Given the "inborn" nature of the innate immune system, it is surprising to find that innate immune function does in fact change with age. Similar patterns of distinct Toll-like-receptor-mediated ...immune responses come to light when one contrasts innate immune development at the beginning of life with that toward the end of life. Importantly, these developmental patterns of innate cytokine responses correlate with clinical patterns of susceptibility to disease: A heightened risk of suffering from excessive inflammation is often detected in prematurely born infants, disappears over the first few months of life, and reappears toward the end of life. In addition, risk periods for particular infections in early life reemerge in older adults. The near-mirror-image patterns that emerge in contrasts of early versus late innate immune ontogeny emphasize changes in host-environment interactions as the underlying molecular and teleologic drivers.
Data drawn from a global compilation of studies quantitatively confirm the long-articulated contention that erosion rates from conventionally plowed agricultural fields average 1-2 orders of ...magnitude greater than rates of soil production, erosion under native vegetation, and long-term geological erosion. The general equivalence of the latter indicates that, considered globally, hillslope soil production and erosion evolve to balance geologic and climate forcing, whereas conventional plow-based agriculture increases erosion rates enough to prove unsustainable. In contrast to how net soil erosion rates in conventionally plowed fields (almost equal to1 mm/yr) can erode through a typical hillslope soil profile over time scales comparable to the longevity of major civilizations, no-till agriculture produces erosion rates much closer to soil production rates and therefore could provide a foundation for sustainable agriculture.
ABO incompatible (ABOi) kidney transplantation is an important modality to facilitate living donor transplant for incompatible pairs. To date, reports of the outcomes from this practice in the United ...States have been limited to single-center studies.
Using the Scientific Registry of Transplant Recipients, we identified 738 patients who underwent live-donor ABOi kidney transplantation between January 1, 1995, and March 31, 2010. These were compared with matched controls that underwent ABO compatible live-donor kidney transplantation. Subgroup analyses among ABOi recipients were performed according to donor blood type, recipient blood type, and transplant center ABOi volume.
When compared with ABO compatible-matched controls, long-term patient survival of ABOi recipients was not significantly different between the cohorts (P=0.2). However, graft loss was significantly higher, particularly in the first 14 days posttransplant (subhazard ratio, 2.34; 95% confidence interval, 1.43-3.84; P=0.001), with little to no difference beyond day 14 (subhazard ratio, 1.28; 95% confidence interval, 0.99-1.54; P=0.058). In subgroup analyses among ABOi recipients, no differences in survival were seen by donor blood type, recipient blood type, or transplant center ABOi volume.
These results support the use and dissemination of ABOi transplantation when a compatible live donor is not available, but caution that the highest period of risk is immediately posttransplant.
Summary
West Nile virus (WNV) is the most important causative agent of viral encephalitis worldwide and an important public health concern in the United States due to its high prevalence, severe ...disease, and the absence of effective treatments. Infection with WNV is mainly asymptomatic, but some individuals develop severe, possibly fatal, neurological disease. Individual host factors play a role in susceptibility to WNV infection, including genetic polymorphisms in key anti‐viral immune genes, but age is the most well‐defined risk factor for susceptibility to severe disease. Ageing is associated with distinct changes in immune cells and a decline in immune function leading to increased susceptibility to infection and reduced responses to vaccination. WNV is detected by pathogen recognition receptors including Toll‐like receptors (TLRs), which show reduced expression and function in ageing. Neutrophils, monocyte/macrophages and dendritic cells, which first recognize and respond to infection, show age‐related impairment of many functions relevant to anti‐viral responses. Natural killer cells control many viral infections and show age‐related changes in phenotype and functional responses. A role for the regulatory receptors Mertk and Axl in blood–brain barrier permeability and in facilitating viral uptake through phospholipid binding may be relevant for susceptibility to WNV, and age‐related up‐regulation of Axl has been noted previously in human dendritic cells. Understanding the specific immune parameters and mechanisms that influence susceptibility to symptomatic WNV may lead to a better understanding of increased susceptibility in elderly individuals and identify potential avenues for therapeutic approaches: an especially relevant goal, as the world's populating is ageing.
West Nile virus (WNV) is the most important causative agent of viral encephalitis worldwide and is an important public health concern in the USA due to its high prevalence, severe disease, and the absence of effective treatments. Individual host factors play a role in susceptibility to WNV infection, but age is the most well‐defined risk factor for susceptibility to severe disease. Understanding the specific immune parameters and mechanisms that influence susceptibility to symptomatic WNV may lead to a better understanding of increased susceptibility in elderly individuals.
Dirt Montgomey, David R; Montgomey, David R
2008., 20120131, 2007, 2007-05-14, 2012-04-10
eBook
Dirt, soil, call it what you want—it's everywhere we go. It is the root of our existence, supporting our feet, our farms, our cities. This fascinating yet disquieting book finds, however, that we are ...running out of dirt, and it's no laughing matter. An engaging natural and cultural history of soil that sweeps from ancient civilizations to modern times, Dirt: The Erosion of Civilizations explores the compelling idea that we are—and have long been—using up Earth's soil. Once bare of protective vegetation and exposed to wind and rain, cultivated soils erode bit by bit, slowly enough to be ignored in a single lifetime but fast enough over centuries to limit the lifespan of civilizations. A rich mix of history, archaeology and geology, Dirt traces the role of soil use and abuse in the history of Mesopotamia, Ancient Greece, the Roman Empire, China, European colonialism, Central America, and the American push westward. We see how soil has shaped us and we have shaped soil—as society after society has risen, prospered, and plowed through a natural endowment of fertile dirt. David R. Montgomery sees in the recent rise of organic and no-till farming the hope for a new agricultural revolution that might help us avoid the fate of previous civilizations.
As we age, the innate immune system becomes dysregulated and is characterized by persistent inflammatory responses that involve multiple immune and non-immune cell types and that vary depending on ...the cell activation state and tissue context. This ageing-associated basal inflammation, particularly in humans, is thought to be induced by several factors, including the reactivation of latent viral infections and the release of endogenous damage-associated ligands of pattern recognition receptors (PRRs). Innate immune cell functions that are required to respond to pathogens or vaccines, such as cell migration and PRR signalling, are also impaired in aged individuals. This immune dysregulation may affect conditions associated with chronic inflammation, such as atherosclerosis and Alzheimer's disease.
Most of future population growth will take place in the world's cities and towns. Yet, there is no well-established, consistent way to measure either urban land or people. Even census-based urban ...concepts and measures undergo frequent revision, impeding rigorous comparisons over time and place. This study presents a new spatial approach to derive consistent urban proxies for the US. It compares census-designated urban blocks with proxies for land-based classifications of built-up areas derived from time-series of the Global Human Settlement Layer (GHSL) for 1990-2010. This comparison provides a new way to understand urban structure and its changes: Most land that is more than 50% built-up, and people living on such land, are officially classified as urban. However, 30% of the census-designated urban population and land is located in less built-up areas that can be characterized as mainly suburban and peri-urban in nature. Such insights are important starting points for a new urban research program: creating globally and temporally consistent proxies to guide modelling of urban change.
The field of desensitization and incompatible transplantation has made great gains over the past decade. There are now several options and effective therapies for many patients who face antibody ...barriers. Kidney paired donation (KPD) and desensitization have traditionally been considered competing strategies and patients have been offered one or the other without regard for the probability of a successful outcome. It is now possible to predict which donor/recipient phenotypes will benefit from each of these modalities. KPD should be favored among patients with immunologic phenotypes that are likely to match without prolonged waiting times. However, as many as 50% of patients with incompatible donors will fail to find a match in a KPD pool and many of these patients could be desensitized to their donor. Positive crossmatch and ABO incompatible transplantation has been accomplished in selective cases without the need for heavy immunosuppression or B‐cell ablative therapy. Patients who are both difficult‐to‐match due to broad sensitization and hard‐to‐desensitize because of strong donor reactivity can often be successfully transplanted through a combination of desensitization and KPD. Using these various modalities it is estimated that most patients with incompatible live donors can undergo successful renal transplantation.
This article reviews the options available for crossing HLA and ABO incompatible barriers and the donor/recipient phenotypes that benefit from these modalities. See editorial by Gebel and Halloran on page 443.
Despite the success of desensitization protocols, antibody‐mediated rejection (AMR) remains a significant contributor to renal allograft failure in patients with donor‐specific antibodies. ...Plasmapheresis and high‐dose intravenous immunoglobulin have proved to be effective treatments to prevent and treat AMR, but irreversible injury in the form of transplant glomerulopathy can commonly manifest months to years later. There is an unmet need to improve the outcomes for patients at risk for AMR. Updated Banff criteria now take into account the increasing understanding of the complex and heterogeneous nature of AMR phenotypes, including the timing of rejection, subclinical and chronic AMR, C4d‐negative AMR, and antibody‐mediated vascular rejection. Treatment for AMR is not standardized, and there is little in the way of evidence‐based treatment guidelines. Refining more precisely the mechanisms of injury responsible for different AMR phenotypes and establishing relevant surrogate endpoints to facilitate more informative studies will likely allow for more accurate determination of prognosis and efficacious intervention using new therapeutic approaches. In addition to plasma exchange and intravenous immunoglobulin, a number of other add‐on therapies have been tried in small studies without consistent benefit, including anti‐CD20, proteasome inhibitors, complement inhibitors, anti‐interleukin‐6 receptor blockers, and immunoglobulin G‐degrading enzyme of Streptococcus pyogenes (called IdeS).
Immunosenescence, describing alterations, including decline of immune responses with age, is comprised of inappropriate elevations, decreases, and dysregulated immune responses, leading to more ...severe consequences of bacterial and viral infections and reduced responses to vaccination. In adaptive immunity, these changes include increased proportions of antigen-experienced B and T cells at the cost of naïve cell populations. Innate immune changes in aging are complex in spanning multiple cell types, activation states, and tissue context. Innate immune responses are dampened in aging, yet there is also a paradoxical increase in certain signaling pathways and cytokine levels. Here, we review recent progress and highlight novel directions for expected advances that can lead the aging field to a new era of discovery that will embrace the complexity of aging in human populations.
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