Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders.

Identification of genetic biomarkers associated with autism spectrum disorders (ASDs) could improve recurrence prediction for families with a child with ASD. Here, we describe clinical microarray findings for 253 longitudinally phenotyped ASD families from the Baby Siblings Research Consortium (BSRC), encompassing 288 infant siblings. By age 3, 103 siblings (35.8%) were diagnosed with ASD and 54 (18.8%) were developing atypically. Thirteen siblings have copy number variants (CNVs) involving ASD-relevant genes: 6 with ASD, 5 atypically developing, and 2 typically developing. Within these families, an ASD-related CNV in a sibling has a positive predictive value (PPV) for ASD or atypical development of 0.83; the Simons Simplex Collection of ASD families shows similar PPVs. Polygenic risk analyses suggest that common genetic variants may also contribute to ASD. CNV findings would have been pre-symptomatically predictive of ASD or atypical development in 11 (7%) of the 157 BSRC siblings who were eventually diagnosed clinically

Increasing illness severity in very low birth weight infants over a 9-year period

BACKGROUND: Recent reports have documented a leveling-off of survival rates in preterm infants through the 1990's. The objective of this study was to determine temporal changes in illness severity in very low birth weight (VLBW) infants in relationship to the outcomes of death and/or severe IVH. METHODS: Cohort study of 1414 VLBW infants cared for in a single level III neonatal intensive care unit in Delaware from 1993–2002. Infants were divided into consecutive 3-year cohorts. Illness severity was measured by two objective methods: the Score for Neonatal Acute Physiology (SNAP), based on data from the 1(st )day of life, and total thyroxine (T(4)), measured on the 5(th )day of life. Death before hospital discharge and severe intraventricular hemorrhage (IVH) were investigated in the study sample in relation to illness severity. The fetal death rate was also investigated. Statistical analyses included both univariate and multivariate analysis. RESULTS: Illness severity, as measured by SNAP and T(4, )increased steadily over the 9-year study period with an associated increase in severe IVH and the combined outcome of death and/or severe IVH. During the final 3 years of the study, the observed increase in illness severity accounted for 86% (95% CI 57–116%) of the variability in the increase in death and/or severe IVH. The fetal death rate dropped from 7.8/1000 (1993–1996) to 5.3/1000 (1999–2002, p = .01) over the course of the study. CONCLUSION: These data demonstrate a progressive increase in illness in VLBW infants over time, associated with an increase in death and/or severe IVH. We speculate that the observed decrease in fetal death, and the increase in neonatal illness, mortality and/or severe IVH over time represent a shift of severely compromised patients that now survive the fetal time period and are presented for care in the neonatal unit

Homocysteine levels in preterm infants: is there an association with intraventricular hemorrhage? A prospective cohort study.

BACKGROUND: The purpose of this study was to characterize total homocysteine (tHcy) levels at birth in preterm and term infants and identify associations with intraventricular hemorrhage (IVH) and other neonatal outcomes such as mortality, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and thrombocytopenia. METHODS: 123 infants \u3c 32 weeks gestation admitted to our Level III nursery were enrolled. A group of 25 term infants were enrolled for comparison. Two blood spots collected on filter paper with admission blood drawing were analyzed by a high performance liquid chromatography (HPLC) method. Statistical analysis included ANOVA, Spearman\u27s Rank Order Correlation and Mann-Whitney U test. RESULTS: The median tHcy was 2.75 micromol/L with an interquartile range of 1.34 - 4.96 micromol/L. There was no difference between preterm and term tHcy (median 2.76, IQR 1.25 - 4.8 micromol/L vs median 2.54, IQR 1.55 - 7.85 micromol/L, p = 0.07). There was no statistically significant difference in tHcy in 31 preterm infants with IVH compared to infants without IVH (median 1.96, IQR 1.09 - 4.35 micromol/L vs median 2.96, IQR 1.51 - 4.84 micromol/L, p = 0.43). There was also no statistically significant difference in tHcy in 7 infants with periventricular leukomalacia (PVL) compared to infants without PVL (median 1.55, IQR 0.25 - 3.45 micromol/L vs median 2.85, IQR 1.34 - 4.82 micromol/L, p = 0.07). Male infants had lower tHcy compared to female; prenatal steroids were associated with a higher tHcy. CONCLUSION: In our population of preterm infants, there is no association between IVH and tHcy. Male gender, prenatal steroids and preeclampsia were associated with differences in tHcy levels

Spatial and Temporal Response of Stream Bacteria to Sources of Dissolved Organic Carbon in a Blackwater Stream System

1. We hypothesized that changes in bacterial colony growth would be correlated to shifts in riparian vegetation (via leachate quality) along a river continuum of a south-eastern, blackwater stream (U.S.A.). Spatially, we expected bacterial assemblages from downstream reaches to utilize more sources of leachate and at higher concentrations than bacteria collected from headwater reaches. Temporally, we predicted higher colony growth on leachate from autumn-shed (senescent) leaves compared with leachate from fresh, green leaves. 2. We examined spatial differences in assemblage growth by culturing bacteria sampled along the stream continuum on gradient plates using leachates from four common riparian species (Taxodium distichum, Carya spp., Acer rubrum and Decumaria barbara). Bacteria from the lowest site were able to use all sources provided and at all concentrations, whereas bacteria from upper reaches could not. Colony density was correlated to relative leachate concentration at all sites along the continuum. 3. Leachates from fresh and senescent A. rubrum leaves were used to determine temporal differences. Winter assemblages of bacteria could not grow on fresh leaf leachate at any concentration but grew well on autumn leaf leachate at higher concentrations. Differential response of bacterial assemblages indicated local adaptation to potential sources of dissolved organic matter. 4. Growth response of stream bacterial colonies appeared to be dependent on the timing and source of leachate as well as on sources of dissolved organic carbon from further upstream. Growth of bacterial assemblages exhibited ‘generalist’ characteristics in headwater reaches and ‘specialist’ characteristics at the mouth of our study stream drainage. Thus, our findings lend support to the argument that variable resource habitats favour a small, generalist assemblage, while environments with stable resource supplies allow for highly diverse assemblages dominated by specialists

Percutaneous treatment of IVC obstruction due to post-resection hepatic torsion associated with IVC thrombosis

Abstract Background Migration of the left hepatic lobe into the potential space following right lobe resection can result in torsion and hepatic venous outflow obstruction with compromised venous return from the IVC. If untreated, significant morbidity and mortality can develop. Case presentation We report a case of a 29-year-old female with Lynch syndrome who underwent right lobe resection for a metastatic hepatic tumor. There was subsequent migration of the liver remnant, torsion of the IVC, and impaired hepatic outflow, successfully treated with thrombectomy and stenting. Conclusion Following right hepatectomy, hepatic venous outflow obstruction should be consdered in the setting of hepatorenal failure and hemodynamic instability. Endovascular stenting is a viable treatment option