Oesophageal atresia: The growth gap

Poor growth is an under-recognised yet significant long-term sequelae of oesophageal atresia(OA) repair. Few studies have specifically explored the reasons for growth impairment in this complex cohort. The association between poor growth with younger age and fundoplication appears to have the strongest supportive evidence, highlighting the need for early involvement of a dietitian and speech pathologist, and consideration of optimal medical reflux management prior to referring for anti-reflux surgery. However, it remains difficult to reach conclusions regarding other factors which may negatively influence growth, due to conflicting findings, inconsistent definitions and lack of validated tool utilisation. While swallowing and feeding difficulties are particularly frequent in younger children, their relationship with growth remains unclear. It is possible that these morbidities impact on the diet of children with OA, but detailed analysis of dietary composition and quality, and its relationship with these complications and growth, has not yet been conducted. Another potential area of research in OA is the role of the microbiota in growth and nutrition. While the microbiota has been linked to growth impairment in other paediatric conditions,it is yet to be investigated in OA. Further research is needed to identify the most,important contributory factors to poor growth, the role of the intestinal microbiota, and effective interventions to maximise growth and nutritional outcomes in this cohort.     

Shapes of early change in psychotherapy under routine outpatient conditions

Although improvement of clients' state is a central concern for psychotherapy, relatively little is known about how change in outcome variables unfolds during psychotherapy. Client progress may follow highly variable temporal courses, and this variation in treatment courses may have important clinical implications. By analyzing treatment progress using growth mixture modeling up to the 6th session in a sample of 192 outpatients treated under routine clinic conditions, the authors identified 5 client groups based on similar progress on the short form versions of the Clinical Outcomes in Routine Evaluation-Outcome Measure. The shapes of early change typical for these client groups were characterized by (a) high initial impairment, (b) low initial impairment, (c) early improvement, (d) medium impairment with continuous treatment progress, or (e) medium impairment with discontinuous treatment progress. Moreover, the shapes of early change were associated with different treatment outcomes and durations, and several intake variables (depression, anxiety, and age) enabled prediction of the shape of early change and/or prediction of individual treatment progress within client groups with similar shapes of change.     

Administration of an antagonist of neurokinin receptors 1, 2, and 3 results in reproductive tract changes in beagle dogs, but not rats

SCH 206272, an antagonist of neurokinin receptors 1, 2, and 3, was administered orally by gavage for 1 month to 8- to 10-month-old dogs at doses of 0, 15, 30, or 60 mg/kg, and to 6-week-old rats at doses of 0, 30, 100, or 300 mg/kg. The most important changes occurred in the reproductive tract of the dogs at all doses. Absolute and relative group mean organ weights for the testes, prostate gland, epididymides, ovaries, and uterus were 33-86% lower than concurrent controls in groups receiving SCH 206272. Organ weight changes were not dose-related. Microscopic changes that correlated with the organ weight changes occurred in all groups receiving SCH 206272. For males, they included minimal to severe atrophy of the testes, epididymides, and prostate gland. In addition, the epididymides exhibited severe oligospermia or aspermia, minimal epithelial apoptosis and mild epithelial vacuolation. In female dogs, the ovaries and uteri appeared immature. Microscopic changes were similar in incidence and severity in dogs receiving 30 or 60 mg/kg, but were slightly less in dogs receiving 15 mg/kg. In contrast, similar findings were not observed in the reproductive tract of male or female rats, despite overlapping systemic, hypothalamic, and pituitary gland concentrations of SCH 206272.     

A histological survey of green fluorescent protein expression in 'green' mice: implications for stem cell research

AIMS: The transgenic enhanced green fluorescent protein (EGFP) expressing 'green' mouse (C57BL/6-TgN(ACTbEGFP)1Osb) is a widely used tool in stem cell research, where the ubiquitous nature of EGFP expression is critical to track the fate of single or small groups of transplanted haematopoietic stem cells (HSC). Our aim was to investigate this assumed ubiquitous expression by performing a detailed histological survey of EGFP expression in these mice. METHODS: Fluorescent microscopy of frozen tissue sections was used to perform a detailed histological survey of the pattern of EGFP expression in these mice. Flow cytometry was also used to determine the expression pattern in blood and bone marrow. RESULTS: Three patterns of EGFP expression were noted. In most tissues there was an apparently stochastic variegation of the transgene, with individual cell types demonstrating highly variable rates of EGFP expression. Certain specific cell types such as pancreatic ductal epithelium, cerebral cortical neurones and glial cells and glomerular mesangial cells consistently lacked EGFP expression, while others, including pancreatic islet cells, expressed EGFP only at extremely low levels, barely distinguishable from background. Lastly, in the colon and stomach the pattern of EGFP expression was suggestive of clonal inactivation. Only cardiac and skeletal muscle showed near ubiquitous expression. CONCLUSIONS: These findings raise questions regarding the 'ubiquitous' expression of EGFP in these transgenic mice and suggest caution in relying overly on EGFP alone as an infallible marker of donor cell origin.     

Reproducibility of reference tissue quantification of dynamic contrast-enhanced data: comparison with a fixed vascular input function

Reference tissues are currently used to analyse dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data. The assessment of tumour response to treatment with anti-cancer drugs is a particularly important application of this type of analysis and requires a measure of reproducibility to define a level above which a significant change due to therapy can be inferred. This study compares the reproducibility of such quantification strategies with that found using a published, group-averaged uptake curve. It is shown that reference tissue quantification gives poorer reproducibility for most parameters than that found using a group-averaged plasma curve (a change in K(trans) of greater than 41.8% and 16.4% would be considered significant in the two approaches, respectively), but successfully incorporates some of the variability observed in plasma kinetics between visits and provides vascular input functions that, across the group, are comparable with the group-averaged curve. This study therefore provides an indirect validation of the methodology.     

A challenged choice: donating spare embryos to stem cell research in Switzerland

RESEARCH QUESTIONS: Couples undergoing IVF in Switzerland may have embryos in excess of their clinical need that they can donate to human embryonic stem cell research. Thus a new practice has emerged in Switzerland when IVF treatment and embryonic stem cell research come into contact. This interface needs to be investigated from an ethical-legal point of view to facilitate a fair informed choice process for the couples involved.METHODS: Ethical analysis, patient perspectives elaboration. Interdisciplinary approach that draws on the research project JESP-ELSI (joint embryonic stem cell research project--ethical legal and societal implications). RESULTS AND CONCLUSIONS: To facilitate the donation of surplus embryos to human embryonic stem cell research, we propose a procedure of informed choice that fits to the current Swiss legal situation. In addition we identify problems within the current legal setting and suggest methods to improve communication at the interface between IVF and embryonic stem cell research from an ethical perspective.