Canopy Disturbances Catalyse Tree Species Shifts in Swiss Forests

Ecosystems - Widely observed inertia of forest communities contrasts with climate change projections that suggest dramatic alterations of forest composition for the coming decades. Disturbances...     

Likely country of origin in publications on randomised controlled trials and controlled clinical trials during the last 60 years

Background

The n-of-1 trial offers a more methodologically sound approach to determining optimum treatment for an individual patient than "trials of therapy" routinely conducted in clinical practice. However, such methodology is rarely used in the UK. This pilot study explores the acceptability of n-of-1 trials to patients in the UK.

Methods

Patients with osteoarthritis of the knee were recruited to their own 12-week n-of-1 trial comparing either two knee supports or an NSAID with simple analgesic. Patients were interviewed at the start and completion of their trial to explore reasons for participation, understanding of the trial design and experiences of participation. Daily diaries were completed to inform future treatment.

Results

Nine patients participated (5 supports, 4 drugs). Patients were keen to participate, believing that the trial may lead to personal gains such as improved symptom control and quality of life. However, recruitment to the pharmacological comparison was more difficult since this could also entail risk. All patients were eager to complete the trial, even when difficulties were encountered. Completing the daily diary provided some patients with greater insight into their condition, which allowed them to improve their self-management. The n-of-1 trial design was viewed as a 'logical' design offering an efficient method of reaching a personalised treatment decision tailored to suit individual needs and preferences.

Conclusion

This pilot study suggests that patients perceive the n-of-1 trial as an acceptable approach to the individualisation of treatment. In addition, further benefits over and above any gained from the interventions can be derived from involvement in such a study.     

Effect of UV Radiation and Other Abiotic Stress Factors on DNA of Different Wild Plant Species Grown in Three Successive Seasons in Alpine and Subalpine Regions

Plants in natural ecosystems are exposed to a combination of UV radiation, ionizing radiation (IR) and other abiotic factors. These factors change with the altitude. We investigated DNA alterations of some wild plants of different plant families in natural ecosystems at three altitudes in Rila Mountain, Bulgaria (1500, 1782, and 2925 m above sea level (a.s.l.) exposed to UV radiation, IR and other abiotic stresses, to assess the tolerance of plant species to the changing environmental conditions in three successive growth seasons. For this purpose, physicochemical, cytogenetic, and molecular methods were applied. DNA damage was assessed by micronucleus test and molecular method comet assay adapted and applied by us to wild plant species from Onagraceae, Rosaceae, Boraginaceae, Saxifragaceae, Orobanchaceae, Asteraceae and Poaceae families, growing at three different altitudes. Variability in the DNA sensitivity and the level of tolerance was observed among the plant species in response to combined abiotic factors assessed by induced DNA damage and gross beta activity. The studied representatives of Poaceae were less susceptible than the other studied species at all three altitudes and showed close level of DNA injuries to that of unaffected control plant grown in laboratory conditions. The lower levels of DNA damage of these wild plant species corresponded to their lower ability to accumulate radionuclides. There was a particularly pronounced low level of DNA injuries in the plant species at the highest altitude. The level of DNA damage showed correlation with the values of some abiotic environmental factors. The results would contribute to the elucidation of the extent of adaptation of plant species to the continuously changing environment and would be useful in selecting sensitive herbaceous monitor species for environmental impact assessment at mountain and alpine sites.     

Saponins from Tribulus terrestris L are less toxic for normal human fibroblasts than for many cancer lines: influence on apoptosis and proliferation

The objective of the study was to explore the influence of saponins derived from Tribulus terrestris L. (TT) on normal human skin fibroblasts and to compare it with their anticancer properties. In this study, [3H]thymidine incorporation and MTT to assess cell proliferation and viability, respectively, and immunoblotting and HPLC analysis to explore intracellular signal transduction pathways have been used. We found that TT caused a dose-dependent decrease in [3H]thymidine incorporation into the DNA of treated fibroblast compared to the untreated controls. Viability of treated cells remained within the control levels with treatment of up to 5 micro g TT/ml medium. It was significantly depressed with incubation in > or =6 micro g TT/ml medium with an IC50 of 12.6 micro g TT/ml of cultivating media. ERK1/2 was significantly dephosphorylated at 5 mins of incubation with TT until the 48th hour, when phosphorylation slightly recovered, but was still below the control levels. In contrast, p38 and JNK phosphorylation was positively influenced, with peaks at 1 hr and 24 hrs of incubation respectively. Phosphorylation/dephosphorylation events of SAPK/MAPK clearly correlated with Mkp-1 induction. Procaspase 3 was activated after 5 mins of incubation and coincided with a rapid actin cleavage. There was a significant decrease of putrescine concentration and a concomitant increase of spermidine and spermine at 2 mins of treatment. According to our results, TT is less toxic for normal human skin fibroblasts in comparison to many cancer lines investigated in previous studies. The molecular mechanism of this cytotoxicity involves up- and downregulation of polyamines' homeostasis, suppression of proliferation, and induction of apoptosis. Further research in this field using animal models would help to explore and interpret the potential properties of TT as an anticancer supplement.     

Estimation of male and female body segment parameters of the Bulgarian population using a 16-segmental mathematical model

Based on a large-scale anthropometric measurements of 5290 individuals (2435 males and 2855 females) of the Bulgarian population aged between 30 and 40 years, we present 16-segmental 3D geometrical model of the human body of the average Bulgarian male and female and calculate mass, volume, location of the mass center and moments of inertia for all the segments for both genders. This study extends current anthropometrical data pool of Caucasian. Wherever possible, the comparison between our model results and data reported in literature for other Caucasian shows an overall good agreement, thus supporting the validity of the described method.     

Disoxaril mutants of Coxsackievirus B1: phenotypic characteristics and analysis of the target VP1 gene

Disoxaril inhibits enterovirus replication by binding to the hydrophobic pocket within the VP1 coat protein, thus stabilizing the virion and blocking its uncoating. Disoxaril-resistant (RES) mutants of the Coxsackievirus B1 (CVB1/RES) were derived from the wild disoxaril-sensitive (SOF) strain (CVB1/SOF) using a selection approach. A disoxaril-dependent (DEP) mutant (CVB1/DEP) was obtained following nine consecutive passages of the disoxaril-resistant mutant in the presence of disoxaril. Phenotypic characteristics of the disoxaril mutants were investigated. A timing-of-addition study of the CVB1/DEP replication demonstrated that in the absence of disoxaril the virus particle assembly stopped. VP1 RNA sequences of disoxaril mutants were compared with the existing Gen Bank CVB1 reference structure. The amino acid sequence of a large VP1 196-258 peptide (disoxaril-binding region) of CVB1/RES was significantly different from that of the CVB1/SOF. Crucially important changes in CVB1/RES were two point mutations, M213H and F237L, both in the ligand-binding pocket. The sequence analysis of the CVB1/DEP showed some reversion to CVB1/SOF. The amino acid sequences of the three VP1 proteins are presented.