Discussion required for correct interpretation

Thank you for the opportunity to comment on the editorial by Romero and colleagues [1], which raises a number of important and interesting questions. Such discussion is mandatory if results of scientific techniques such as gene array are to be correctly interpreted and used as the basis for future improvements in patient care

Labor-associated gene expression in the human uterine fundus, lower segment, and cervix

Background Preterm labor, failure to progress, and postpartum hemorrhage are the common causes of maternal and neonatal mortality or morbidity. All result from defects in the complex mechanisms controlling labor, which coordinate changes in the uterine fundus, lower segment, and cervix. We aimed to assess labor-associated gene expression profiles in these functionally distinct areas of the human uterus by using microarrays. Methods and Findings Samples of uterine fundus, lower segment, and cervix were obtained from patients at term (mean +/- 6 SD = 39.1 +/- 0.5 wk) prior to the onset of labor (n = 6), or in active phase of labor with spontaneous onset (n = 7). Expression of 12,626 genes was evaluated using microarrays ( Human Genome U95A; Affymetrix) and compared between labor and non-labor samples. Genes with the largest labor-associated change and the lowest variability in expression are likely to be fundamental for parturition, so gene expression was ranked accordingly. From 500 genes with the highest rank we identified genes with similar expression profiles using two independent clustering techniques. Sets of genes with a probability of chance grouping by both techniques less than 0.01 represented 71.2%, 81.8%, and 79.8% of the 500 genes in the fundus, lower segment, and cervix, respectively. We identified 14, 14, and 12 those sets of genes in the fundus, lower segment, and cervix, respectively. This enabled networks of coregulated and co-expressed genes to be discovered. Many genes within the same cluster shared similar functions or had functions pertinent to the process of labor. Conclusions Our results provide support for many of the established processes of parturition and also describe novel-to-labor genes not previously associated with this process. The elucidation of these mechanisms likely to be fundamental for controlling labor is an important prerequisite to the development of effective treatments for major obstetric problems - including prematurity, with its long-term consequences to the health of mother and offspring

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

Event-related alpha suppression in response to facial motion

This article has been made available through the Brunel Open Access Publishing Fund.While biological motion refers to both face and body movements, little is known about the visual perception of facial motion. We therefore examined alpha wave suppression as a reduction in power is thought to reflect visual activity, in addition to attentional reorienting and memory processes. Nineteen neurologically healthy adults were tested on their ability to discriminate between successive facial motion captures. These animations exhibited both rigid and non-rigid facial motion, as well as speech expressions. The structural and surface appearance of these facial animations did not differ, thus participants decisions were based solely on differences in facial movements. Upright, orientation-inverted and luminance-inverted facial stimuli were compared. At occipital and parieto-occipital regions, upright facial motion evoked a transient increase in alpha which was then followed by a significant reduction. This finding is discussed in terms of neural efficiency, gating mechanisms and neural synchronization. Moreover, there was no difference in the amount of alpha suppression evoked by each facial stimulus at occipital regions, suggesting early visual processing remains unaffected by manipulation paradigms. However, upright facial motion evoked greater suppression at parieto-occipital sites, and did so in the shortest latency. Increased activity within this region may reflect higher attentional reorienting to natural facial motion but also involvement of areas associated with the visual control of body effectors. © 2014 Girges et al

Heart failure and excess mortality after aortic valve replacement in aortic stenosis

INTRODUCTION: In aortic stenosis (AS), the heart transitions from adaptive compensation to an AS cardiomyopathy and eventually leads to decompensation with heart failure. Better understanding of the underpinning pathophysiological mechanisms is required in order to inform strategies to prevent decompensation. AREAS COVERED: In this review, we therefore aim to appraise the current pathophysiological understanding of adaptive and maladaptive processes in AS, appraise potential avenues of adjunctive therapy before or after AVR and highlight areas of further research in the management of heart failure post AVR. EXPERT OPINION: Tailored strategies for the timing of intervention accounting for individual patient's response to the afterload insult are underway, and promise to guide better management in the future. Further clinical trials of adjunctive pharmacological and device therapy to either cardioprotect prior to intervention or promote reverse remodelling and recovery after intervention are needed to mitigate the risk of heart failure and excess mortality

Childbirth experience questionnaire: validating its use in the United Kingdom

BACKGROUND: The Childbirth Experience Questionnaire (CEQ) was developed in Sweden in 2010 and validated in 920 primiparous women. It has not been validated in the United Kingdom (UK). Measuring the impact of an intervention on a woman's childbirth experience is arguably as important as measuring its impact on outcomes such as caesarean delivery and perinatal morbidity or mortality and yet surprisingly it is rarely done. The lack of a robust validated tool for evaluating labour experience in the UK is a topical issue in the UK at present. Indeed NICE say 'A standardised method to measure and quantify women's psychological and emotional wellbeing and their birth experiences is urgently required to support any study investigating the effectiveness of interventions, techniques or strategies during birth.' METHODS: The Childbirth Experience Questionnaire and part of the Care Quality Commission Maternity Survey (2010) was sent to 350 women at one month postnatal. The CEQ was sent again two weeks later. The CEQ was tested for face validity among 25 postnatal mothers. Demographic data and delivery data was used to establish construct validity of the CEQ using the method of known-groups validation. The results of the scored CEQ sent out twice were used to measure test-retest reliability of the CEQ by calculating the quadratic weighted index of agreement between the two scores. Criterion validity was measured by calculating the Pearson correlation coefficient for the CEQ and Maternity Survey scores. RESULTS: Face validity of the CEQ in a UK population was demonstrated with all respondents stating it was easy to understand and complete. A statistically significantly higher CEQ score for subgroups of women known to report a better birth outcome demonstrated construct validity of the CEQ. A weighted kappa of 0.68 demonstrated test-retest reliability of the CEQ. A Pearson correlation co-efficient of 0.73 demonstrated a strong correlation between the results of the CEQ and the results of the 'gold standard' assessment of childbirth experience in the UK: the Maternity Survey and hence criterion validity of the CEQ. CONCLUSIONS: The Childbirth Experience Questionnaire is a valid and reliable measure of childbirth experience in the UK population