The Role of Streptococcal Cell-Envelope Proteases in Bacterial Evasion of the Innate Immune System

Bacteria possess the ability to evolve varied and ingenious strategies to outwit the host immune system, instigating an evolutionary arms race. Proteases are amongst the many weapons employed by bacteria, which specifically cleave and neutralize key signalling molecules required for a coordinated immune response. In this article, we focus on a family of S8 subtilisin-like serine proteases expressed as cell-envelope proteases (CEPs) by group A and group B streptococci. Two of these proteases known as Streptococcus pyogenes CEP (SpyCEP) and C5a peptidase cleave the chemokine CXCL8 and the complement fragment C5a, respectively. Both CXCL8 and C5a are potent neutrophil-recruiting chemokines, and by neutralizing their activity, streptococci evade a key defence mechanism of innate immunity. We review the mechanisms by which CXCL8 and C5a recruit neutrophils and the characterization of SpyCEP and C5a peptidase, including both in vitro and in vivo studies. Recently described structural insights into the function of this CEP family are also discussed. We conclude by examining the progress of prototypic vaccines incorporating SpyCEP and C5a peptidase in their preparation. Since streptococci-producing SpyCEP and C5a peptidase are responsible for a considerable global disease burden, targeting these proteases by vaccination strategies or by small-molecule antagonists should provide protection from and promote the resolution of streptococcal infections.     

Developing a Web 2.0 Diabetes Care Support System with Evaluation from Care Provider Perspectives

Diabetes is a life-long illness condition that many diabetic patients end up with related complications resulted largely from lacking of proper supports. The success of diabetes care relies mainly on patient’s daily self-care activities and care providers’ continuous support. However, the self-care activities are socially bounded with patient’s everyday schedules that can easily be forgotten or neglected and the care support from providers has yet been fully implemented. This study develops a Web 2.0 diabetes care support system for patients to integrate required self-care activities with different context in order to enhance patient’s care knowledge and behavior adherence. The system also supports care managers in a health service center to conduct patient management through collecting patient’s daily physiological information, sharing care information, and maintaining patient-provider relationships. After the development, we evaluate the acceptance of the system through a group of nursing staffs.     

Arteriovenous brain malformations: is functional MR imaging reliable for studying language reorganization in patients? Initial observations

PURPOSE: To determine whether the blood flow abnormalities frequently associated with arteriovenous malformations (AVMs) can alter functional magnetic resonance (MR) imaging evaluation of language lateralization and whether reorganization of language function occurs in patients with brain AVMs. MATERIALS AND METHODS: Eleven patients with left-hemisphere brain AVMs and 10 age-matched control subjects were examined with 1.5-T blood oxygen level-dependent (BOLD) functional MR imaging. Verbal fluency, sentence repetition, and story listening tasks were performed. The functional MR imaging laterality index in the frontal and temporal lobes was defined as the (L - R)/(L + R) ratio, where L and R are the numbers of activated pixels in the left and right hemispheres, respectively. Statistical analyses were performed with Wilcoxon signed rank, Fisher exact, and Kruskal-Wallis tests. RESULTS: Control subjects had left-sided language dominance, although symmetric pixel counts were observed in the frontal lobes in two subjects and in the temporal lobes in one subject. Six patients had left-sided language dominance similar to that observed in control subjects. Five of these patients had AVMs outside frontal or temporal language areas, without flow abnormalities. Five patients had abnormally right-sided asymmetric indexes (below mean control subject value - 2 SDs), which suggested language reorganization (P <.05). Results of Wada examination and/or postembolization functional MR imaging performed in two of these patients showed that the abnormal laterality indexes were at least partly due to severe flow abnormalities that impaired detection of BOLD MR imaging signal intensity. CONCLUSION: These data suggest that flow abnormalities may interfere with language lateralization assessment with functional MR imaging.