Thyroid Hormones Are Not Associated with Plasma Osteocalcin Levels in Adult Population with Normal Thyroid Function

Thyroid hormones (THs) play an indispensable role in skeletal development and bone remodeling. Some studies have reported associations of THs with serum osteocalcin (OC) levels, but the results are quite inconsistent and the molecular mechanism of their simultaneous or interdependent activity on bone is almost unknown. Therefore, the aim of this study was to determine the possible associations of plasma THs with plasma OC levels and the possible mediating effect of OC on the relationship between THs and bone mineral density (BMD). For this purpose, out of the initial 1981 participants, we selected healthy euthyroid participants controlled for available confounding factors that can affect thyroid function and bone metabolism (N = 694). Given our results, we could not confirm any associations of THs with plasma OC levels nor the mediating effect of OC on the relationship between THs and BMD in euthyroid population. In the group of women controlled for menopause status (N = 396), we found a significant negative association of body mass index (BMI) with OC levels (β = −0.14, p = 0.03). We also found a negative association of free triiodothyronine (fT3) (β = −0.01, p = 0.02) and age (β = −0.003, p < 0.001) with BMD, and a positive association of BMI (β = 0.004, p < 0.001) and male gender (β = 0.1, p < 0.001) with BMD. In addition, we found significantly higher plasma OC levels and lower values of BMD in postmenopausal euthyroid women compared with premenopausal euthyroid women. In our opinion, the results of previous studies suggesting an association between circulating THs and serum OC levels may be influenced by an inconsistent selection of participants and the influence of confounding factors

Evaluation of nitrogen use efficiency in the Maksimir 3 Synthetic maize population

Nitrogen use efficiency (NUE) has become an important trait for sustainable agriculture. Traits present in maize (Zea mays L) landraces that contribute to adaptation in nitrogen-limited environments are not easily implemented directly into modern maize breeding programs. Thus, the landraces might be improved by recurrent selection and afterwards used as source of certain traits for elite breeding material. The Maksimir 3 Synthetic (M3S) maize popu¬lation was created from landraces traditionally grown under low levels of soil fertility. The synthetic was subjected to recurrent selection for yield during three cycles and for improved NUE in the fourth cycle. In order to determine the effect of four cycles of recurrent selection, performance of populations per se (S0), population testcrosses, and populations per se selfed (S1) were evaluated in field trials under high and low nitrogen input conditions at four lo¬cations during 2010. The S0 populations had significantly higher grain yield (+20.6%), ear diameter (+2.6%), 1000 kernel weight (+3.3%) and ear leaf chlorophyll content (+31.2%) at the high nitrogen fertilization rate as compared to the low nitrogen fertilization rate. The S1 populations and testcross populations responded similarly to nitrogen fertilization. Genotype x nitrogen interaction for yield was not significant, but indication of specific adaptation to the nitrogen deficient environments was found. After the fourth cycle of recurrent selection, a significant increase in grain yield was found at both levels of nitrogen fertilization

Normative equations for central augmentation index:Assessment of inter-population applicability and how it could be improved

Common reference values of arterial stiffness indices could be effective screening tool in detecting vascular phenotypes at risk. However, populations of the same ethnicity may differ in vascular phenotype due to different environmental pressure. We examined applicability of normative equations for central augmentation index (cAIx) derived from Danish population with low cardiovascular risk on the corresponding Croatian population from the Mediterranean area. Disagreement between measured and predicted cAIx was assessed by Bland-Altman analysis. Both, cAIx-age distribution and normative equation fitted on Croatian data were highly comparable to Danish low-risk sample. Contrarily, Bland-Altman analysis of cAIx disagreement revealed a curvilinear deviation from the line of full agreement indicating that the equations were not equally applicable across age ranges. Stratification of individual data into age decades eliminated curvilinearity in all but the 30–39 (men) and 40–49 (women) decades. In other decades, linear disagreement independent of age persisted indicating that cAIx determinants other than age were not envisaged/compensated for by proposed equations. Therefore, established normative equations are equally applicable to both Nordic and Mediterranean populations but are of limited use. If designed for narrower age ranges, the equations’ sensitivity in detecting vascular phenotypes at risk and applicability to different populations could be improved

Genome-wide meta-analysis identifies novel loci associated with parathyroid hormone level

Abstract Background Parathyroid hormone (PTH) is one of the principal regulators of calcium homeostasis. Although serum PTH level is mostly accounted by genetic factors, genetic background underlying PTH level is insufficiently known. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels. Methods We performed GWAS meta-analysis within two genetically isolated Croatian populations followed by replication analysis in a Croatian mainland population and we also combined results across all three analyzed populations. The analyses included 2596 individuals. A total of 7,411,206 variants, imputed using the 1000 Genomes reference panel, were analysed for the association. In addition, a sex-specific GWAS meta-analyses were performed. Results Polymorphisms with the lowest P-values were located on chromosome 4 approximately 84 kb of the 5′ of RASGEF1B gene. The most significant SNP was rs11099476 (P = 1.15 × 10−8). Sex-specific analysis identified genome-wide significant association of the variant rs77178854, located within DPP10 gene in females only (P = 2.21 × 10− 9). There were no genome-wide significant findings in the meta-analysis of males. Conclusions We identified two biologically plausible novel loci associated with PTH levels, providing us with further insights into the genetics of this complex trait

Evaluation of genetic susceptibility to childhood allergy and asthma in an African American urban population

<p>Abstract</p> <p>Background</p> <p>Asthma and allergy represent complex phenotypes, which disproportionately burden ethnic minorities in the United States. Strong evidence for genomic factors predisposing subjects to asthma/allergy is available. However, methods to utilize this information to identify high risk groups are variable and replication of genetic associations in African Americans is warranted.</p> <p>Methods</p> <p>We evaluated 41 single nucleotide polymorphisms (SNP) and a deletion corresponding to 11 genes demonstrating association with asthma in the literature, for association with asthma, atopy, testing positive for food allergens, eosinophilia, and total serum IgE among 141 African American children living in Detroit, Michigan. Independent SNP and haplotype associations were investigated for association with each trait, and subsequently assessed in concert using a genetic risk score (GRS).</p> <p>Results</p> <p>Statistically significant associations with asthma were observed for SNPs in <it>GSTM1, MS4A2</it>, and <it>GSTP1 </it>genes, after correction for multiple testing. Chromosome 11 haplotype CTACGAGGCC (corresponding to <it>MS4A2 </it>rs574700, rs1441586, rs556917, rs502581, rs502419 and <it>GSTP1 </it>rs6591256, rs17593068, rs1695, rs1871042, rs947895) was associated with a nearly five-fold increase in the odds of asthma (Odds Ratio (OR) = 4.8, <it>p </it>= 0.007). The GRS was significantly associated with a higher odds of asthma (OR = 1.61, 95% Confidence Interval = 1.21, 2.13; <it>p </it>= 0.001).</p> <p>Conclusions</p> <p>Variation in genes associated with asthma in predominantly non-African ethnic groups contributed to increased odds of asthma in this African American study population. Evaluating all significant variants in concert helped to identify the highest risk subset of this group.</p

Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts

The Economic Burden of Infective Endocarditis due to Injection Drug Use in Australia: A Single Centre Study—University Hospital Geelong, Barwon Health, Victoria

Background. Injection drug use (IDU) is a well-recognized risk factor for infective endocarditis (IE). Associated complications from IDU result in significant morbidity and mortality with substantial cost implications. The aim of this study was to determine the cost burden associated with the management of IE due to IDU (IE-IDU). Methods. We used data collected prospectively on patients with a diagnosis of IE-IDU as part of the international collaboration on endocarditis (ICE). The cost of medical treatment was estimated based on diagnosis-related groups (DRG) and weighted inlier equivalent separation (WIES). Results. There were 23 episodes from 21 patients in 12 years (2002 to 2014). The costing was done for 22 episodes due to data missing on 1 patient. The median age was 39 years. The gender distribution was equal. Heroin (71%) and methamphetamine (33%) were the most frequently used. 74% (17/23) required intensive care unit (ICU) admission. The median ICU length of stay (LOS) was 4 days (IQR (Interquartile range); 2 to 40 days) whilst median total hospital LOS was 40 days (IQR; 1 to 119 days). Twelve patients (52%) underwent valve replacement surgery. Mortality was 13% (3/23). The total medical cost for the 22 episodes is estimated at $1,628,359 Australian dollars (AUD). The median cost per episode was a median cost of$ 61363 AUD (IQR: $2806 to$266,357 AUD). We did not account for lost productivity and collateral costs attributed to concurrent morbidity. Conclusion. Within the limitations of this small retrospective study, we report that the management of infective endocarditis caused by injection drug use can be associated with significant financial cost