The distribution of intra-twin birth weight discordance and its association with total twin birth weight, gestational age, and neonatal mortality

OBJECTIVE: To determine an appropriate cutoff value to differentiate physiologic and pathologic birth weight discordance, to determine the prevalence of birth weight discordance > or =25% among twin pregnancies in different sub-populations, and to examine its clinical significance. STUDY DESIGN: Historical cohort study of 147,262 twin sets registered in the United States between 1995 and 1997. RESULTS: The prevalence of birth weight discordance > or =25% among twin pregnancies was 8.6%. The prevalence of birth weight discordance > or =25% was significantly decreased with increasing total twin birth weight deciles, was more frequently found in twins with discordant gender (9.1%) than in those twins with concordant gender (8.3%) and in mothers whose age was 30 years or older (9.1%) than those of younger mothers (8.1%). Birth weight discordance > or =25% was associated with earlier gestational age at delivery (35.0 weeks versus 36.0 weeks) and higher neonatal mortality (5.4% versus 2.3%) as compared to twins with lower birth weight discordance. CONCLUSIONS: The prevalence of birth weight discordance > or =25% among twin pregnancies was 8.6%, which is associated with lower gestational age at delivery and higher neonatal mortality rates, and may represent a pathologic process.     

A formulation of tissue- and water-equivalent materials using the stoichiometric analysis method for CT-number calibration in radiotherapy treatment planning

Tissue- and water-equivalent materials (TEMs) are widely used in quality assurance and calibration procedures, both in radiodiagnostics and radiotherapy. In radiotherapy, particularly, the TEMs are often used for computed tomography (CT) number calibration in treatment planning systems. However, currently available TEMs may not be very accurate in the determination of the calibration curves due to their limitation in mimicking radiation characteristics of the corresponding real tissues in both low- and high-energy ranges. Therefore, we are proposing a new formulation of TEMs using a stoichiometric analysis method to obtain TEMs for the calibration purposes. We combined the stoichiometric calibration and the basic data method to compose base materials to develop TEMs matching standard real tissues from ICRU Report 44 and 46. First, the CT numbers of six materials with known elemental compositions were measured to get constants for the stoichiometric calibration. The results of the stoichiometric calibration were used together with the basic data method to formulate new TEMs. These new TEMs were scanned to validate their CT numbers. The electron density and the stopping power calibration curves were also generated. The absolute differences of the measured CT numbers of the new TEMs were less than 4 HU for the soft tissues and less than 22 HU for the bone compared to the ICRU real tissues. Furthermore, the calculated relative electron density and electron and proton stopping powers of the new TEMs differed by less than 2% from the corresponding ICRU real tissues. The new TEMs which were formulated using the proposed technique increase the simplicity of the calibration process and preserve the accuracy of the stoichiometric calibration simultaneously.     

Elevated Plasma Clara Cell Secretory Protein Concentration Is Associated with High‐Grade Primary Graft Dysfunction

Primary graft dysfunction (PGD) is the leading cause of early posttransplant morbidity and mortality after lung transplantation. Clara cell secretory protein (CC16) is produced by the nonciliated lung epithelium and may serve as a plasma marker of epithelial cell injury. We hypothesized that elevated levels of CC16 would be associated with increased odds of PGD. We performed a prospective cohort study of 104 lung transplant recipients. Median plasma CC16 levels were determined at three time points: pretransplant and 6 and 24 h posttransplant. The primary outcome was the development of grade 3 PGD within the first 72 h after transplantation. Multivariable logistic regression was performed to evaluate for confounding by donor and recipient demographics and surgical characteristics. Twenty‐nine patients (28%) developed grade 3 PGD within the first 72 h. The median CC16 level 6 h after transplant was significantly higher in patients with PGD [13.8 ng/mL (IQR 7.9, 30.4 ng/mL)] than in patients without PGD [8.2 ng/mL (IQR 4.5, 19.1 ng/mL)], p = 0.02. Elevated CC16 levels were associated with increased odds of PGD after lung transplantation. Damage to airway epithelium or altered alveolar permeability as a result of lung ischemia and reperfusion may explain this association.     

Identification of homogeneous genetic architecture of multiple genetically correlated traits by block clustering of genome‐wide associations

Genome‐wide association studies (GWAS) using high‐density genotyping platforms offer an unbiased strategy to identify new candidate genes for osteoporosis. It is imperative to be able to clearly distinguish signal from noise by focusing on the best phenotype in a genetic study. We performed GWAS of multiple phenotypes associated with fractures [bone mineral density (BMD), bone quantitative ultrasound (QUS), bone geometry, and muscle mass] with approximately 433,000 single‐nucleotide polymorphisms (SNPs) and created a database of resulting associations. We performed analysis of GWAS data from 23 phenotypes by a novel modification of a block clustering algorithm followed by gene‐set enrichment analysis. A data matrix of standardized regression coefficients was partitioned along both axes—SNPs and phenotypes. Each partition represents a distinct cluster of SNPs that have similar effects over a particular set of phenotypes. Application of this method to our data shows several SNP‐phenotype connections. We found a strong cluster of association coefficients of high magnitude for 10 traits (BMD at several skeletal sites, ultrasound measures, cross‐sectional bone area, and section modulus of femoral neck and shaft). These clustered traits were highly genetically correlated. Gene‐set enrichment analyses indicated the augmentation of genes that cluster with the 10 osteoporosis‐related traits in pathways such as aldosterone signaling in epithelial cells, role of osteoblasts, osteoclasts, and chondrocytes in rheumatoid arthritis, and Parkinson signaling. In addition to several known candidate genes, we also identified PRKCH and SCNN1B as potential candidate genes for multiple bone traits. In conclusion, our mining of GWAS results revealed the similarity of association results between bone strength phenotypes that may be attributed to pleiotropic effects of genes. This knowledge may prove helpful in identifying novel genes and pathways that underlie several correlated phenotypes, as well as in deciphering genetic and phenotypic modularity underlying osteoporosis risk. © 2011 American Society for Bone and Mineral Research.     

Human renal organic anion transporter 4 operates as an asymmetric urate transporter

Human organic anion transporter 4 (hOAT4) is located at the apical membrane of proximal tubule cells and involved in renal secretion and reabsorption of endogenous substances as well as many drugs and xenobiotics. This study reevaluated the physiologic role, transport mode, and driving forces of hOAT4. 6-Carboxyfluorescein (6-CF) uptake into HEK293 cells that stably expressed hOAT4 was saturable, resulting in a K(m) of 108 muM. 6-CF as well as [(3)H]estrone sulfate ([(3)H]ES) accumulation by HEK293-hOAT4 cells were abolished by ES, dehydroepiandrosterone sulfate, sulfinpyrazone, benzbromarone, and probenecid, whereas several OA, including p-aminohippurate (PAH), lactate, pyrazinoate, nicotinate, glutarate, and the diuretic hydrochlorothiazide (HCTZ) exhibited a slight or a NS inhibitory effect. PAH and glutarate are not taken up by HEK293-hOAT4 cells, but they trans-stimulated 6-CF and [(3)H]ES uptake, indicating an asymmetric interaction of hOAT4 with these substrates. In chloride-free medium, HEK293-hOAT4-mediated [(3)H]PAH efflux was almost abolished, whereas addition of ES restored it comparable to Ringer solution, consistent with a physiologic ES/PAH or PAH/Cl(-) exchange mode of hOAT4. Moreover, an acidification of the uptake medium increased 6-CF as well as [(3)H]ES uptake, which was reduced by nigericin, suggesting that hOAT4 also can operate as an OA/OH(-) exchanger. hOAT4 facilitates substantial uptake of [(14)C]urate, which was elevated 2.6-fold by intracellular HCTZ. Thus, hOAT4 is the long-postulated, low-affinity apical urate anion exchanger that facilitates HCTZ-associated hyperuricemia.     

Adverse birth outcomes and associated factors among mothers who delivered in Bale zone hospitals,Oromia Region,Southeast Ethiopia

ObjectiveAdverse birth outcomes, which include stillbirth, preterm birth, low birthweight, congenital abnormalities, and stillbirth, are the leading cause of neonatal and infant mortality worldwide. We assessed adverse birth outcomes and associated factors among mothers who gave birth in Bale zone hospitals, Oromia, Southeast Ethiopia.MethodsWe used systematic random sampling in this cross-sectional study. We identified factors associated with adverse birth outcomes using bivariate analysis and multivariable logistic regression analysis.ResultsThe proportion of adverse birth outcomes among participants was 21%. Of 576 births, 70 (12.2%) were low birthweight, 49 (8.5%) were preterm birth, 45 (7.8%) were stillbirth, and 18 (3.1%) infants had congenital anomalies. Inadequate antenatal care (adjusted odds ratio [AOR] = 6.58, 95% confidence interval [CI] 3.25–13.32), multiple pregnancy (AOR  =  4.74, 95% CI 1.55–14.45), premature rupture of membranes in the current pregnancy (AOR = 2.31, 95% CI 1.26–4.21), hemoglobin level  < 11 g/dL (AOR = 3.22, 95% CI 1.85–5.58), and mid-upper arm circumference less than 23 cm (AOR = 5.93, 95% CI 3.49–10.08) were all significantly associated with adverse birth outcomes.ConclusionsApproximately one in five study participants had adverse birth outcomes. Increasing antenatal care uptake, ferrous supplementation during pregnancy, and improving the quality of maternal health services are recommended.