Matrix metalloproteinases and angiogenic factors: predictors of survival after radical prostatectomy for clinically organ-confined prostate cancer?

The aim of the present study was to investigate whether biomarkers improve the prediction of recurrence-free, disease-specific, and overall survival in patients with clinically localized prostate cancer. A tissue microarray was constructed from prostate specimens of 278 patients who underwent open radical retropubic prostatectomy for clinically localized prostate cancer. For immunohistochemical studies, antibodies were used against matrix metalloproteinase (MMP)-2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-19, as well as against vascular endothelial growth factor, hypoxia-induced factor 1 , basic fibroblast growth factor, and cluster of differentiation 31. Univariate and multivariable analyses were performed to evaluate the potential predictors of overall, disease-specific, and recurrence-free survival. In univariate analysis of patients with clinically organ-confined prostate cancer, only higher expression levels of MMP-9 (hazard ratio [0.6], 95% CI 0.45-0.8) had a protective effect in terms of overall survival. This positive effect of high MMP-9 expression was also observed for recurrence-free (HR 0.88, 95% CI 0.78-0.99) and disease-specific survival (HR 0.5, 95% CI 0.36-0.73). In multivariable analysis, none of these potential markers was found to be an independent prognostic factor of survival. Of all MMPs and angiogenic factors tested, MMP-9 expression has the potential as a prognostic marker in patients undergoing radical prostatectomy for clinically organ-confined cases of prostate cancer.

The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer

Choline positron emission tomography (PET)/computed tomography (CT) is a currently used diagnostic tool in restaging prostate cancer (PCa) patients with increasing prostate-specific antigen (PSA) after either radical prostatectomy (RP) or external-beam radiation therapy (EBRT). However, no final recommendations have been made on the use of this modality for patient management.

Mapping of atrial tachycardias after catheter ablation for atrial fibrillation: use of bi-atrial activation patterns to facilitate recognition of origin

Mapping and ablation of atrial tachycardias (ATs) secondary to catheter ablation of atrial fibrillation (AF) is often challenging due to the complex atrial substrate, different AT mechanisms, and potential origin not only in the left atrium (LA) but also from the right atrium (RA) and the adjacent thoracic veins.

Prognostic significance of CD8+ T lymphocytes in breast cancer depends upon both oestrogen receptor status and histological grade

Results of previous studies on the influence of tumour infiltrating lymphocytes on prognosis of women with breast cancer have been mixed. This study re-evaluates the role of tumour-infiltrating lymphocytes as a prognostic marker in women with breast cancer.

Recruitment dynamics of the grove-dominant tree Microberlinia bisulcata in African rain forest: extending the light response versus adult longevity trade-off concept

In groves of ectomycorrhizal caesalpiniaceous species in the Atlantic coastal forest of Central Africa the dominant tree Microberlinia bisulcata, which is shade-intolerant as a seedling but highly light-responding as a sapling, shows very limited regeneration. M. bisulcata saplings were mapped in an 82.5-ha plot at Korup and found to be located significantly far (>40 m) away from adults, a result confirmed by direct testing in a second 56-ha plot. Sapling growth over 6 years, the distribution of newly emerging seedlings around adults, recruitment of saplings in a large opening and the outward extent of seedlings at the grove edge were also investigated. Two processes appear to have been operating: (1) a very strong and consistent restriction of the very numerous seedlings establishing after masting close to adults, and (2) a strong but highly spatially variable promotion of distant survivors by increased light from the deaths of large trees of species other than M. bisulcata (which itself has very low mortality rate). This leads to an apparent escape-from-adults effect. To maintain saplings in the shade between multiple short periods of release ectomycorrhizal connections to other co-occurring caesalp species may enable a rachet-type mechanism. The recorded sapling dynamics currently contribute an essential part of the long-term cycling of the groves. M. bisulcata is an interesting example of an important group of tropical trees, particularly in Africa, which are both highly light-demanding when young yet capable also of forming very large forest emergents. To more comprehensively explain tropical tree responses, the case is made for adding a new dimension to the trade-off concept of early tree light-response versus adult longevity.

Quantification of oxidized levels of specific RNA species using an aldehyde reactive probe

Emerging evidence has shown that oxidation of RNA, including messenger RNA (mRNA), is elevated in several age-related diseases, although investigation of oxidized levels of individual RNA species has been limited. Recently we reported that an aldehyde reactive probe (ARP) quantitatively reacts with oxidatively modified depurinated/depyrimidinated (abasic) RNA. Here we report a novel method to isolate oxidized RNA using ARP and streptavidin beads. An oligo RNA containing abasic sites that were derivatized with ARP was pulled down by streptavidin beads, whereas a control oligo RNA was not. In vitro oxidized RNA, as well as total cellular RNA, isolated from oxidatively stressed cells was also pulled down, dependent on oxidation level, and concentrated in the pull-down fraction. Quantitative reverse transcription polymerase chain reaction (RT-PCR) using RNA in the pull-down fraction demonstrated that several gene transcripts were uniquely increased in the fraction by oxidative stress. Thus, our method selectively concentrates oxidized RNA by pull-down and enables the assessment of oxidation levels of individual RNA species. (C) 2011 Elsevier Inc. All rights reserved.

Potential drought stress in a Swiss mountain catchment-Ensemble forecasting of high mountain soil moisture reveals a drastic decrease, despite major uncertainties

Climate change is expected to profoundly influence the hydrosphere of mountain ecosystems. The focus of current process-based research is centered on the reaction of glaciers and runoff to climate change; spatially explicit impacts on soil moisture remain widely neglected. We spatio-temporally analyzed the impact of the climate on soil moisture in a mesoscale high mountain catchment to facilitate the development of mitigation and adaptation strategies at the level of vegetation patterns. Two regional climate models were downscaled using three different approaches (statistical downscaling, delta change, and direct use) to drive a hydrological model (WaSiM-ETH) for reference and scenario period (1960–1990 and 2070–2100), resulting in an ensemble forecast of six members. For all ensembles members we found large changes in temperature, resulting in decreasing snow and ice storage and earlier runoff, but only small changes in evapotranspiration. The occurrence of downscaled dry spells was found to fluctuate greatly, causing soil moisture depletion and drought stress potential to show high variability in both space and time. In general, the choice of the downscaling approach had a stronger influence on the results than the applied regional climate model. All of the results indicate that summer soil moisture decreases, which leads to more frequent declines below a critical soil moisture level and an advanced evapotranspiration deficit. Forests up to an elevation of 1800 m a.s.l. are likely to be threatened the most, while alpine areas and most pastures remain nearly unaffected. Nevertheless, the ensemble variability was found to be extremely high and should be interpreted as a bandwidth of possible future drought stress situations.

Optimization of corticosteroid induced osteoporosis in ovariectomized sheep. A bone histomorphometric study

During osteoporosis induction in sheep, side effects of the steroids were observed in previous studies. The aim of this study was to improve the induction regimen consisting of ovariectomy, calcium/vitamin D- restricted diet and methylprednisolone (-MP)- medication with respect to the bone metabolism and to reduce the adverse side effects. Thirty-six ewes (age 6.5 +/- 0.6 years) were divided into four MP-administration groups (n = 9) with a total dose of 1800 mg MP: group 1: 20 mg/day, group 2: 60 mg/every third day, group 3: 3 x 500 mg and 1 x 300 mg at intervals of three weeks, group 4: weekly administration, starting at 70 mg and weekly reduction by 10 mg. After double-labelling with Calcein Green and Xylenol Orange, bone biopsy specimens were taken from the iliac crest (IC) at the beginning and four weeks after the last MP injection, and additionally from the vertebral body (VB) at the end of the experiment. Bone samples were processed into stained and fluorescent sections, static and dynamic measurements were performed. There were no significant differences for static parameters between the groups initially. The bone perimeter and the bone area values were significantly higher in the VB than in the IC (Pm: 26%, p < 0.0001, Ar: 11%, p < 0.0166). A significant decrease (20%) of the bone area was observed after corticosteroid-induced osteoporosis (p < 0.0004). For the dynamic parameters, no significant difference between the groups was found. Presence of Calcein Green and Xylenol Orange labels were noted in 50% of the biopsies in the IC, 100% in the VB. Group 3 showed the lowest prevalence of adverse side effects. The bone metabolism changes were observed in all four groups, and the VB bone metabolism was higher when compared to the IC. In conclusion, when using equal amounts of steroids adverse side effects can be reduced by decreasing the number of administrations without reducing the effect regarding corticosteroid-induced osteoporosis. This information is useful to reduce the discomfort of the animals in this sheep model of corticosteroid-induced osteoporosis.

Identification of pathogen and host-response markers correlated with periodontal disease

BACKGROUND: Periodontitis is the major cause of tooth loss in adults and is linked to systemic illnesses, such as cardiovascular disease and stroke. The development of rapid point-of-care (POC) chairside diagnostics has the potential for the early detection of periodontal infection and progression to identify incipient disease and reduce health care costs. However, validation of effective diagnostics requires the identification and verification of biomarkers correlated with disease progression. This clinical study sought to determine the ability of putative host- and microbially derived biomarkers to identify periodontal disease status from whole saliva and plaque biofilm. METHODS: One hundred human subjects were equally recruited into a healthy/gingivitis group or a periodontitis population. Whole saliva was collected from all subjects and analyzed using antibody arrays to measure the levels of multiple proinflammatory cytokines and bone resorptive/turnover markers. RESULTS: Salivary biomarker data were correlated to comprehensive clinical, radiographic, and microbial plaque biofilm levels measured by quantitative polymerase chain reaction (qPCR) for the generation of models for periodontal disease identification. Significantly elevated levels of matrix metalloproteinase (MMP)-8 and -9 were found in subjects with advanced periodontitis with Random Forest importance scores of 7.1 and 5.1, respectively. The generation of receiver operating characteristic curves demonstrated that permutations of salivary biomarkers and pathogen biofilm values augmented the prediction of disease category. Multiple combinations of salivary biomarkers (especially MMP-8 and -9 and osteoprotegerin) combined with red-complex anaerobic periodontal pathogens (such as Porphyromonas gingivalis or Treponema denticola) provided highly accurate predictions of periodontal disease category. Elevated salivary MMP-8 and T. denticola biofilm levels displayed robust combinatorial characteristics in predicting periodontal disease severity (area under the curve = 0.88; odds ratio = 24.6; 95% confidence interval: 5.2 to 116.5). CONCLUSIONS: Using qPCR and sensitive immunoassays, we identified host- and bacterially derived biomarkers correlated with periodontal disease. This approach offers significant potential for the discovery of biomarker signatures useful in the development of rapid POC chairside diagnostics for oral and systemic diseases. Studies are ongoing to apply this approach to the longitudinal predictions of disease activity.

The ethnolinguistic identity of the domesticators of Asian rice

Linguistic palaeontology permits the identification of two language families whose linguistic ancestors pose the likeliest candidates for the original domesticators of rice, viz. Hmong-Mien and Austroasiatic. In the 2009 model, the ancient Hmong-Mien was identified as the primary domesticators of Asian rice, and the ancient Austroasiatics as the secondary domesticators. Recent rice genetic research leads to the modification of this model for rice domestication, but falls short of identifying the original locus of rice domestication. At the same time, the precise whereabouts of the Austroasiatic homeland remains disputed. Linguistic evidence unrelated to rice agriculture has been adduced to support a southern homeland for Austroasiatic somewhere within the Bay of Bengal littoral. The implications of new rice genetic research are discussed, the linguistic palaeontological evidence is reassessed, and an enduring problem with the archaeology of rice agriculture is highlighted.