Interactions of short-term and chronic treadmill training with aging of the left ventricle of the heart

With aging, there is a decline in cardiac function accompanying increasing risk of arrhythmias. These effects are likely to be mechanistically associated with age-associated changes in calcium regulation within cardiac myocytes. Previous studies suggest that lifelong exercise can potentially reduce age-associated changes in the heart. Although exercise itself is associated with changes in cardiac function, little is known about the interactions of aging and exercise with respect to myocyte calcium regulation. To investigate this, adult (12 months) and old (24 months) C57/Bl6 mice were trained using moderate-intensity treadmill running. In response to 10 weeks’ training, comparable cardiac hypertrophic responses were observed, although aging independently associated with additional cardiac hypertrophy. Old animals also showed increased L- and T-type calcium channels, the sodium–calcium exchange, sarcoendoplasmic reticulum calcium ATPase, and collagen (by 50%, 92%, 66%, 88%, and 113% respectively). Short-term exercise training increased D-type and T-type calcium channels in old animals only, whereas an increase in sodium–calcium exchange was seen only in adult animals. Long-term (12 months) training generally opposed the effects of aging. Significant hypertrophy remained in long-term trained old animals, but levels of sarcoendoplasmic reticulum calcium ATPase, sodium–calcium exchange, and collagen were not significantly different from those found in the adult trained animals

Oral administration of pharmacologically active substances to squid : a methodological description

Author Posting. © Marine Biological Laboratory, 2009. This article is posted here by permission of Marine Biological Laboratory for personal use, not for redistribution. The definitive version was published in Biological Bulletin 216 (2009): 1-6.The squid giant synapse is a well-defined experimental preparation for the study of ligand-dependant synaptic transmission. Its large size gives direct experimental access to both presynaptic and postsynaptic junctional elements, allowing direct optical, biophysical, and electrophysiological analysis of depolarization-release coupling. However, this important model has not been utilized in pharmacological studies, other than those implementable acutely in the in vitro condition. A method is presented for oral administration of bioactive substances to living squid. Electrophysiological characterization and direct determination of drug absorption into the nervous system demonstrate the administration method described here to be appropriate for pharmacological research.The studies were supported by National Institute of Health Grant NS13742 (to RLL and MS)

Association between the timing of childhood adversity and epigenetic patterns across childhood and adolescence:findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort

BACKGROUND: Childhood adversity is a potent determinant of health across development and is associated with altered DNA methylation signatures, which might be more common in children exposed during sensitive periods in development. However, it remains unclear whether adversity has persistent epigenetic associations across childhood and adolescence. We aimed to examine the relationship between time-varying adversity (defined through sensitive period, accumulation of risk, and recency life course hypotheses) and genome-wide DNA methylation, measured three times from birth to adolescence, using data from a prospective, longitudinal cohort study.METHODS: We first investigated the relationship between the timing of exposure to childhood adversity between birth and 11 years and blood DNA methylation at age 15 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort study. Our analytic sample included ALSPAC participants with DNA methylation data and complete childhood adversity data between birth and 11 years. We analysed seven types of adversity (caregiver physical or emotional abuse, sexual or physical abuse [by anyone], maternal psychopathology, one-adult households, family instability, financial hardship, and neighbourhood disadvantage) reported by mothers five to eight times between birth and 11 years. We used the structured life course modelling approach (SLCMA) to identify time-varying associations between childhood adversity and adolescent DNA methylation. Top loci were identified using an R 2 threshold of 0·035 (ie, ≥3·5% of DNA methylation variance explained by adversity). We attempted to replicate these associations using data from the Raine Study and Future of Families and Child Wellbeing Study (FFCWS). We also assessed the persistence of adversity-DNA methylation associations we previously identified from age 7 blood DNA methylation into adolescence and the influence of adversity on DNA methylation trajectories from ages 0-15 years. FINDINGS: Of 13 988 children in the ALSPAC cohort, 609-665 children (311-337 [50-51%] boys and 298-332 [49-50%] girls) had complete data available for at least one of the seven childhood adversities and DNA methylation at 15 years. Exposure to adversity was associated with differences in DNA methylation at 15 years for 41 loci (R 2 ≥0·035). Sensitive periods were the most often selected life course hypothesis by the SLCMA. 20 (49%) of 41 loci were associated with adversities occurring between age 3 and 5 years. Exposure to one-adult households was associated with differences in DNA methylation at 20 [49%] of 41 loci, exposure to financial hardship was associated with changes at nine (22%) loci, and physical or sexual abuse was associated with changes at four (10%) loci. We replicated the direction of associations for 18 (90%) of 20 loci associated with exposure to one-adult household using adolescent blood DNA methylation from the Raine Study and 18 (64%) of 28 loci using saliva DNA methylation from the FFCWS. The directions of effects for 11 one-adult household loci were replicated in both cohorts. Differences in DNA methylation at 15 years were not present at 7 years and differences identified at 7 years were no longer apparent by 15 years. We also identified six distinct DNA methylation trajectories from these patterns of stability and persistence. INTERPRETATION: These findings highlight the time-varying effect of childhood adversity on DNA methylation profiles across development, which might link exposure to adversity to potential adverse health outcomes in children and adolescents. If replicated, these epigenetic signatures could ultimately serve as biological indicators or early warning signs of initiated disease processes, helping identify people at greater risk for the adverse health consequences of childhood adversity.FUNDING: Canadian Institutes of Health Research, Cohort and Longitudinal Studies Enhancement Resources, EU's Horizon 2020, US National Institute of Mental Health.</p

The effect of a brief social intervention on the examination results of UK medical students: a cluster randomised controlled trial

Background: Ethnic minority (EM) medical students and doctors underperform academically, but little evidence exists on how to ameliorate the problem. Psychologists Cohen et al. recently demonstrated that a written self-affirmation intervention substantially improved EM adolescents' school grades several months later. Cohen et al.'s methods were replicated in the different setting of UK undergraduate medical education.Methods: All 348 Year 3 white (W) and EM students at one UK medical school were randomly allocated to an intervention condition (writing about one's own values) or a control condition (writing about another's values), via their tutor group. Students and assessors were blind to the existence of the study. Group comparisons on post-intervention written and OSCE (clinical) assessment scores adjusted for baseline written assessment scores were made using two-way analysis of covariance. All assessment scores were transformed to z-scores (mean = 0 standard deviation = 1) for ease of comparison. Comparisons between types of words used in essays were calculated using t-tests. The study was covered by University Ethics Committee guidelines.Results: Groups were statistically identical at baseline on demographic and psychological factors, and analysis was by intention to treat [intervention group EM n = 95, W n = 79; control group EM n = 77; W n = 84]. As predicted, there was a significant ethnicity by intervention interaction [F(4,334) = 5.74; p = 0.017] on the written assessment. Unexpectedly, this was due to decreased scores in the W intervention group [mean difference = 0.283; (95% CI = 0.093 to 0.474] not improved EM intervention group scores [mean difference = -0.060 (95% CI = -0.268 to 0.148)]. On the OSCE, both W and EM intervention groups outperformed controls [mean difference = 0.261; (95% CI = -0.047 to -0.476; p = 0.013)]. The intervention group used more optimistic words (p < 0.001) and more "I" and "self" pronouns in their essays (p < 0.001), whereas the control group used more "other" pronouns (p < 0.001) and more negations (p < 0.001).Discussion: Cohen et al.'s finding that a brief self-affirmation task narrowed the ethnic academic achievement gap was replicated on the written assessment but against expectations, this was due to reduced performance in the W group. On the OSCE, the intervention improved performance in both W and EM groups. In the intervention condition, participants tended to write about themselves and used more optimistic words than in the control group, indicating the task was completed as requested. The study shows that minimal interventions can have substantial educational outcomes several months later, which has implications for the multitude of seemingly trivial changes in teaching that are made on an everyday basis, whose consequences are never formally assessed

The IGNITE (investigation to guide new insight into translational effectiveness) trial: Protocol for a translational study of an evidenced-based wellness program in fire departments

<p>Abstract</p> <p>Background</p> <p>Worksites are important locations for interventions to promote health. However, occupational programs with documented efficacy often are not used, and those being implemented have not been studied. The research in this report was funded through the American Reinvestment and Recovery Act Challenge Topic 'Pathways for Translational Research,' to define and prioritize determinants that enable and hinder translation of evidenced-based health interventions in well-defined settings.</p> <p>Methods</p> <p>The IGNITE (investigation to guide new insights for translational effectiveness) trial is a prospective cohort study of a worksite wellness and injury reduction program from adoption to final outcomes among 12 fire departments. It will employ a mixed methods strategy to define a translational model. We will assess decision to adopt, installation, use, and outcomes (reach, individual outcomes, and economic effects) using onsite measurements, surveys, focus groups, and key informant interviews. Quantitative data will be used to define the model and conduct mediation analysis of each translational phase. Qualitative data will expand on, challenge, and confirm survey findings and allow a more thorough understanding and convergent validity by overcoming biases in qualitative and quantitative methods used alone.</p> <p>Discussion</p> <p>Findings will inform worksite wellness in fire departments. The resultant prioritized influences and model of effective translation can be validated and manipulated in these and other settings to more efficiently move science to service.</p

Crop Updates 2007 - Lupins, Pulses and Oilseeds

This session covers forty eight papers from different authors: 2006 REGIONAL ROUNDUP 1. South east agricultural region, Mark Seymour1 and Jacinta Falconer2, 1Department of Agriculture and Food, 2Cooperative Bulk Handling Group 2. Central agricultural region, Ian Pritchard, Department of Agriculture and Food 3. Great Southern and Lakes region, Rodger Beermier, Department of Agriculture and Food 4. Northern agricultural region, Wayne Parker and Martin Harries, Department of Agriculture and Food LUPINS 5. Development of anthracnose resistant and early flowering albus lupins (Lupinus albus L) in Western Australia, Kedar Adhikari and Geoff Thomas, Department of Agriculture and Food 6. New lupins adapted to the south coast, Peter White, Bevan Buirchell and Mike Baker, Department of Agriculture and Food 7. Lupin species and row spacing interactions by environment, Martin Harries, Peter White, Bob French, Jo Walker, Mike Baker and Laurie Maiolo, Department of Agriculture and Food 8. The interaction of lupin species row spacing and soil type, Martin Harries, Bob French, Laurie Maiolo and Jo Walker, Department of Agriculture and Food 9. The effects of row spacing and crop density on competitiveness of lupins with wild radish, Bob French and Laurie Maiolo, Department of Agriculture and Food 10. The effect of time of sowing and radish weed density on lupin yield, Martin Harries and Jo Walker, Department of Agriculture and Food 11. Interaction of time of sowing and weed management in lupins, Martin Harries and Jo Walker, Department of Agriculture and Food 12. Delayed sowing as a strategy to manage annual ryegrass, Bob French and Laurie Maiolo, Department of Agriculture and Food 13. Is delayed sowing a good strategy for weed management in lupins? Bob French, Department of Agriculture and Food 14. Lupins aren’t lupins when it comes to simazine, Peter White and Leigh Smith, Department of Agriculture and Food 15. Seed yield and anthracnose resistance of Tanjil mutants tolerant to metribuzin, Ping Si1, Bevan Buirchell1,2 and Mark Sweetingham1,2, 1Centre for Legumes in Mediterranean Agriculture, Australia; 2Department of Agriculture and Food 16. The effect of herbicides on nodulation in lupins, Lorne Mills1, Harmohinder Dhammu2 and Beng Tan1, 1Curtin University of Technology and 2Department of Agriculture and Food 17. Effect of fertiliser placements and watering regimes on lupin growth and seed yield in the central grain belt of Western Australia, Qifu Ma1, Zed Rengel1, Bill Bowden2, Ross Brennan2, Reg Lunt2 and Tim Hilder2, 1Soil Science & Plant Nutrition UWA, 2Department of Agriculture and Food 18. Development of a forecasting model for Bean Yellow Mosaic Virus in lupins, T. Maling1,2, A. Diggle1, D. Thackray1,2, R.A.C. Jones2, and K.H.M. Siddique1, 1Centre for Legumes in Mediterranean Agriculture, The University of Western Australia; 2Department of Agriculture and Food 19. Manufacturing of lupin tempe,Vijay Jayasena1,4, Leonardus Kardono2,4, Ken Quail3,4 and Ranil Coorey1,4, 1Curtin University of Technology, Perth, Australia, 2Indonesian Institute of Sciences (LIPI), Indonesia, 3BRI Australia Ltd, Sydney, Australia, 4Grain Foods CRC, Sydney, Australia 20. The impact of lupin based ingredients in ice-cream, Hannah Williams, Lee Sheer Yap and Vijay Jayasena, Curtin University of Technology, Perth WA 21. The acceptability of muffins substituted with varying concentrations of lupin flour, Anthony James, Don Elani Jayawardena and Vijay Jayasena, Curtin University of Technology, PerthWA PULSES 22. Chickpea variety evaluation, Kerry Regan1, Rod Hunter1, Tanveer Khan1,2and Jenny Garlinge1, 1Department of Agriculture and Food, 2CLIMA, The University of Western Australia 23. Advanced breeding trials of desi chickpea, Khan, T.N.1, Siddique, K.H.M.3, Clarke, H.2, Turner, N.C.2, MacLeod, W.1, Morgan, S.1, and Harris, A.1, 1Department of Agriculture and Food, 2Centre for Legumes in Mediterranean Agriculture, 3TheUniversity of Western Australia 24. Ascochyta resistance in chickpea lines in Crop Variety Testing (CVT) of 2006, Tanveer Khan1 2, Bill MacLeod1, Alan Harris1, Stuart Morgan1and Kerry Regan1, 1Department of Agriculture and Food, 2CLIMA, The University of Western Australia 25. Yield evaluation of ascochyta blight resistant Kabuli chickpeas, Kerry Regan1and Kadambot Siddique2, 1Department of Agriculture and Food, 2Institute of Agriculture, The University of Western Australia 26. Pulse WA Chickpea Industry Survey 2006, Mark Seymour1, Ian Pritchard1, Wayne Parker1and Alan Meldrum2, 1Department of Agriculture and Food, 2Pulse Australia 27. Genes from the wild as a valuable genetic resource for chickpea improvement, Heather Clarke1, Helen Bowers1and Kadambot Siddique2, 1Centre for Legumes in Mediterranean Agriculture, 2Institute of Agriculture, The University of Western Australia 28. International screening of chickpea for resistance to Botrytis grey mould, B. MacLeod1, Dr T. Khan1, Prof. K.H.M. Siddique2and Dr A. Bakr3, 1Department of Agriculture and Food, 2The University of Western Australia, 3Bangladesh Agricultural Research Institute 29. Balance® in chickpea is safest applied post sowing to a level seed bed, Wayne Parker, Department of Agriculture and Food, 30. Demonstrations of Genesis 510 chickpea, Wayne Parker, Department of Agriculture and Food 31. Field pea 2006, Ian Pritchard, Department of Agriculture and Food 32. Field pea variety evaluation, Kerry Regan1, Rod Hunter1, Tanveer Khan1,2 and Jenny Garlinge1, 1Department of Agriculture and Food, 2CLIMA, The University of Western Australia 33. Breeding highlights of the Australian Field Pea Improvement Program (AFPIP),Kerry Regan1, Tanveer Khan1,2, Phillip Chambers1, Chris Veitch1, Stuart Morgan1 , Alan Harris1and Tony Leonforte3, 1Department of Agriculture and Food, 2CLIMA, The University of Western Australia, 3Department of Primary Industries, Victoria 34. Field pea germplasm enhancement for black spot resistance, Tanveer Khan, Kerry Regan, Stuart Morgan, Alan Harris and Phillip Chambers, Department of Agriculture and Food 35. Validation of Blackspot spore release model and testing moderately resistant field pea line, Mark Seymour, Ian Pritchard, Rodger Beermier, Pam Burgess and Leanne Young, Department of Agriculture and Food 36. Yield losses from sowing field pea seed infected with Pea Seed-borne Mosaic Virus, Brenda Coutts, Donna O’Keefe, Rhonda Pearce, Monica Kehoe and Roger Jones, Department of Agriculture and Food 37. Faba bean in 2006, Mark Seymour, Department of Agriculture and Food 38. Germplasm evaluation – faba bean, Mark Seymour1, Terri Jasper1, Ian Pritchard1, Mike Baker1 and Tim Pope1,2, 1Department of Agriculture and Food, , 2CLIMA, The University of Western Australia 39. Breeding highlights of the Coordinated Improvement Program for Australian Lentils (CIPAL), Kerry Regan1, Chris Veitch1, Phillip Chambers1 and Michael Materne2, 1Department of Agriculture and Food, 2Department of Primary Industries, Victoria 40. Screening pulse lentil germplasm for tolerance to alternate herbicides, Ping Si1, Mike Walsh2 and Mark Sweetingham1,3, 1Centre for Legumes in Mediterranean Agriculture, 2West Australian Herbicide Resistance Initiative, 3Department of Agriculture and Food 41. Genomic synteny in legumes: Application to crop breeding, Phan, H.T.T.1, Ellwood, S.R.1, Hane, J.1, Williams, A.1, Ford, R.2, Thomas, S.3 and Oliver R1, 1Australian Centre of Necrotrophic Plant Pathogens, Murdoch University, 2BioMarka, University of Melbourne, 3NSW Department of Primary Industries 42. Tolerance of lupins, chickpeas and canola to Balanceâ(Isoxaflutole) and Galleryâ (Isoxaben), Leigh Smith and Peter White, Department of Agriculture and Food CANOLA AND OILSEEDS 43. The performance of TT Canola varieties in the National Variety Test (NVT),WA,2006,Katie Robinson, Research Agronomist, Agritech Crop Research 44. Evaluation of Brassica crops for biodiesel in Western Australia, Mohammad Amjad, Graham Walton, Pat Fels and Andy Sutherland, Department of Agriculture and Food 45. Production risk of canola in different rainfall zones in Western Australia, Imma Farré1, Michael Robertson2 and Senthold Asseng3, 1Department of Agriculture and Food, 2CSIRO Sustainable Ecosystems, 3CSIRO Plant Industry 46. Future directions of blackleg management – dynamics of blackleg susceptibility in canola varieties, Ravjit Khangura, Moin Salam and Bill MacLeod, Department of Agriculture and Food 47. Appendix 1: Contributors 48. Appendix 2: List of common acronym

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone