Effect of carbohydrate feeding on the bone metabolic response to running

Bone resorption is increased after running, with no change in bone formation. Feeding during exercise might attenuate this increase, preventing associated problems for bone. This study investigated the immediate and short-term bone metabolic responses to carbohydrate (CHO) feeding during treadmill running. Ten men completed two 7-day trials, once being fed CHO (8% glucose immediately before, every 20 min during, and immediately after exercise at a rate of 0.7 g CHO·kg body mass-1·h-1) and once being fed placebo (PBO). On day 4 of each trial, participants completed a 120-min treadmill run at 70% of maximal oxygen consumption (VO2 max). Blood was taken at baseline (BASE), immediately after exercise (EE), after 60 (R1) and 120 (R2) min of recovery, and on three follow-up days (FU1-FU3). Markers of bone resorption [COOH-terminal telopeptide region of collagen type 1 (β-CTX)] and formation [NH2-terminal propeptides of procollagen type 1 (P1NP)] were measured, along with osteocalcin (OC), parathyroid hormone (PTH), albumin-adjusted calcium (ACa), phosphate, glucagon-like peptide-2 (GLP-2), interleukin-6 (IL-6), insulin, cortisol, leptin, and osteoprotogerin (OPG). Area under the curve was calculated in terms of the immediate (BASE, EE, R1, and R2) and short-term (BASE, FU1, FU2, and FU3) responses to exercise. β-CTX, P1NP, and IL-6 responses to exercise were significantly lower in the immediate postexercise period with CHO feeding compared with PBO (β-CTX: P=0.028; P1NP: P=0.021; IL-6: P=0.036), although there was no difference in the short-term response (β-CTX: P=0.856; P1NP: P=0.721; IL-6: P=0.327). No other variable was significantly affected by CHO feeding during exercise. We conclude that CHO feeding during exercise attenuated the β-CTX and P1NP responses in the hours but not days following exercise, indicating an acute effect of CHO feeding on bone turnover

Tumor dormancy and surgery-driven interruption of dormancy in breast cancer: learning from failures

Primary tumor removal, usually considered intrinsically beneficial, can perturb metastatic homeostasis, and for some patients results in the acceleration of metastatic cancer. The continuous-growth model is required to yield to an interrupted-growth model, the implications of which are episodes of tumor dormancy. This Review analyzes the recent evolution of two paradigms related to the development of breast cancer metastases. The evolution of the paradigms described herein is supported by a growing body of findings from experimental models, and is required to explain breast cancer recurrence dynamics for patients undergoing surgery with or without adjuvant chemotherapyOther Research Uni

The Modulation of LFP Characteristics In The Freely Moving Common Marmoset

The hippocampus is a neural structure critical for navigation. Neurons in this region, along with others, create a functional network which generates large-amplitude modulations known as local field potential (LFP) activity. Prior LFP research has predominantly used rodent animal models, however recent studies have shown that frequencies associated with navigation in other mammals do not correlate to those of the rodent. We hypothesized that LFP characteristics in the common marmoset are modulated by the speed and axis of travel of the animal. Two marmosets were placed in a free moving 3-dimensional environment where movement and neurological activity were recorded. Results showed LFP modulation based on movement, including significant changes in power with movement speed and vertical motion. We provide evidence of theta bout activity and other non-rodent-like characteristics, prompting discussion on the generalization of findings in rodent models such as mice and rats to primate navigation

Menopausal Status Dependence of the Timing of Breast Cancer Recurrence after Surgical Removal of the Primary Tumour

Introduction: Information on the metastasis process in breast cancer patients undergoing primary tumour removal may be extracted from an analysis of the timing of clinical recurrence. Methods: The hazard rate for local-regional and/or distant recurrence as the first event during the first 4 years after surgery was studied in 1173 patients undergoing mastectomy alone as primary treatment for operable breast cancer. Subset analyses were performed according to tumour size, axillary nodal status and menopausal status. Results: A sharp two-peaked hazard function was observed for node-positive pre-menopausal patients, whereas results from node-positive post-menopausal women always displayed a single broad peak. The first narrow peak among pre-menopausal women showed a very steep rise to a maximum about 8–10 months after mastectomy. The second peak was considerably broader, reaching its maximum at 28–30 months. Post-menopausal patients displayed a wide, nearly symmetrical peak with maximum risk at about 18–20 months. Peaks displayed increasing height with increasing axillary lymph node involvement. No multi-peaked pattern was evident for either pre-menopausal or post-menopausal node-negative patients; however, this finding should be considered cautiously because of the limited number of events. Tumour size influenced recurrence risk but not its timing. Findings resulting from the different subsets of patients were remarkably coherent and each observed peak maintained the same position on the time axis in all analysed subsets. Conclusions: The risk of early recurrence for node positive patients is dependent on menopausal status. The amount of axillary nodal involvement and the tumour size modulate the risk value at any given time. For pre-menopausal node-positive patients, the abrupt increase of the first narrow peak of the recurrence risk suggests a triggering event that synchronises early risk. We suggest that this event is the surgical removal of the primary tumour. The later, broader, more symmetrical risk peaks indicate that some features of the corresponding metastatic development may present stochastic traits. A metastasis development model incorporating tumour dormancy in specific micro-metastatic phases, stochastic transitions between them and sudden acceleration of the metastatic process by surgery can explain these risk dynamics

Developmental Origin of Oligodendrocyte Lineage Cells Determines Response to Demyelination and Susceptibility to Age-Associated Functional Decline.

Oligodendrocyte progenitors (OPs) arise from distinct ventral and dorsal domains within the ventricular germinal zones of the embryonic CNS. The functional significance, if any, of these different populations is not known. Using dual-color reporter mice to distinguish ventrally and dorsally derived OPs, we show that, in response to focal demyelination of the young adult spinal cord or corpus callosum, dorsally derived OPs undergo enhanced proliferation, recruitment, and differentiation as compared with their ventral counterparts, making a proportionally larger contribution to remyelination. However, with increasing age (up to 13 months), the dorsally derived OPs become less able to differentiate into mature oligodendrocytes. Comparison of dorsally and ventrally derived OPs in culture revealed inherent differences in their migration and differentiation capacities. Therefore, the responsiveness of OPs to demyelination, their contribution to remyelination, and their susceptibility to age-associated functional decline are markedly dependent on their developmental site of origin in the developing neural tube.A.H.C. was funded by a Wellcome Trust Integrated Training Fellowship (096384/Z/11/Z). Work in R.J.M.F.’s laboratory was funded by The UK Multiple Sclerosis Society (941) and by a core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute. Work in W.D.R.’s laboratory was funded by the Medical Research Council (G0800575), the Wellcome Trust (WT100269AIA), and the European Research Council (293544).This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.celrep.2016.03.06

A Bayesian inverse dynamic approach for impulsive wave loading reconstruction: Theory, laboratory and field application

The measurement of wave forces acting on marine structures is a complicated task, both during physical experiments and, even more so, in the field. Force transducers adopted in laboratory experiments require a minimum level of structural movement, thus violating the main assumption of fully rigid structure and introducing a dynamic response of the system. Sometimes the induced vibrations are so intense that they completely nullify the reliability of the experiments. On-site, it is even more complex, since there are no force transducers of the size and capacity able to measure such massive force intensity acting over the very large domain of a marine structure. To this end, this investigation proposes a Bayesian methodology aimed to remove the undesired effects from the directly (laboratory applications) or indirectly (field applications) measured wave forces. The paper presents three applications of the method: i) a theoretical application on a synthetic signal for which MATLAB® procedures are provided, ii) an experimental application on laboratory data collected during experiments aimed to model broken wave loading on a cylinder upon a shoal and iii) a field application designed to reconstruct the wave force that generated recorded vibrations on the Wolf Rock lighthouse during Hurricane Ophelia. The proposed methodology allows the inclusion of existing information on breaking and broken wave forces through the process-based informative prior distributions, while it also provides the formal framework for uncertainty quantification of the results through the posterior distribution. Notable findings are that the broken wave loading shows similar features for both laboratory and field data. The load time series is characterised by an initial impulsive component constituted by two peaks and followed by a delayed smoother one. The first two peaks are due to the initial impact of the aerated front and to the sudden deceleration of the falling water mass previously upward accelerated by the initial impact. The third, less intense peak, is due to the interaction between the cylinder and remaining water mass carried by the individual wave. Finally, the method allows to properly identify the length of the impulsive loading component. The implications of this length on the use of the impulse theory for the assessment or design of marine structures are discussed