Folate catabolites in spot urine as non-invasive biomarkers of folate status during habitual intake and folic acid supplementation.

Folate status, as reflected by red blood cell (RCF) and plasma folates (PF), is related to health and disease risk. Folate degradation products para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (apABG) in 24 hour urine have recently been shown to correlate with blood folate. Since blood sampling and collection of 24 hour urine are cumbersome, we investigated whether the determination of urinary folate catabolites in fasted spot urine is a suitable non-invasive biomarker for folate status in subjects before and during folic acid supplementation. Immediate effects of oral folic acid bolus intake on urinary folate catabolites were assessed in a short-term pre-study. In the main study we included 53 healthy men. Of these, 29 were selected for a 12 week folic acid supplementation (400 µg). Blood, 24 hour and spot urine were collected at baseline and after 6 and 12 weeks and PF, RCF, urinary apABG and pABG were determined. Intake of a 400 µg folic acid bolus resulted in immediate increase of urinary catabolites. In the main study pABG and apABG concentrations in spot urine correlated well with their excretion in 24 hour urine. In healthy men consuming habitual diet, pABG showed closer correlation with PF (rs = 0.676) and RCF (rs = 0.649) than apABG (rs = 0.264, ns and 0.543). Supplementation led to significantly increased folate in plasma and red cells as well as elevated urinary folate catabolites, while only pABG correlated significantly with PF (rs = 0.574) after 12 weeks. Quantification of folate catabolites in fasted spot urine seems suitable as a non-invasive alternative to blood or 24 hour urine analysis for evaluation of folate status in populations consuming habitual diet. In non-steady-state conditions (folic acid supplementation) correlations between folate marker (RCF, PF, urinary catabolites) decrease due to differing kinetics

Surgery and postoperative radiotherapy a valid treatment for advanced oropharyngeal carcinoma

Since 1992 we have prospectively included all head and neck cancer patients in our health region in a departmental based register. Our hospital takes care of all head and neck cancer patients in our health region consisting of approximately 1 million people. In 1997, we evaluated the results of the treatment of oropharyngeal cancer in the 1992–1997 period. On the basis of this evaluation, we changed our treatment policy for tonsillar and base of tongue carcinoma. We first changed the treatment for the lesions with worst prognosis, i.e., those with T3–T4 carcinomas, from radiotherapy only, to radical surgery and postoperative radiotherapy. We have since that time increasingly also operated the smaller oropharyngeal carcinomas. The 2 years’ overall survival and disease-specific survival for all patients diagnosed in the 1992–1997 period was 56 and 63%, respectively. The results from a similar group of patients in the 6 years’ period from 2000 to 2005, after the change in treatment, have increased to 83 and 88%. When we looked at the subgroup of patients in the 2000–2005 period treated with surgery and postoperative radiotherapy, 45 out of 69 patients (65%) presenting with an oropharyngeal cancer were fit for operation. With radical surgery and postoperative radiation therapy, the 2 years overall survival is now 91%. The 2-year disease-specific survival is 96% and the locoregional control is 98%. This is a marked improvement as compared to radiotherapy alone and definitely competitive with modern radiochemotherapy

The uronic acid content of coccolith-associated polysaccharides provides insight into coccolithogenesis and past climate

Unicellular phytoplanktonic algae (coccolithophores) are among the most prolific producers of calcium carbonate on the planet, with a production of ∼1026 coccoliths per year. During their lith formation, coccolithophores mainly employ coccolith-associated polysaccharides (CAPs) for the regulation of crystal nucleation and growth. These macromolecules interact with the intracellular calcifying compartment (coccolith vesicle) through the charged carboxyl groups of their uronic acid residues. Here we report the isolation of CAPs from modern day coccolithophores and their prehistoric predecessors and we demonstrate that their uronic acid content (UAC) offers a species-specific signature. We also show that there is a correlation between the UAC of CAPs and the internal saturation state of the coccolith vesicle that, for most geologically abundant species, is inextricably linked to carbon availability. These findings suggest that the UAC of CAPs reports on the adaptation of coccolithogenesis to environmental changes and can be used for the estimation of past CO2 concentrations

Preoperative elevation of serum C – reactive protein is predictive for prognosis in myeloma bone disease after surgery

We investigated whether preoperative levels of serum C-reactive protein (CRP) and its correlation with tumour clinicopathological findings adds prognostic information beyond the time of diagnosis in patients with myeloma bone disease (MM) to facilitate the surgical decision-making process. Six hundred and fifty-eight myeloma patients were evaluated retrospectively for surgery. Clinicopathological variables of patients who underwent surgery (n=71) were compared between patients with preoperative CRP ⩾6 mg l−1 and those with CRP <6 mg l−1. Univariate and multivariate analyses were performed to identify prognostic factors after surgery. Patients with an increase of CRP prior to surgery showed inferior survival compared to patients with normal levels. Patients with normal CRP levels at diagnosis but elevations prior to surgery do seem to have a similar unfavourable overall survival (OS) than patients with an increase both, at diagnosis and at surgery. Conversely, patients with normal CRP levels prior to surgery still have the best OS, irrespective of their basic values. Multivariate analysis revealed preoperative CRP levels above 6 mg l−1 Lactate dehydrogenase (LDH) above normal, and osteolyses in long weight bearing bones as independent predictors of survival. These findings suggest that in patients with MM serum levels of CRP increase during disease activity and might be significantly correlated with specific disease characteristics including adverse prognostic features such as osteolyses in long weight bearing bones. Thus, preoperative elevated CRP serum levels might be considered as independent predictor of prognosis and could provide additional prognostic information for the risk stratification before surgical treatment in patients with myeloma bone disease

Understanding mechanisms of asphaltene adsorption from organic solvent on mica

The adsorption process of asphaltene onto molecularly smooth mica surfaces from toluene solutions of various concentrations (0.01-1 wt %) was studied using a surface forces apparatus (SFA). Adsorption of asphaltenes onto mica was found to be highly dependent on adsorption time and asphaltene concentration of the solution. The adsorption of asphaltenes led to an attractive bridging force between the mica surfaces in asphaltene solution. The adsorption process was identified as being controlled by the diffusion of asphaltenes from the bulk solution to the mica surface with a diffusion coefficient on the order of 10-10 m2/s at room temperature, depending on the asphaltene bulk concentration. This diffusion coefficient corresponds to a hydrodynamic molecular radius of approximately 0.5 nm, indicating that asphaltene diffuses to mica surfaces as individual molecules at very low concentration (e.g., 0.01 wt %). Atomic force microscopy images of the adsorbed asphaltenes on mica support the results of the SFA force measurements. The results from the SFA force measurements provide valuable insights into the molecular interactions (e.g., steric repulsion and bridging attraction as a function of distance) of asphaltenes in organic media and hence their roles in crude oil and bitumen production

Decrease in coccolithophore calcification and CO2 since the middle Miocene

International audienceMarine algae are instrumental in carbon cycling and atmospheric carbon dioxide (CO2) regulation. One group, coccolithophores, uses carbon to photosynthesize and to calcify, covering their cells with chalk platelets (coccoliths). How ocean acidification influences coccolithophore calcification is strongly debated, and the effects of carbonate chemistry changes in the geological past are poorly understood. This paper relates degree of coccolith calcification to cellular calcification, and presents the first records of size-normalized coccolith thickness spanning the last 14 Myr from tropical oceans. Degree of calcification was highest in the low-pH, high-CO2 Miocene ocean, but decreased significantly between 6 and 4 Myr ago. Based on this and concurrent trends in a new alkenone εp record, we propose that decreasing CO2 partly drove the observed trend via reduced cellular bicarbonate allocation to calcification. This trend reversed in the late Pleistocene despite low CO2, suggesting an additional regulator of calcification such as alkalinity

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Changes to the Fossil Record of Insects through Fifteen Years of Discovery

The first and last occurrences of hexapod families in the fossil record are compiled from publications up to end-2009. The major features of these data are compared with those of previous datasets (1993 and 1994). About a third of families (>400) are new to the fossil record since 1994, over half of the earlier, existing families have experienced changes in their known stratigraphic range and only about ten percent have unchanged ranges. Despite these significant additions to knowledge, the broad pattern of described richness through time remains similar, with described richness increasing steadily through geological history and a shift in dominant taxa, from Palaeoptera and Polyneoptera to Paraneoptera and Holometabola, after the Palaeozoic. However, after detrending, described richness is not well correlated with the earlier datasets, indicating significant changes in shorter-term patterns. There is reduced Palaeozoic richness, peaking at a different time, and a less pronounced Permian decline. A pronounced Triassic peak and decline is shown, and the plateau from the mid Early Cretaceous to the end of the period remains, albeit at substantially higher richness compared to earlier datasets. Origination and extinction rates are broadly similar to before, with a broad decline in both through time but episodic peaks, including end-Permian turnover. Origination more consistently exceeds extinction compared to previous datasets and exceptions are mainly in the Palaeozoic. These changes suggest that some inferences about causal mechanisms in insect macroevolution are likely to differ as well