Recovery after unilateral knee replacement due to severe osteoarthritis and progression in the contralateral knee: a randomised clinical trial comparing daily 2000 IU versus 800 IU vitamin D.

To test whether daily high-dose vitamin D improves recovery after unilateral total knee replacement. Data come from a 24-month randomised, double-blind clinical trial. Adults aged 60 and older undergoing unilateral joint replacement due to severe knee osteoarthritis were 6-8 weeks after surgery randomly assigned to receive daily high-dose (2000 IU) or standard-dose (800 IU) vitamin D <sub>3</sub> . The primary endpoints were symptoms (Western Ontario and McMaster Universities Arthritis Index pain and function scores) assessed at baseline, 6, 12, 18 and 24 months in both knees, and the rate of falls over 24 months. The secondary outcomes were sit-to-stand performance, gait speed, physical activity and radiographic progression in the contralateral knee. We recruited 273 participants, 137 were randomised to receive 2000 IU and 136 were randomised to receive 800 IU vitamin D per day. 2000 IU vitamin D increased 25-hydroxyvitamin D levels to 45.6 ng/mL and 800 IU vitamin D to 37.1 ng/mL at month 24 (p<0.0001). While symptoms improved significantly in the operated knee and remained stable in the contralateral knee over time, none of the primary or secondary endpoints differed by treatment group over time. The rate of falls over 24 months was 1.05 with 2000 IU and 1.07 with 800 IU (p=0.84). 30.5% of participants in the 2000 IU and 31.3% of participants in the 800 IU group had radiographic progression in the contralateral knee over 24 months (p=0.88). Our findings suggest that a 24-month treatment with daily 2000 IU vitamin D did not show greater benefits or harm than a daily standard dose of 800 IU among older adults undergoing unilateral total knee replacement

Induction of apoptosis in human lymphocytes treated with Viscum album L. is mediated by the mistletoe lectins

Viscum album L. (VAL) is a phytopreparation used in adjuvant cancer therapy with both immunostimulatory and DNA stabilizing properties at low drug concentrations and cytostatic/cytotoxic properties at higher concentrations. The present work examines the cytotoxic effects of VAL extracts produced from mistletoes grown on different host trees and of purified toxic proteins from VAL, such as the D-galactose-specific lectin I (ML I), the N-acetyl-D-galactosamine-specific ML II and ML III, and crude viscotoxins towards cultured human lymphocytes. The decrease in the number of cultured lymphocytes and blast cells treated with whole plant extracts from VAL was host tree-specific. Nevertheless, there was no close correlation to the content of MLs or viscotoxins. Using the purified proteins, it became obvious that the cell killing was mediated by the induction of apoptosis, as measured by the appearance of a hypodiploid DNA peak using flow cytometry. ML III was the most effective to induce apoptosis, followed by ML II and ML I, while the viscotoxins and oligosaccharides from VAL did not. By measuring the surface expression of IL-2R alpha chains, transferrin receptors and APO-1/Fas molecules on non-apoptotic T cells, no significant changes were observed at low ML concentrations (1 ng/ml), but their decrease at higher ones. Our findings suggest that there might be at least two different ways of cell killing operative in VAL-mediated cytotoxicity: (a) the typical apoptotic cell death with the appearance of hypo-diploid nuclei, and (b) a direct or indirect killing by damaging the cell membrane with subsequent influx of Ca2+ and of the DNA intercalating dye propidium iodide and cell shrinkage. These effects might not be exclusive, as they probably occur simultaneously

Classification of buried soils, cultural, and colluvial deposits in the Viking town Hedeby

Objective classification of settlement deposits is a prerequisite for understanding human-environment interactions at habitation sites. This paper presents a novel approach combining a relatively fine-scale sampling strategy, a multimethod geoarchaeological investigation of cores and multivariate statistics to aid in the classification and interpretation of complex and intricately stratified archaeological deposits. Heterogeneous settlement deposits, buried soils, colluvial, fluvial, and fluvioglacial sediments from cores retrieved in the Viking settlement Hedeby were investigated using six cost-effectively measurable geoecological parameters: loss on ignition at 550°C, magnetic susceptibility, contents of stones, artifacts, bones, and charcoal with wood. Principal component analysis allowed identifying variables that would sufficiently describe data and cluster analysis enabled the classification of the materials. As a result, 13 classes were distinguished with a detailed and reliable differentiation of materials of natural and cultural genesis. Based on spatial distribution patterns of the classes, hypotheses regarding land use in the adjacent areas were made: Waste disposal in the valley of Hedeby-brook and metallurgic activities north of it. This approach is valuable for coring-based research at settlements, in particular at tightly managed heritage sites, and for surveys to identify potential excavation sites, whereas the set of variables must be adjusted according to local conditions