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

MIR-99a and MIR-99b Modulate TGF-β Induced Epithelial to Mesenchymal Plasticity in Normal Murine Mammary Gland Cells

Epithelial to mesenchymal transition (EMT) is a key process during embryonic development and disease development and progression. During EMT, epithelial cells lose epithelial features and express mesenchymal cell markers, which correlate with increased cell migration and invasion. Transforming growth factor-β (TGF-β) is a multifunctional cytokine that induces EMT in multiple cell types. The TGF-β pathway is regulated by microRNAs (miRNAs), which are small non-coding RNAs regulating the translation of specific messenger RNAs

Increased Fitness of Rice Plants to Abiotic Stress Via Habitat Adapted Symbiosis: A Strategy for Mitigating Impacts of Climate Change

Climate change and catastrophic events have contributed to rice shortages in several regions due to decreased water availability and soil salinization. Although not adapted to salt or drought stress, two commercial rice varieties achieved tolerance to these stresses by colonizing them with Class 2 fungal endophytes isolated from plants growing across moisture and salinity gradients

Calf health from birth to weaning. II. Management of diarrhoea in pre-weaned calves

Calfhood diseases have a major impact on the economic viability of cattle operations. The second of this three part review series considers the management of diarrhoeic diseases in pre-weaned calves. In neonatal calf diarrhoea, oral rehydration therapy is the single most important therapeutic measure to be carried out by the farmer and is usually successful if instigated immediately after diarrhoea has developed. Continued feeding of milk or milk replacer to diarrhoeic calves is important, to prevent malnourishment and weight loss in affected calves. Indiscriminative antibiotic treatment of uncomplicated diarrhoea is discouraged, whereas systemically ill calves can benefit from systemic antibiotic treatment for the prevention of septicaemia or concurrent diseases. Ancillary treatments and specific preventive measures are discussed. Eimeriosis has a high economic impact on the farming industries due to direct cost of treatment and calf losses, but especially due to decreased performance of clinically as well as sub-clinically affected animals. Emphasis lies on prophylactic or metaphylactic treatment, since the degree of damage to the intestinal mucosa once diarrhoea has developed, makes therapeutic intervention unrewarding

Bistable Percepts in the Brain: fMRI Contrasts Monocular Pattern Rivalry and Binocular Rivalry

The neural correlates of binocular rivalry have been actively debated in recent years, and are of considerable interest as they may shed light on mechanisms of conscious awareness. In a related phenomenon, monocular rivalry, a composite image is shown to both eyes. The subject experiences perceptual alternations in which the two stimulus components alternate in clarity or salience. The experience is similar to perceptual alternations in binocular rivalry, although the reduction in visibility of the suppressed component is greater for binocular rivalry, especially at higher stimulus contrasts. We used fMRI at 3T to image activity in visual cortex while subjects perceived either monocular or binocular rivalry, or a matched non-rivalrous control condition. The stimulus patterns were left/right oblique gratings with the luminance contrast set at 9%, 18% or 36%. Compared to a blank screen, both binocular and monocular rivalry showed a U-shaped function of activation as a function of stimulus contrast, i.e. higher activity for most areas at 9% and 36%. The sites of cortical activation for monocular rivalry included occipital pole (V1, V2, V3), ventral temporal, and superior parietal cortex. The additional areas for binocular rivalry included lateral occipital regions, as well as inferior parietal cortex close to the temporoparietal junction (TPJ). In particular, higher-tier areas MT+ and V3A were more active for binocular than monocular rivalry for all contrasts. In comparison, activation in V2 and V3 was reduced for binocular compared to monocular rivalry at the higher contrasts that evoked stronger binocular perceptual suppression, indicating that the effects of suppression are not limited to interocular suppression in V1

Cost-effectiveness of cognitive behaviour therapy versus talking and usual care for depressed older people in primary care

Background: Whilst evidence suggests cognitive behaviour therapy (CBT) may be effective for depressed older people in a primary care setting, few studies have examined its cost-effectiveness. The aim of this study was to compare the cost-effectiveness of cognitive behaviour therapy (CBT), a talking control (TC) and treatment as usual (TAU), delivered in a primary care setting, for older people with depression.Methods: Cost data generated from a single blind randomised controlled trial of 204 people aged 65 years or more were offered only Treatment as Usual, or TAU plus up to twelve sessions of CBT or a talking control is presented. The Beck Depression Inventory II (BDI-II) was the main outcome measure for depression. Direct treatment costs were compared with reductions in depression scores. Cost-effectiveness analysis was conducted using non-parametric bootstrapping. The primary analysis focussed on the cost-effectiveness of CBT compared with TAU at 10 months follow up.Results: Complete cost data were available for 198 patients at 4 and 10 month follow up. There were no significant differences between groups in baseline costs. The majority of health service contacts at follow up were made with general practitioners. Fewer contacts with mental health services were recorded in patients allocated to CBT, though these differences were not significant. Overall total per patient costs (including intervention costs) were significantly higher in the CBT group compared with the TAU group at 10 month follow up (difference 427 pound, 95% CI: 56 pound - 787 pound, p < 0.001). Reductions in BDI-II scores were significantly greater in the CBT group (difference 3.6 points, 95% CI: 0.7-6.5 points, p = 0.018). CBT is associated with an incremental cost of 120 pound per additional point reduction in BDI score and a 90% probability of being considered cost-effective if purchasers are willing to pay up to 270 pound per point reduction in the BDI-II score.Conclusions: CBT is significantly more costly than TAU alone or TAU plus TC, but more clinically effective. Based on current estimates, CBT is likely to be recommended as a cost-effective treatment option for this patient group if the value placed on a unit reduction in BDI-II is greater than 115 pound