Lyme disease—another transfusion risk?

Lyme disease (or Lyme borreliosis) is caused by a spirochetal bacteria, Borrelia burgdorferi. Increased recognition of the disease and increased exposure to the vector (ticks) capable of spreading B. burgdorferi from animal hosts have resulted in a rise in the number of cases of Lyme borreliosis reported in the United States. There are three stages of the clinical course of Lyme borreliosis; however, not all those infected will have typical manifestations of each stage, such as the arthritis of the third stage. Routine blood cultures will rarely document bacteremia and serologic testing is not yet reliable. Early treatment can prevent later stages of Lyme borreliosis. There is evidence that transmission of B. burgdorferi by blood transfusion is possible, but, to date, there has been no documentation of transfusion- associated Lyme borreliosis. Thus, no new recommendations for screening donors to identify possible carriers of B. burgdorferi are suggested at this time.     

Development and evaluation of a critical care e-learning scenario

This paper describes the development and evaluation of a critical care e-learning scenario for student nurses. At present, there are insufficient opportunities in the United Kingdom (UK) for student nurses to experience clinical placements where their skills in care of the critically-ill can be developed. There is therefore a need for new learning materials that help learners recognise the signs of clinical deterioration and rehearse the management of critically-ill patients. One way of meeting this need is by using electronic care scenarios. Several electronic care scenarios have been developed at Swansea University as part of the eWARD project. This article describes the design and evaluation of a critical care scenario that follows the care of a road casualty (John Macadam) after admission to an intensive care unit. The scenario was designed by an advisory team comprising a clinical lecturer and e-learning specialists. After using the scenario, 144 nursing students completed a Web-based questionnaire that collected demographic and attitudinal data for analysis using SPSS. Nursing students had a strongly positive attitude to the scenario with median scores in excess of 20 compared to maxima of 25 for scales measuring ease-of-use, interactivity, realism and confidence. None of the demographic data collected had a significant effect on these attitudes. The positive attitude of student nurses to this scenario strongly supports its use to help learners to (1) acquire knowledge and awareness when real life placements in these settings are not available and (2) extend their knowledge after coming across similar situations in practice.     

Alterations in galectin-3 expression and distribution correlate with breast cancer progression: functional analysis of galectin-3 in breast epithelial-endothelial interactions

To define the role of galectin-3 in breast cancer progression, we have used a novel three-dimensional co-culture system that recapitulates in vivo reciprocal functional breast epithelial-endothelial cell-cell and cell-matrix interactions, and examined the expression of galectin-3 mRNA and protein in human breast tumors and xenografts. Galectin-3 is required for the stabilization of epithelial-endothelial interaction networks because immunoneutralization with galectin-3 antibodies abolishes the interactions in a dose-dependent manner. Co-culture of epithelial cells with endothelial cells results in increase in levels of secreted galectin-3 and presence of proteolytically processed form of galectin-3 in the conditioned media. In contrast, intracellular galectin-3 predominantly exists in the intact form. This difference in sensitivity to proteolytic processing of secreted versus intracellular galectin-3 probably arises from differences in accessibility of protease-sensitive sites, levels, and/or type of activated protease(s), and may be indicative of different functional roles for intact and processed galectin-3. To determine whether the proteolytically cleaved galectin-3 retains its ability to bind to endothelial cells, binding assays were performed with the full-length and matrix metallopeoteinase-2-cleaved recombinant galectin-3. Although a dose-dependent increase in binding to human umbilical vein endothelial cells was observed with both full-length and cleaved galectin-3, proteolytically cleaved galectin-3 displayed approximately 20-fold higher affinity for human umbilical vein endothelial cells as compared to the full-length protein. Examination of galectin-3 expression in breast tumors and xenografts revealed elevated levels of galectin-3 mRNA and protein in the luminal epithelial cells of normal and benign ducts, down-regulation in early grades of ductal carcinoma in situ (DCIS), and re-expression in peripheral tumor cells as DCIS lesions progressed to comedo-DCIS and invasive carcinomas. These data suggest that galectin-3 expression is associated with specific morphological precursor subtypes of breast cancer and undergoes a transitional shift in expression from luminal to peripheral cells as tumors progressed to comedo-DCIS or invasive carcinomas. Such a localized expression of galectin-3 in cancer cells proximal to the stroma could lead to increased invasive potential by inducing novel or better interactions with the stromal counterparts.     

Endoplasmic reticulum protein BI-1 regulates Ca²⁺-mediated bioenergetics to promote autophagy

Autophagy is a lysosomal degradation pathway that converts macromolecules into substrates for energy production during nutrient-scarce conditions such as those encountered in tumor microenvironments. Constitutive mitochondrial uptake of endoplasmic reticulum (ER) Ca²⁺ mediated by inositol triphosphate receptors (IP₃Rs) maintains cellular bioenergetics, thus suppressing autophagy. We show that the ER membrane protein Bax inhibitor-1 (BI-1) promotes autophagy in an IP₃R-dependent manner. By reducing steady-state levels of ER Ca²⁺ via IP₃Rs, BI-1 influences mitochondrial bioenergetics, reducing oxygen consumption, impacting cellular ATP levels, and stimulating autophagy. Furthermore, BI-1-deficient mice show reduced basal autophagy, and experimentally reducing BI-1 expression impairs tumor xenograft growth in vivo. BI-1''s ability to promote autophagy could be dissociated from its known function as a modulator of IRE1 signaling in the context of ER stress. The results reveal BI-1 as a novel autophagy regulator that bridges Ca²⁺ signaling between ER and mitochondria, reducing cellular oxygen consumption and contributing to cellular resilience in the face of metabolic stress.     

Multilocus analysis of Cryptosporidium hominis and Cryptosporidium parvum isolates from sporadic and outbreak-related human cases and C. parvum isolates from sporadic livestock cases in the United Kingdom

Cryptosporidium parvum and Cryptosporidium hominis isolates from sporadic, drinking water-associated, and intrafamilial human cases together with C. parvum isolates from sporadic cases in livestock were collected in the United Kingdom between 1995 and 1999. The isolates were characterized by analysis of three microsatellite markers (ML1, GP15, and MS5) using PCR amplification. Within C. hominis, four alleles were detected within the GP15 and MS5 loci, and a single type was detected with ML1. C. parvum was more polymorphic; 12 alleles were detected with GP15, 6 were detected with MS5, and 3 were detected with ML1. Multilocus analysis of polymorphisms within the three microsatellite loci was combined with those reported previously for an extrachromosomal small double-stranded RNA. Forty multilocus types were detected within these two species: 9 were detected in C. hominis, and 31 were detected in C. parvum. In C. hominis, heterogeneity was almost exclusively found in samples from sporadic cases. Similarity analysis identified three main groups within C. parvum, and the group that predominated in human infection was also found in livestock. Multilocus types of C. parvum previously identified only in humans were not detected in livestock. Isolates of both C. hominis and C. parvum from separate waterborne outbreaks were genetically homogeneous, suggesting preferential or point source transmission of certain types of these two species of parasites.     

HLA-DRB1 associations with disease susceptibility and clinical course in Australians with multiple sclerosis

Human leucocyte antigen (HLA)-DRB1*1501 and other class II alleles influence susceptibility to multiple sclerosis (MS), but their contribution if any to the clinical course of MS remains uncertain. Here, we have investigated DRB1 alleles in a large sample of 1230 Australian MS cases, with some enrichment for subjects with primary progressive (PPMS) disease ( n  = 246) and 1210 healthy controls. Using logistic regression, we found that DRB1*1501 was strongly associated with risk ( P  = 7 × 10⁻⁴⁵), as expected, and after adjusting for DRB1*1501, a predisposing effect was also observed for DRB1*03 ( P  = 5 × 10⁻⁷). Individuals homozygous for either DRB1*15 or DRB1*03 were considerably more at risk of MS than heterozygotes and non-carriers. Both the DRB1*04 and the DRB1*01/DRB1*15 genotype combination, respectively, protected against PPMS in comparison to subjects with relapsing disease. Together, these data provide further evidence of heterogeneity at the DRB1 locus and confirm the importance of HLA variants in the phenotypic expression of MS.