Group studio cycling; an effective intervention to improve cardio-metabolic health in overweight physically inactive individuals

Introduction: Supervised, laboratory based studies of high intensity interval training (HIIT) is effective at improving health markers in groups at risk of cardiovascular and metabolic disease. Studio cycling, incorporating aerobic and high intensity exercise, may offer a platform for the implementation of HIIT within the wider community. Methods: Eight, overweight, physically inactive (<1.5 hr·wk-1) but otherwise healthy volunteers completed eight weeks of supervised studio cycling lasting 20-50 minutes 3 times per week. Participants underwent assessment for maximal oxygen uptake (VO2max) body composition, blood lipids, glucose tolerance and insulin resistance before and after the intervention. Results: Adherence to training was >95%. Mean and peak intensity were equivalent to 83% and 97% of HRmax·VO2max increased from 27.1 ± 4.7 mL·kg·min-1 to 30.3 ± 4.3 mL·kg·min-1 (p < 0.0001). Body fat percentage was reduced by 13.6% from 31.8 ± 2.4% to 27.5 ± 4.5% (p < 0.05). Total cholesterol (4.8 ± 1.1 mmol·L-1 to 4.2 ± 1.2 mmol·L-1) and low-density lipoprotein cholesterol (2.6 ± 0.9 mmol·L-1 to 2.0 ± 1.2 mmol·L-1) were reduced (both p < 0.05). There were no significant differences to glucose tolerance or insulin resistance. Discussion: Group exercise is effective at improving the cardio-metabolic health in previously physically inactive overweight individuals. Coupled with the high adherence rate, studio cycling offers an effective intervention improving cardiovascular health in physically inactive cohorts. Conclusions: Studio cycling can be implemented as a highly effective high intensity interval training intervention for improving health in overweight, inactive individuals and may promote improved exercise adherence

Mir142 loss unlocks IDH2R140-dependent leukemogenesis through antagonistic regulation of HOX genes

AML is a genetically heterogeneous disease and understanding how different co-occurring mutations cooperate to drive leukemogenesis will be crucial for improving diagnostic and therapeutic options for patients. MIR142 mutations have been recurrently detected in IDH-mutated AML samples. Here, we have used a mouse model to investigate the interaction between these two mutations and demonstrate a striking synergy between Mir142 loss-of-function and IDH2R140Q, with only recipients of double mutant cells succumbing to leukemia. Transcriptomic analysis of the non-leukemic single and leukemic double mutant progenitors, isolated from these mice, suggested a novel mechanism of cooperation whereby Mir142 loss-of-function counteracts aberrant silencing of Hoxa cluster genes by IDH2R140Q. Our analysis suggests that IDH2R140Q is an incoherent oncogene, with both positive and negative impacts on leukemogenesis, which requires the action of cooperating mutations to alleviate repression of Hoxa genes in order to advance to leukemia. This model, therefore, provides a compelling rationale for understanding how different mutations cooperate to drive leukemogenesis and the context-dependent effects of oncogenic mutations

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

Does public awareness increase support for invasive species management?:Promising evidence across taxa and landscape types

Management of invasive species often raises substantial conflicts of interest. Since such conflicts can hamper proposed management actions, managers, decision makers and researchers increasingly recognize the need to consider the social dimensions of invasive species management. In this exploratory study, we aimed (1) to explore whether species’ taxonomic position (i.e. animals vs. plants) and type of invaded landscape (i.e. urban vs. nonurban) might influence public perception about the management of invasive species, and (2) to assess the potential of public awareness to increase public support for invasive species management. We reviewed the scientific literature on the conflicts of interest around the management of alien species and administered two-phased questionnaires (before and after providing information on the target species and its management) to members of the public in South Africa and the UK (n = 240). Our review suggests that lack of public support for the management of invasive animals in both urban and non-urban areas derives mainly from moralistic value disagreements, while the management of invasive plants in non-urban areas mostly causes conflicts based on utilitarian value disagreements. Despite these general trends, conflicts are context dependent and can originate from a wide variety of different views. Notably, informing the public about the invasive status and negative impacts of the species targeted for management appeared to increase public support for the management actions. Therefore, our results align with the view that increased public awareness might increase the public support for the management of invasive species, independent of taxonomic position and type of landscape

Microglial activation and chronic neurodegeneration

Microglia, the resident innate immune cells in the brain, have long been implicated in the pathology of neurode-generative diseases. Accumulating evidence points to activated microglia as a chronic source of multiple neurotoxic factors, including tumor necrosis factor-α, nitric oxide, interleukin-1β, and reactive oxygen species (ROS), driving progressive neuron damage. Microglia can become chronically activated by either a single stimulus (e.g., lipopolysaccharide or neuron damage) or multiple stimuli exposures to result in cumulative neuronal loss with time. Although the mechanisms driving these phenomena are just beginning to be understood, reactive microgliosis (the microglial response to neuron damage) and ROS have been implicated as key mechanisms of chronic and neurotoxic microglial activation, particularly in the case of Parkinson’s disease. We review the mechanisms of neurotoxicity associated with chronic microglial activation and discuss the role of neuronal death and microglial ROS driving the chronic and toxic microglial phenotype

Measuring the accuracy of propofol target-controlled infusion (TCI) before and after surgery with major blood loss

Target-controlled infusion (TCI) is based on pharmacokinetic models designed to achieve a desired drug level in the blood. TCI's predictive accuracy of plasma propofol levels at the end of surgery with major blood loss has not been well established. This prospective observational study included adult patients (BMI 20-35 kg/m2) undergoing surgery with expected blood loss ≥ 1500 mL. The study was conducted with the Schnider TCI propofol model (Alaris PK Infusion Pump, CareFusion, Switzerland). Propofol levels were assessed in steady-state at the end of anaesthesia induction (Tinitial) and before the end of surgery (Tfinal). Predicted propofol levels (CTCI) were compared to measured levels (Cblood). Twenty-one patients were included. The median estimated blood loss was 1600 mL (IQR 1000-2300), and the median fluid balance at Tfinal was + 3200 mL (IQR 2320-4715). Heart rate, mean arterial blood pressure, and blood lactate did not differ significantly between Tinitial and Tfinal. The median bispectral index (0-100) was 50 (IQR 42-54) and 49 (IQR 42-56) at the two respective time points. At Tinitial, median CTCI was 2.2 µmol/L (IQR 2-2.45) and Cblood was 2.0 µmol/L (bias 0.3 µmol/L, limits of agreement - 1.1 to 1.3, p = 0.33). CTCI and Cblood at Tfinal were 2.0 µmol/L (IQR 1.6-2.2) and 1 µmol/L (IQR 0.8-1.4), respectively (bias 0.6 µmol/L, limits of agreement - 0.89 to 1.4, p < 0.0001). Propofol TCI allows clinically unproblematic conduct of general anaesthesia. In cases of major blood loss, the probability of propofol TCI overestimating plasma levels increases.Trial registration German Clinical Trials Register (DRKS; DRKS00009312)