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1.
Pleiotropic effects of statins: do they matter?   总被引:7,自引:0,他引:7  
Treatment with the 3-hydroxy-3-methylglutaryl coenyzme A reductase inhibitors (or statins) reduces the risk for cardiovascular events across a broad spectrum of patient profiles, as evidenced by both primary prevention and secondary prevention trials. Improved survival by way of reduced deaths from coronary heart disease was also reported with these agents, which are primarily indicated for substantial reduction in LDL-cholesterol levels. However, the statins are extremely complex drugs and exhibit a wide variety of vascular effects that may or may not be dependent on their lipid-modifying properties. These so-called pleiotropic effects include alterations of endothelial function, inflammation, coagulation, and plaque stability. The relative contribution of the nonlipid effects of statin therapy to the well-documented clinical benefits is currently under intense investigation.  相似文献   

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The current literature investigating the impact of retirement and the associated spousal spillover effects overlooks the unintended effects of retirement on spouses in vulnerable health, namely spouses with long-term health conditions (LTHCs). In this paper, we fill this gap in the literature and investigate the impact of an individual’s retirement on their partner’s health outcomes when their partner has LTHCs. Given the inherent identification challenges associated with entry into retirement, we use the pension-qualifying age in Australia as an instrument. Based on data from the Household Income and Labour Dynamics in Australia survey, we find that the husband’s retirement has a positive impact on the wife’s quality-adjusted life years (QALY) and other physical and mental health outcomes. We also identify redistribution of domestic workload as a key transmission mechanism of the spousal spillover effects. Women with LTHCs will see their QALY and health improve only if their husband devotes more time to domestic tasks after retirement.  相似文献   

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The use of particulate carriers holds great promise for the development of effective and affordable recombinant vaccines. Rational development requires a detailed understanding of particle up-take and processing mechanisms to target cellular pathways capable of stimulating the required immune responses safely. These mechanisms are in turn based on how the host has evolved to recognize and process pathogens. Pathogens, as well as particulate vaccines, come in a wide range of sizes and biochemical compositions. Some of these also provide 'danger signals' so that antigen 'senting cells (APC), usually dendritic cells (DC), acquire specific stimulatory activity. Herein, we provide an overview of the types of particles currently under investigation for the formulation of vaccines, discuss cellular uptake mechanisms (endocytosis, macropinocytosis, phagocytosis, clathrin-dependent and/or caveloae-mediated) for pathogens and particles of different sizes, as well as antigen possessing and presentation by APC in general, and DC in particular. Since particle size and composition can influence the immune response, inducing humoral and/or cellular immunity, activating CD8 T cells and/or CD4 T cells of T helper 1 and/or T helper 2 type, particle characteristics have a major impact on vaccine efficacy. Recently developed methods for the formulation of particulate vaccines are presented in this issue of Methods, showcasing a range of "cutting edge" particulate vaccines that employ particles ranging from nano to micro-sized. This special issue of Methods further addresses practical issues of production, affordability, reproducibility and stability of formulation, and also includes a discussion of the economic and regulatory challenges encountered in developing vaccines for veterinary use and for common Third World infectious diseases.  相似文献   

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In this paper we address the following question: can a single cell of the cellular slime mold Dictyostelium discoideum serve as a pacemaker for the aggregation phase? Whether or not this is possible is determined by the relative importance of cyclic AMP production due to self-stimulation as compared to diffusion of cyclic AMP away from the cell and extracellular degradation. We determine the conditions under which a single cell on an infinite place can emit periodic signals of cyclic AMP using a model developed previously for signal relay and adaptation in Dictyostelium. Elsewhere it has been shown that this model provides an accurate representation of the stimulus-response behavior of Dictyostelium for a variety of experimental conditions.  相似文献   

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Recent studies and analyses have confirmed that baseline prostate volume is related to progression of benign prostatic hyperplasia (BPH) as well as to negative outcomes related to BPH, such as acute urinary retention (AUR) and need for surgery, and can also predict response to therapy. Other investigations have determined that prostate-specific antigen (PSA) level has good predictive value for assessing prostate volume. Strong evidence exists that baseline serum PSA level, like baseline prostate volume, predicts future prostate growth. Randomized placebo-controlled finasteride trials have shown that men with larger prostate volumes and higher PSA levels experience a clinically significant response to therapy compared with those with smaller prostate volumes and lower PSA levels. It has also been demonstrated that men with larger prostate glands and higher PSA levels are at increased risk for AUR and BPH-related surgery but that finasteride reduces these risks. Moreover, doxazosin and finasteride, alone and in combination, have been shown to significantly reduce BPH clinical progression.  相似文献   

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Most penguin species lay two eggs 3–4 days apart that hatch 1–2 days apart. Hypotheses to explain the shorter incubation period for the second egg include differences in porosity of the eggshells. Eggs with more or larger pores and/or thinner shells have higher gas exchange rates and faster embryonic development. We used eggshells from hatchling Magellanic Penguins Spheniscus magellanicus to test whether eggshell thickness and pore density affect incubation period. We expected: (i) second eggs to have thinner shells and/or more pores than first eggs; (ii) eggs to have thinner shells and/or more pores if they were laid by older females, later in the season, or in burrow nests (more humid than open nests under bushes). We found no support for these hypotheses. Egg pores and shell thickness were not related to incubation period. Eggs from the same clutch were similar in eggshell thickness and pore density. Female age, laying date and nest type were poor predictors of eggshell thickness and pore density. Egg pores, we conclude, have little explanatory power for differences in incubation time of eggs in Magellanic Penguins, and suggest that synchronous onset of incubation matters.  相似文献   

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Guilds or functional groups: does it matter?   总被引:10,自引:0,他引:10  
Jacques Blondel 《Oikos》2003,100(2):223-231
Although most researchers use the terms "guild" and "functional group" more or less synonymously, these two concepts bear different meanings. The guild concept refers primarily to the mechanisms of resource sharing by species in a competitive context whereas the functional groups concept is concerned with how a resource or any other ecological component is processed by different species to provide a specific ecosystem service or function. In many cases but not necessarily all, the two concepts are the two "faces" or "sides" of the same coin: the sharing by species of a similar resource is the guild facet (structural), while the ecosystem processes these species eventually perform through resource exploitation is the functional group facet. The two concepts differ in that competitive relationships within groups of species are not the focus of the functional group approach, exactly as processes or functions are not the focus of the guild approach. A group of species can be considered either as a guild or a functional group depending on the question addressed. Guild and functional group membership is independent of phylogenetic relationships but because species tend to share similar life history traits and adaptations through common evolutionary history, guild and functional group associates are often closely related. The concept of guild has had broader application in animal studies than in plant studies, whereas the reverse is true for the concept of functional group. Recent methodological advances to objectively partition species into guilds and functional groups, taking into consideration the most relevant characters or traits for delineating them, provide the means to construct an operational framework for making in situ and ex situ experiments that are urgently needed for a better understanding of the role of species in ecosystem functioning, especially in relation to global change concerns.  相似文献   

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In a previous epidemiological study, where we studied the prevalence of subjective symptoms among mobile phone (MP) users, we found as an interesting side finding that the prevalence of many of the subjective symptoms increased with increasing calling time and number of calls per day. In this extrapolative study, we have selected 2402 people from the epidemiological study who used any of the four most common GSM MP. We used the information about the prevalence of symptoms, calling time per day, and number of calls per day and combined it with measurements of the Specific Absorption Rate (SAR). We defined three volumes in the head and measured the maximum SAR averaged over a cube of 1 g tissue (SAR(1g)) in each volume. Two new exposure parameters Specific Absorption per Day (SAD) and Specific Absorption per Call (SAC) have been devised and are obtained as combinations of SAR, calling time per day, and number of calls per day, respectively. The results indicates that SAR values >0.5 W/kg may be an important factor for the prevalence of some of the symptoms, especially in combination with long calling times per day.  相似文献   

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Endophytic fungi inhabit living plant tissues without causing disease symptoms. Although abundant, the extent of their contribution to fungal biodiversity remains unclear. Since endophytic fungi are poorly known, especially in the tropics, current estimates of fungal species are probably conservative. Here we tested strategies for sampling endophytic fungi in tropical plants. We compared the number of fungi isolated from 400 mm2 leaf pieces that were divided into increasingly small fragments. Leaf pieces were surface-sterilized, cut into fragments and plated on culture media. For a given area, cutting leaf pieces into smaller fragments significantly increased the number of fungal morphospecies recovered. There was a strong linear relationship between size of fragments and number of fungi isolated. By extrapolation, an estimated 16 +/- 3 fungi could be recovered from a 2 x 2 cm leaf piece, using infinitely small fragments. This represents a large part of the fungal diversity estimated to exist in leaf endophytes in a population. We conclude that reducing the size and increasing the number of leaf fragments will increase the number of fungal species isolated. This strategy will help to estimate real values of endophytic fungal diversity.  相似文献   

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《Ostrich》2013,84(1-2):30-38
It has been suggested that the 'right' biogeographic patterns will only arise with a species concept reflecting the finest splitting of terminal phylogenetic branches. The significance of taxonomic resolution was assessed using distributional data for all resident African land-birds, held at the Zoological Museum of Copenhagen. The primary database (in a one-degree geographical grid) served as a template for creating two new databases: one, where the distributional records were allocated to species according to the 'Speciation Atlases' for African birds (Hall and Moreau 1970, Snow 1978) and two, according to the finest taxonomic splitting that has since then been suggested in the literature. With this spatial resolution, the species richness pattern is almost exactly the same whether old or new taxonomy is used. The endemism follows another pattern with marked local aggregates. The location of principal aggregates are quite robust to recent splitting, although a slightly more complex structure appears. Also some small new areas of endemism emerge, each with 2–3 narrow endemics. However, large portions of African savannah and lowland rainforest are still characterised by a total lack of narrow endemism. Based on the current understanding of diversification processes and adaptive re-distribution it is suggested that the uneven distribution of narrowly endemic and widespread species will persist even if it were possible, in the future, to define terminal taxa in a consistent way.  相似文献   

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It has sometimes been assumed that children are more sensitive than adults to the effects of radiofrequency (RF) fields associated with cellular wireless telephones. However, relatively few in vitro or animal models have examined this possibility.In vitro studies have used several cell types, from both humans and rodents, including primary cells, embryonic cell lines, undifferentiated cancer cell lines, and stem cells. Overall, the balance of evidence does not suggest that field-related effects occur in any cell type: gene and protein expression were not significantly changed by exposure in nine out of 15 studies; genotoxicity was evaluated in 13 papers and in most, of these studies, no damage to DNA was detected; eight studies failed to demonstrate induction of apoptosis; and three studies reported lack of oxidative stress induction by RF-exposures. Five of eight studies investigating the effects of combined exposures to RF fields and chemical or physical agents reported a lack of field-related effects.In addition, few papers have been published on the effects of low level exposure of immature animals. The available results are very limited, both in terms of signals used and biological endpoints investigated, but the evidence does not indicate that prenatal or early postnatal exposures are associated with acute adverse responses or the development of detrimental changes in the long-term. Overall, this suggests that young animals may not be significantly more sensitive than adults, but there is clearly a need for further studies to be carried out.  相似文献   

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Drastic declines in insect populations, ‘Ecological Armageddon’, have recently gained increased attention in the scientific community, and are commonly considered to be the consequence of large‐scale factors such as land‐use changes, use of pesticides, climate change and habitat fragmentation. Artificial light at night (ALAN), a pervasive global change that strongly impacts insects, remains, however, infrequently recognised as a potential contributor to the observed declines. Here, we provide a summary of recent evidence of impacts of ALAN on insects and discuss how these impacts can drive declines in insect populations in light‐polluted areas. ALAN can increase overall environmental pressure on insect populations, and this is particularly important in agroecosystems where insect communities provide important ecosystem services (such as natural pest control, pollination, conservation of soil structure and fertility and nutrient cycling), and are already under considerable environmental pressure. We discuss how changes in insect populations driven by ALAN and ALAN itself may hinder these services to influence crop production and biodiversity in agricultural landscapes. Understanding the contribution of ALAN and other factors to the decline of insects is an important step towards mitigation and the recovery of the insect fauna in our landscapes. In future studies, the role of increased nocturnal illumination also needs to be examined as a possible causal factor of insect declines in the ongoing ‘Ecological Armageddon’, along with the more commonly examined factors. Given the large scale of agricultural land use and the potential of ALAN to indirectly and directly impact crop production and biodiversity, a better understanding of effects of ALAN in agroecosystems is urgently needed.  相似文献   

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Extruded pellets containing activated carbon (AC) can be used to sow native seeds while simultaneously applying herbicide to control invasive species. Incorporating AC in pellets has been demonstrated to protect native seeds; however, there may be unintended detrimental impacts to seedling emergence. We aimed to optimize seed position within pellets to maximize emergence and survival of the perennial shrub Jacksonia furcellata. Seeds were positioned at 2 mm (top), 6 mm (middle), and 12 mm (bottom) within pellets (with or without AC), sown on or below the soil surface, and compared to non-pelleted seeds sown under the soil surface in the equivalent positions (2, 6, and 12 mm depth). Trays were treated with a pre-emergent herbicide (Simazine) or left unsprayed. Emergence (without herbicide) was significantly higher from seeds positioned at the bottom of pellets without AC sown on the soil surface (70%), compared to non-pelleted seeds sown at the bottom (12 mm below the soil surface; 57%). However, emergence was inhibited when seeds were positioned in the middle (6 mm) of pellets with AC (32%). When treated with Simazine, survival was highest from seeds positioned at the bottom of pellets with AC (60%), compared to pellets without AC (15%) and non-pelleted seeds sown at the bottom (12 mm below the soil surface; 15%). Jacksonia furcellata seeds positioned at the bottom of pellets, sown on the soil surface, shows promise to minimize negative impacts to emergence, and maximize herbicide protection. Further testing with additional species is required to refine pellet production (e.g. recipe, extrusion, and shape) for optimal emergence.  相似文献   

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《Trends in parasitology》2023,39(4):251-259
Treatment failure (TF) jeopardizes the management of parasitic diseases, including leishmaniasis. From the parasite’s point of view, drug resistance (DR) is generally considered as central to TF. However, the link between TF and DR, as measured by in vitro drug susceptibility assays, is unclear, some studies revealing an association between treatment outcome and drug susceptibility, others not. Here we address three fundamental questions aiming to shed light on these ambiguities. First, are the right assays being used to measure DR? Second, are the parasites studied, which are generally those that adapt to in vitro culture, actually appropriate? Finally, are other parasite factors – such as the development of quiescent forms that are recalcitrant to drugs – responsible for TF without DR?  相似文献   

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