Mast cells are well accepted as important sentinel cells for host defence against selected pathogens. Their location at mucosal surfaces and ability to mobilize multiple aspects of early immune responses makes them critical contributors to effective immunity in several experimental settings. However, the interactions of mast cells with viruses and pathogen products are complex and can have both detrimental and positive impacts. There is substantial evidence for mast cell mobilization and activation of effector cells and mobilization of dendritic cells following viral challenge. These cells are a major and under-appreciated local source of type I and III interferons following viral challenge. However, mast cells have also been implicated in inappropriate inflammatory responses, long term fibrosis, and vascular leakage associated with viral infections. Progress in combating infection and boosting effective immunity requires a better understanding of mast cell responses to viral infection and the pathogen products and receptors we can employ to modify such responses. In this review, we outline some of the key known responses of mast cells to viral infection and their major responses to pathogen products. We have placed an emphasis on data obtained from human mast cells and aim to provide a framework for considering the complex interactions between mast cells and pathogens with a view to exploiting this knowledge therapeutically. Long-lived resident mast cells and their responses to viruses and pathogen products provide excellent opportunities to modify local immune responses that remain to be fully exploited in cancer immunotherapy, vaccination, and treatment of infectious diseases.

Systemic sclerosis (SSc) is a chronic debilitating idiopathic disorder, characterized by deposition of excessive extracellular matrix (ECM) proteins such as collagen which leads to fibrosis of the skin and other internal organs. During normal tissue repair and remodeling, the accumulation and turnover of ECM proteins are tightly regulated by the interaction of matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of metalloproteinases (TIMPs). SSc is associated with dysregulation of the activity of these proteolytic and inhibitory proteins within the tissue microenvironment, tipping the balance toward fibrosis. The resultant ECM accumulation further perpetuates tissue stiffness and decreased function, contributing to poor clinical outcomes. Understanding the expression and function of these endogenous enzymes and inhibitors within specific tissues is therefore critical to the development of therapies for SSc. This brief review describes recent advances in our understanding of the functions and mechanisms of ECM remodeling by metalloproteinases and their inhibitors in the skin and lungs affected in SSc. It highlights recent progress on potential candidates for intervention and therapeutic approaches for treating SSc fibrosis.

One of the major problems in the construction industry is that of fragmentation. This hasled to an increased adoption of design-build (DB) as a procurement route in recent years.This move attempts to solve problems associated with the use of the traditional designbid-build method.The performance of DB projects is investigated under three aspects, namely quality, timeand cost. Results of the opinion survey concluded that contractors, architects and clientsagreed that DB projects perform well in these three areas. This confirms the inherent advantagesthat DB has to offer. It is concluded that DB is indeed a worthwhile procurementroute but the various participants must understand its structure and accept the changesinvolved.

Background: Internet adoption during the past decade has provided opportunities for innovation in advanced cardiac life support (ACLS) training. With pressure on budgets across health care systems, there is a need for more cost-effective solutions. Recently, traditional ACLS training has evolved from passive to active learning technologies. The objective of this study is to compare the cost, cost-savings and return on investment (ROI) of blended ACLS (B-ACLS) and face-to-face ACLS (F-ACLS) in Singapore. Methods: B-ACLS and F-ACLS courses are offered in two training institutes in Singapore. Direct and indirect costs of training were obtained from one of the training providers. ROI was computed using cost-savings over total cost if B-ACLS was used instead of F-ACLS. Results: The estimated annual cost to conduct B-ACLS and F-ACLS were S$43,467 and S$72,793, respectively. Discounted total cost of training over the life of the course (five years) was S$107,960 for B-ACLS and S$280,162 for F-ACLS. Annual productivity loss cost account for 52% and 23% of the costs among the F-ACLS and B-ACLS, respectively. B-ACLS yielded a 160% return on the money invested. There would be 61% savings over the life of the course if B-ACLS were to be used instead of F-ACLS. Conclusion: The B-ACLS course provides significant cost-savings to the provider and a positive ROI. B-ACLS should be more widely adopted as the preferred mode of ACLS training. As a start, physicians looking for reaccreditation of the ACLS training should be encouraged to take B-ACLS instead of F-ACLS.

Mast cells are specialized, tissue resident, immune effector cells able to respond to a wide range of stimuli. MCs are involved in the regulation of a variety of physiological functions, including vasodilation, angiogenesis and pathogen elimination. In addition, MCs recruit and regulate the functions of many immune cells such as dendritic cells, macrophages, T cells, B cells and eosinophils through their selective production of multiple cytokines and chemokines. MCs generate and release multi-potent molecules, such as histamine, proteases, prostanoids, leukotrienes, heparin, and many cytokines, chemokines, and growth factors through both degranulation dependent and independent pathways. Recent studies suggested that metabolic shifts dictate the activation and granule content secretion by MCs, however the metabolic signaling promoting these events is at its infancy. Lipid metabolism is recognized as a pivotal immunometabolic regulator during immune cell activation. Peroxisomes are organelles found across all eukaryotes, with a pivotal role in lipid metabolism and the detoxification of reactive oxygen species. Peroxisomes are one of the emerging axes in immunometabolism. Here we identified the peroxisome as an essential player in MCs activation. We determined that lack of functional peroxisomes in murine MCs causes a significant reduction of interleukin-6, Tumor necrosis factor and InterleukinL-13 following immunoglobulin IgE-mediated and Toll like receptor 2 and 4 activation compared to the Wild type (WT) BMMCs. We linked these defects in cytokine release to defects in free fatty acids homeostasis. In conclusion, our study identified the importance of peroxisomal fatty acids homeostasis in regulating mast cell-mediated immune functions.