duplicated genes.We report the identification and characterization of two hypoxia-inducible genes in zebrafish that are co-ortholgs of human IGF binding protein-1 (IGFBP-1). IGFBP-1 is a secreted protein that binds to IGF and modulates IGF actions in somatic growth, development, and aging. Like their human and mouse counterparts, in adult zebrafish igfbp-1a and igfbp-1b are exclusively expressed in the liver. During embryogenesis, the two genes are expressed in overlapping spatial domains but with distinct temporal patterns. While zebrafish IGFBP-1a mRNA was easily detected throughout embryogenesis, IGFBP-1b mRNA was detectable only in advanced stages. Hypoxia induces igfbp-1a expression in early embryogenesis, but induces the igfbp-1b expression later in embryogenesis. Both IGFBP-1a and -b are capable of IGF binding, but IGFBP-1b has much lower affinities for IGF-I and -II because of greater dissociation rates. Overexpression of IGFBP-1a and -1b in zebrafish embryos caused significant decreases in growth and developmental rates. When tested in cultured zebrafish embryonic cells, IGFBP-1a and -1b both inhibited IGF-1-induced cell proliferation but the activity of IGFBP-1b was significantly weaker.These results indicate subfunction partitioning of the duplicated IGFBP-1 genes at the levels of gene expression, physiological regulation, protein structure, and biological actions. The duplicated IGFBP-1 may provide additional flexibility in fine-tuning IGF signaling activities under hypoxia and other catabolic conditions

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways