Assessment of cognitive function in female rheumatoid arthritis patients: associations with cerebrovascular pathology, depression and anxiety.

We assessed cognitive function of female rheumatoid arthritis (RA) patients and analyze the determinants, with special focus on cerebrovascular morphology. Sixty methotrexate (MTX-) or biologic-treated RA patients and 39 healthy controls were included in a cross-sectional study. Smoking habits, alcohol intake and time spent in education were recorded. Standard measures were performed to assess cognitive function (Montreal Cognitive Assessment, MOCA; Trail Making Test, TMT; Victoria Stroop Test, VST; Wechsler Adult Intelligence Scale, WAIS; Benton Visual Retention test, BVRT), depression (Beck Depression Inventory, BDI), anxiety (State-Trait Anxiety Inventory, STAIT/S) and general health status (Short Form 36, SF-36). Mean disease activity (28-joint Disease Activity Score, mDAS28; erythrocyte sedimentation rate, mESR; C-reactive protein, mCRP) of the past 12 months was calculated; anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were assessed. Cerebral vascular lesions and atrophy, carotid intima-media thickness (cIMT) and plaques, as well as median cerebral artery (MCA) circulatory reserve capacity (CRC) were assessed by brain magnetic resonance imaging (MRI), carotid ultrasound and transcranial Doppler, respectively. Cognitive function tests showed impairment in RA vs controls. Biologic- vs MTX-treated subgroups differed in TMT-A. Correlations were identified between cognitive function and depression/anxiety tests. WAIS, STAIS, STAIT and BDI correlated with most SF-36 domains. Numerous cognitive tests correlated with age and lower education. Some also correlated with disease duration, mESR and mDAS28. Regarding vascular pathophysiology, cerebral vascular lesions were associated with VST-A, carotid plaques with multiple cognitive parameters, while MCA and CRC with MOCA, BVRT and BDI. RA patients have significant cognitive impairment. Cognitive dysfunction may occur together with or independently of depression/anxiety. Older patients and those with lower education are at higher risk to develop cognitive impairment. Cognitive screening might be a useful tool to identify subgroups to be further investigated for cerebrovascular pathologies.

Meso-scale environmental heterogeneity drives plant trait distributions in fragmented dry grasslands.

Environmental heterogeneity shapes the patterns of resources and limiting factors and therefore can be an important driver of plant community composition through the selection of the most adaptive functional traits. In this study, we explored plant trait-environment relationships in environmentally heterogeneous microsite complexes at the meso-scale (few meters), and used ancient Bulgarian and Hungarian burial mounds covered by dry grasslands as a model habitat. We assessed within-site trait variability typical of certain microsites with different combinations of environmental parameters (mound slopes with different aspects, mound tops, and surrounding plain grasslands) using a dataset of 480 vegetation plots. For this we calculated community-weighted means (CWMs) and abundance models. We found that despite their small size, the vegetation on mounds was characterized by different sets of functional traits (higher canopy, higher level of clonality, and heavier seeds) compared to the plain grasslands. North-facing slopes with mild environmental conditions were characterized by perennial species with light seeds, short flowering period, and a high proportion of dwarf shrubs sharply contrasted from the plain grasslands and from the south-facing slopes and mound tops with harsh environmental conditions. Patterns predicted by CWMs and abundance models differed in the case of certain traits (perenniality, canopy height, and leaf dry matter content), suggesting that environmental factors do not necessarily affect trait optima directly, but influence them indirectly through correlating traits. Due to the large relative differences in environmental parameters, contrasts in trait composition among microsites were mostly consistent and independent from the macroclimate. Mounds with high environmental heterogeneity can considerably increase variability in plant functional traits and ecological strategies at the site and landscape levels. The large trait variation on topographically heterogeneous landscape features can increase community resilience against climate change or stochastic disturbances, which underlines their conservation importance.

Co-seeding grasses and forbs supports restoration of species-rich grasslands and improves weed control in ex-arable land.

Sowing is widely used for the restoration of species-rich grasslands but still there are knowledge gaps regarding the most suitable application of different seed mixtures. We tested the effect of seed mixtures application timing on the establishment of sown forbs and weed control. 36 experimental plots with nine sowing treatments were established in an abandoned cropland in Hungary. Grass-seeds, diverse forb seed mixture and the combination of the two were applied: diverse forb mixture was sown simultaneously or 1, 2 or 3 years after grass sowing, in plots sown previously with grass or in empty plots (fallows). All sowing treatments supported the rapid establishment of the sown species in large cover and hampered weed encroachment. Forbs performed better when sown into fallows than in grass-matrix and forbs establishment was worse in older fallows than in younger ones. Grasses expressed a strong priority effect, especially when forbs were sown at least two years later than grasses. We also investigated the relation between seed germinability, weather parameters and establishment success. Germination rate in the greenhouse could not predict the establishment success of forbs in the field and showed great differences between years, hence we recommend sowing target forbs in multiple years.

Vertical distribution of soil seed bank and the ecological importance of deeply buried seeds in alkaline grasslands.

Background: Soil seed banks play a central role in vegetation dynamics and may be an important source of ecological restoration. However, the vast majority of seed bank studies examined only the uppermost soil layers (0-10 cm); hence, our knowledge on the depth distribution of seed bank and the ecological significance of deeply buried seeds is limited. The aim of our study was to examine the fine-scale vertical distribution of soil seed bank to a depth of 80 cm, which is one of the largest studied depth gradients so far. Our model systems were alkaline grasslands in East-Hungary, characterised by harsh environmental conditions, due to Solonetz soil reference group with Vertic horizon. We asked the following questions: (1) How do the seedling density and species richness of soil seed bank change along a vertical gradient and to what depth can germinable seeds be detected? (2) What is the relationship between the depth distribution of the germinable seeds and the species traits? Methods: In each of the five study sites, four soil cores (4 cm diameter) of 80 cm depth were collected with an auger for soil seed bank analysis. Each sample was divided into sixteen 5-cm segments by depth (320 segments in total). Samples were concentrated by washing over sieves and then germinated in an unheated greenhouse. Soil penetration resistance was measured in situ next to each core location (0-80 cm depth, 1-cm resolution). We tested the number and species richness of seedlings observed in the soil segments (N = 320), using negative binomial generalized linear regression models, in which sampling layer and penetration resistance were the predictor variables. We ran the models for morphological groups (graminoids/forbs), ecological groups (grassland species/weeds) and life-form categories (short-lived/perennial). We also tested whether seed shape index, seed mass, water requirement or salt tolerance of the species influence the vertical distribution of their seed bank. Results: Germinable seed density and species richness in the seed bank decreased with increasing soil depth and penetration resistance. However, we detected nine germinable seeds of six species even in the deepest soil layer. Forbs, grassland species and short-lived species occurred in large abundance in deep layers, from where graminoids, weeds and perennial species were missing. Round-shaped seeds were more abundant in deeper soil layers compared to elongated ones, but seed mass and ecological indicator values did not influence the vertical seed bank distribution. Our research draws attention to the potential ecological importance of the deeply buried seeds that may be a source of recovery after severe disturbance. As Vertisols cover 335 million hectares worldwide, these findings can be relevant for many regions and ecosystems globally. We highlight the need for similar studies in other soil and habitat types to test whether the presence of deep buried seeds is specific to soils with Vertic characteristics.

[Adverse events during biological therapy -- focusing on dermatological side-effects]. / Biológiai terápia során észlelt mellékhatások -- különös tekintettel a borgyógyászati szövodményekre.

UNLABELLED: Biological response modifiers, especially tumour necrosis factor inhibitors have been proved to be very effective in the treatment of various immune mediated rheumatological, gastroenterological and dermatological diseases in the last 15 years. With their increasing use, the incidence of their adverse effects are more precisely defined. The aim of this cohort study was to analyse the adverse effects occurred within the study period in patients receiving biological therapy for rheumatological and dermatological autoimmune diseases. METHODS: 324 patients within a 3 years study period were treated with biological response modifiers (adalimumab: 92, etanercept: 107, infliximab: 125). The primary diagnoses were rheumotoid arthritis (n = 174), ankylosing spondylitis (n = 60), psoriatic arthritis (n = 11), and psoriasis vulgaris (79). RESULTS: Hypersensitive reactions were observed in 11 of the patients (3.4%), 7 of which were serious and needed treatment termination. Infections constituted the majority of side effects, which were localised to skin in 10 (3.1%) and to respiratory tract in 9 (2.8%). However, most of these were mild or moderate reactions. Malignant skin tumour developed in 1 case (0.3%) only. Drug induced inflammatory disorders occurred in some cases: onset of new psoriasis was observed in 1 and flares of the existing disease were detected in additional three. Lichenoid exanthema developed in one. (n = 5, 1.5%) CONCLUSION: The use of TNF-α blockers may provoke a broad spectrum of dermatological side effects. Our results suggest that the majority of these are infectious and inflammatory disorders, the latter may relatively often appear as drug induced psoriasis. The occurrence of malignancies was very low in our series.

Linking environmental heterogeneity and plant diversity: The ecological role of small natural features in homogeneous landscapes.

Small natural features (SNFs), such as road verges, midfield islets, rocky outcrops and ancient burial mounds, provide safe havens for species of natural habitats in human-modified landscapes; therefore, their great ecological importance is in contrast to their small size. SNFs often have a high topographical heterogeneity and abiotic conditions, which differ from their surroundings; therefore, they provide a unique opportunity for establishing links between environmental heterogeneity (EH) and biodiversity. However, no study has so far investigated the EH components of topographically heterogeneous SNFs in a comprehensive framework, by linking environmental and biotic parameters. To fill this knowledge gap, we evaluated the EH components and their effect on biodiversity on ancient mounds covered by semi-natural grasslands in the Pannonian (Hungary) and Continental (Bulgaria) biogeographical regions. We designated 16 study sites, each containing a few-metre-high mounds with five microsites (top, north-, east-, south- and west-facing slopes) and a nearby plain grassland. At each microsite, we measured soil moisture, soil chemical properties, solar radiation and microclimate; and recorded the cover of vascular plants in a total of 480 plots. On the mounds, topographical heterogeneity was associated with sharp differences in microclimate and soil properties. Besides the contrast between mild north-facing and harsh south-facing slopes, east- and west-facing slopes also sustained unique microsites characterised by dynamic diurnal changes in air temperature and vapour pressure deficit. Various combinations of the EH components resulted in unique plant species compositions within the microsites, and supported the co-occurrence of species typical of contrasting habitat types, even within a couple of metres. By combining high-resolution measurements of abiotic factors with fine-scale vegetation sampling, our study provides evidence that widespread SNFs with complex topography harbour several grassland-specialist plant species and introduce a high level of EH to otherwise homogeneous plain landscapes, which cover one third of the global land area.

The activities of drug inactive ingredients on biological targets.

Excipients, considered "inactive ingredients," are a major component of formulated drugs and play key roles in their pharmacokinetics. Despite their pervasiveness, whether they are active on any targets has not been systematically explored. We computed the likelihood that approved excipients would bind to molecular targets. Testing in vitro revealed 25 excipient activities, ranging from low-nanomolar to high-micromolar concentration. Another 109 activities were identified by testing against clinical safety targets. In cellular models, five excipients had fingerprints predictive of system-level toxicity. Exposures of seven excipients were investigated, and in certain populations, two of these may reach levels of in vitro target potency, including brain and gut exposure of thimerosal and its major metabolite, which had dopamine D3 receptor dissociation constant K d values of 320 and 210 nM, respectively. Although most excipients deserve their status as inert, many approved excipients may directly modulate physiologically relevant targets.