Pregnancy outcomes after weekly oral administration of ethanol during gestation in the pig-tailed macaque (Macaca nemestrina)

Ethanol was orally administered once per week to gravid pig-tailed macaques (Macaca nemestrina) in doses of 0.3, 0.6, 1.2, 1.8, 2.5, 3.3, or 4.1 g/kg. A control group received a sucrose solution, isocaloric and isovolemic to the highest ethanol dose. Pregnancy was followed after 116 possible conceptions in 54 females. Peak plasma ethanol concentrations (PPECs) ranged from 24 +/- 6 mg/dl at the 0.3 g/kg dose to 549 +/- 71 mg/dl at the 4.1 g/kg dose. An increased rate of spontaneous abortion was related to ethanol exposure at and above 1.8 g/kg (mean PPEC = 205 mg/dl). Pregnancy failure in the first 30 days of gestation increased at doses above 2.5 g/kg. The effect on pregnancy outcome of weekly exposure to ethanol in this nonhuman primate is comparable to available data on humans. The methodology of this study represents an effective model for studying ethanol teratogenesis in a nonhuman primate.     

Physical anomalies and developmental delays in nonhuman primate infants exposed to weekly doses of ethanol during gestation

Ethanol was orally administered once per week to 54 gravid pigtailed macaques (Macaca nemestrina) in doses of 0.0, 0.3, 0.6, 1.2, 1.8, 2.5 or 4.1 gm/kg from the 1st week in gestation or in doses of 2.5, 3.3, or 4.1 gm/kg from the 5th week. Mean maternal mean peak plasma ethanol concentrations (MPPEC) ranged from 24 +/- 6 mg/dl at the 0.3 gm/kg dose to 549 +/- 71 mg/dl at the 4.1 gm/kg dose. Thirty-three viable infants were followed from birth to 6 months of age and assessed for growth, health, congenital anomalies and developmental rate. Facial anomalies, growth deficiency, or central nervous system dysfunction were found in 57% of the alcohol-exposed animals. No animal showed all the features of the human fetal alcohol syndrome. Ten of the twelve animals (83%) with mean MPPEC above 140 mg/dl had evidence of a teratogenic impact. The animals with full gestational exposure to ethanol and mean MPPEC between 140 and 249 mg/dl had much more severe and consistent cognitive abnormalities than the animals with delayed gestational exposures, even though the latter were exposed to mean MPPEC between 260 and 540 mg/dl. Conclusions from this study included: 1) ethanol-related behavioral teratogenesis occurred without accompanying physical anomalies, 2) measurable teratogenic effects from weekly exposures occurred only at intoxicating doses of ethanol, and 3) early gestational exposure to ethanol appeared to be more damaging to cognitive function than later and considerably greater alcohol exposure.     

Novel Miscanthus hybrids: Modelling productivity on marginal land in Europe using dynamics of canopy development determined by light interception

New biomass crop hybrids for bioeconomic expansion require yield projections to determine their potential for strategic land use planning in the face of global challenges. Our biomass growth simulation incorporates radiation interception and conversion efficiency. Models often use leaf area to predict interception which is demanding to determine accurately, so instead we use low-cost rapid light interception measurements using a simple laboratory-made line ceptometer and relate the dynamics of canopy closure to thermal time, and to measurements of biomass. We apply the model to project the European biomass potentials of new market-ready hybrids for 2020–2030. Field measurements are easier to collect, the calibration is seasonally dynamic and reduces influence of weather variation between field sites. The model obtained is conservative, being calibrated by crops of varying establishment and varying maturity on less productive (marginal) land. This results in conservative projections of miscanthus hybrids for 2020–2030 based on 10% land use conversion of the least (productive) grassland and arable for farm diversification, which show a European potential of 80.7–89.7 Mt year⁻¹ biomass, with potential for 1.2–1.3 EJ year⁻¹ energy and 36.3–40.3 Mt year⁻¹ carbon capture, with seeded Miscanthus sacchariflorus × sinensis displaying highest yield potential. Simulated biomass projections must be viewed in light of the field measurements on less productive land with high soil water deficits. We are attempting to model the results from an ambitious and novel project combining new hybrids across Europe with agronomy which has not been perfected on less productive sites. Nevertheless, at the time of energy sourcing issues, seed-propagated miscanthus hybrids for the upscaled provision of bioenergy offer an alternative source of renewable energy. If European countries provide incentives for growers to invest, seeded hybrids can improve product availability and biomass yields over the current commercial miscanthus variety.     

Potential impacts on ecosystem services of land use transitions to second‐generation bioenergy crops in GB

We present the first assessment of the impact of land use change (LUC) to second‐generation (2G) bioenergy crops on ecosystem services (ES) resolved spatially for Great Britain (GB). A systematic approach was used to assess available evidence on the impacts of LUC from arable, semi‐improved grassland or woodland/forest, to 2G bioenergy crops, for which a quantitative ‘threat matrix’ was developed. The threat matrix was used to estimate potential impacts of transitions to either Miscanthus, short‐rotation coppice (SRC, willow and poplar) or short‐rotation forestry (SRF). The ES effects were found to be largely dependent on previous land uses rather than the choice of 2G crop when assessing the technical potential of available biomass with a transition from arable crops resulting in the most positive effect on ES. Combining these data with constraint masks and available land for SRC and Miscanthus (SRF omitted from this stage due to lack of data), south‐west and north‐west England were identified as areas where Miscanthus and SRC could be grown, respectively, with favourable combinations of economic viability, carbon sequestration, high yield and positive ES benefits. This study also suggests that not all prospective planting of Miscanthus and SRC can be allocated to agricultural land class (ALC) ALC 3 and ALC 4 and suitable areas of ALC 5 are only minimally available. Beneficial impacts were found on 146 583 and 71 890 ha when planting Miscanthus or SRC, respectively, under baseline planting conditions rising to 293 247 and 91 318 ha, respectively, under 2020 planting scenarios. The results provide an insight into the interplay between land availability, original land uses, bioenergy crop type and yield in determining overall positive or negative impacts of bioenergy cropping on ecosystems services and go some way towards developing a framework for quantifying wider ES impacts of this important LUC.     

Kinetic and docking studies of cytosolic/tumor-associated carbonic anhydrase isozymes I,II and IX with some hydroxylic compounds

A series of hydroxylic compounds (1–10, NK-154 and NK-168) have been assayed for the inhibition of three physiologically relevant carbonic anhydrase isozymes, the cytosolic isozymes I, II and tumor-associated isozyme IX. The investigated compounds showed inhibition constants in the range of 0.068–4003, 0.012–9.9 and 0.025–115?μm at the hCA I, hCA II and hCA IX enzymes, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico studies were also applied. Molecular docking scores of the studied compounds are calculated using scoring algorithms, namely Glide/induced fit docking. The inhibitory potencies of the novel compounds were analyzed at the human isoforms hCA I, hCA II and hCA IX as targets and the K_I values were calculated.     

Breast MRI in nonpalpable breast lesions: a randomized trial with diagnostic and therapeutic outcome – MONET – study

Background

In orthodontic treatment, anchorage control is a fundamental aspect. Usually conventional mechanism for orthodontic anchorage control can be either extraoral or intraoral that is headgear or intermaxillary elastics. Their use are combined with various side effects such as tipping of occlusal plane or undesirable movements of teeth. Especially in cases, where key-teeth are missing, conventional anchorage defined as tooth-borne anchorage will meet limitations. Therefore, the use of endosseous implants for anchorage purposes are increasingly used to achieve positional stability and maximum anchorage.

Methods/Design

The intended study is designed as a prospective, multicenter randomized controlled trial (RCT), comparing and contrasting the effect of early loading of palatal implant therapy versus implant loading after 12 weeks post implantation using the new ortho-implant type II anchor system device (Orthosystem Straumann, Basel, Switzerland). 124 participants, mainly adult males or females, whose diagnoses require temporary stationary implant-based anchorage treatment will be randomized 1:1 to one of two treatment groups: group 1 will receive a loading of implant standard therapy after a healing period of 12 week (gold standard), whereas group 2 will receive an early loading of orthodontic implants within 1 week after implant insertion. Participants will be at least followed for 12 months after implant placement. The primary endpoint is to investigate the behavior of early loaded palatal implants in order to find out if shorter healing periods might be justified to accelerate active orthodontic treatment. Secondary outcomes will focus e.g. on achievement of orthodontic treatment goals and quantity of direct implant-bone interface of removed bone specimens. As tertiary objective, a histologic and microtomography evaluation of all retrieved implants will be performed to obtain data on the performance of the SLA surface in human bone evaluation of all retrieved implants. Additionally, resonance frequency analysis (RFA, Osstell? mentor) will be used at different times for clinically monitoring the implant stability and for histological comparison in order to measure the reliability of the resonance frequency measuring device.

Trial registration

Current Controlled Trials ISRCTN97142521.     

Successful immunotherapy with matrix metalloproteinase-derived peptides in adjuvant arthritis depends on the timing of peptide administration

We have recently found that matrix metalloproteinases (MMPs) are targets for T-cell and B-cell reactivity in experimental arthritis. In the present article, we investigate whether modulation of MMP-specific T-cell responses could influence the course of adjuvant arthritis (AA). Lewis rats were treated nasally with MMP peptides prior to or after AA induction. Administration of the MMP-10 or the MMP-16 peptide prior to AA induction reduced the arthritic symptoms. In contrast, administration of the MMP-10 peptide after AA induction aggravated the arthritic symptoms. The present study shows the possible usefulness of MMP peptides for immunotherapy. However, a clear understanding of proper timing of peptide administration is crucial for the development of such therapies.