Maggot secretions suppress pro-inflammatory responses of human monocytes through elevation of cyclic AMP

AIMS/HYPOTHESIS: Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. As monocytes may contribute to the excessive inflammatory responses in such wounds, this study focussed on the effects of maggot secretions on the pro-inflammatory activities of these cells. METHODS: Freshly isolated monocytes were incubated with a range of secretions for 1 h and then stimulated with lipopolysaccharides (range 0-100 ng/ml) or lipoteichoic acid (range 0-5 microg/ml) for 18 h. The expression of cell surface molecules, cytokine and chemokine levels in culture supernatants, cell viability, chemotaxis, and phagocytosis and killing of Staphylococcus aureus were measured. RESULTS: Maggot secretions dose-dependently inhibited production of the pro-inflammatory cytokines TNF-alpha, IL-12p40 and macrophage migration inhibitory factor by lipopolysaccharides- and lipoteichoic acid-stimulated monocytes, while enhancing production of the anti-inflammatory cytokine IL-10. Expression of cell surface receptors involved in pathogen recognition remained unaffected by secretions. In addition, maggot secretions altered the chemokine profile of monocytes by downregulating macrophage inflammatory protein-1beta and upregulating monocyte chemoattractant protein-1 and IL-8. Nevertheless, chemotactic responses of monocytes were inhibited by secretions. Furthermore, maggot secretions did not affect phagocytosis and intracellular killing of S. aureus by human monocytes. Finally, secretions induced a transient rise in the intracellular cyclic AMP concentration in monocytes and Rp-cyclic AMPS inhibited the effects of secretions. CONCLUSIONS/INTERPRETATION: Maggot secretions inhibit the pro-inflammatory responses of human monocytes through a cyclic AMP-dependent mechanism. Regulation of the inflammatory processes by maggots contributes to their beneficial effects on chronic wound

A High Through-Put Reverse Genetic Screen Identifies Two Genes Involved in Remote Memory in Mice

Previous studies have revealed that the initial stages of memory formation require several genes involved in synaptic, transcriptional and translational mechanisms. In contrast, very little is known about the molecular and cellular mechanisms underlying later stages of memory, including remote memory (i.e. 7-day memory). To identify genes required for remote memory, we screened randomly selected mouse strains harboring known mutations. In our primary reverse genetic screen, we identified 4 putative remote memory mutant strains out of a total of 54 lines analyzed. Additionally, we found 11 other mutant strains with other abnormal profiles. Secondary screens confirmed that mutations of integrin β2 (Itgβ2) and steryl-O-acyl transferase 1 (Soat1) specifically disrupted remote memory. This study identifies some of the first genes required for remote memory, and suggests that screens of targeted mutants may be an efficient strategy to identify molecular requirements for this process

What is known about the patient's experience of medical tourism? A scoping review

<p>Abstract</p> <p>Background</p> <p>Medical tourism is understood as travel abroad with the intention of obtaining non-emergency medical services. This practice is the subject of increasing interest, but little is known about its scope.</p> <p>Methods</p> <p>A comprehensive scoping review of published academic articles, media sources, and grey literature reports was performed to answer the question: what is known about the patient's experience of medical tourism? The review was accomplished in three steps: (1) identifying the question and relevant literature; (2) selecting the literature; (3) charting, collating, and summarizing the information. Overall themes were identified from this process.</p> <p>Results</p> <p>291 sources were identified for review from the databases searched, the majority of which were media pieces (<it>n </it>= 176). A further 57 sources were included for review after hand searching reference lists. Of the 348 sources that were gathered, 216 were ultimately included in this scoping review. Only a small minority of sources reported on empirical studies that involved the collection of primary data (<it>n </it>= 5). The four themes identified via the review were: (1) decision-making (e.g., push and pull factors that operate to shape patients' decisions); (2) motivations (e.g., procedure-, cost-, and travel-based factors motivating patients to seek care abroad); (3) risks (e.g., health and travel risks); and (4) first-hand accounts (e.g., patients' experiential accounts of having gone abroad for medical care). These themes represent the most discussed issues about the patient's experience of medical tourism in the English-language academic, media, and grey literatures.</p> <p>Conclusions</p> <p>This review demonstrates the need for additional research on numerous issues, including: (1) understanding how multiple information sources are consulted and evaluated by patients before deciding upon medical tourism; (2) examining how patients understand the risks of care abroad; (3) gathering patients' prospective and retrospective accounts; and (4) the push and pull factors, as well as the motives of patients to participate in medical tourism. The findings from this scoping review and the knowledge gaps it uncovered also demonstrate that there is great potential for new contributions to our understanding of the patient's experience of medical tourism.</p

Tumor Transcriptome Sequencing Reveals Allelic Expression Imbalances Associated with Copy Number Alterations

Due to growing throughput and shrinking cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide study of gene expression and copy number alterations in primary tumors. The sequencing of transcripts (RNA-Seq) should offer several advantages over microarray-based methods, including the ability to detect somatic mutations and accurately measure allele-specific expression. To investigate these advantages we have applied a novel, strand-specific RNA-Seq method to tumors and matched normal tissue from three patients with oral squamous cell carcinomas. Additionally, to better understand the genomic determinants of the gene expression changes observed, we have sequenced the tumor and normal genomes of one of these patients. We demonstrate here that our RNA-Seq method accurately measures allelic imbalance and that measurement on the genome-wide scale yields novel insights into cancer etiology. As expected, the set of genes differentially expressed in the tumors is enriched for cell adhesion and differentiation functions, but, unexpectedly, the set of allelically imbalanced genes is also enriched for these same cancer-related functions. By comparing the transcriptomic perturbations observed in one patient to his underlying normal and tumor genomes, we find that allelic imbalance in the tumor is associated with copy number mutations and that copy number mutations are, in turn, strongly associated with changes in transcript abundance. These results support a model in which allele-specific deletions and duplications drive allele-specific changes in gene expression in the developing tumor