Eicosapentaenoic acid and oxypurinol in the treatment of muscle wasting in a mouse model of cancer cachexia

Cancer cachexia is a wasting condition, driven by systemic inflammation and oxidative stress. This study investigated eicosapentaenoic acid (EPA) in combination with oxypurinol as a treatment in a mouse model of cancer cachexia. Mice with cancer cachexia were randomized into 4 treatment groups (EPA (0.4 g/kg/day), oxypurinol (1 mmol/L ad-lib), combination, or control), and euthanized after 29 days. Analysis of oxidative damage to DNA, mRNA analysis of pro-oxidant, antioxidant and proteolytic pathway components, along with enzyme activity of pro- and antioxidants were completed on gastrocnemius muscle. The control group displayed earlier onset of tumor compared to EPA and oxypurinol groups (P&lt;0.001). The EPA group maintained body weight for an extended duration (20 days) compared to the oxypurinol (5 days) and combination (8 days) groups (P&lt;0.05). EPA (18.2&plusmn;3.2 pg/ml) and combination (18.4&plusmn;3.7 pg/ml) groups had significantly higher 8-OH-dG levels than the control group (12.9&plusmn;1.4 pg/ml, P&le;0.05) indicating increased oxidative damage to DNA. mRNA levels of GPx1, MURF1 and MAFbx were higher following EPA treatment compared to control (P&le;0.05). Whereas oxypurinol was associated with higher GPx1, MnSOD, CAT, XDH, MURF1, MAFbx and UbB mRNA compared to control (P&le;0.05). Activity of total SOD was higher in the oxypurinol group (32.2&plusmn;1.5 U/ml) compared to control (27.0&plusmn;1.3 U/ml, P&lt;0.01), GPx activity was lower in the EPA group (8.76&plusmn;2.0 U/ml) compared to control (14.0&plusmn;1.9 U/ml, P&lt;0.05), and catalase activity was lower in the combination group (14.4&plusmn;2.8 U/ml) compared to control (20.9&plusmn;2.0 U/ml, P&lt;0.01). There was no change in XO activity. The increased rate of weight decline in mice treated with oxypurinol indicates that XO may play a protective role during the progression of cancer cachexia, and its inhibition is detrimental to outcomes. In combination with EPA, there was little significant improvement from control, indicating oxypurinol is unlikely to be a viable treatment compound in cancer cachexia.<br /

Midlife women, bone health, vegetables, herbs and fruit study. The Scarborough Fair study protocol

BACKGROUND: Bone loss is accelerated in middle aged women but increased fruit/vegetable intake positively affects bone health by provision of micronutrients essential for bone formation, buffer precursors which reduce acid load and phytochemicals affecting inflammation and oxidative stress. Animal studies demonstrated bone resorption inhibiting properties of specific vegetables, fruit and herbs a decade ago. Objective: To increase fruit/vegetable intake in post menopausal women to 9 servings/day using a food specific approach to significantly reduce dietary acid load and include specific vegetables, fruit and herbs with bone resorbing inhibiting properties to assess effect on bone turnover, metabolic and inflammatory markers. METHODS/DESIGN: The Scarborough Fair Study is a randomised active comparator controlled multi centre trial. It aimed to increase fruit and vegetable intake in 100 post menopausal women from ≤ 5 servings/day to ≥ 9 servings/day for 3 months. The women in the dietary intervention were randomly assigned to one of the two arms of the study. Both groups consumed ≥ 9 servings/day of fruit/vegetables and selected herbs but the diet of each group emphasised different fruit/vegetables/herbs with one group (B) selecting from a range of vegetables, fruit and culinary herbs with bone resorbing inhibiting properties. 50 women formed a negative control group (Group C usual diet). Primary outcome variables were plasma bone markers assessed at baseline, 6 weeks and 12 weeks. Secondary outcome variables were plasma inflammation and metabolic markers and urinary electrolytes (calcium, magnesium, potassium and sodium) assessed at baseline and 12 weeks. Dietary intake and urine pH change also were outcome variables. The dietary change was calculated with 3 day diet diaries and a 24 hour recall. Intervention participants kept a twice weekly record of fruit, vegetable and herb intake and urine pH. DISCUSSION: This study will provide information on midlife women’s bone health and how a dietary intervention increasing fruit and vegetable/herb intake affects bone, inflammatory and metabolic markers and urinary electrolyte excretion. It assesses changes in nutrient intake, estimated dietary acid load and sodium: potassium ratios. The study also explores whether specific fruit/vegetables and herbs with bone resorbing properties has an effect on bone markers. TRIAL REGISTRATION: ACTRN 1261100076394

What Drives Inventory Accumulation? : News on Rates of Return and Marginal Costs

We study the effects of news shocks on inventory accumulation in a structural VAR framework. We establish that inventories react strongly and positively to news about future increases in total factor productivity. Theory suggests that the transmission channel of news shocks to inventories works through movements in marginal costs, through movements in sales, or through interest rates. We provide evidence that changes in external and internal rates of return are central to the transmission for such news shocks. We do not find evidence of a strong substitution effect that shifts production from the present into the future

Revisiting diversity and difference in early childhood through children’s news media

Children’s access to certain knowledge, often deemed inappropriate for children by adults, has been at the core of many controversies in children’s early education. This is particularly the case in terms of the censorship associated with children’s access to what has been broadly viewed as ‘difficult knowledge’ – bodies of knowledge pertaining to sexuality, death, war, poverty, and violence, for example. In some western countries, the discourse of childhood innocence has been a powerful mediator/regulator of children’s access to knowledge and has influenced how children are viewed as active citizens in their everyday lives (Robinson, 2013). However, it is now more widely accepted that children are competent, knowing beings in and of the world, readily taking up, processing and challenging messages about a raft of uncomfortable and inequitable realities, from global warming, to sexism, to racial intolerance, to class prejudice (Osgood et al., 2016). This view of children and childhood requires that approaches to pedagogy, policy and practice around diversity and difference in early childhood education attend to children as knowers and doers in the world (Osgood, 2012; Osgood and Robinson, 2019; Robinson and Jones Díaz, 2016)

Geotechnical properties of paper recycling waste streams

This paper studies two waste streams of the paper recycling industry for potential use in geotechnical applications. Namely, de-inking paper sludge from the secondary treatment stage, and paper sludge ash (PSA) obtained from the incineration of this sludge. Salient geotechnical properties of the statically compacted sludge before and after stabilisation with lime or PSA are presented. Tests include shear box testing, uniaxial compressive strength (UCS) testing, 1-D swelling and compression in oedometric conditions, p-wave velocity measurements using a Portable Ultrasonic Non-destructive Digital Indicating Tester (PUNDIT), and filter paper testing to determine water retention characteristics. The volume changes of the untreated sludge were found to be considerable in all above tests; however its shear strength at a highly compacted state was overall adequate. Chemical stabilization of the sludge was effective in reducing volume changes. The PSA was also assessed as a silt soil stabiliser. As geomaterial stabiliser, PSA was found to have a similar or better performance than lime. Overall the results are encouraging and indicate that it is possible to use paper industry waste in geotechnical applications

The Effect of Crystallization on the Pulsations of White Dwarf Stars

We consider the pulsational properties of white dwarf star models with temperatures appropriate for the ZZ Ceti instability strip and with masses large enough that they should be substantially crystallized. Our work is motivated by the existence of a potentially crystallized DAV, BPM 37093, and the expectation that digital surveys in progress will yield many more such massive pulsators. A crystallized core makes possible a new class of oscillations, the torsional modes, although we expect these modes to couple at most weakly to any motions in the fluid and therefore to remain unobservable. The p-modes should be affected at the level of a few percent in period, but are unlikely to be present with observable amplitudes in crystallizing white dwarfs any more than they are in the other ZZ Ceti's. Most relevant to the observed light variations in white dwarfs are the g-modes. We find that the kinetic energy of these modes is effectively excluded from the crystallized cores of our models. As increasing crystallization pushes these modes farther out from the center, the mean period spacing between radial overtones increases substantially with the crystallized mass fraction. In addition, the degree and structure of mode trapping is affected. The fact that some periods are strongly affected by changes in the crystallized mass fraction while others are not suggests that we may be able to disentangle the effects of crystallization from those due to different surface layer masses.Comment: 18 pages, 5 figures, accepted on 1999 July 2 for publication in the Astrophysical Journa

Observations of the Cosmic Microwave Background and Implications for Cosmology and Large Scale Structure

Observations of the Cosmic Microwave Background (CMB) are discussed, with particular emphasis on current ground-based experiments and on future satellite, balloon and interferometer experiments. Observational techniques and the effects of contaminating foregrounds are highlighted. Recent CMB data is used with large scale structure (LSS) data to constrain cosmological parameters and the complementary nature of CMB, LSS and supernova distance data is emphasized.Comment: 23 pages, 10 figures. Phil. Trans. R. Soc. Lond. A., 1998, in pres

Deprescribing intervention activities mapped to guiding principles for use in general practice: a scoping review

Objective: To identify and characterise activities for deprescribing used in general practice and to map the identified activities to pioneering principles of deprescribing. Setting: Primary care. Data sources: Medline, EMBASE (Ovid), CINAHL, Australian New Zealand Clinical Trials Registry (ANZCTR), Clinicaltrials.gov, ISRCTN registry, OpenGrey, Annals of Family Medicine, BMC Family Practice, Family Practice and British Journal of General Practice (BJGP) from inception to the end of June 2021. Study: selection Included studies were original research (randomised controlled trial, quasi-experimental, cohort study, qualitative and case studies), protocol papers and protocol registrations. Data extraction: Screening and data extraction was completed by one reviewer; 10% of the studies were independently reviewed by a second reviewer. Coding of full-text articles in NVivo was conducted and mapped to five deprescribing principles. Results: Fifty studies were included. The most frequently used activities were identification of appropriate patients for deprescribing (76%), patient education (50%), general practitioners (GP) education (48%), and development and use of a tapering schedule (38%). Six activities did not align with the five deprescribing principles. As such, two principles (engage practice staff in education and appropriate identification of patients, and provide feedback to staff about deprescribing occurrences within the practice) were added. Conclusion: Activities and guiding principles for deprescribing should be paired together to provide an accessible and comprehensive guide to deprescribing by GPs. The addition of two principles suggests that practice staff and practice management teams may play an instrumental role in sustaining deprescribing processes within clinical practice. Future research is required to determine the most of effective activities to use within each principle and by whom