High-frequency vs. conventional ventilation at the time of CDH repair is not associated with higher mortality and oxygen dependency: a retrospective cohort study.

PURPOSE: The VICI-trial reported that in patients with congenital diaphragmatic hernia (CDH), mortality or bronchopulmonary dysplasia (BPD) were equivalent using conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation. The purpose of this study was to determine if the mode of ventilation at the time of CDH repair affected mortality or oxygen dependence at 28 days. METHODS: We performed a retrospective cohort study of infants born wih CDH from 1991 to 2015. A generalized linear model was applied to the data using a propensity score analysis. RESULTS: Eighty patients met the inclusion criteria; at the time of surgery 39 (48.8%) patients were on HFV and 41 (51.3%) patients were on CMV. In the HFV group, 16 (47.1%) patients remained oxygen dependent and there were 5 (12.8%) deaths at 28 days. In the CMV group, 5 (12.2%) patients remained oxygen dependent at 28 days but none had died. The base model demonstrated that the HFV group had increased rates of oxygen dependence [OR = 6.40 (2.13, 22.2), p = 0.002]. However, after propensity score analysis, we found no difference between HFV and CMV. CONCLUSION: Our study suggests that in infants with CDH, there is no significant difference between HFV and CMV in oxygen dependency or death.

Cerebral oxygenation monitoring of ex-preterm infants during the infant car seat challenge test.

The American Academy of Pediatrics and until recently the Canadian Paediatric Society recommend preterm infants undergo an Infant Car Seat Challenge test prior to discharge to rule out systemic oxygen desaturation when placed at a 45-degree angle in a car seat. Near-infrared spectroscopy (NIRS) provides objective measurements of the impact of systemic oxygen (SO2) desaturation, bradycardia, or both on cerebral regional oxygen saturation (rSO2). OBJECTIVE: To characterize baseline cerebral rSO2 during a car seat trial in preterm infants ready for discharge. DESIGN/METHODS: A prospective observational study was performed in 20 infants (32 ± 5 weeks [mean] at a postmenstrual age 37 ± 6 weeks [mean]). Cerebral rSO2 was continuously monitored by placing a NIRS transducer on head during Infant Car Seat Challenge (ICSC). Failure of an ICSC was defined as two SO2 desaturation events below 85% for more than 20 seconds or one event below 80% for 10 seconds. RESULTS: The lowest SO2 was 70% with a lowest NIRS recording of 68%. Three infants failed their ICSC, with the lowest rSO2 in these three infants being 68%, above the lowest acceptable limit of 55%. Heart rate but not SO2 appears to influence rSO2 over the range of cerebral oxygenation seen. CONCLUSIONS: Baseline cerebral rSO2 during ICSC oscillates between 68 and 90%. There were no episodes of significant cerebral oxygen desaturation in studied infants regardless of whether they passed or failed the ICSC. We postulate that former preterm infants are capable through cerebral autoregulation, of maintaining adequate cerebral blood flow in the presence of either systemic oxygen desaturation or bradycardia when they are otherwise ready for discharge.

Early versus delayed extubation in extremely preterm neonates: a retrospective cohort study.

OBJECTIVE: To evaluate clinical outcomes associated with extubation timing among extremely preterm neonates. DESIGN/METHODS: Neonates <26 weeks' GA admitted to four tertiary neonatal centers were included if they met predetermined extubation criteria within first postnatal week and classified into early extubation (≤24 h; exposure group) and delayed extubation (>24 h; control group) after meeting extubation criteria. Patients with known severe IVH and/or significant PDA prior to meeting extubation criteria were excluded. RESULTS: Of 197 included infants, 75 were in exposure group. Survival without BPD (aOR 1.26; 95% CI 0.62-2.56; P = 0.52) and survival without severe IVH (aOR 1.98; 95% CI 0.93-4.23; P = 0.08) were not different, adjusted for GA, SNAP, number of surfactant doses and center. CONCLUSIONS: Extubation within 24 h of meeting extubation criteria in neonates <26 weeks' GA was not associated with survival without BPD or survival without severe IVH. However, confounding by indication cannot be ruled out without a prospective trial.

Physical Activity Preferences Among Older Adults: A Systematic Review.

The objective of this study was to identify preferences for physical activity among adults aged 65 years and over. A systematic review was conducted. A search strategy without language and date restriction (up until March 31, 2017) was developed for PubMed, CINAHL, PsycINFO, ERIC, and SPORTDiscus. Study selection and data extraction were performed independently by two reviewers. A total of 21 independent primary studies were included in the systematic review. Irrespective of the methodologies used and samples, a majority of older adults prefer to walk and engage in physical activity continuously for about 30 min. These findings are mainly generalizable to White females from the United States. Two-thirds of the studies were at high risk of selection bias, which suggests additional caution when interpreting the review findings. Nonetheless, policymakers, community organizations, and healthcare providers should consider walkability in their efforts to promote physical activity in older adults.

Functions of maize genes encoding pyruvate phosphate dikinase in developing endosperm.

Maize opaque2 (o2) mutations are beneficial for endosperm nutritional quality but cause negative pleiotropic effects for reasons that are not fully understood. Direct targets of the bZIP transcriptional regulator encoded by o2 include pdk1 and pdk2 that specify pyruvate phosphate dikinase (PPDK). This enzyme reversibly converts AMP, pyrophosphate, and phosphoenolpyruvate to ATP, orthophosphate, and pyruvate and provides diverse functions in plants. This study addressed PPDK function in maize starchy endosperm where it is highly abundant during grain fill. pdk1 and pdk2 were inactivated individually by transposon insertions, and both genes were simultaneously targeted by endosperm-specific RNAi. pdk2 accounts for the large majority of endosperm PPDK, whereas pdk1 specifies the abundant mesophyll form. The pdk1- mutation is seedling-lethal, indicating that C4 photosynthesis is essential in maize. RNAi expression in transgenic endosperm eliminated detectable PPDK protein and enzyme activity. Transgenic kernels weighed the same on average as nontransgenic siblings, with normal endosperm starch and total N contents, indicating that PPDK is not required for net storage compound synthesis. An opaque phenotype resulted from complete PPDK knockout, including loss of vitreous endosperm character similar to the phenotype conditioned by o2-. Concentrations of multiple glycolytic intermediates were elevated in transgenic endosperm, energy charge was altered, and starch granules were more numerous but smaller on average than normal. The data indicate that PPDK modulates endosperm metabolism, potentially through reversible adjustments to energy charge, and reveal that o2- mutations can affect the opaque phenotype through regulation of PPDK in addition to their previously demonstrated effects on storage protein gene expression.

Parent-of-Origin-Effect rough endosperm Mutants in Maize.

Parent-of-origin-effect loci have non-Mendelian inheritance in which phenotypes are determined by either the maternal or paternal allele alone. In angiosperms, parent-of-origin effects can be caused by loci required for gametophyte development or by imprinted genes needed for seed development. Few parent-of-origin-effect loci have been identified in maize (Zea mays) even though there are a large number of imprinted genes known from transcriptomics. We screened rough endosperm (rgh) mutants for parent-of-origin effects using reciprocal crosses with inbred parents. Six maternal rough endosperm (mre) and three paternal rough endosperm (pre) mutants were identified with three mre loci mapped. When inherited from the female parent, mre/+ seeds reduce grain fill with a rough, etched, or pitted endosperm surface. Pollen transmission of pre mutants results in rgh endosperm as well as embryo lethality. Eight of the mutants had significant distortion from the expected one-to-one ratio for parent-of-origin effects. Linked markers for mre1, mre2, and mre3 indicated that the mutant alleles have no bias in transmission. Histological analysis of mre1, mre2, mre3, and pre*-949 showed altered timing of starch grain accumulation and basal endosperm transfer cell layer (BETL) development. The mre1 locus delays BETL and starchy endosperm development, while mre2 and pre*-949 cause ectopic starchy endosperm differentiation. We conclude that many parent-of-origin effects in maize have incomplete penetrance of kernel phenotypes and that there is a large diversity of endosperm developmental roles for parent-of-origin-effect loci.

Sequence-indexed mutations in maize using the UniformMu transposon-tagging population.

BACKGROUND: Gene knockouts are a critical resource for functional genomics. In Arabidopsis, comprehensive knockout collections were generated by amplifying and sequencing genomic DNA flanking insertion mutants. These Flanking Sequence Tags (FSTs) map each mutant to a specific locus within the genome. In maize, FSTs have been generated using DNA transposons. Transposable elements can generate unstable insertions that are difficult to analyze for simple knockout phenotypes. Transposons can also generate somatic insertions that fail to segregate in subsequent generations. RESULTS: Transposon insertion sites from 106 UniformMu FSTs were tested for inheritance by locus-specific PCR. We confirmed 89% of the FSTs to be germinal transposon insertions. We found no evidence for somatic insertions within the 11% of insertion sites that were not confirmed. Instead, this subset of insertion sites had errors in locus-specific primer design due to incomplete or low-quality genomic sequences. The locus-specific PCR assays identified a knockout of a 6-phosphogluconate dehydrogenase gene that co-segregates with a seed mutant phenotype. The mutant phenotype linked to this knockout generates novel hypotheses about the role for the plastid-localized oxidative pentose phosphate pathway during grain-fill. CONCLUSION: We show that FSTs from the UniformMu population identify stable, germinal insertion sites in maize. Moreover, we show that these sequence-indexed mutations can be readily used for reverse genetic analysis. We conclude from these data that the current collection of 1,882 non-redundant insertion sites from UniformMu provide a genome-wide resource for reverse genetics.

Steady-state transposon mutagenesis in inbred maize.

We implement a novel strategy for harnessing the power of high-copy transposons for functional analysis of the maize genome, and report behavioral features of the Mutator system in a uniform inbred background. The unique UniformMu population and database facilitate high-throughput molecular analysis of Mu-tagged mutants and gene knockouts. Key features of the population include: (i) high mutation frequencies (7% independent seed mutations) and moderation of copy number (approximately 57 total Mu elements; 1-2 MuDR copies per plant) were maintained by continuous back-crossing into a phenotypically uniform inbred background; (ii) a bz1-mum9 marker enabled selection of stable lines (loss of MuDR), inhibiting further transpositions in lines selected for molecular analysis; (iii) build-up of mutation load was prevented by screening Mu-active parents to exclude plants carrying pre-existing seed mutations. To create a database of genomic sequences flanking Mu insertions, selected mutant lines were analyzed by sequencing of MuTAIL PCR clone libraries. These sequences were annotated and clustered to facilitate bioinformatic subtraction of ancestral elements and identification of insertions unique to mutant lines. New insertions targeted low-copy, gene-rich sequences, and in silico mapping revealed a random distribution of insertions over the genome. Our results indicate that Mu populations differ markedly in the occurrence of Mu insertion hotspots and the frequency of suppressible mutations. We suggest that controlled MuDR copy number in UniformMu lines is a key determinant of these differences. The public database (http://uniformmu.org; http://endosperm.info) includes pedigree and phenotypic data for over 2000 independent seed mutants selected from a population of 31 548 F2 lines and integrated with analyses of 34 255 MuTAIL sequences.

Pharmacokinetics of famotidine in infants.

BACKGROUND: Although famotidine pharmacokinetics are similar in adults and children older than 1 year of age, they differ in neonates owing to developmental immaturity in renal function. Little is currently known about the pharmacokinetics of famotidine in infants aged between 1 month and 1 year, a period when renal function is maturing. OBJECTIVE: To characterise the pharmacokinetics of famotidine in infants. DESIGN: This was a two-part multicentre study with both single dose (Part I, open-label) and multiple dose (Part II, randomised) arms. PATIENTS: Thirty-six infants (20 females and 16 males) who required treatment with famotidine and who had an indwelling arterial or venous catheter for reasons unrelated to the study. METHODS: Infants in Part I were administered a single dose of famotidine 0.5 mg/kg; the dose was intravenous or oral according to the judgement of the attending physician. Infants receiving 0.5 mg/kg intravenously were divided into two groups by age, and pharmacokinetic parameters in infants 0-3 months and >3 to 12 months of age were compared. Infants in Part II were randomised to one of the following treatments: 0.25 mg/kg/dose intravenously or 0.5 mg/kg/dose orally on day 1 and subsequent days, or 0.25 mg/kg/dose intravenously or 0.5 mg/kg/dose orally on day 1 followed by doses of either 0.5 mg/kg/dose intravenously or 1 mg/kg/dose orally on subsequent days. From day 2 onwards, age-adjusted dose administration regimens (once daily in infants <3 months of age and every 12 hours in infants >3 months of age) were used; the total number of famotidine doses ranged from 3 to 11 and the total number of days of dose administration ranged from two to eight. RESULTS: In infants <3 months of age, plasma and renal clearance of famotidine were decreased compared with infants >3 months of age. Pharmacokinetic parameters for the older infants (i.e. those >3 months) were similar to those previously reported for children and adults. Approximate dose-proportionality, no accumulation on multiple dosing and an estimated bioavailability similar to adult values were also observed. CONCLUSION: A short course of famotidine therapy in infants appears generally well tolerated, and the characteristics of famotidine pharmacokinetics during the first year of life are explained to a great degree by the development of renal function, the primary route of elimination for this drug.