Early time course of Akt phosphorylation after endurance and resistance exercise

Purpose The aim of this study was to determine the early time course of exercise-induced signaling after divergent contractile activity associated with resistance and endurance exercise. Methods Sixteen male subjects were randomly assigned to either a cycling (CYC; n = 8, 60 min, 70% V?O2peak) or resistance (REX; n = 8, 8×5 leg extension, 80% one-repetition maximum, 3-min recovery) exercise group. Serial muscle biopsies were obtained from vastus lateralis at rest before, immediately after, and after 15, 30, and 60 min of passive recovery to determine early signaling responses after exercise. Results There were comparable increases from rest in AktThr308/Ser473 and mTORSer2448 phosphorylation during the postexercise time course that peaked 30-60 min after both CYC and REX (P<0.05). There were also similar patterns in p70S6K Thr389 and 4E-BP1Thr37/46 phosphorylation, but a greater magnitude of effect was observed for REX and CYC, respectively (P<0.05). However, AMPKThr172 phosphorylation was only significantly elevated after CYC (P<0.05), and we observed divergent responses for glycogen synthaseSer641 and AS160 phosphorylation that were enhanced after CYC but not REX (P<0.05). Conclusions We show a similar time course for Akt-mTOR-S6K phosphorylation during the initial 60-min recovery period after divergent contractile stimuli. Conversely, enhanced phosphorylation status of proteins that promote glucose transport and glycogen synthesis only occurred after endurance exercise. Our results indicate that endurance and resistance exercise initiate translational signaling, but high-load, low-repetition contractile activity failed to promote phosphorylation of pathways regulating glucose metabolism.

Effect of consecutive repeated sprint and resistance exercise bouts on acute adaptive responses in human skeletal muscle

We examined acute molecular responses in skeletal muscle to repeated sprint and resistance exercise bouts. Six men [age, 24.7 ± 6.3 yr; body mass, 81.6 ± 7.3 kg; peak oxygen uptake, 47 ± 9.9 ml·kg -1 ·min -1; one repetition maximum (1-RM) leg extension 92.2 ± 12.5 kg; means ± SD] were randomly assigned to trials consisting of either resistance exercise (8 × 5 leg extension, 80% 1-RM) followed by repeated sprints (10 × 6 s, 0.75 N·m torque·kg -1) or vice-versa. Muscle biopsies from vastus lateralis were obtained at rest, 15 min after each exercise bout, and following 3-h recovery to determine early signaling and mRNA responses. There was divergent exercise order-dependent phosphorylation of p70 S6K (S6K). Specifically, initial resistance exercise increased S6K phosphorylation (?75% P < 0.05), but there was no effect when resistance exercise was undertaken after sprints. Exercise decreased IGF-I mRNA following 3-h recovery (?50%, P = 0.06) independent of order, while muscle RING finger mRNA was elevated with a moderate exercise order effect (P < 0.01). When resistance exercise was followed by repeated sprints PGC-1? mRNA was increased (REX1-SPR2; P = 0.02) with a modest distinction between exercise orders. Repeated sprints may promote acute interference on resistance exercise responses by attenuating translation initiation signaling and exacerbating ubiquitin ligase expression. Indeed, repeated sprints appear to generate the overriding acute exercise-induced response when undertaking concurrent repeated sprint and resistance exercise. Accordingly, we suggest that sprint-activities are isolated from resistance training and that adequate recovery time is considered within periodized training plans that incorporate these divergent exercise modes.

Effect of high-frequency resistance exercise on adaptive responses in skeletal muscle

PURPOSE: Regulation of skeletal muscle mass is highly dependent on contractile loading. The purpose of this study was to examine changes in growth factor and inflammatory pathways following high-frequency resistance training. METHODS: Using a novel design in which male Sprague-Dawley rats undertook a "stacked" resistance training protocol designed to generate a summation of transient exercise-induced signaling responses (four bouts of three sets × 10 repetitions of squat exercise, separated by 3 h of recovery), we determined the effects of high training frequency on signaling pathways and transcriptional activity regulating muscle mass. RESULTS: The stacked training regimen resulted in acute suppression of insulin-like growth factor 1 mRNA abundance (P < 0.05) and Akt phosphorylation (P < 0.05), an effect that persisted 48 h after the final training bout. Conversely, stacked training elicited a coordinated increase in the expression of tumor necrosis factor alpha, inhibitor kappa B kinase alpha/beta activity (P < 0.05), and p38 mitogen-activated protein kinase phosphorylation (P < 0.05) at 3 h after each training bout. In addition, the stacked series of resistance exercise bouts induced an increase in p70 S6 kinase phosphorylation 3 h after bouts ×3 and ×4, independent of the phosphorylation state of Akt. CONCLUSIONS: Our results indicate that high resistance training frequency extends the transient activation of inflammatory signaling cascades, concomitant with persistent suppression of key mediators of anabolic responses. We provide novel insights into the effects of the timing of exercise-induced overload and recovery on signal transduction pathways and transcriptional activity regulating skeletal muscle mass in vivo.

The molecular bases of training adaptation

Skeletal muscle is a malleable tissue capable of altering the type and amount of protein in response to disruptions to cellular homeostasis. The process of exercise-induced adaptation in skeletal muscle involves a multitude of signalling mechanisms initiating replication of specific DNA genetic sequences, enabling subsequent translation of the genetic message and ultimately generating a series of amino acids that form new proteins. The functional consequences of these adaptations are determined by training volume, intensity and frequency, and the half-life of the protein. Moreover, many features of the training adaptation are specific to the type of stimulus, such as the mode of exercise. Prolonged endurance training elicits a variety of metabolic and morphological changes, including mitochondrial biogenesis, fast-to-slow fibre-type transformation and substrate metabolism. In contrast, heavy resistance exercise stimulates synthesis of contractile proteins responsible for muscle hypertrophy and increases in maximal contractile force output. Concomitant with the vastly different functional outcomes induced by these diverse exercise modes, the genetic and molecular mechanisms of adaptation are distinct. With recent advances in technology, it is now possible to study the effects of various training interventions on a variety of signalling proteins and early-response genes in skeletal muscle. Although it cannot presently be claimed that such scientific endeavours have influenced the training practices of elite athletes, these new and exciting technologies have provided insight into how current training techniques result in specific muscular adaptations, and may ultimately provide clues for future and novel training methodologies. Greater knowledge of the mechanisms and interaction of exercise-induced adaptive pathways in skeletal muscle is important for our understanding of the aetiology of disease, maintenance of metabolic and functional capacity with aging, and training for athletic performance. This article highlights the effects of exercise on molecular and genetic mechanisms of training adaptation in skeletal muscle.

Early life predictors of preschool overweight and obesity : a case–control study in Sri Lanka

Background Childhood obesity increases the risk of obesity in adulthood and is associated with cardiovascular disease risk factors. Our aim was to assess the early life risk factors associated with overweight and obesity among preschool children. Methods In this case–control study, from the 1087 preschool children measured, age, sex and ethnicity matched 71 cases and 71 controls were recruited. Cases and controls were defined according to the WHO 2006 growth standards. The birth and growth characteristics were extracted from the child health development records. Infant feeding practices and maternal factors were obtained from the mother. Rapid weight gain was defined as an increase in weight-for-age Z score (WHO standards) above 0.67 SD from birth to 2 years. The magnitude and significant difference in mean values of the variables associated with overweight and obesity were evaluated using logistic regressions and paired t-test, respectively. Results Cases had significantly shorter duration (months) of breastfeeding (19.4, 24.6, p = 0.003), and smaller duration (months) of exclusive breastfeeding (3.7, 5.1, p = 0.001) compared to controls. Rapid weight gain (OR = 6.3, 95% CI = 2.04–19.49), first born status (OR = 3.6, 95% CI = 1.17-10.91) and pre-pregnancy obesity (OR = 4.0, 95% CI = 1.46-10.76) were positively associated with overweight and obesity. Breastfeeding more than 2 years (OR = 0.2, 95% CI = 0.06-0.57) was negatively associated with overweight and obesity. Conclusion Rapid weight gain within first two years, first–born status and pre-pregnancy obesity of the mother contributed for preschool obesity. Our results suggest that intervention may be indicated earlier in infancy and during the toddler and preschool years to tackle the increasing prevalence of obesity.

Traits of fear resistance and susceptibility in an advanced intercross line

Genetic variability in the strength and precision of fear memory is hypothesised to contribute to the etiology of anxiety disorders, including post-traumatic stress disorder. We generated fear-susceptible (F-S) or fear-resistant (F-R) phenotypes from an F8 advanced intercross line (AIL) of C57BL/6J and DBA/2J inbred mice by selective breeding. We identified specific traits underlying individual variability in Pavlovian conditioned fear learning and memory. Offspring of selected lines differed in the acquisition of conditioned fear. Furthermore, F-S mice showed greater cued fear memory and generalised fear in response to a novel context than F-R mice. F-S mice showed greater basal corticosterone levels and hypothalamic corticotrophin-releasing hormone (CRH) mRNA levels than F-R mice, consistent with higher hypothalamic-pituitary-adrenal (HPA) axis drive. Hypothalamic mineralocorticoid receptor and CRH receptor 1 mRNA levels were decreased in F-S mice as compared with F-R mice. Manganese-enhanced magnetic resonance imaging (MEMRI) was used to investigate basal levels of brain activity. MEMRI identified a pattern of increased brain activity in F-S mice that was driven primarily by the hippocampus and amygdala, indicating excessive limbic circuit activity in F-S mice as compared with F-R mice. Thus, selection pressure applied to the AIL population leads to the accumulation of heritable trait-relevant characteristics within each line, whereas non-behaviorally relevant traits remain distributed. Selected lines therefore minimise false-positive associations between behavioral phenotypes and physiology. We demonstrate that intrinsic differences in HPA axis function and limbic excitability contribute to phenotypic differences in the acquisition and consolidation of associative fear memory. Identification of system-wide traits predisposing to variability in fear memory may help in the direction of more targeted and efficacious treatments for fear-related pathology. Through short-term selection in a B6D2 advanced intercross line we created mouse populations divergent for the retention of Pavlovian fear memory. Trait distinctions in HPA-axis drive and fear network circuitry could be made between naïve animals in the two lines. These data demonstrate underlying physiological and neurological differences between Fear-Susceptible and Fear-Resistant animals in a natural population. F-S and F-R mice may therefore be relevant to a spectrum of disorders including depression, anxiety disorders and PTSD for which altered fear processing occurs.

Aqueous phase synthesis of copper nanoparticles : a link between heavy metal resistance and nanoparticle synthesis ability in bacterial systems

We demonstrate aqueous phase biosynthesis of phase-pure metallic copper nanoparticles (CuNPs) using a silver resistant bacterium Morganella morganii. This is particularly important considering that there has been no report that demonstrates biosynthesis and stabilization of pure copper nanoparticles in the aqueous phase. Electrochemical analysis of bacterial cells exposed to Cu2+ ions provides new insights into the mechanistic aspect of Cu2+ ion reduction within the bacterial cell and indicates a strong link between the silver and copper resistance machinery of bacteria in the context of metal ion reduction. The outcomes of this study take us a step closer towards designing rational strategies for biosynthesis of different metal nanoparticles using microorganisms.

Living the indie life : mapping creative teams in a 48 hour game jam and playing with data

In contemporary game development circles the ‘game making jam’ has become an important rite of passage and baptism event, an exploration space and a central indie lifestyle affirmation and community event. Game jams have recently become a focus for design researchers interested in the creative process. In this paper we tell the story of an established local game jam and our various documentation and data collection methods. We present the beginnings of the current project, which seeks to map the creative teams and their process in the space of the challenge, and which aims to enable participants to be more than the objects of the data collection. A perceived issue is that typical documentation approaches are ‘about’ the event as opposed to ‘made by’ the participants and are thus both at odds with the spirit of the jam as a phenomenon and do not really access the rich playful potential of participant experience. In the data collection and visualisation projects described here, we focus on using collected data to re-include the participants in telling stories about their experiences of the event as a place-based experience. Our goal is to find a means to encourage production of ‘anecdata’ - data based on individual story telling that is subjective, malleable, and resists collection via formal mechanisms - and to enable mimesis, or active narrating, on the part of the participants. We present a concept design for data as game based on the logic of early medieval maps and we reflect on how we could enable participation in the data collection itself.

Review : "Quality of life: the assessment, analysis and interpretation of patient-reported outcomes (2nd Ed.)" by Peter M. Fayers & David Machin

An updated version, this excellent text is a timely addition to the library of any nurse researching in oncology or other settings where individuals’ quality of life must be understood. Health-related quality of life should be a central aspect of studies concerned with health and illness. Indeed, considerable evidence has recently emerged in oncology and other research settings that selfreported quality of life is of great prognostic significance and may be the most reliable predictor of subsequent morbidity and mortality. From a nursing perspective, it is also gratifying to note that novel therapy and other oncology studies increasingly recognize the importance of understanding patients’ subjective experiences of an intervention over time and to ascertain whether patients perceive that a new intervention makes a difference to their quality of life and treatment outcomes. Measurements of quality of life are now routine in clinical trials of chemotherapy drugs and are often considered the prime outcome of interest in the cost/benefit analyses of these treatments. The authors have extensive experience in qualityof- life assessment in cancer clinical trials, where most of the pioneering work into quality of life has been conducted. That said, many of the health-related qualityof- life issues discussed are common to many illnesses, and researchers outside of cancer should find the book equally helpful.

End-of-life care pathways for improving outcomes in caring for the dying (Review)

Background This is an updated version of a Cochrane review first published in Issue 1, 2010 of The Cochrane Library. In many clinical areas, integrated care pathways are utilised as structured multidisciplinary care plans that detail essential steps in caring for patients with specific clinical problems. In particular, care pathways for the dying have been developed as a model to improve care of patients who are in the last days of life. The care pathways were designed with an aim of ensuring that the most appropriate management occurs at the most appropriate time and that it is provided by the most appropriate health professional. There have been sustained concerns about the safety of implementing end-of-life care pathways, particularly in the UK. Therefore, there is a significant need for clinicians and policy makers to be informed about the effects of end-of-life care pathways with a systematic review. Objectives To assess the effects of end-of-life care pathways, compared with usual care (no pathway) or with care guided by another end-of-life care pathway across all healthcare settings (e.g. hospitals, residential aged care facilities, community). In particular, we aimed to assess the effects on symptom severity and quality of life of people who are dying; those related to the care such as families, carers and health professionals; or a combination of these. Search Methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2013), MEDLINE, EMBASE, PsycINFO, CINAHL, review articles and reference lists of relevant articles.We conducted the original search in September 2009, and the updated search in June 2013. Selection Criteria All randomised controlled trials (RCTs), quasi-randomised trial or high-quality controlled before-and-after studies comparing use versus non-use of an end-of-life care pathway in caring for the dying. Data Collection and Analysis Two review authors assessed the results of the searches against the predetermined criteria for inclusion. Main Results The original review identified 920 titles. The updated search found 2042 potentially relevant titles (including the original 920), but no additional studies met criteria for inclusion in the review update. Authors’ Conclusions With sustained concerns about the safety of the pathway implementation and the lack of available evidence on important patient and relative outcomes, recommendations for the use of end-of-life pathways in caring for the dying cannot be made. Since the last version of this review, no new studies met criteria for inclusion in the review update. With recently documented concerns related to the potential adverse effects associated with Liverpool Care Pathway (the most commonly used end-of-life care pathway), we do not recommend decision making based on indirect or low-quality evidence. All health services using end-of-life care pathways are encouraged to have their use of the pathway, to date, independently audited. Any subsequent use should be based on carefully documented evaluations. Large RCTs or other well-designed controlled studies are urgently required for the evaluation of the use of end-of-life care pathways in caring for dying people in various clinical settings. In future studies, outcome measures should include benefits or harms concerning the outcomes of interest in this review in relation to patients, families, carers and health professionals.

What roles do team climate, roster control, and work life conflict play in shiftworkers’ fatigue longitudinally?

The study aimed to examine shiftworkers fatigue and the longitudinal relationships that impact on fatigue such as team climate, work life conflict, control of shifts and shift type in shift working nurses. We used a quantitative survey methodology and analysed data with a moderated hierarchical multiple regression. After matching across two time periods 18 months apart, the sample consisted of 166 nurses from one Australian hospital. Of these nurses, 61 worked two rotating day shifts (morning & afternoon/evening) and 105 were rotating shiftworkers who worked three shifts (morning afternoon/evening and nights). The findings suggest that control over shift scheduling can have significant effects on fatigue for both two-shift and three-shift workers. A significant negative relationship between positive team climate and fatigue was moderated by shift type. At both Time 1 and Time 2, work life conflict was the strongest predictor of concurrent fatigue, but over time it was not.

Measuring the burden of disease in Shandong province : an adoption of the disability-adjusted life year [应用伤残调整寿命年测量山东省居民疾病负担]

Objective To estimate the burden of diseases in Shandong province by the means of DALY (Disability- adjusted life year) thus to investigate the key public health problems referencing for health policy making. Methods DALYs were calculated following the procedures developed for the Global Burden of Disease (GBD) study to ensure comparability. We measured YLLs using the mortality data of 19 Disease Surveillance Points (DSPs) in Shandong Province during 2000 and 2005. YLDs were estimated based on data for WPRO in the 2002 GBD study published by WHO. Results During this period, the average DALYs loss by all causes for the residents of DSPs in Shandong was 149.74 per thousand persons each year. Noncommunicable diseases accounted for 76.63% of the disability adjusted life years, communicable diseases and other disorders represented 14.13%, and injuries 9.24%. Nearly half of the DALYs (45%) happened among the elderly (60+). Malignant neoplasm was the number one cause of DALYs loss in the male, followed by neuropsychiatric disorder, injury, cerebrovascular disease, heart disease，etc. However, neuropsychiatric disorder possessed the largest single contributor to DALY in the female and followed by heart disease, malignant neoplasm, cerebrovascular disease and respiratory disease. Conclusion Non-communicable diseases such as circulatory diseases, neuropsychiatric disorders and malignant neoplasms were the main causes of disease burden in Shandong province. The importance of neuropsychiatric disorders was more striking and should be recognized properly. The lack of morbidity data is the main limitation of this study. Abstract in Chinese 目的 应用伤残调整寿命年测量山东省居民疾病负担,提出该地区主要卫生问题,为卫生决策提供科学依据. 方法 以山东省2000-2005年19个疾病监测点的死因监测资料为基础,利用世界卫生组织(WHO)提供的方法计算不同疾病在不同性别年龄人群所造成的伤残调整寿命年(DALYs),其中,YIJDs根据WHO公布的亚太区2002年疾病负担数据进行估算. 结果 2000-2005年山东省疾病监测系统居民因为早死和残疾年平均损失149.74个DALYs/千人,其中,76.6%的DALYs损失因慢性非传染性疾病所致,14.1%由传染性疾病等引起,9.2%因为意外伤害造成;接近1/2(45%)的DALYs损失发生在60岁以上人群;恶性肿瘤为造成男性居民DALYs损失的首位原因,其次为精神行为疾患、意外伤害、脑血管病和心脏病等,女性居民则以精神行为疾患为DALYs首位原因,其次为心脏病、恶性肿瘤、脑血管病和呼吸系统疾病. 结论 以循环系统疾病、精神行为疾惠和恶性肿瘤为首的慢性非传染性疾病为造成山东省疾病负担DALYs损失的主要原因.对于精神行为疾患的重要性的认识有待于进一步提高,研究的主要局限性在于发病率资料的缺乏.

Development of a children's acute cough specific quality of life questionnaire (Pac-Qol)

The high burden of parental concern in children with chronic cough has been well documented. Acute cough in children (lasting less than 2 weeks) also has a significant impact on families, reflected by the number of doctor visits for cough. Currently there is no validated acute cough specific quality of life (QOL) measure for children. The objective of this study is to develop and validate an acute cough specific QOL questionnaire (PAC-QOL) for paediatric use. Here we present our data on item selection. Methods Two independent focus groups were conducted to determine relevant items. Parents discussed the impact of their child’s current or previous episodes of acute cough on their child, themselves and their family functioning. Transcripts were analyzed to determine whether discussions had reached an item saturation point. Items were also compared against our previously validated parent-centred children’s chronic cough specific QOL questionnaire (PC-QOL), which was used as a model. The newly developed acute cough specific QOL questionnaire is designed to assess the level of frequency of parents’ feelings and worry related to their child’s acute cough, using a 24-h time-point reference. Results Newly identified acute cough specific items include parental worry around whether or not they should take their child to a doctor or emergency department, and frequency of seeking assistance from friends and family. Conclusions While there are similarities between items identified for both acute and chronic cough, there are distinct features. Further data will be collected for item reduction and validation of this children’s acute cough specific QOL questionnaire.

Hospitalisation of Indigenous children in the Northern Territory for lower respiratory illness in the first year of life

Objective To describe the epidemiology of acute lower respiratory infection (ALRI) and bronchiectasis in Northern Territory Indigenous infants hospitalised in the first year of life. Design A historical cohort study constructed from the NT Hospital Discharge Dataset and the NT Imm(u)nisation Register. Participants and setting All NT resident Indigenous infants, born 1 January 1999 to 31 December 2004, admitted to NT public hospitals and followed up to 12 months of age. Main outcome measures Incidence of ALRI and bronchiectasis (ICD-10-AM codes) and radiologically confirmed pneumonia (World Health Organization protocol). Results Data on 9295 infants, 8498 child-years of observation and 15 948 hospitalised episodes of care were analysed. ALRI incidence was 426.7 episodes per 1000 child-years (95% Cl, 416.2-437.2). Incidence rates were two times higher (relative risk, 2.12; 95% Cl, 1.98-2.27) for infants in Central Australia compared with those in the Top End. The median age at first admission for an ALRI was 4.6 months (interquartile range, 2.6-7.3). Bronchiolitis accounted for most of the disease burden, with a rate of 227 per 1000 child-years. The incidence of first diagnosis of bronchiectasis was 1.18 per 1000 child-years (95% Cl, 0.60-2.16). One or more key comorbidities were present in 1445 of the 3227 (44.8%) episodes of care for ALRI. Conclusions Rates of ALRI and bronchiectasis in NT Indigenous infants are excessive, with early onset, frequent repeat episodes, and a high prevalence of comorbidities. These high rates of disease demand urgent attention.