The ins and outs of Mycobacterium tuberculosis protein export

Mycobacterium tuberculosis is an important pathogen that infects approximately one-third of the world's population and kills almost two million people annually. An important aspect of M.?tuberculosis physiology and pathogenesis is its ability to export proteins into and across the thick mycobacterial cell envelope, where they are ideally positioned to interact with the host. In addition to the specific proteins that are exported by M.?tuberculosis, the systems through which these proteins are exported represent potential targets for future drug development. M.?tuberculosis possesses two well-known and conserved export systems: the housekeeping Sec pathway and the Tat pathway. In addition, M.?tuberculosis possesses specialized export systems including the accessory SecA2 pathway and five ESX pathways. Here we review the current understanding of each of these export systems, with a focus on M.?tuberculosis, and discuss the contribution of each system to disease and physiology.     

Infectious disease surveillance and modelling across geographic frontiers and scientific specialties

Infectious disease surveillance for mass gatherings (MGs) can be directed locally and globally; however, epidemic intelligence from these two levels is not well integrated. Modelling activities related to MGs have historically focused on crowd behaviours around MG focal points and their relation to the safety of attendees. The integration of developments in internet-based global infectious disease surveillance, transportation modelling of populations travelling to and from MGs, mobile phone technology for surveillance during MGs, metapopulation epidemic modelling, and crowd behaviour modelling is important for progress in MG health. Integration of surveillance across geographic frontiers and modelling across scientific specialties could produce the first real-time risk monitoring and assessment platform that could strengthen awareness of global infectious disease threats before, during, and immediately after MGs. An integrated platform of this kind could help identify infectious disease threats of international concern at the earliest stages possible; provide insights into which diseases are most likely to spread into the MG; help with anticipatory surveillance at the MG; enable mathematical modelling to predict the spread of infectious diseases to and from MGs; simulate the effect of public health interventions aimed at different local and global levels; serve as a foundation for scientific research and innovation in MG health; and strengthen engagement between the scientific community and stakeholders at local, national, and global levels.     

A model-based tool to predict the propagation of infectious disease via airports

Epidemics of novel or re-emerging infectious diseases have quickly spread globally via air travel, as highlighted by pandemic H1N1 influenza in 2009 (pH1N1). Federal, state, and local public health responders must be able to plan for and respond to these events at aviation points of entry. The emergence of a novel influenza virus and its spread to the United States were simulated for February 2009 from 55 international metropolitan areas using three basic reproduction numbers (R(0)): 1.53, 1.70, and 1.90. Empirical data from the pH1N1 virus were used to validate our SEIR model. Time to entry to the U.S. during the early stages of a prototypical novel communicable disease was predicted based on the aviation network patterns and the epidemiology of the disease. For example, approximately 96% of origins (R(0) of 1.53) propagated a disease into the U.S. in under 75 days, 90% of these origins propagated a disease in under 50 days. An R(0) of 1.53 reproduced the pH1NI observations. The ability to anticipate the rate and location of disease introduction into the U.S. provides greater opportunity to plan responses based on the scenario as it is unfolding. This simulation tool can aid public health officials to assess risk and leverage resources efficiently.     

Scleroderma Mimics

Scleroderma is a rare systemic autoimmune disease with multiple organ manifestations, including skin fibrosis. The groups of disorders classified as scleroderma mimics share the common thread of skin thickening but are otherwise quite incongruous in terms of underlying disease process and other organ involvement. This article reviews the clinical presentation, etiology, and treatment options available for scleroderma mimics, including morphea, scleredema, diabetic cheiroarthropathy, scleromyxedema, nephrogenic systemic fibrosis, and eosinophilic fasciitis. Through greater understanding of these diseases and the associated extradermal implications, we hope to facilitate recognition of scleroderma and its mimics.     

Is There Attenuation of Benefit of Invasive Therapy in Patients with Chronic Kidney Disease? Results from Randomized Trials and Registry Data

Chronic kidney disease (CKD) is not only a common comorbidity among patients presenting with acute coronary syndrome (ACS), it is also an entity that portends worse short- and long-term prognosis. Differences in the pathophysiology of arterial atherosclerosis and calcification, chronic inflammation, platelet reactivity, and thrombogenicity in patients with and without CKD underpin the increased vulnerability of CKD patients with ACS to subsequent ischemic and bleeding complications. These differences, as well as the frequent exclusion of CKD patients from randomized control trials, create uncertainty regarding the benefit of invasive treatment for ACS in patients with CKD. The limited evidence from randomized trials suggests a benefit with invasive treatment in CKD patients with ACS. However, some data from registry studies suggest no benefit or even harm with invasive therapy. Thus, the optimal management of ACS in patients with CKD, in particular end-stage CKD, remains uncertain. In this article we review the characteristics of coronary artery disease in patients with CKD, the available evidence pertaining to the outcomes of CKD patients with ACS with invasive versus conservative therapy, and potential areas for reducing complications of invasive therapy in this high-risk subset of patients.