Ctr2 Links Copper Homeostasis to Polysaccharide Capsule Formation and Phagocytosis Inhibition in the Human Fungal Pathogen Cryptococcus neoformans

Cryptococcus neoformans is a human opportunistic fungal pathogen responsible for ∼1/3 of HIV/AIDS deaths worldwide. This budding yeast expresses a polysaccharide capsule necessary for virulence. Capsule production inhibits phagocytosis by macrophages. Here we describe results that link copper homeostasis to capsule production and the inhibition of phagocytosis. Specifically, using Agrobacterium-mediated insertional mutagenesis, we identified an insertion in the promoter region of the putative copper transporter-encoding gene CTR2 that results in reduced expression of CTR2 and increased phagocytosis by murine RAW264.7 macrophages. The mutant also displayed sensitivity to copper starvation and defects in polysaccharide capsule production and melanization. These defects were all reversed by genetic correction of the promoter insertion by homologous targeting. Several melanization-defective mutants identified previously, those in the RIM20, RIM101, and VPS25 genes, also display sensitivity to copper starvation, reduced capsule production and increased phagocytosis. Together these results indicate a previously undescribed link between copper homeostasis to polysaccharide capsule production and phagocytosis inhibition in Cryptococcus neoformans

To retain or remove the syndesmotic screw: a review of literature

Introduction: Syndesmotic positioning screws are frequently placed in unstable ankle fractures. Many facets of adequate placement techniques have been the subject of various studies. Whether or not the syndesmosis screw should be removed prior to weight-bearing is still debated. In this study, the recent literature is reviewed concerning the need for removal of the syndesmotic screw. Materials and methods: A comprehensive literature search was conducted in the electronic databases of the Cochrane Library, Pubmed Medline and EMbase from January 2000 to October 2010. Results: A total of seven studies were identified in the literature. Most studies found no difference in outcome between retained or removed screws. Patients with screws that were broken, or showed loosening, had similar or improved outcome compared to patients with removed screws. Removal of the syndesmotic screws, when deemed necessary, is usually not performed before 8-12 weeks. Conclusion: There is paucity in randomized controlled trials on the absolute need for removal of the syndesmotic screw. However, current literature suggests that it might be reserved for intact screws that cause hardware irritation or reduced range of motion after 4-6 months

Self-assessment of morbidity following radical hysterectomy for cervical cancer.

The aim of this study was to assess the magnitude of the morbidity following radical surgery for early stage cervical cancer. We performed a retrospective survey of all women who had undergone a radical hysterectomy and lymphadenectomy between the months of July 1995 and December 1996 inclusive at either the Royal Marsden or St George's Hospital (n =38), using a detailed questionnaire on bladder, ano-rectal and sexual function, both before and after treatment. Sixteen women (44.4%) received adjuvant radiotherapy. The mean interval between surgery and inquiry was 16.4% months (range 8-25 months). The mean age at the time of surgery was 40.5 years. Thirty-six out of 38 women contacted responded (94.7%). Overall 33 women (91.7%) reported new bladder, ano-rectal or sexual symptoms. Complaints of urinary incontinence, particularly of urge incontinence, and of voiding difficulties increased significantly after surgery (P <0.05). However, only 5.3% of women had sought treatment. Tenesmus increased significantly (P <0.05), while increases in diarrhoea and faecal incontinence were not statistically significant (P =0.051). Although 12.9% of women stated an improvement in their sex lives, 54.8% thought that their sex life was worse after treatment, and 12.9% of women had ceased sexual activity altogether. Of women of childbearing age 53.8% felt adversely affected by their loss of fertility. Bladder, ano-rectal and sexual symptoms are very common following radical hysterectomy for cervical cancer, with adverse effect on quality of life, and persist into the second year after treatment