Immuno-Virological Discordance and the Risk of Non-AIDS and AIDS Events in a Large Observational Cohort of HIV-Patients in Europe

Background

The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated.

Methods

Patients in EuroSIDA starting at least 1 new antiretroviral drug with CD4<350 cells/µl and viral load (VL)>500 copies/mL were followed-up from the first day of VL< = 50 copies/ml until a new fatal/non-fatal non-AIDS/AIDS event. Considered non-AIDS events included non-AIDS malignancies, pancreatitis, severe liver disease with hepatic encephalopathy (>grade 3), cardio- and cerebrovascular events, and end-stage renal disease. Patients were classified over time according to whether current CD4 count was above (non-ID) or below (ID) baseline level. Relative rates (RR) of events were calculated for ID vs. non-ID using adjusted Poisson regression models.

Results

2,913 patients contributed 11,491 person-years for the analysis of non-AIDS. 241 pre-specified non-AIDS events (including 84 deaths) and 89 AIDS events (including 10 deaths) occurred. The RR of developing pre-specified non-AIDS events for ID vs. non-ID was 1.96 (95% CI 1.37–2.81, p<0.001) in unadjusted analysis and 1.43 (0.94–2.17, p = 0.095) after controlling for current CD4 count. ID was not associated with the risk of AIDS events (aRR 0.76, 95% CI 0.41–1.38, p = 0.361).

Conclusion

Compared to CD4 responders, patients with immuno-virological discordance may be at increased risk of developing non-AIDS events. Further studies are warranted to establish whether in patients with ID, strategies to directly modify CD4 count response may be needed besides the use of ART.     

It is still not for the old iron: adjuvant effects of carbonyl iron in experimental autoimmune encephalomyelitis induction

Experimental autoimmune encephalomyelitis (EAE) is a model of multiple sclerosis. Dark Agouti rats immunized with spinal cord homogenate (SCH) and carbonyl iron (CI), as an adjuvant, develop severe hyperacute form of EAE. They succumb to EAE earlier and have higher clinical scores and lethality rate in comparison to counterparts immunized with SCH + complete Freund's adjuvant. There is no difference in the number of cells or in histological presentation of the CNS infiltrates of rats immunized with the two adjuvants. However, there are more granulocytes, NK and NKT cells, and less CD4(+) T cells in the spinal cord infiltrates of SCH + CI-immunized animals. Nitric oxide (NO)-generating enzyme inducible NO synthase have higher expression in spinal cord of SCH + CI-immunized rats, and this corresponds to more intensive nitrotyrosine formation in the CNS tissue of these rats. Abundant infiltration of granulocytes and NK cells into the CNS and excessive generation of peroxynitrite within the CNS of SCH + CI-immunized rats might account for the severe neurological deficits induced by immunization with CI. These factors should be closely examined in the fulminant forms of multiple sclerosis and acute disseminated encephalomyelitis, as they could represent a promising targets for therapy.     

Natural and Modified (1→3)-β-D-Glucans in Health Promotion and Disease Alleviation

ABSTRACT

A number of polysaccharides with β -glycosidic linkage are widespread in nature in a variety of sources. All have a common structure and the (1→3)-β-D-glucan backbone is essential. They have attracted attention over the years because of their bioactive and medicinal properties. In many cases their functional role is a mystery, in others it is well established. Because of their insoluble chemical nature, particulate (1→3)-β-D-glucans are not suitable for many medical applications. Various methods of changing or modifying the β-D-glucan chemical structure and transforming it to a soluble form have been published. The β-D-glucan bioactive properties can be affected positively or negatively by such modifications. This review examines β-glucan sources in nature, health effects and structure-activity relationships. It presents the current state of β-D-glucan solubilization methods and discusses their effectiveness and application possibilities for the future.     

Nasal vaccination with myelin oligodendrocyte glycoprotein reduces stroke size by inducing IL-10-producing CD4+ T cells

Inflammation plays an important role in ischemic stroke and in humans IL-10 may have a beneficial effect in stroke. We mucosally administered myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide to C57BL/6 mice before middle cerebral artery occlusion (MCAO) to induce an anti-inflammatory T cell response directed at CNS myelin. Nasal and oral administration of MOG(35-55) peptide decreased ischemic infarct size at 24 and 72 h after MCAO surgery. Nasal MOG(35-55) peptide was most efficacious and reduced infarct size by 70% at 24 h and by 50% at 72 h (p 相似文献   

Central European Greylag Geese Anser anser show a shortening of migration distance and earlier spring arrival over 60 years

Global climate change can cause pronounced changes in species? migratory behaviour. Numerous recent studies have demonstrated climate‐driven changes in migration distance and spring arrival date in waterbirds, but detailed studies based on long‐term records of individual recapture or re‐sighting events are scarce. Using re‐sighting data from 430 marked individuals spanning a 60‐year period (winters 1956/1957 to 2015/2016), we assessed patterns in migration distance and spring arrival date, wintering‐site fidelity and survival in the increasing central European breeding population of Greylag Geese Anser anser. We demonstrate a long‐term decrease in migration distance, changes in the wintering range caused by winter partial short‐stopping, and the earlier arrival of geese on their breeding grounds. Greylag Geese marked on central Europe moulting grounds have not been recorded wintering in Spain since 1986 or in Tunisia and Algeria since 2004. The migration distance and spring arrival of geese indicated an effect of temperature at the breeding site and values of the NAO index. Greylag Geese migrate shorter distances and arrive earlier in milder winters. We suggest that shifts in the migratory behaviour of Central European Greylag Geese are individual temperature‐dependent decisions to take advantage of wintering grounds becoming more favourable closer to their breeding grounds, allowing birds to acquire breeding territories earlier.     

Necrotic tumor cells oppositely affect nitric oxide production in tumor cell lines and macrophages

Nitric oxide (NO) is a highly reactive free radical with profound tumoricidal activity, produced by both macrophages and tumor cells. While it has been postulated that necrotic tumor cells can augment macrophage anti-tumor action, we investigated the effect of tumor cell necrosis on NO synthesis and viability of L929 fibrosarcoma and C6 astrocytoma cell lines. The presence of necrotic tumor cells dose-dependently reduced NO production in IFN-gamma stimulated L929 cells, and rescued them from NO-dependent autotoxicity. This effect was mediated through soluble products, since it was completely preserved after blocking the contact between the necrotic and live cells. On the other hand, apoptotic tumor cells were unable to suppress IFN-gamma-triggered NO release and subsequent decrease of cell respiration in L929 cultures. Similar results were obtained with C6 astrocytoma cell line. This down-regulation of NO synthesis in response to necrotic cell products was not specific for tumor cell lines, since necrotic tumor cells markedly suppressed NO production in cytokine-stimulated primary fibroblasts and astrocytes. In contrast, both murine and rat peritoneal macrophages readily increased their basal or IFN-gamma-induced NO production when incubated with necrotic tumor cells. Taken together, these results suggest that tumor cell necrosis might promote or restrict tumor growth through suppression or enhancement of NO synthesis in tumor cells and macrophages, respectively, with net effect presumably depending on the extent of macrophage infiltration.     

Changes in habitat suitability influence non‐breeding distribution of waterbirds in central Europe

Waterbird species have different requirements with respect to their non‐breeding areas, aiming to survive and gain condition during the non‐breeding period. Selection of non‐breeding areas could change over time and space driven by climate change and species habitat requirements. To help explain the mechanism shaping non‐breeding area selection, we provide site‐specific analyses of distributional changes in wintering waterbirds in central Europe, located at the centre of their flyways. We use wintering waterbirds as a highly dynamic model group monitored over a long‐time scale of 50 years (1966–2015). We identified species habitat requirements and changes in habitat use at the level of 733 individual non‐breeding (specifically wintering) sites for 12 waterbird species using citizen‐science monitoring data. We calculated site‐specific mean numbers and estimated site‐specific trends in numbers. The site‐specific approach revealed a general effect of mean winter temperature of site (seven of 12 species), wetland type (all species) and land cover (all species) on site‐specific numbers. We found increasing site‐specific trends in numbers in the northern and/or eastern part of the study area (Mute Swan Cygnus olor, Eurasian Teal Anas crecca, Common Pochard Aythya ferina, Great Cormorant Phalacrocorax carbo and Eurasian Coot Fulica atra). Common Merganser Mergus merganser, Great Cormorant, Grey Heron Ardea cinerea, Common Pochard, Eurasian Coot and Common Moorhen Galinulla chloropus increased their site‐specific numbers on standing industrial waters with traditionally low fish stock. The site‐specific dynamics of bird numbers helped us to identify general preference for sites reducing winter harshness (warmer areas, running waters and more wetlands in the site vicinity), as well as indicating climate‐driven changes in spatial use of wintering sites (northern/north‐eastern range changes and changes in preference for industrial waters). This fine‐scale (site‐specific) approach can reveal large‐scale range and distribution shifts driven by climate and environmental changes regardless of the availability of large‐scale datasets.     

Repeated exposure to enhanced UV-B radiation in successive generations increases developmental instability (leaf fluctuating asymmetry) in a desert annual

Populations of the desert annual Dimorphotheca sinuata , derived from a common seed stock, were exposed concurrently over four successive generations to either ambient (representing no stratospheric ozone depletion) or elevated (representing 20% stratospheric ozone depletion) UV-B levels during their complete life cycle. Leaf fluctuating asymmetry (FA) was measured in populations of plants grown from seeds of selected generations which had experienced different UV-B exposure histories, and from seeds collected from a wild population of this species which grows in a naturally enhanced UV-B environment. These measured plants had been grown in a greenhouse under essentially UV-B-free conditions. Leaf FA was significantly increased by greater numbers of enhanced UV-B exposures in the parentage of the seed. There was a linear to exponential dose–response relationship between number of UV-B exposure iterations in seed parentage and leaf FA, suggesting that damage to DNA caused by UV-B exposure during plant development may not be fully repaired, and thus be inherited by offspring and accumulated over successive generations in this species. Leaf FA of plants grown from seed from the wild population was not significantly greater than that of control plants whose parentage experienced only ambient UV-B exposures, although this negative result may have been due to low sampling intensity and measurement resolution, and the relatively low UV-B enhancement experienced by the wild population. We conclude that leaf FA may constitute a relatively sensitive yet inexpensive means of quantifying UV-B damage to plants.     

Do frugivorous birds concentrate their foraging activities on those alien plants with the most abundant and nutritious fruits in the South African Mediterranean-climate region?

Alien plants with abundant and nutritious fruits may compete more effectively for avian dispersal services than native shrubs. This premise was examined by comparing daily foraging activity (visitation frequency, foraging bird number and foraging period) by four frugivorous bird species of different size on fruits of two native and two alien shrub species co-occurring at four different sites. Also, the quantities of seeds consumed daily by each of the four birds species from fruits of the four shrub species were measured and compared with the numbers of fruits and seeds, and the mass of fruits present in the shrub canopies as well as with their fruit monosaccharide concentrations. The quantities of seed consumed daily by four different size bird species (Columba arquatrix, Colius striatus, Pycnonotus capensis, Zosterops pallidus subsp capensis) were positively correlated with the numbers of seeds per m² of canopy area and with fruit mass and fruit monosaccharide content per m² of canopy area, as well as with the monosaccharide concentration of individual fruits, except in the C. arquatrix (African olive pigeon). All four bird species displayed the highest daily visitation frequencies on fruits of the alien Solanum mauritianum which were more abundant and nutritious than fruits of the other alien Lantana camara and fruits the natives Olea europaea subsp africana and Chrysanthemoides monilifera. They also all consumed greater quantities of seed daily from fruits of the alien S. mauritianum than from fruits of the other shrub species. These results corroborate proposals that frugivorous birds concentrate their foraging activities on those alien plants with the most abundant and nutritious fruits.