Oxidation of monoterpenes catalysed by a water-soluble Mn(III) PEG-porphyrin in a biphasic medium

It is well established that the transformation of abundant and cheap natural products, such as terpenoids, can produce other more valuable compounds. Thymoquinone, which has a commercial value significantly higher than that of its precursors, can be obtained by oxidation of carvacrol and thymol. In this work, a new water-soluble Mn-III PEG-porphyrin is reported as catalyst in a water/hexane (1:1) biphasic medium for the oxidation of carvacrol and thymol into thymoquinone. The reactions were performed using tert-butyl hydroperoxide as oxidant in the presence of ammonium acetate as co-catalyst, reaching 94 and 78% of conversion after 5 h of reaction for thymol and carvacrol, respectively. Experiments with oregano essential oil as substrate revealed selective transformation of thymol and carvacrol into thymoquinone. The main advantage of this biphasic system based on a water-soluble catalyst and on substrates and products soluble in hexane, is the straightforward isolation, recovery and recycling of the catalyst by simple phase separation. Recycling studies of the Mn-III PEG-porphyrin using thymol as substrate showed high conversion values throughout four catalytic cycles

Multimodal Treatment Eliminates Cancer Stem Cells and Leads to Long-Term Survival in Primary Human Pancreatic Cancer Tissue Xenografts.

Copyright: 2013 Hermann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PURPOSE: In spite of intense research efforts, pancreatic ductal adenocarcinoma remains one of the most deadly malignancies in the world. We and others have previously identified a subpopulation of pancreatic cancer stem cells within the tumor as a critical therapeutic target and additionally shown that the tumor stroma represents not only a restrictive barrier for successful drug delivery, but also serves as a paracrine niche for cancer stem cells. Therefore, we embarked on a large-scale investigation on the effects of combining chemotherapy, hedgehog pathway inhibition, and mTOR inhibition in a preclinical mouse model of pancreatic cancer. EXPERIMENTAL DESIGN: Prospective and randomized testing in a set of almost 200 subcutaneous and orthotopic implanted whole-tissue primary human tumor xenografts. RESULTS: The combined targeting of highly chemoresistant cancer stem cells as well as their more differentiated progenies, together with abrogation of the tumor microenvironment by targeting the stroma and enhancing tissue penetration of the chemotherapeutic agent translated into significantly prolonged survival in preclinical models of human pancreatic cancer. Most pronounced therapeutic effects were observed in gemcitabine-resistant patient-derived tumors. Intriguingly, the proposed triple therapy approach could be further enhanced by using a PEGylated formulation of gemcitabine, which significantly increased its bioavailability and tissue penetration, resulting in a further improved overall outcome. CONCLUSIONS: This multimodal therapeutic strategy should be further explored in the clinical setting as its success may eventually improve the poor prognosis of patients with pancreatic ductal adenocarcinoma

Is distortion of the bioprosthesis ring a risk factor for early calcification ?

<p>Abstract</p> <p>Background</p> <p>As the population ages, bioprosthesis are increasingly being used in cardiac valve replacement. Pericardial bioprosthesis combine an excellent hemodynamic performance with low thrombogenicity, but valve failure associated with calcification remains a concern with these valves. We describe distortion of the bioprosthesis ring as a risk factor for early calcification.</p> <p>Methods</p> <p>A total of 510 patients over the age of 70 years underwent isolated aortic valve replacement with the Mitroflow (A12) pericardial bioprosthesis. Thirty two patients (6,2%) have undergone a second aortic valve replacement due to structural valve dysfunction resulting from valve calcification. In all patients a chest radiography and coronary angiography was performed before reoperation. A 64 Multidetector Computed Tomography (MDCT) with retrospective ECG gating study was performed in four patients to evaluate the aortic bioprosthesis.</p> <p>Results</p> <p>Chest radiography showed in all patients an irregular bioprosthesis ring. At preoperative coronary angiography a distorted bioprosthesis ring was detected in all patients. Macroscopic findings of the explanted bioprostheses included extensive calcification in all specimens.</p> <p>Conclusion</p> <p>There was a possible relationship between early bioprosthetic calcification and radiologic distortion of the bioprosthesis ring.</p

Variations of training load, monotony, and strain and dose-response relationships with maximal aerobic speed, maximal oxygen uptake, and isokinetic strength in professional soccer players

This study aimed to identify variations in weekly training load, training monotony, and training strain across a 10-week period (during both, pre- and in-season phases); and to analyze the dose-response relationships between training markers and maximal aerobic speed (MAS), maximal oxygen uptake, and isokinetic strength. Twenty-seven professional soccer players (24.9±3.5 years old) were monitored across the 10-week period using global positioning system units. Players were also tested for maximal aerobic speed, maximal oxygen uptake, and isokinetic strength before and after 10 weeks of training. Large positive correlations were found between sum of training load and extension peak torque in the right lower limb (r = 0.57, 90%CI[0.15;0.82]) and the ratio agonist/antagonist in the right lower limb (r = 0.51, [0.06;0.78]). It was observed that loading measures fluctuated across the period of the study and that the load was meaningfully associated with changes in the fitness status of players. However, those magnitudes of correlations were small-to-large, suggesting that variations in fitness level cannot be exclusively explained by the accumulated load and loading profile

Examining the impact of 11 long-standing health conditions on health-related quality of life using the EQ-5D in a general population sample

Objectives Health-related quality of life (HRQoL) measures have been increasingly used in economic evaluations for policy guidance. We investigate the impact of 11 self-reported long-standing health conditions on HRQoL using the EQ-5D in a UK sample. Methods We used data from 13,955 patients in the South Yorkshire Cohort study collected between 2010 and 2012 containing the EQ-5D, a preference-based measure. Ordinary least squares (OLS), Tobit and two-part regression analyses were undertaken to estimate the impact of 11 long-standing health conditions on HRQoL at the individual level. Results The results varied significantly with the regression models employed. In the OLS and Tobit models, pain had the largest negative impact on HRQoL, followed by depression, osteoarthritis and anxiety/nerves, after controlling for all other conditions and sociodemographic characteristics. The magnitude of coefficients was higher in the Tobit model than in the OLS model. In the two-part model, these four long-standing health conditions were statistically significant, but the magnitude of coefficients decreased significantly compared to that in the OLS and Tobit models and was ranked from pain followed by depression, anxiety/nerves and osteoarthritis. Conclusions Pain, depression, osteoarthritis and anxiety/nerves are associated with the greatest losses of HRQoL in the UK population. The estimates presented in this article should be used to inform economic evaluations when assessing health care interventions, though improvements can be made in terms of diagnostic information and obtaining longitudinal data

Does training with amplitude modulated tones affect tone-vocoded speech perception?

Temporal-envelope cues are essential for successful speech perception. We asked here whether training on stimuli containing temporal-envelope cues without speech content can improve the perception of spectrally-degraded (vocoded) speech in which the temporal-envelope (but not the temporal fine structure) is mainly preserved. Two groups of listeners were trained on different amplitude-modulation (AM) based tasks, either AM detection or AM-rate discrimination (21 blocks of 60 trials during two days, 1260 trials; frequency range: 4Hz, 8Hz, and 16Hz), while an additional control group did not undertake any training. Consonant identification in vocoded vowel-consonant-vowel stimuli was tested before and after training on the AM tasks (or at an equivalent time interval for the control group). Following training, only the trained groups showed a significant improvement in the perception of vocoded speech, but the improvement did not significantly differ from that observed for controls. Thus, we do not find convincing evidence that this amount of training with temporal-envelope cues without speech content provide significant benefit for vocoded speech intelligibility. Alternative training regimens using vocoded speech along the linguistic hierarchy should be explored

How many people have had a myocardial infarction? Prevalence estimated using historical hospital data

<p>Abstract</p> <p>Background</p> <p>Health administrative data are increasingly used to examine disease occurrence. However, health administrative data are typically available for a limited number of years – posing challenges for estimating disease prevalence and incidence. The objective of this study is to estimate the prevalence of people previously hospitalized with an acute myocardial infarction (AMI) using 17 years of hospital data and to create a registry of people with myocardial infarction.</p> <p>Methods</p> <p>Myocardial infarction prevalence in Ontario 2004 was estimated using four methods: 1) observed hospital admissions from 1988 to 2004; 2) observed (1988 to 2004) and extrapolated unobserved events (prior to 1988) using a "back tracing" method using Poisson models; 3) DisMod incidence-prevalence-mortality model; 4) self-reported heart disease from the population-based Canadian Community Health Survey (CCHS) in 2000/2001. Individual respondents of the CCHS were individually linked to hospital discharge records to examine the agreement between self-report and hospital AMI admission.</p> <p>Results</p> <p>170,061 Ontario residents who were alive on March 31, 2004, and over age 20 years survived an AMI hospital admission between 1988 to 2004 (cumulative incidence 1.8%). This estimate increased to 2.03% (95% CI 2.01 to 2.05) after adding extrapolated cases that likely occurred before 1988. The estimated prevalence appeared stable with 5 to 10 years of historic hospital data. All 17 years of data were needed to create a reasonably complete registry (90% of estimated prevalent cases). The estimated prevalence using both DisMod and self-reported "heart attack" was higher (2.5% and 2.7% respectively). There was poor agreement between self-reported "heart attack" and the likelihood of having an observed AMI admission (sensitivity = 63.5%, positive predictive value = 54.3%).</p> <p>Conclusion</p> <p>Estimating myocardial infarction prevalence using a limited number of years of hospital data is feasible, and validity increases when unobserved events are added to observed events. The "back tracing" method is simple, reliable, and produces a myocardial infarction registry with high estimated "completeness" for jurisdictions with linked hospital data.</p