Pig conceptuses secrete estrogen and interferons to differentially regulate uterine STAT1 in a temporal and cell type-specific manner

Conceptus trophectoderm and uterine luminal epithelial cells interact via endocrine, paracrine, and autocrine modulators to mediate pregnancy recognition and implantation. Pig conceptuses not only release estrogens for pregnancy recognition but also secrete interferons during implantation. Because interferon-stimulated genes are increased by interferons secreted for pregnancy recognition in ruminants, we asked whether the interferon-stimulated gene, STAT1, is up-regulated in pig endometrium by conceptus estrogens and/or interferons. STAT1 expression in response to day of pregnancy, estrogen injection, and intrauterine infusion of conceptus secretory proteins in pigs indicated 1) estrogen increases STAT1 in luminal epithelial cells, 2) conceptus secretory proteins that contain interferons increase STAT1 in stroma, 3) STAT1 increases in close proximity to the conceptus, and 4) early estrogen results in conceptus death and no STAT1 in stroma. The interactions of estrogen and interferons to regulate cell-type-specific expression of STAT1 highlight the complex interplay between endometrium and conceptus for pregnancy recognition and implantation.     

Dysregulated TRK signalling is a therapeutic target in CYLD defective tumours

Individuals with germline mutations in the tumour-suppressor gene CYLD are at high risk of developing disfiguring cutaneous appendageal tumours, the defining tumour being the highly organised cylindroma. Here, we analysed CYLD mutant tumour genomes by array comparative genomic hybridisation and gene expression microarray analysis. CYLD mutant tumours were characterised by an absence of copy-number aberrations apart from LOH chromosome 16q, the genomic location of the CYLD gene. Gene expression profiling of CYLD mutant tumours showed dysregulated tropomyosin kinase (TRK) signalling, with overexpression of TRKB and TRKC in tumours when compared with perilesional skin. Immunohistochemical analysis of a tumour microarray showed strong membranous TRKB and TRKC staining in cylindromas, as well as elevated levels of ERK phosphorylation and BCL2 expression. Membranous TRKC overexpression was also observed in 70% of sporadic BCCs. RNA interference-mediated silencing of TRKB and TRKC, as well as treatment with the small-molecule TRK inhibitor lestaurtinib, reduced colony formation and proliferation in 3D primary cell cultures established from CYLD mutant tumours. These results suggest that TRK inhibition could be used as a strategy to treat tumours with loss of functional CYLD.     

Psychophysiological correlates of dissociation, handedness, and hemispheric lateralization

Dissociation involves a disruption of typically integrated functions including consciousness, information perception, and memory; however, dissociation may not always be of a pathologic nature. Increasingly, studies are identifying relations between inconsistent handedness, mixed hemispheric lateralization, and dissociative symptomatology in both clinical and nonclinical populations. The current study explored whether a nonclinical sample of individuals scoring high in dissociation would display an inconsistent handedness in conjunction with a left hemispheric lateralization as measured by electroencephalography. Twenty-seven participants (12 males and 15 females) aged between 20 and 59 years (M = 29.1 year, SD = 11.2 years), completed the Dissociative Experiences Scale and Waterloo Handedness Questionnaire Revised after determining laterality. As predicted, inconsistently handed participants scoring high in dissociation displayed left hemispheric lateralization across frontal, central, and parietal regions. Conversely, right lateralization was found within Delta frequency band across temporal regions. The study provides a good framework for future research investigating the neurophysiological correlates underpinning dissociative symptomatology.     

Improving outcomes in geriatric surgery: Is there more to the equation?

The era of geriatric surgery has arrived with increased global life expectancy. The need to optimize outcomes in this group of patients goes beyond traditional outcomes such as postoperative morbidity and mortality indicators. Recognizing risk factors that impact adverse surgical outcomes such as frailty and sarcopenia, individualizing optimization strategies such as prehabilitation and a multidisciplinary geriatric surgical service have been shown to improve postoperative outcomes and help the older surgical patient regain premorbid function and maintain quality of life. There needs to be a concerted effort to increase awareness of this increasingly important topic in practicing surgeons around the world to meet the challenges of the aging population.     

Warfarin treatment of chronic idiopathic urticaria and angio-oedema

BACKGROUND: Chronic idiopathic urticaria is a disabling condition that does not always respond to antihistamine drugs and other agents are sometimes needed to control disease activity. Warfarin has demonstrated efficacy in single unblinded case studies [1] but has been dismissed by others [2]. OBJECTIVE: We investigated the effect of warfarin treatment in eight patients with chronic idiopathic urticaria unresponsive to antihistamines in an open study. Six of the eight patients responded to treatment and three had a dramatic response. These three were included in a double-blind placebo-controlled trial of warfarin therapy to confirm significant benefit from treatment. METHODS: The three warfarin responders had their stable warfarin dose encapsulated and placebo capsules were provided. A double-blind placebo-controlled crossover trial was performed on each patient. Visual analogue scores recorded disease activity. RESULTS: Comparison of visual analogue scores showed a significant benefit while on warfarin with a reduction in pruritus and angio-oedema. CONCLUSION: This is the first double-blind placebo-controlled study to show a response of chronic idiopathic urticaria to warfarin. The mechanisms of action are unclear and require further study.     

‘Levels’ of attainment in nursing practice: reality or illusion?

In earlier research based on an analysis of course documentation, it had been found that there was little consensus among nurse educators concerning the parameters which distinguish levels of practice skills, particularly those which differentiate diploma and degree qualifications in the United Kingdom. This result was confirmed and strengthened in the current study. Lecturers in nursing, when presented with a sorting task using 40 statements derived from course documentation selected from the earlier study, were unable to distinguish statements describing diploma level from those describing degree level practice. Possible reasons for the difficulty are discussed. It is concluded that the attempt to represent practice skill in a hierarchy of assessment for degree or diploma qualifications is premature since the parameters of practice remain unreliably specified.     

Transposon mutagenesis in Legionella pneumophila. I.--Persistence of suicide and broad host-range plasmids.

Two of three highly virulent strains of Legionella pneumophila could act as recipients at high frequencies in conjugation experiments with Escherichia coli donor strains carrying broad host-range plasmids belonging to incompatibility groups N, P and W. All broad host-range and most transposon-delivery plasmids persisted within transconjugants with high stability. Only one (pSUP1021) of several vehicles designed for the delivery of transposons into the chromosome of Gram-negative bacteria was found to yield transposon mutants of Legionella at a detectable frequency.