Bone mineral health is sensitively related to environmental cadmium exposure- experimental and human data

Exposure to cadmium (Cd) is recognised as one of the risk factors for osteoporosis, although critical exposure levels and exact mechanisms are still unknown. Here, we first confirmed that in male Wistar rats challenged orally with 6 different levels of Cd (0.3–10 mg/kg b.w.), over 28 days, there was a direct dose relationship to bone Cd concentration. Moreover, bone mineral content was significantly diminished by ∼15% (p < 0.0001) plateauing already at the lowest exposure level. For the other essential bone elements zinc (Zn) loss was most marked. Having established the sensitive metrics (measures of Cd exposure), we then applied them to 20 randomly selected human femoral head bone samples from 16 independent subjects. Bone Cd concentration was inversely proportional to trabecular bone mineral density and mineral (calcium) content and Zn content of bone, but not the donor's age. Our findings, through direct bone analyses, support the emerging epidemiological view that bone health, adjudged by mineral density, is extremely sensitive to even background levels of environmental Cd. Importantly, however, our data also suggest that Cd may play an even greater role in compromised bone health than prior indirect estimates of exposure could reveal. Environmental Cd may be a substantially determining factor in osteoporosis and large cohort studies with direct bone analyses are now merited

Growth and yield of mixed versus pure stands of Scots pine (Pinus sylvestris L. ) and European beech (Fagus sylvatica L.) analysed along a productivity gradient through Europe

Mixing of complementary tree species may increase stand productivity, mitigate the effects of drought and other risks, and pave the way to forest production systems which may be more resource-use efficient and stable in the face of climate change. However, systematic empirical studies on mixing effects are still missing for many commercially important and widespread species combinations. Here we studied the growth of Scots pine (Pinus sylvestris L.) and European beech (Fagus sylvatica L.) in mixed versus pure stands on 32 triplets located along a productivity gradient through Europe, reaching from Sweden to Bulgaria and from Spain to the Ukraine. Stand inventory and taking increment cores on the mainly 60-80 year-old trees and 0.02-1.55 ha sized, fully stocked plots provided insight how species mixing modifies the structure, dynamics and productivity compared with neighbouring pure stands. In mixture standing volume (+12 %), stand density (+20 %), basal area growth (+12 %), and stand volume growth (+8 %) were higher than the weighted mean of the neighbouring pure stands. Scots pine and European beech contributed rather equally to the overyielding and overdensity. In mixed stands mean diameter (+20 %) and height (+6 %) of Scots pine was ahead, while both diameter and height growth of European beech were behind (−8 %). The overyielding and overdensity were independent of the site index, the stand growth and yield, and climatic variables despite the wide variation in precipitation (520-1175 mm year−1), mean annual temperature (6-10.5 °C), and the drought index by de Martonne (28-61 mm °C−1) on the sites. Therefore, this species combination is potentially useful for increasing productivity across a wide range of site and climatic conditions. Given the significant overyielding of stand basal area growth but the absence of any relationship with site index and climatic variables, we hypothesize that the overyielding and overdensity results from several different types of interactions (light-, water-, and nutrient-related) that are all important in different circumstances. We discuss the relevance of the results for ecological theory and for the ongoing silvicultural transition from pure to mixed stands and their adaptation to climate change.The networking in this study has been sup-ported by COST Action FP1206 EuMIXFOR. All contributors thanktheir national funding institutions to establish, measure, and analysedata from the triplets. The first author also thanks the BayerischenStaatsforsten (BaySF) for supporting the establishment of the plots,the Bavarian State Ministry for Nutrition, Agriculture, and Forestryfor permanent support of the project W 07 ‘‘Long-term experimentalplots for forest growth and yield research’’ (# 7831-22209-2013) andthe German Science Foundation for providing the funds for the pro-jects PR 292/12-1 ‘‘Tree and stand-level growth reactions on droughtin mixed versus pure forests of Norway spruce and European beech’’.Thanks are also due to Ulrich Kern for the graphical artwork, and totwo anonymous reviewers for their constructive criticism

Maternal cadmium, iron and zinc levels, DNA methylation and birth weight

Background Cadmium (Cd) is a ubiquitous and environmentally persistent toxic metal that has been implicated in neurotoxicity, carcinogenesis and obesity and essential metals including zinc (Zn) and iron (Fe) may alter these outcomes. However mechanisms underlying these relationships remain limited. Methods We examined whether maternal Cd levels during early pregnancy were associated with offspring DNA methylation at regulatory sequences of genomically imprinted genes and weight at birth, and whether Fe and Zn altered these associations. Cd, Fe and Zn were measured in maternal blood of 319 women ≤12 weeks gestation. Offspring umbilical cord blood leukocyte DNA methylation at regulatory differentially methylated regions (DMRs) of 8 imprinted genes was measured using bisulfite pyrosequencing. Regression models were used to examine the relationships among Cd, Fe, Zn, and DMR methylation and birth weight. Results Elevated maternal blood Cd levels were associated with lower birth weight (p = 0.03). Higher maternal blood Cd levels were also associated with lower offspring methylation at the PEG3 DMR in females (β = 0.55, se = 0.17, p = 0.05), and at the MEG3 DMR in males (β = 0.72, se = 0.3, p = 0.08), however the latter association was not statistically significant. Associations between Cd and PEG3 and PLAGL1 DNA methylation were stronger in infants born to women with low concentrations of Fe (p < 0.05). Conclusions Our data suggest the association between pre-natal Cd and offspring DNA methylation at regulatory sequences of imprinted genes may be sex- and gene-specific. Essential metals such as Zn may mitigate DNA methylation response to Cd exposure. Larger studies are required

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

The role of intracellular trafficking of CdSe/ZnS QDs on their consequent toxicity profile

Nanoparticle interactions with cellular membranes and the kinetics of their transport and localization are important determinants of their functionality and their biological consequences. Understanding these phenomena is fundamental for the translation of such NPs from in vitro to in vivo systems for bioimaging and medical applications. Two CdSe/ZnS quantum dots (QD) with differing surface functionality (NH2 or COOH moieties) were used here for investigating the intracellular uptake and transport kinetics of these QDs.status: publishe

Online remote monitoring of patients with differentiated thyroid carcinomas and neuroendocrine tumors treated with high doses of radionuclides

Background: Telemedicine could be very useful for patients in remote areas experiencing adverse drug reactions or being in need of sophisticated diagnostic or therapeutic procedures. The aim of this article is to show the experience of our Department of Nuclear Medicine (DNM) in telemonitoring patients with differentiated thyroid carcinomas and neuroendocrine tumors. Subjects and Methods: The DNM at the Clinical Center Kragujevac, Serbia, uses continuous remote monitoring of patients' vital functions, including heart rate, electrocardiogram, respiration rate, blood pressure, and oxygen saturation, as well as video surveillance of the physical isolation area for patients with neuroendocrine tumors (NETs) and some patients with differentiated thyroid carcinomas (DTCs), during administration of radionuclide therapy and for the days following treatment. Results: The DNM used a telemonitoring system for 156 patients with either DTC or NET who received radionuclide therapy during the last 3 years. There were 32 interventions on patients in the physical isolation area based on changes of the patients' vital functions detected by the telemonitoring system. Twenty-five patients (78%) experienced symptoms, whereas the other seven patients (22%) were symptomless. A responsible physician intervened with treatment of tachycardia (18 cases), hypertension (10 cases), hypotension (2 cases), ventricular extrasystoles (1 case), and ST-segment depression (1 case). After administration of the treatment the health status of the patients was normalized. Conclusion: From our experience gained over the past 3 years, this model of organization and supervision with a telemonitoring system of patients receiving radionuclide therapy ensures a high level of safety for the patient, with significant reduction of staff costs. © Copyright 2012, Mary Ann Liebert, Inc

Cadmium, Mercury and Lead in Hypericum perforatum L. collected in Western Serbia

Wild population of Hypericum perforatum growing in Western Serbia was analyzed for the content of important environmental pollutants cadmium, mercury and lead. Metal contents were determined by inductively coupled plasma optical emission spectrometry. Obtained results showed that levels of mercury and lead were under while cadmium concentrations exceeded limits recommended for medicinal plants. High levels of cadmium in investigated plants can be the result of soil enriched with cadmium as well as the ability of Hypericum perforatum to accumulate cadmium

Glass-ceramics obtained by the crystallization of basalt

The possibility to obtain glass-ceramics from basalt from the locality on Vrelo (Kopaonik mt.) is shown in this paper. The parent rock was ground to fraction -0.4 +0.1 mm, and then melted at 1250 - 1300°C. The crystallization melted bazaltic glass at 950°C during the time interval of 3 hours caused synthesis of a glass-ceramic material with a microstructure that has excellent mechanical properties according to the determined dynamic modulus of elasticity and uniaxial compresive strength. The phase composition of the obtained glass ceramic material was determined by XRPD using Rietveld refinement and SEM. Two phases were found: pyroxene which corresponds to omphacite of the composition (Na0.199 K0.180 Ca0.471 Mg0.249)1.1(Mg0.271Fe0.299Al0.430)1.0(Si1.704Ti0.046Al0.250)2.0O6 and glass with an approximate relationship 69:31