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.     

Actualización en fascitis necrotizante

Necrotizing fasciitis is defined as a rapidly progressive infection of the skin and soft tissue that usually involves severe systemic toxicity. The incidence of this infection has increased in the last few decades and is estimated to affect one out of every 100,000 inhabitants in western European countries. This disease is the most serious form of skin and soft tissue infection, due to rapid destruction and necrosis of the fascia and subcutaneous fat, and the development of shock and multiorgan failure in about one third of patients.Although there are several predisposing factors for the development of the disease, especially for type I, or polymicrobial, necrotizing fasciitis, many patients are young and have no underlying chronic diseases, as is the case for type II, or streptococcal, necrotizing fasciitis. The diagnosis is mainly clinical, and urgent surgical consultation is required as soon as possible once suspicion is high, as the main determinant of mortality is the delay in surgical treatment. Overall mortality remains high, affecting more than 25% of patients. Surgical debridement is the mainstay of treatment, along with hemodynamic support and broad-spectrum antibiotics.     

A Profile for Predicting Attrition from Exercise in Older Adults

The purpose of this study was to determine a profile for predicting attrition among older adults involved in a 12-month exercise program. The parent study was a single-blinded randomized controlled trial. The study took place between 2006 and 2009 within a university setting. Older adults (N?=?179) completed baseline assessments of functional performance and psychosocial measures. Participants who were randomized, elected to receive treatment, and did not complete the exercise program were considered “dropouts” (n?=?35). Those who completed the program (n?=?144) were classified as “completers.” A latent profile analysis revealed two distinct patterns of memory complaints, self-efficacy to overcome barriers to exercise, balance performance, and stair performance. Dropouts were nearly twice as likely to be members of the profile that exhibited a higher degree of memory complaints, lower self-efficacy for overcoming exercise barriers, poorer single leg balance, and longer times to walk down stairs. The results provide an initial validation of a profile for discriminating between “dropouts” and “completers,” one that may have considerable utility for screening older adults prior to study entry.     

Measuring health outcomes of adolescents: report from a pilot study

There is a need to understand the practicality, validity and reliability of using utility measures with children and adolescents. We designed a pilot study in order to help guide the selection of an appropriate health-related quality-of-life (HRQoL) questionnaire for adolescents to be used in the context of a large randomised controlled trial (RCT) of family therapy versus standard treatment for adolescents aged 11–17 years. The pilot study was carried out on a school sample of adolescents in the same age range as the RCT. Adolescents were asked to fill in three HRQoL questionnaires: the standard EQ-5D, the licensed Health Utilities Index HUI, and the child-friendly version of the standard EQ-5D: the EQ-5D for youth (EQ-5D-Y). This report explores the problems with the language and concepts embodied within those HRQoL questionnaires and open discussion regarding how we can value the health of adolescents for cost-utility analysis in a larger study.     

Characteristics of Suicide from 1998–2001 in a Metropolitan Area

In order to establish effective suicide preventive programs, it is important to know the etiologic factors and causal relationships between suicide and behavior. Coroner data was analyzed for the 468 suicides that occurred in Indianapolis, Indiana during 1998–2001. The age-adjusted suicide rate was 14.08 per 100,000. Almost one-half of the victims had a mental illness and 26% had a history of alcohol/substance abuse. The leading risk factors for suicide were age, impaired health, psychosocial stressors, and access to firearms. This information can be used by health departments and mental health professionals to help reduce suicide.     

Assessing Strengths in Residential Treatment: Looking at the Whole Child

This article outlines the importance of assessing both within-child and environmental strengths for children and adolescents admitted to residential treatment facilities (RTFs). Discussed are the theoretical underpinnings behind strength-based assessment, as well as a number of organizations and initiatives that aim at raising the bar for children's care, creating a holistic viewpoint. Assessments such as the BASC-2, ASEBA, and Vineland-II are well-established measures that have moved to meet these demands, and measures like the BERS-2, RSCA, and DESSA have an overt strengths orientation. The CASA and the DCASC are omnibus strengths measures that can be utilized to fill the “intake gap.”