Human haematopoietic stem cells express Oct4 pseudogenes and lack the ability to initiate Oct4 promoter-driven gene expression

The transcription factor Oct4 is well defined as a key regulator of embryonic stem (ES) cell pluripotency. In recent years, the role of Oct4 has purportedly extended to the self renewal and maintenance of multipotency in adult stem cell (ASC) populations. This profile has arisen mainly from reports utilising reverse transcription-polymerase chain reaction (RT-PCR) based methodologies and has since come under scrutiny following the discovery that many developmental genes have multiple pseudogenes associated with them. Six known pseudogenes exist for Oct4, all of which exhibit very high sequence homology (three >97%), and for this reason the generation of artefacts may have contributed to false identification of Oct4 in somatic cell populations. While ASC lack a molecular blueprint of transcription factors proposed to be involved with 'stemness' as described for ES cells, it is not unreasonable to assume that similar gene patterns may exist. The focus of this work was to corroborate reports that Oct4 is involved in the regulation of ASC self-renewal and differentiation, using a combination of methodologies to rule out pseudogene interference. Haematopoietic stem cells (HSC) derived from human umbilical cord blood (UCB) and various differentiated cell lines underwent RT-PCR, product sequencing and transfection studies using an Oct4 promoter-driven reporter. In summary, only the positive control expressed Oct4, with all other cell types expressing a variety of Oct4 pseudogenes. Somatic cells were incapable of utilising an exogenous Oct4 promoter construct, leading to the conclusion that Oct4 does not appear involved in the multipotency of human HSC from UCB

A new growth chart for preterm babies: Babson and Benda's chart updated with recent data and a new format

BACKGROUND: The Babson and Benda 1976 "fetal-infant growth graph" for preterm infants is commonly used in neonatal intensive care. Its limits include the small sample size which provides low confidence in the extremes of the data, the 26 weeks start and the 500 gram graph increments. The purpose of this study was to develop an updated growth chart beginning at 22 weeks based on a meta-analysis of published reference studies. METHODS: The literature was searched from 1980 to 2002 for more recent data to complete the pre and post term sections of the chart. Data were selected from population studies with large sample sizes. Comparisons were made between the new chart and the Babson and Benda graph. To validate the growth chart the growth results from the National Institute of Child Health and Human Development Neonatal Research Network (NICHD) were superimposed on the new chart. RESULTS: The new data produced curves that generally followed patterns similar to the old growth graph. Mean differences between the curves of the two charts reached statistical significance after term. Babson's 10(th )percentiles fell between the new data percentiles: the 5th to 17th for weight, the 5th and 15th for head circumference, and the 6th and 16th for length. The growth patterns of the NICHD infants deviated away from the curves of the chart in the first weeks after birth. When the infants reached an average weight of 2 kilograms, those with a birthweight in the range of 700 to 1000 grams had achieved greater than the 10(th )percentile on average for head growth, but remained below the 3(rd )percentile for weight and length. CONCLUSION: The updated growth chart allows a comparison of an infant's growth first with the fetus as early as 22 weeks and then with the term infant to 10 weeks. Comparison of the size of the NICHD infants at a weight of 2 kilograms provides evidence that on average preterm infants are growth retarded with respect to weight and length while their head size has caught up to birth percentiles. As with all meta-analyses, the validity of this growth chart is limited by the heterogeneity of the data sources. Further validation is needed to illustrate the growth patterns of preterm infants to older ages

Estimating the burden of antimicrobial resistance: a systematic literature review.

Background: Accurate estimates of the burden of antimicrobial resistance (AMR) are needed to establish the magnitude of this global threat in terms of both health and cost, and to paramaterise cost-effectiveness evaluations of interventions aiming to tackle the problem. This review aimed to establish the alternative methodologies used in estimating AMR burden in order to appraise the current evidence base. Methods: MEDLINE, EMBASE, Scopus, EconLit, PubMed and grey literature were searched. English language studies evaluating the impact of AMR (from any microbe) on patient, payer/provider and economic burden published between January 2013 and December 2015 were included. Independent screening of title/abstracts followed by full texts was performed using pre-specified criteria. A study quality score (from zero to one) was derived using Newcastle-Ottawa and Philips checklists. Extracted study data were used to compare study method and resulting burden estimate, according to perspective. Monetary costs were converted into 2013 USD. Results: Out of 5187 unique retrievals, 214 studies were included. One hundred eighty-seven studies estimated patient health, 75 studies estimated payer/provider and 11 studies estimated economic burden. 64% of included studies were single centre. The majority of studies estimating patient or provider/payer burden used regression techniques. 48% of studies estimating mortality burden found a significant impact from resistance, excess healthcare system costs ranged from non-significance to $1 billion per year, whilst economic burden ranged from$21,832 per case to over $3 trillion in GDP loss. Median quality scores (interquartile range) for patient, payer/provider and economic burden studies were 0.67 (0.56-0.67), 0.56 (0.46-0.67) and 0.53 (0.44-0.60) respectively. Conclusions: This study highlights what methodological assumptions and biases can occur dependent on chosen outcome and perspective. Currently, there is considerable variability in burden estimates, which can lead in-turn to inaccurate intervention evaluations and poor policy/investment decisions. Future research should utilise the recommendations presented in this review. Trial registration: This systematic review is registered with PROSPERO (PROSPERO CRD42016037510)