Brain injury in preterm infants with surgical necrotizing enterocolitis: clinical and bowel pathological correlates.

BACKGROUND: The objective of this study was to determine the risk factors and outcomes of white matter brain injury (WMBI) on magnetic resonance imaging (MRI) at term-equivalent age in infants with surgical necrotizing enterocolitis (NEC). METHODS: This retrospective study compared clinical/pathological information between infants with and those without WMBI. RESULTS: Out of 69 infants with surgical NEC, 17 (24.6%) had mild WMBI, 13 (18.8%) had moderate WMBI, and six (8.7%) had severe WMBI on the brain MRI. Several clinical factors (gestational age, more red blood cell (RBC) transfusions before NEC onset, pneumoperitoneum, earlier NEC onset age, postoperative ileus, acute kidney injury (AKI) by serum creatinine, postnatal steroids, hospital stay) and histopathological findings (necrosis, hemorrhage) had univariate associations with WMBI. Associations with RBC transfusion (odds ratio (OR) 23.6 [95% confidence interval (CI): 4.73-117.97]; p = 0.0001), age at NEC onset (OR 0.30 [95%CI: 0.11-0.84]; p = 0.021), necrosis (OR 0.10 [95%CI: 0.01-0.90]; p = 0.040), and bowel hemorrhage (OR 7.79 [95%CI: 2.19-27.72]; p = 0.002) persisted in multivariable association with grade 3-4 WMBI. The infants with WMBI had lower mean motor, cognitive, language scores, and higher ophthalmic morbidity at 2 years of age. CONCLUSIONS: The WMBI was most likely associated with earlier NEC onset, higher RBC transfusions, and less necrosis and greater hemorrhage lesions on intestinal pathology in preterm infants with surgical NEC. IMPACT: In preterm infants with surgical NEC, brain MRI showed injury in the white matter in 52%, gray matter in 10%, and cerebellar region in 30%. Preterm infants with severe WMBI (grade 3-4) had less necrosis and greater hemorrhagic lesions on histopathology of the bowel. Preterm infants with WMBI were more likely to have a more severe postoperative course, AKI, and longer length of hospitalization. Neuroprotective strategies to prevent brain injury in preterm infants with surgical NEC are needed with the goal of improving the neurodevelopmental outcomes.

Contrasting subsurface denitrification characteristics under temperate pasture lands and its implications for nutrient management in agricultural catchments.

Subsurface denitrification plays a key role in the reduction or 'attenuation' of nitrate contamination of groundwater and surface waters. We investigated subsurface denitrification characteristics in the vadose zone and shallow groundwater at four sites under pastoral farming in the Manawatu River catchment, located in the lower part of North Island, New Zealand. The denitrification potential of the vadose zone was determined by the laboratory incubation assays measuring the denitrifying enzyme activity (DEA) in soil samples collected from different soil horizons (up to 2.1 m below ground surface), whereas denitrification rates in shallow groundwaters were measured in situ by single-well, push-pull tests conducted in piezometers installed at multiple depths at the study sites. Soils and underlying geology, defining hydrogeologic settings, appear to influence the spatial variability of subsurface denitrification characteristics at the study sites. Where the vadose zone is thin and composed of coarse-textured soils, percolation of nitrate was evident in observed high nitrate-nitrogen concentrations (>5 mg L-1) in oxic and young shallow groundwaters, but low nitrate-nitrogen concentrations (<0.05 mg L-1) were observed in the reduced shallow groundwater found underneath the fine textured soils and/or a thick vadose zone. This was confirmed by the push-pull tests measuring denitrification rates from 0.08 to 1.07 mg N L-1 h-1 in the reduced shallow groundwaters (dissolved oxygen or DO < 0.5 mg L-1), while negligible in the oxic groundwaters (DO > 5 mg L-1) found at the study sites. These contrasting subsurface denitrification characteristics determine the ultimate delivery of nitrate losses from agricultural soils to receiving waters, where the fine textured thick vadose zone and reducing groundwater conditions offer nitrate reduction in the subsurface environment.

Improved predictability of peak periphyton in rivers using site-specific accrual periods and long-term water quality datasets.

Prevention of excessive periphyton standing crop (quantified as chlorophyll a) is among primary objectives for river management. Defensible instream nutrient criteria to achieve periphyton chlorophyll a targets at the site scale require robust predictive models. Such models have proved elusive because peak chlorophyll a depends on multiple factors in addition to nutrients. A key predictor may be accrual period, which depends on river flow variability and the flow magnitudes (effective flows, EF) at which periphyton biomass removal is initiated. In this study we used a seven-year dataset from 44 gravel-bed river sites in the Manawatu-Whanganui region, New Zealand, to explore the relative importance of accrual period, nutrients, and other variables in explaining peak chlorophyll a, using a regression approach. We also assessed the effect of combining data from multiple years. Previous empirical studies have used a universal flow metric (3 × median flow) to define accrual period (Da3). We calculated site-specific EF, which varied from 2 × to 15 × median flow. Accrual period based on EF (DaEF) outperformed Da3 in models. However, in the study region, more variance in chlorophyll a was explained by conductivity (EC) and dissolved inorganic nitrogen (DIN) than by DaEF. The best models derived from multi-year datasets included EC, DIN and DaEF as predictors and accounted for up to 82% of the variance in peak chlorophyll a. Models from annual data were weaker and more variable in strength and predictors. The models indicated that EC and DaEF should be considered when setting DIN criteria for periphyton outcomes in the study region. The principles we used in developing the models may have broad relevance to the management of periphyton in other regions.

Denitrification potential in the subsurface environment in the Manawatu River catchment, New Zealand: Indications from oxidation-reduction conditions, hydrogeological factors, and implications for nutrient management.

A sound understanding of the effects of hydrogeological factors on loss, transport and transformation of farm nutrients is essential for predicting their impacts on ecosystem health of receiving waters. We assessed the potential of groundwater to attenuate nitrate through denitrification, and the distribution of this potential across the Tararua Groundwater Management Zone (GWMZ) in the Manawatu River catchment, New Zealand. We combined a number of methods in an unprecedented manner to confirm findings and obtain supporting evidence for the features that determine the subsurface denitrification characteristics. Our results showed that the denitrification characteristics of groundwater varied considerably in the Tararua GWMZ. The southern part of the Tararua GWMZ contained mainly oxic groundwater with low potential to denitrify, whereas the middle and northern parts of the Tararua GWMZ contained reduced groundwater with high denitrification potential. The hydrogeological features that influence denitrification potential in groundwater were identified as soil texture and drainage class, and the aquifer material or rock type. Low dissolved oxygen levels and nitrate concentrations were found in groundwater where the combinations of soil and rock types had poor drainage characteristics as opposed to higher concentrations in groundwater under well-drained soils and rocks (e.g. gravels). Intensive pastoral farming over well-drained soils and rocks showed high nitrate concentration in groundwater. This spatial variability in denitrification potential of groundwater offers a targeted management of nutrients runoff and leaching from pastoral lands to reduce their impacts on receiving surface waters.

Use of fully modified 2'-O-methyl antisense oligos for loss-of-function studies in vertebrate embryos.

Antisense oligonucleotides are commonly employed to study the roles of genes in development. Although morpholino phosphorodiamidate oligonucleotides (morpholinos) are widely used to block translation or splicing of target gene products' the usefulness of other modifications in mediating RNase-H independent inhibition of gene activity in embryos has not been investigated. In this study, we investigated the extent that fully modified 2'-O-methyl oligonucleotides (2'-OMe oligos) that can function as translation inhibiting reagents in vivo, using Xenopus and zebrafish embryos. We find that oligos against Xenopus ß-catenin, wnt11, and bmp4 and against zebrafish chordin (chd), which can efficiently and specifically generate embryonic loss-of-function phenotypes comparable with morpholino injection and other methods. These results show that fully modified 2'-OMe oligos can function as RNase-H independent antisense reagents in vertebrate embryos and can thus serve as an alternative modification to morpholinos in some cases.