Exercise-induced muscle damage, plasma cytokines and markers of neutrophil activation

Introduction: Unaccustomed eccentric exercise often results in muscle damage and neutrophil activation. We examined changes in plasma cytokines stress hormones, creatine kinase activity and myoglobin concentration, neutrophil surface receptor expression, degranulation, and the capacity of neutrophils to generate reactive oxygen species in response to in vitro stimulation after downhill running. Methods: Ten well-trained male runners ran downhill on a treadmill at a gradient of -10% for 45 min at 60% V̇O2max. Blood was sampled immediately before (PRE) and after (POST), 1 h (1 h POST), and 24 h (24 h POST) after exercise. Results: At POST, there were significant increases (P < 0.01) in neutrophil count (32%), plasma interleukin (IL)-6 concentration (460%), myoglobin (Mb) concentration (1100%), and creatine kinase (CK) activity (40%). At 1 h POST, there were further increases above preexercise values for neutrophil count (85%), plasma Mb levels (1800%), and CK activity (56%), and plasma IL-6 concentration remained above preexercise values (410%) (P < 0.01). At 24 h POST, neutrophil counts and plasma IL-6 levels had returned to baseline, whereas plasma Mb concentration (100%) and CK activity (420%) were elevated above preexercise values (P < 0.01). There were no significant changes in neutrophil receptor expression, degranulation and respiratory burst activity, and plasma IL-8 and granulocyte-colony stimulating factor concentrations at any time after exercise. Neutrophil count correlated with plasma Mb concentration at POST (r = 0.64, P < 0.05), and with plasma CK activity at POST (r = 0.83, P < 0.01) and 1 h POST (r = 0.78, P < 0.01). Conclusion: Neutrophil activation remains unchanged after downhill running in well-trained runners, despite increases in plasma markers of muscle damage.

Computer simulation of underground blast response of pile in saturated soil

This paper treats the blast response of a pile foundation in saturated sand using explicit nonlinear finite element analysis, considering complex material behavior of soil and soil–pile interaction. Blast wave propagation in the soil is studied and the horizontal deformation of pile and effective stresses in the pile are presented. Results indicate that the upper part of the pile to be vulnerable and the pile response decays with distance from the explosive. The findings of this research provide valuable information on the effects of underground explosions on pile foundation and will guide future development, validation and application of computer models.

Intracellular trafficking and secretion of inflammatory cytokines

The secretion of cytokines by immune cells plays a significant role in determining the course of an inflammatory response. The levels and timing of each cytokine released are critical for mounting an effective but confined response, whereas excessive or dysregulated inflammation contributes to many diseases. Cytokines are both culprits and targets for effective treatments in some diseases. The multiple points and mechanisms that have evolved for cellular control of cytokine secretion highlight the potency of these mediators and the fine tuning required to manage inflammation. Cytokine production in cells is regulated by cell signaling, and at mRNA and protein synthesis levels. Thereafter, the intracellular transport pathways and molecular trafficking machinery have intricate and essential roles in dictating the release and activity of cytokines. The trafficking machinery and secretory (exocytic) pathways are complex and highly regulated in many cells, involving specialized membranes, molecules and organelles that enable these cells to deliver cytokines to often-distinct areas of the cell surface, in a timely manner. This review provides an overview of secretory pathways - both conventional and unconventional - and key families of trafficking machinery. The prevailing knowledge about the trafficking and secretion of a number of individual cytokines is also summarized. In conclusion, we present emerging concepts about the functional plasticity of secretory pathways and their modulation for controlling cytokines and inflammation.

Gender differences in rumination : a meta-analysis

Starting in adolescence and continuing through adulthood, women are twice as likely as men to experience depression. According to the response styles theory (RST), gender differences in depression result, in part, from women's tendency to ruminate more than men. A meta-analysis was performed to evaluate gender differences in rumination in adults (k = 59; N = 14,321); additionally, an analysis of subtypes of rumination - brooding and reflection - was conducted (k = 23). Fixed effects analyses indicated that women scored higher than men in rumination (d = .24, p < .01, SEd = .02), brooding (d = .19, p < .01, SEd = .03) and reflection (d = .17, p < .01, SEd = .03); there was no evidence of heterogeneity or publication bias across studies for these effect sizes. Although statistically significant, the effect sizes for gender differences in rumination were small in magnitude. Results are discussed with respect to the RST and gender differences in depression

ATM is required for the cellular response to thymidine induced replication fork stress

Genetically distinct checkpoints, activated as a consequence of either DNA replication arrest or ionizing radiation-induced DNA damage, integrate DNA repair responses into the cell cycle programme. The ataxia-telangiectasia mutated (ATM) protein kinase blocks cell cycle progression in response to DNA double strand breaks, whereas the related ATR is important in maintaining the integrity of the DNA replication apparatus. Here, we show that thymidine, which slows the progression of replication forks by depleting cellular pools of dCTP, induces a novel DNA damage response that, uniquely, depends on both ATM and ATR. Thymidine induces ATM-mediated phosphorylation of Chk2 and NBS1 and an ATM-independent phosphorylation of Chk1 and SMC1. AT cells exposed to thymidine showed decreased viability and failed to induce homologous recombination repair (HRR). Taken together, our results implicate ATM in the HRR-mediated rescue of replication forks impaired by thymidine treatment.

Chromatin modifications involved in the DNA damage response to double strand breaks

In eukaryotes, genomic DNA is tightly compacted into a protein-DNA complex known as chromatin. This dense structure presents a barrier to DNA-dependent processes including transcription, replication and DNA repair. The repressive structure of chromatin is overcome by ATP-dependent chromatin remodelling complexes and chromatin-modifying enzymes. There is now ample evidence that DNA double-strand breaks (DSBs) elicit various histone modifications (such as acetylation, deacetylation, and phosphorylation) that function combinatorially to control the dynamic structure of the chromatin microenvironment. The role of these mechanisms during transcription and replication has been well studied, while the research into their impact on regulation of DNA damage response is rapidly gaining momentum. How chromatin structure is remodeled in response to DNA damage and how such alterations influence DSB repair are currently significant questions. This review will summarise the major chromatin modifications and chromatin remodelling complexes implicated in the DNA damage response to DSBs.

Environmental pollution from shipbreaking industry : international law and national legal response

The international legal regime on shipbreaking is in its formative years. At the international level, the shipbreaking industry is partially governed by the Basel Convention on the Control of Transboundary Movements of Hazardous Wastes and their Disposal. However, how far this convention will be applicable for all aspects of transboundary movement of end-of-life ships is still, at least in the view of some scholars, a debatable issue. Against this backdrop, the International Maritime Organisation (IMO) has adopted a new, legally binding convention for shipbreaking. There is a rising voice from the developing countries that the convention is likely to impose more obligations on recycling facilities in the developing countries than on shipowners from rich nations. This may be identified as a clear derogation from the globally recognized international environmental law principle of common but differentiated treatment. This article will examine in detail major international conventions regulating transboundary movement and environmentally sound disposal of obsolete ships, as well as the corresponding laws of Bangladesh for implementing these conventions in the domestic arena. Moreover this article will examine in detail the recently adopted IMO Ship Recycling Convention.

Prescribing practices of Australian dispensing doctors

Background: In response to health workforce shortages policymakers have considered expanding the roles that a health professional may perform. A more traditional combination of health professional roles is that of a dispensing doctor (DD) who routinely prescribes and dispenses pharmaceuticals. A systematic review conducted on mainly overseas DDs’ practices found that DDs tended to prescribe more items per patients, less often generically, and showed poorer adherence to best practice. Convenience for patients was cited by both patients and DDs as the main reason for dispensing. In Australia, rural doctors are allowed to dispense Pharmaceutical Benefit Scheme (PBS) subsidised pharmaceutical benefits if there is no reasonable pharmacy coverage. Little was known about the practices of these Australian DDs. Objectives: To examine the PBS prescribing patterns of dispensing with matched non-dispensing doctors and identify factors that influence prescribing behaviour. Method: A sequential explanatory (QUAN-->qual) mixed methodology was utilised. Firstly, rurality-matched DDs’ and non-DDs’ PBS data for fiscal years 2005-7 were analysed against criteria distilled from a systematic review and stakeholder consultations. Secondly, structured interviews were conducted with a purposive sample of DDs to examine the quantitative findings. Key findings: DDs prescribed significantly fewer PBS prescriptions per patients but used Regulation 24 significantly more than non-DDs. Regulation 24 biased the prescribing data. DDs prescribed proportionally more penicillin type antibiotics, adrenergic inhalants and non-steroidal anti-inflammatories as compared to non-DDs. Reasons offered by DD-respondents highlighted that prescribing was influenced by an awareness of cost to the patients, peer pressure and confidential prescriber feedback provided on a regular basis. Implications: This innovative census study does not support international data that DDs are less judicious in their prescribing. There is some evidence that DDs might reduce health inequity between rural and urban Australian, and that the DD health model is valuable to patients in isolated communities.

The time course of in vivo recovery of transverse strain in high-stress tendons following exercise

Objective To evaluate the time course of the recovery of transverse strain in the Achilles and patellar tendon following a bout of resistance exercise. Methods Seventeen healthy adults underwent sonographic examination of the right patellar (n=9) and Achilles (n=8) tendons immediately prior to and following 90 repetitions of weight-bearing quadriceps and gastrocnemius-resistance exercise performed against an effective resistance of 175% and 250% body weight, respectively. Sagittal tendon thickness was determined 20 mm from the enthesis and transverse strain, as defined by the stretch ratio, was repeatedly monitored over a 24 h recovery period. Results Resistance exercise resulted in an immediate decrease in Achilles (t7=10.6, p<0.01) and patellar (t8=8.9, p<0.01) tendon thickness, resulting in an average transverse stretch ratio of 0.86±0.04 and 0.82±0.05, which was not significantly different between tendons. The magnitude of the immediate transverse strain response, however, was reduced with advancing age (r=0.63, p<0.01). Recovery in transverse strain was prolonged compared with the duration of loading and exponential in nature. The average primary recovery time was not significantly different between the Achilles (6.5±3.2 h) and patellar (7.1±3.2 h) tendons. Body weight accounted for 62% and 64% of the variation in recovery time, respectively. Conclusions Despite structural and biochemical differences between the Achilles and patellar tendon, the mechanisms underlying transverse creep recovery in vivo appear similar and are highly time dependent. These novel findings have important implications concerning the time required for the mechanical recovery of high-stress tendons following an acute bout of exercise.

The acute transverse strain response of the patellar tendon to quadriceps exercise

Introduction: The human patellar tendon is highly adaptive to changes in habitual loading but little is known about its acute mechanical response to exercise. This research evaluated the immediate transverse strain response of the patellar tendon to a bout of resistive quadriceps exercise. Methods: Twelve healthy adult males (mean age 34.0+/-12.1 years, height 1.75+/-0.09 m and weight 76.7+/-12.3 kg) free of knee pain participated in the research. A 10-5 MHz linear-array transducer was used to acquire standardised sagittal sonograms of the right patellar tendon immediately prior to and following 90 repetitions of a double-leg parallel-squat exercise performed against a resistance of 175% bodyweight. Tendon thickness was determined 20-mm distal to the pole of the patellar and transverse Hencky strain was calculated as the natural log of the ratio of post- to pre-exercise tendon thickness and expressed as a percentage. Measures of tendon echotexture (echogenicity and entropy) were also calculated from subsequent gray-scale profiles. Results: Quadriceps exercise resulted in an immediate decrease in patellar tendon thickness (P<.05), equating to a transverse strain of -22.5+/-3.4%, and was accompanied by increased tendon echogenicity (P<.05) and decreased entropy (P<.05). The transverse strain response of the patellar tendon was significantly correlated with both tendon echogenicity (r = -0.58, P<.05) and entropy following exercise (r=0.73, P<.05), while older age was associated with greater entropy of the patellar tendon prior to exercise (r=0.79, P<.05) and a reduced transverse strain response (r=0.61, P<.05) following exercise. Conclusions: This study is the first to show that quadriceps exercise invokes structural alignment and fluid movement within the matrix that are manifest by changes in echotexture and transverse strain in the patellar tendon., (C)2012The American College of Sports Medicine

Decision and reasons for calling an ambulance : patients’ perspective

Background: Demand for pre-hospital emergency care is increasing in Australia as in many other countries. Using posthoc criteria such as triage, diagnosis and admission status, some authors view a considerable number of these as "inappropriate". Yet, calling an ambulance at the time of emergency is rarely studied from the patients’ or their carers’ perspective. This study interviewed patients about the decision, circumstances surrounding and reasons for calling an ambulance in Queensland, Australia. Methods: A cross-sectional survey of patients attending a sample of eight public hospital emergency departments in Queensland was undertaken between March and May 2011. In total, 911 questionnaires were collected (response rate: 67%), of whom 226 (24.8%) had arrived by ambulance. Results: In 35.6% of ambulance arrivals, the decision to request an ambulance was made by the patient; 25% by a doctor; 20% by a family member, friend or carer. Other callers included nurse, people at work or school, and passers-by. Reasons to request an ambulance included urgency (87%) and severity (84%) of the condition. Other reasons included requiring special care (76%), getting higher priority at the emergency department (34%), not having a car (34%), and financial concerns (17%). Decision to request an ambulance varied significantly according to the time of illness onset (e.g. on the day, week before), and location (e.g. home, outside). Conclusion: The decision to call an ambulance is made mostly by non-medical professionals in a perceived emergency situation. They call the ambulance for different reasons but mainly take into account the patient’s welfare and safety. Better understanding of these reasons will affect the direction and effectiveness of demand management strategies.

Transcriptome analysis of neutrophils after endurance exercise reveals novel signaling mechanisms in the immune response to physiological stress

Neutrophils serve as an intriguing model for the study of innate immune cellular activity induced by physiological stress. We measured changes in the transcriptome of circulating neutrophils following an experimental exercise trial (EXTRI) consisting of 1 h of intense cycling immediately followed by 1 h of intense running. Blood samples were taken at baseline, 3 h, 48 h, and 96 h post-EXTRI from eight healthy, endurance-trained, male subjects. RNA was extracted from isolated neutrophils. Differential gene expression was evaluated using Illumina microarrays and validated with quantitative PCR. Gene set enrichment analysis identified enriched molecular signatures chosen from the Molecular Signatures Database. Blood concentrations of muscle damage indexes, neutrophils, interleukin (IL)-6 and IL-10 were increased (P < 0.05) 3 h post-EXTRI. Upregulated groups of functionally related genes 3 h post-EXTRI included gene sets associated with the recognition of tissue damage, the IL-1 receptor, and Toll-like receptor (TLR) pathways (familywise error rate, P value < 0.05). The core enrichment for these pathways included TLRs, low-affinity immunoglobulin receptors, S100 calcium binding protein A12, and negative regulators of innate immunity, e.g., IL-1 receptor antagonist, and IL-1 receptor associated kinase-3. Plasma myoglobin changes correlated with neutrophil TLR4 gene expression (r = 0.74; P < 0.05). Neutrophils had returned to their nonactivated state 48 h post-EXTRI, indicating that their initial proinflammatory response was transient and rapidly counterregulated. This study provides novel insight into the signaling mechanisms underlying the neutrophil responses to endurance exercise, suggesting that their transcriptional activity was particularly induced by damage-associated molecule patterns, hypothetically originating from the leakage of muscle components into the circulation.

(Re)imagining the world : children's literature's response to changing times

(Re)Imagining the world: Children’s Literature’s Response to Changing Times considers how writers of fiction for children imagine ‘the world’, not one universal world, but different worlds: imaginary, strange, familiar, even monstrous worlds. The chapters in this collection discuss how fiction for children engages with some of the changes brought about by new technologies, information literacy, consumerism, migration, politics, different family structures, cosmopolitanism, and new and old monsters. They also invite us to think about how memory shapes our understanding of the past, and how fiction engages our emotions, our capacity to empathize, our desire to discover, and what the future may hold. The contributors bring different perspectives from education, postcolonial studies, literary criticism, cultural studies, childhood studies, postmodernism, and the social sciences. With a wide coverage of texts from different countries, and scholarly and lively discussions, this collection is itself a testament to the power of the human imagination and the significance of children’s literature in the education of young people.

Damage identification and condition assessment of building structures using frequency response functions and neural networks

This thesis investigated the viability of using Frequency Response Functions in combination with Artificial Neural Network technique in damage assessment of building structures. The proposed approach can help overcome some of limitations associated with previously developed vibration based methods and assist in delivering more accurate and robust damage identification results. Excellent results are obtained for damage identification of the case studies proving that the proposed approach has been developed successfully.

Addressing vulnerability and human rights in disaster response mechanisms in Oceania

The Oceania region is an area particularly prone to natural disasters such as cyclones, tsunamis, floods, droughts, earthquakes and volcanic eruptions. Many of the nations in the region are Small Island Developing States (SIDS), yet even within wealthy states such as Australia and New Zealand there are groups which are vulnerable to disaster. Vulnerability to natural disaster can be understood in human rights terms, as natural disasters threaten the enjoyment of a number of rights which are guaranteed under international law, including rights to health, housing, food, water and even the right to life itself. The impacts of climate change threaten to exacerbate these vulnerabilities, yet, despite the foreseeability of further natural disasters as a result of climate change, there currently exists no comprehensive international framework for disaster response offering practical and/or legally reliable mechanisms to assist at‐risk states and communities. This paper sets out to explore the human rights issues presented by natural disasters and examine the extent to which these issues can be addressed by disaster response frameworks at the international, regional and national levels.