Radiation mitigating properties of the lignan component in flaxseed

BACKGROUND: Wholegrain flaxseed (FS), and its lignan component (FLC) consisting mainly of secoisolariciresinol diglucoside (SDG), have potent lung radioprotective properties while not abrogating the efficacy of radiotherapy. However, while the whole grain was recently shown to also have potent mitigating properties in a thoracic radiation pneumonopathy model, the bioactive component in the grain responsible for the mitigation of lung damage was never identified. Lungs may be exposed to radiation therapeutically for thoracic malignancies or incidentally following detonation of a radiological dispersion device. This could potentially lead to pulmonary inflammation, oxidative tissue injury, and fibrosis. This study aimed to evaluate the radiation mitigating effects of FLC in a mouse model of radiation pneumonopathy. METHODS: We evaluated FLC-supplemented diets containing SDG lignan levels comparable to those in 10% and 20% whole grain diets. 10% or 20% FLC diets as compared to an isocaloric control diet (0% FLC) were given to mice (C57/BL6) (n=15-30 mice/group) at 24, 48, or 72-hours after single-dose (13.5 Gy) thoracic x-ray treatment (XRT). Mice were evaluated 4 months post-XRT for blood oxygenation, lung inflammation, fibrosis, cytokine and oxidative damage levels, and survival. RESULTS: FLC significantly mitigated radiation-related animal death. Specifically, mice fed 0% FLC demonstrated 36.7% survival 4 months post-XRT compared to 60–73.3% survival in mice fed 10%-20% FLC initiated 24–72 hours post-XRT. FLC also mitigated radiation-induced lung fibrosis whereby 10% FLC initiated 24-hours post-XRT significantly decreased fibrosis as compared to mice fed control diet while the corresponding TGF-beta1 levels detected immunohistochemically were also decreased. Additionally, 10-20% FLC initiated at any time point post radiation exposure, mitigated radiation-induced lung injury evidenced by decreased bronchoalveolar lavage (BAL) protein and inflammatory cytokine/chemokine release at 16 weeks post-XRT. Importantly, neutrophilic and overall inflammatory cell infiltrate in airways and levels of nitrotyrosine and malondialdehyde (protein and lipid oxidation, respectively) were also mitigated by the lignan diet. CONCLUSIONS: Dietary FLC given early post-XRT mitigated radiation effects by decreasing inflammation, lung injury and eventual fibrosis while improving survival. FLC may be a useful agent, mitigating adverse effects of radiation in individuals exposed to incidental radiation, inhaled radioisotopes or even after the initiation of radiation therapy to treat malignancy

Measuring the Physiologic Properties of Oral Lesions Receiving Fractionated Photodynamic Therapy

Photodynamic therapy (PDT) can treat superficial, early‐stage disease with minimal damage to underlying tissues and without cumulative dose‐limiting toxicity. Treatment efficacy is affected by disease physiologic properties, but these properties are not routinely measured. We assessed diffuse reflectance spectroscopy (DRS) for the noninvasive, contact measurement of tissue hemoglobin oxygen saturation (StO2) and total hemoglobin concentration ([tHb]) in the premalignant or superficial microinvasive oral lesions of patients treated with 5‐aminolevulinic acid (ALA)‐PDT. Patients were enrolled on a Phase 1 study of ALA‐PDT that evaluated fluences of 50, 100, 150 or 200 J cm−2 delivered at 100 mW cm−2. To test the feasibility of incorporating DRS measurements within the illumination period, studies were performed in patients who received fractionated (two‐part) illumination that included a dark interval of 90–180 s. Using DRS, tissue oxygenation at different depths within the lesion could also be assessed. DRS could be performed concurrently with contact measurements of photosensitizer levels by fluorescence spectroscopy, but a separate noncontact fluorescence spectroscopy system provided continuous assessment of photobleaching during illumination to greater tissue depths. Results establish that the integration of DRS into PDT of early‐stage oral disease is feasible, and motivates further studies to evaluate its predictive and dosimetric value.Diffuse reflectance spectroscopy with a contact probe was employed as part of a fluorescence and reflectance spectroscopy system to measure the tissue hemoglobin oxygen saturation and hemoglobin content of lesions of premalignant or early microinvasive cancer of the oral cavity. Studies demonstrate the feasibility of incorporating these measurements into treatment with fractionated (two‐part) photodynamic therapy (PDT) using 5‐aminolevulinic acid. Patient‐specific differences in physiologic parameters were detectable at baseline and at times during and after PDT. Photobleaching of photosensitizer was measured by its fluorescence. Results establish the utility of rationally designed spectroscopy probes toward personalized dosimetry in PDT of oral disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113767/1/php12475.pd

Quality differences assessment in canned sardine (Sardina pilchardus) by fluorescence detection

5 páginas, 4 figuras, 2 tablas.-- This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Agricultural and Food Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jf970056lChilled (0, 2, 6, 10, 13, and 15 days) and frozen (0, 0.5, 2, 4, 8, and 12 months) sardines were used to determine the influence of such storage times of fish over the quality of the final canned product. Traditional determinations of lipid quality (free fatty acids content, thiobarbituric acid index, and polyene index) were studied and compared with the formation of fluorescent compounds expressed as the ratio between fluorescence readings taken at two excitation/emission maxima (393/463 and 327/415 nm). No clear correlations were found between the common measurements of lipid deterioration and the time of storage prior to canning. Satisfactory correlations were found between the fluorescence ratio obtained from the filling medium of cans and the time of storage of the starting material (r = 0.90 and 0.91 in brine- and oil-canned samples, respectively). According to the present results, fluorescence detection of interaction compounds can provide a rapid and sensible method to assess quality differences in the final product as it relates to the quality of the raw material usedWe thank the Xunta de Galicia for financial support (Project XUGA 402 01B93).Peer reviewe

Statistical learning model of the sense of agency

A sense of agency (SoA) is the experience of subjective awareness regarding the control of one’s actions. Humans have a natural tendency to generate prediction models of the environment and adapt their models according to changes in the environment. The SoA is associated with the degree of the adaptation of the prediction models, e.g., insufficient adaptation causes low predictability and lowers the SoA over the environment. Thus, identifying the mechanisms behind the adaptation process of a prediction model related to the SoA is essential for understanding the generative process of the SoA. In the first half of the current study, we constructed a mathematical model in which the SoA represents a likelihood value for a given observation (sensory feedback) in a prediction model of the environment and in which the prediction model is updated according to the likelihood value. From our mathematical model, we theoretically derived a testable hypothesis that the prediction model is updated according to a Bayesian rule or a stochastic gradient. In the second half of our study, we focused on the experimental examination of this hypothesis. In our experiment, human subjects were repeatedly asked to observe a moving square on a computer screen and press a button after a beep sound. The button press resulted in an abrupt jump of the moving square on the screen. Experiencing the various stochastic time intervals between the action execution (button-press) and the consequent event (square jumping) caused gradual changes in the subjects’ degree of their SoA. By comparing the above theoretical hypothesis with the experimental results, we concluded that the update (adaptation) rule of the prediction model based on the SoA is better described by a Bayesian update than by a stochastic gradient descent

Optical depth estimates and effective critical densities of dense gas tracers in the inner parts of nearby galaxy discs

High critical density molecular lines like HCN (1-0) or HCO+ (1-0) represent our best tool to study currently star-forming, dense molecular gas at extragalactic distances. The optical depth of these lines is a key ingredient to estimate the effective density required to excite emission. However, constraints on this quantity are even scarcer in the literature than measurements of the high-density tracers themselves. Here, we combine new observations of HCN, HCO+ and HNC(1-0) and their optically thin isotopologuesH13CN,H13CO+ andHN13C (1-0) to measure isotopologue line ratios.We use IRAM30-m observations from the large programme EMPIRE and new Atacama Large Millimetre/submillimetre Array observations, which together target six nearby star-forming galaxies. Using spectral stacking techniques, we calculate or place strong upper limits on the HCN/H13CN, HCO+/H13CO+ and HNC/HN13C line ratios in the inner parts of these galaxies. Under simple assumptions, we use these to estimate the optical depths of HCN (1-0) and HCO+ (1-0) to be t ~ 2-11 in the active, inner regions of our targets. The critical densities are consequently lowered to values between 5 and 20 × 105 cm-3, 1 and 3 × 105 cm-3 and 9 × 104 cm-3 for HCN, HCO+ and HNC, respectively.We study the impact of having different beam-filling factors, η, on these estimates and find that the effective critical densities decrease by a factor of η12 /η13 τ12. A comparison to existing work in NGC 5194 and NGC 253 shows the HCN/H13CN and HCO+/H13CO+ ratios in agreement with our measurements within the uncertainties. The same is true for studies in other environments such as the Galactic Centre or nuclear regions of active galactic nucleus dominated nearby galaxie

To treat or not to treat: comparison of different criteria used to determine whether weight loss is to be recommended

Background: Excess body fat is a major risk factor for disease primarily due to its endocrine activity. In recent years several criteria have been introduced to evaluate this factor. Nevertheless, treatment need is currently assessed only on the basis of an individual's Body Mass Index (BMI), calculated as body weight (in kg) divided by height in m2. The aim of our study was to determine whether application of the BMI, compared to adiposity-based criteria, results in underestimation of the number of subjects needing lifestyle intervention. Methods: We compared treatment need based on BMI classification with four adiposity-based criteria: percentage body fat (%BF), considered both alone and in relation to metabolic syndrome risk (MS), waist circumference (WC), as an index of abdominal fat, and Body Fat Mass Index (BFMI, calculated as fat mass in kg divided by height in m2) in 63 volunteers (23 men and 40 women, aged 20 – 65 years). Results: According to the classification based on BMI, 6.3% of subjects were underweight, 52.4% were normal weight, 30.2% were overweight, and 11.1% were obese. Agreement between the BMI categories and the other classification criteria categories varied; the most notable discrepancy emerged in the underweight and overweight categories. BMI compared to almost all of the other adiposity-based criteria, identified a lower percentage of subjects for whom treatment would be recommended. In particular, the proportion of subjects for whom clinicians would strongly recommend weight loss on the basis of their BMI (11.1%) was significantly lower than those identified according to WC (25.4%, p = 0.004), %BF (28.6%, p = 0.003), and MS (33.9%, p = 0.002). Conclusion: The use of the BMI alone, as opposed to an assessment based on body composition, to identify individuals needing lifestyle intervention may lead to unfortunate misclassifications. Population-specific data on the relationships between body composition, morbidity, and mortality are needed to improve the diagnosis and treatment of at-risk individual

Successful Cognitive Aging in Rats: A Role for mGluR5 Glutamate Receptors, Homer 1 Proteins and Downstream Signaling Pathways

Normal aging is associated with impairments in cognition, especially learning and memory. However, major individual differences are known to exist. Using the classical Morris Water Maze (MWM) task, we discriminated a population of 24-months old Long Evans aged rats in two groups - memory-impaired (AI) and memory-unimpaired (AU) in comparison with 6-months old adult animals. AI rats presented deficits in learning, reverse memory and retention. At the molecular level, an increase in metabotropic glutamate receptors 5 (mGluR5) was observed in post-synaptic densities (PSD) in the hippocampus of AU rats after training. Scaffolding Homer 1b/c proteins binding to group 1 mGluR facilitate coupling with its signaling effectors while Homer 1a reduces it. Both Homer 1a and 1b/c levels were up-regulated in the hippocampus PSD of AU animals following MWM task. Using immunohistochemistry we further demonstrated that mGluR5 as well as Homer 1b/c stainings were enhanced in the CA1 hippocampus sub-field of AU animals. In fact mGluR5 and Homer 1 isoforms were more abundant and co-localized in the hippocampal dendrites in AU rats. However, the ratio of Homer 1a/Homer 1b/c bound to mGluR5 in the PSD was four times lower for AU animals compared to AI rats. Consequently, AU animals presented higher PKCγ, ERK, p70S6K, mTOR and CREB activation. Finally the expression of immediate early gene Arc/Arg3.1 was shown to be higher in AU rats in accordance with its role in spatial memory consolidation. On the basis of these results, a model of successful cognitive aging with a critical role for mGluR5, Homer 1 proteins and downstream signalling pathways is proposed here

Dietary intakes in infertile women a pilot study

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens