Treatment of drug-eluting stent restenosis: an emerging challenge.

Drug eluting stent (DES) restenosis has emerged as a significant clinical entity owing to the increasing use of DES in complex lesions and patients. However, to date, there is a paucity of studies that have addressed the management of DES restenosis and the resulting outcome, leaving the interventional cardiologist with a therapeutic dilemma. The purpose of this paper is therefore to provide a concise review of available data's dealing with the treatment of DES restenosis, including the outcome of patients treated for DES restenosis, the prognostic importance of the angiographic pattern and the available therapeutic modalities.

Beliefs and practices in the assessment of workplace pollutants

OBJECTIVES: A survey was undertaken among Swiss occupational hygienists and other professionals to identify the different exposure assessment methods used, the contextual parameters observed and the uses, difficulties and possible developments of exposure models for field application. METHODS: A questionnaire was mailed to 121 occupational hygienists, all members of the Swiss Occupational Hygiene Society. A shorter questionnaire was also sent to registered occupational physicians and selected safety specialists. Descriptive statistics and multivariate analyses were performed. RESULTS: The response rate for occupational hygienists was 60%. The so-called expert judgement appeared to be the most widely used method, but its efficiency and reliability were both judged with very low scores. Long-term sampling was perceived as the most efficient and reliable method. Various determinants of exposure, such as emission rate and work activity, were often considered important, even though they were not included in the exposure assessment processes. Near field local phenomena determinants were also judged important for operator exposure estimation. CONCLUSION: Exposure models should be improved to integrate factors which are more easily accessible to practitioners. Descriptors of emission and local phenomena should also be included.

Treatment implications of the emerging molecular classification system for melanoma.

Melanoma is an aggressive disease with few standard treatment options. The conventional classification system for this disease is based on histological growth patterns, with division into four subtypes: superficial spreading, lentigo maligna, nodular, and acral lentiginous. Major limitations of this classification system are absence of prognostic importance and little correlation with treatment outcomes. Recent preclinical and clinical findings support the notion that melanoma is not one malignant disorder but rather a family of distinct molecular diseases. Incorporation of genetic signatures into the conventional histopathological classification of melanoma has great implications for development of new and effective treatments. Genes of the mitogen-associated protein kinase (MAPK) pathway harbour alterations sometimes identified in people with melanoma. The mutation Val600Glu in the BRAF oncogene (designated BRAF(V600E)) has been associated with sensitivity in vitro and in vivo to agents that inhibit BRAF(V600E) or MEK (a kinase in the MAPK pathway). Melanomas arising from mucosal, acral, chronically sun-damaged surfaces sometimes have oncogenic mutations in KIT, against which several inhibitors have shown clinical efficacy. Some uveal melanomas have activating mutations in GNAQ and GNA11, rendering them potentially susceptible to MEK inhibition. These findings suggest that prospective genotyping of patients with melanoma should be used increasingly as we work to develop new and effective treatments for this disease.

Nutrigenomics and nutrigenetics: the emerging faces of nutrition.

The recognition that nutrients have the ability to interact and modulate molecular mechanisms underlying an organism's physiological functions has prompted a revolution in the field of nutrition. Performing population-scaled epidemiological studies in the absence of genetic knowledge may result in erroneous scientific conclusions and misinformed nutritional recommendations. To circumvent such issues and more comprehensively probe the relationship between genes and diet, the field of nutrition has begun to capitalize on both the technologies and supporting analytical software brought forth in the post-genomic era. The creation of nutrigenomics and nutrigenetics, two fields with distinct approaches to elucidate the interaction between diet and genes but with a common ultimate goal to optimize health through the personalization of diet, provide powerful approaches to unravel the complex relationship between nutritional molecules, genetic polymorphisms, and the biological system as a whole. Reluctance to embrace these new fields exists primarily due to the fear that producing overwhelming quantities of biological data within the confines of a single study will submerge the original query; however, the current review aims to position nutrigenomics and nutrigenetics as the emerging faces of nutrition that, when considered with more classical approaches, will provide the necessary stepping stones to achieve the ambitious goal of optimizing an individual's health via nutritional intervention.

Emerging viral infections after hematopoietic cell transplantation.

This overview summarizes recent data on emerging viruses after hematopoietic cell transplantation (HCT), including adenovirus, BK virus, human metapneumovirus (hMPV), and human herpesvirus (HHV) 6. The increased recognition of these infections is due to improved molecular detection methods, increased surveillance and more profound immunosuppression in the host. Adenovirus can cause serious disease especially in T-cell depleted transplant recipients. Adenovirus viremia is an important risk factor for disease in this setting. BK virus has been associated with hemorrhagic cystitis in HCT recipients. BK viremia is significantly associated with hemorrhagic cystitis. hMPV shows a seasonal distribution and can cause fatal pneumonia in HCT recipients. hMPV may be the etiology of some cases previously categorized as idiopathic pneumonia syndrome. HHV-6 commonly leads to viremia in HCT recipients. HHV-6 has been strongly associated with encephalitis and delayed platelet engraftment. Prospective studies are needed to further examine epidemiology, disease associations, and management strategies for these viruses.

Inhibition of tumor angiogenesis by non-steroidal anti-inflammatory drugs: emerging mechanisms and therapeutic perspectives.

Chronic intake of non steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced risk of developing gastrointestinal tumors, in particular colon cancer. Increasing evidence indicates that NSAID exert tumor-suppressive activity on pre-malignant lesions (polyps) in humans and on established experimental tumors in mice. Some of the tumor-suppressive effects of NSAIDs depend on the inhibition of cyclooxygenase-2 (COX-2), a key enzyme in the synthesis of prostaglandins and thromboxane, which is highly expressed in inflammation and cancer. Recent findings indicate that NSAIDs exert their anti-tumor effects by suppressing tumor angiogenesis. The availability of COX-2-specific NSAIDs opens the possibility of using this drug class as anti-angiogenic agents in combination with chemotheapy or radiotherapy for the treatment of human cancer. Here we will briefly review recent advances in the understanding of the mechanism by which NSAIDs suppress tumor angiogenesis and discuss their potential clinical application as anti-cancer agents.

Emerging therapies for gout.

Over the past decade much has been learned about the mechanisms of crystal-induced inflammation and renal excretion of uric acid, which has led to more specific targeting of gout therapies and a more potent approach to future management of gout. This article outlines agents being developed for more aggressive lowering of urate and more specific anti-inflammatory activity. The emerging urate-lowering therapies include lesinurad, arhalofenate, ulodesine, and levotofisopam. Novel gout-specific anti-inflammatories include the interleukin-1β inhibitors anakinra, canakinumab, and rilonacept, the melanocortins, and caspase inhibitors. The historic shortcomings of current gout treatment may, in part, be overcome by these novel approaches.

A spatially explicit life cycle inventory of the global textile chain

Life cycle analyses (LCA) approaches require adaptation to reflect the increasing delocalization of production to emerging countries. This work addresses this challenge by establishing a country-level, spatially explicit life cycle inventory (LCI). This study comprises three separate dimensions. The first dimension is spatial: processes and emissions are allocated to the country in which they take place and modeled to take into account local factors. Emerging economies China and India are the location of production, the consumption occurs in Germany, an Organisation for Economic Cooperation and Development country. The second dimension is the product level: we consider two distinct textile garments, a cotton T-shirt and a polyester jacket, in order to highlight potential differences in the production and use phases. The third dimension is the inventory composition: we track CO2, SO2, NO (x), and particulates, four major atmospheric pollutants, as well as energy use. This third dimension enriches the analysis of the spatial differentiation (first dimension) and distinct products (second dimension). We describe the textile production and use processes and define a functional unit for a garment. We then model important processes using a hierarchy of preferential data sources. We place special emphasis on the modeling of the principal local energy processes: electricity and transport in emerging countries. The spatially explicit inventory is disaggregated by country of location of the emissions and analyzed according to the dimensions of the study: location, product, and pollutant. The inventory shows striking differences between the two products considered as well as between the different pollutants considered. For the T-shirt, over 70% of the energy use and CO2 emissions occur in the consuming country, whereas for the jacket, more than 70% occur in the producing country. This reversal of proportions is due to differences in the use phase of the garments. For SO2, in contrast, over two thirds of the emissions occur in the country of production for both T-shirt and jacket. The difference in emission patterns between CO2 and SO2 is due to local electricity processes, justifying our emphasis on local energy infrastructure. The complexity of considering differences in location, product, and pollutant is rewarded by a much richer understanding of a global production-consumption chain. The inclusion of two different products in the LCI highlights the importance of the definition of a product's functional unit in the analysis and implications of results. Several use-phase scenarios demonstrate the importance of consumer behavior over equipment efficiency. The spatial emission patterns of the different pollutants allow us to understand the role of various energy infrastructure elements. The emission patterns furthermore inform the debate on the Environmental Kuznets Curve, which applies only to pollutants which can be easily filtered and does not take into account the effects of production displacement. We also discuss the appropriateness and limitations of applying the LCA methodology in a global context, especially in developing countries. Our spatial LCI method yields important insights in the quantity and pattern of emissions due to different product life cycle stages, dependent on the local technology, emphasizing the importance of consumer behavior. From a life cycle perspective, consumer education promoting air-drying and cool washing is more important than efficient appliances. Spatial LCI with country-specific data is a promising method, necessary for the challenges of globalized production-consumption chains. We recommend inventory reporting of final energy forms, such as electricity, and modular LCA databases, which would allow the easy modification of underlying energy infrastructure.

Is chytridiomycosis an emerging infectious disease in Asia?

The disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has caused dramatic amphibian population declines and extinctions in Australia, Central and North America, and Europe. Bd is associated with >200 species extinctions of amphibians, but not all species that become infected are susceptible to the disease. Specifically, Bd has rapidly emerged in some areas of the world, such as in Australia, USA, and throughout Central and South America, causing population and species collapse. The mechanism behind the rapid global emergence of the disease is poorly understood, in part due to an incomplete picture of the global distribution of Bd. At present, there is a considerable amount of geographic bias in survey effort for Bd, with Asia being the most neglected continent. To date, Bd surveys have been published for few Asian countries, and infected amphibians have been reported only from Indonesia, South Korea, China and Japan. Thus far, there have been no substantiated reports of enigmatic or suspected disease-caused population declines of the kind that has been attributed to Bd in other areas. In order to gain a more detailed picture of the distribution of Bd in Asia, we undertook a widespread, opportunistic survey of over 3,000 amphibians for Bd throughout Asia and adjoining Papua New Guinea. Survey sites spanned 15 countries, approximately 36° latitude, 111° longitude, and over 2000 m in elevation. Bd prevalence was very low throughout our survey area (2.35% overall) and infected animals were not clumped as would be expected in epizootic events. This suggests that Bd is either newly emerging in Asia, endemic at low prevalence, or that some other ecological factor is preventing Bd from fully invading Asian amphibians. The current observed pattern in Asia differs from that in many other parts of the world.

Regulation of innate immunity by signaling pathways emerging from the endoplasmic reticulum.

The innate immune system has evolved the capacity to detect specific pathogens and to interrogate cell and tissue integrity in order to mount an appropriate immune response. Loss of homeostasis in the endoplasmic reticulum (ER) triggers the ER-stress response, a hallmark of many inflammatory and infectious diseases. The IRE1/XBP1 branch of the ER-stress signaling pathway has been recently shown to regulate and be regulated by innate immune signaling pathways in both the presence and absence of ER-stress. By contrast, innate immune pathways negatively affect the activation of two other branches of the ER-stress response as evidenced by reduced expression of the pro-apoptotic transcription factor CHOP. Here we will discuss how innate immune pathways and ER-signaling intersect to regulate the intensity and duration of innate immune responses.