Exercising Our Brains, Muscles and Cells to Fight the Ageing Process

Life expectancy is increasing, but the time spent in good health (health-span) is not keeping pace, with implications for health, social care, and pensions resulting in estimated costs more than doubling by 2050. Thus, understanding the many factors that contribute to healthy ageing versus frailty, and potential things we can do to promote healthy ageing is important. For example, how does stress, being physically inactive and poor dietary practices affect our body, leading to unhealthy ageing? As part of the 2015 Pint of Science series, researchers interested in brain health, muscle function and the immune system from the School of Sport, Exercise and Rehabilitation Sciences at the University of Birmingham, UK discussed the effects that ageing itself and stress, physical activity and nutrition can have on our health and wellbeing. The objective of our presentation was to question the lifestyle that we lead and discuss realistic alternatives to incorporate healthy activity, such a exercise, into our lifestyles to improve our healthy ageing. Here, we summarise this presentation and illustrate the effectiveness of physical activity for ageing healthily

Adaptive Controller Effects on Pilot Behavior

Adaptive control provides robustness and resilience for highly uncertain, and potentially unpredictable, flight dynamics characteristic. Some of the recent flight experiences of pilot-in-the-loop with an adaptive controller have exhibited unpredicted interactions. In retrospect, this is not surprising once it is realized that there are now two adaptive controllers interacting, the software adaptive control system and the pilot. An experiment was conducted to categorize these interactions on the pilot with an adaptive controller during control surface failures. One of the objectives of this experiment was to determine how the adaptation time of the controller affects pilots. The pitch and roll errors, and stick input increased for increasing adaptation time and during the segment when the adaptive controller was adapting. Not surprisingly, altitude, cross track and angle deviations, and vertical velocity also increase during the failure and then slowly return to pre-failure levels. Subjects may change their behavior even as an adaptive controller is adapting with additional stick inputs. Therefore, the adaptive controller should adapt as fast as possible to minimize flight track errors. This will minimize undesirable interactions between the pilot and the adaptive controller and maintain maneuvering precision

Emergency Department Clinicians’ Attitudes Toward Opioid Use Disorder and Emergency Department-initiated Buprenorphine Treatment: A Mixed-Methods Study

Introduction: Emergency department (ED) visits related to opioid use disorder (OUD) have increased nearly twofold over the last decade. Treatment with buprenorphine has been demonstrated to decrease opioid-related overdose deaths. In this study, we aimed to better understand ED clinicians’ attitudes toward the initiation of buprenorphine treatment in the ED.Methods: We performed a mixed-methods study consisting of a survey of 174 ED clinicians (attending physicians, residents, and physician assistants) and semi-structured interviews with 17 attending emergency physicians at a tertiary-care academic hospital.Results: A total of 93 ED clinicians (53% of those contacted) completed the survey. While 80% of respondents agreed that buprenorphine should be administered in the ED for patients requesting treatment, only 44% felt that they were prepared to discuss medication for addiction treatment. Compared to clinicians with fewer than five years of practice, those with greater experience were less likely to approve of ED-initiated buprenorphine. In our qualitative analysis, physicians had differing perspectives on the role that the ED should play in treating OUD. Most physicians felt that a buprenorphine-based intervention in the ED would be feasible with institutional support, including training opportunities, protocol support within the electronic health record, counseling and support staff, and a robust referral system for outpatient follow-up.Conclusion: ED clinicians’ perception of buprenorphine varied by years of practice and training level. Most ED clinicians did not feel prepared to initiate buprenorphine in the ED. Qualitative interviews identified several addressable barriers to ED-initiated buprenorphine

Liver Glucokinase and Lipid Metabolism

Control of energy metabolism is crucial for optimal functioning of organs and tissues. Amongst all nutrients, glucose is the principal energy source for most cells and, therefore, minimum blood glucose levels must be guaranteed. Alterations in glycaemia can lead to hyperglycaemic states (producing protein glycosylation and toxicity in glucose-sensitive cells) or hypoglycaemic states (that can affect brain function), both harmful. Therefore, mechanisms must exist to keep glycaemia in a narrow physiological range (4-8 mM) independently of the nutritional state. To achieve control of blood glucose levels, our body has a complex, interorgan signaling system using nutrients (glucose, lipids, amino acids), hormones (insulin, glucagon, ghrelin, etc.) and the autonomic nervous system. In response to these signals, organs and tissues (mainly intestine, endocrine pancreas, liver, skeletal muscle, adipose tissue, brain and adrenal glands) adapt their function to energetic requirements. The liver plays a pivotal role in the maintenance of glucose homeostasis by continuously adapting its metabolism to energetic needs. In the fed state, when blood glucose levels are high and there is insulin, liver takes-up part glucose to replenish glycogen stores. Besides, when glucose stores are full, the liver has the capacity to synthesize lipids de novo from glucose for-long term energy storage. Lipids are packaged in very low-density lipoprotein (VLDL) particles and then transported to the adipose tissue. Conversely during starvation, when glycaemia falls and glucagon increases, the liver produces glucose to maintain circulating glucose levels by breaking down glycogen stores or by synthesizing glucose de novo through gluconeogenesis. Gluconeogenesis, as an energy-consuming pathway, is linked to -oxidation of fatty acids (fuel supplier pathway)..

The Effect of a Community-Based, Primary Health Care Exercise Program on Inflammatory Biomarkers and Hormone Levels

The aim of this study was to analyze the impact of a community-based exercise program in primary care on inflammatory biomarkers and hormone levels. The 1-year quasiexperimental study involved 13 women (mean age = 56.8 ± 11.4 years) and it was developed in two basic health care units in Rio Claro City, Brazil. The physical exercise intervention was comprised of two, 60-minute sessions/week. The inflammatory biomarkers were measured at baseline, 6 months, and 1 year. Repeated measures ANOVA analyses indicated that the intervention was effective in reducing CRP and TNFα after 1 year compared to baseline and 6 months . There were no changes in IL10, IL6, and insulin after 1 year. However, leptin significantly increased at 1 year . The major finding of this study is that a community-based exercise program can result in a decrease or maintenance of inflammatory biomarkers after 1 year, and thus has the potential to be a viable public health approach for chronic disease prevention

Liver GlucokinaseA456V Induces Potent Hypoglycemia without Dyslipidemia through a Paradoxical Induction of the Catalytic Subunit of Glucose-6-Phosphatase

Recent reports point out the importance of the complex GK-GKRP in controlling glucose and lipid homeostasis. Several GK mutations affect GKRP binding, resulting in permanent activation of the enzyme. We hypothesize that hepatic overexpression of a mutated form of GK, GKA456V, described in a patient with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) and could provide a model to study the consequences of GK-GKRP deregulation in vivo. GKA456V was overexpressed in the liver of streptozotocin diabetic mice. Metabolite profiling in serum and liver extracts, together with changes in key components of glucose and lipid homeostasis, were analyzed and compared to GK wild-type transfected livers. Cell compartmentalization of the mutant but not the wild-type GK was clearly affected in vivo, demonstrating impaired GKRP regulation. GKA456V overexpression markedly reduced blood glucose in the absence of dyslipidemia, in contrast to wild-type GK-overexpressing mice. Evidence in glucose utilization did not correlate with increased glycogen nor lactate levels in the liver. PEPCK mRNA was not affected, whereas the mRNA for the catalytic subunit of glucose-6-phosphatase was upregulated ~4 folds in the liver of GKA456V-treated animals, suggesting that glucose cycling was stimulated. Our results provide new insights into the complex GK regulatory network and validate liver-specific GK activation as a strategy for diabetes therapy

Ocean nutrient pathways associated with passage of a storm

Storms that affect ocean surface layer dynamics and primary production are a frequent occurrence in the open North Atlantic Ocean. In this study we use an interdisciplinary dataset collected in the region to quantify nutrient supply by two pathways associated with a storm event: entrainment of nutrients during a period of high wind forcing and subsequent shear-spiking at the pycnocline due to interactions of storm generated inertial currents with wind. The post-storm increase in surface layer nitrate (by ~20 mmol m?2) was predominantly driven by the first pathway: nutrient intrusion during the storm. Alignment of post-storm inertial currents and surface wind stress caused shear instabilities at the ocean pycnocline, forming the second pathway for nutrient transport into the euphotic zone. During the alignment period, pulses of high turbulent nitrate flux through the pycnocline (up to 1 mmol m?2 day?1; approximately 25 times higher than the background flux) were detected. However, the impact of the post-storm supply was an order of magnitude lower than during the storm due to the short duration of the pulses. Cumulatively, the storm passage was equivalent to 2.5-5 % of the nitrate supplied by winter convection and had a significant effect compared to previously reported (sub)-mesoscale dynamics in the region. As storms occur frequently, they can form an important component in local nutrient budgets

Social information use in adolescents with conduct problems and varying levels of callous‐unemotional traits

BACKGROUND: Adolescents with conduct problems (CP) are characterised by difficulties with social relationships and display atypical social cognition, such as when interpreting emotional expressions or engaging in social problem-solving. One important aspect of social cognition that warrants investigation is the degree to which these adolescents factor others' views into their already held beliefs, and strategies used to do so. Effective social information use enables attunement to social environment, cooperation, and social problem-solving. Difficulties in this regard could contribute to problems in social interactions in adolescents with CP, and may vary with adolescents' high (CP/HCU) versus low levels of callous-unemotional traits (CP/LCU). METHODS: We compared social information use in boys (11–16 years) with CP/HCU (n = 32), CP/LCU (n = 31) and typically developing (TD) peers (n = 45), matched for IQ. Participants provided estimates of numbers of animals on a screen, saw another adolescent's estimate, and could adjust their initial estimate. We compared two aspects of social information use: (1) degree of adjustment of initial estimate towards another's estimate and (2) strategy use when adjusting estimates. RESULTS: Degree of adjustment towards another's estimate did not vary across groups, but strategy use did. Adolescents with CP/LCU compromised less following social information than TD peers. CONCLUSIONS: Findings suggest that while adolescents with CP are able to take social information into account, those with CP/LCU use this information in a way that differs from other groups and could be less efficient. This warrants further systematic investigation as it could represent a target for behaviour management strategies. Overall, this study highlights the need for more research delineating the social-cognitive profile of adolescents with CP/LCU

Synthesis, Cell-Surface Binding, and Cellular Uptake of Fluorescently Labeled Glucose−DNA Conjugates with Different Carbohydrate Presentation

8 páginas, 5 figurasOligonucleotide conjugates carrying carbohydrates at the 5′-end have been prepared. Glucose, fucose, and saccharides containing glucose at the nonreducing end were attached to DNA strands using the classical phosphoramidite chemistry. Two types of spacers and a dendron scaffold helped to obtain a diversity of sugar presentations in the DNA conjugates. Cellular surface adsorption and cellular uptake of carbohydrate oligonucleotide antisense sequences were measured using flow cytometric analysis. Conjugates with the glucose moiety linked through long spacers (15 to 18 atom distances) were internalized better than those with short linkers (4 atom distance) and than DNA control strands without sugar modification. Conjugates with tetravalent presentation of glucose did not improve cell uptake.This work was supported by Consejo Superior de Investigaciones Científicas (PIF06-045); Spanish Ministry of Science (grants BFU2007-63287, BFU2007-62062, CTQ2006-01123,CTQ2009-13705), Generalitat de Catalunya (2009/SGR/208),and Instituto de Salud Carlos III (CIBER-BNN, CB06_01_0019). RL thanks CSIC for a JAE contract.Peer reviewe