Heritable and nutritional influences on bone mineral mass

Osteoporosis is the net result of the maximal amount of bone mineral mass achieved by the end of pubertal growth (peak bone mass) minus post-menopausal and elderly bone losses. Peak bone mineral mass is determined from early childhood by both heritable and environmental factors. Recent developments in the molecular epidemiology of osteoporosis have shown the interest, but also the limitations, of specific molecular markers, such as the vitamin D receptor gene polymorphisms Bsm 1 and Fok 1, to explain bone mineral density differences across the population. Importantly, however, interactions between VDR gene polymorphisms and environmental factors, particularly dietary calcium, have provided new insights into the complex determination of bone mineral mas

The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43

The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With this approach, we identified neuroLNC, a neuron-specific nuclear lncRNA conserved from rodents to humans. NeuroLNC is tuned by synaptic activity and influences several other essential aspects of neuronal development including calcium influx, neuritogenesis, and neuronal migration in vivo. We defined the molecular interactors of neuroLNC in detail using chromatin isolation by RNA purification, RNA interactome analysis, and protein mass spectrometry. We found that the effects of neuroLNC on synaptic vesicle release require interaction with the RNA-binding protein TDP-43 (TAR DNA binding protein-43) and the selective stabilization of mRNAs encoding for presynaptic proteins. These results provide the first proof of an lncRNA that orchestrates neuronal excitability by influencing presynaptic function

Pubertal timing and body mass index gain from birth to maturity in relation with femoral neck BMD and distal tibia microstructure in healthy female subjects

Summary: Childhood body mass index (BMI) gain is linked to hip fracture risk in elderly. In healthy girls, menarcheal age is inversely related to BMI gain during childhood and to femoral neck areal bone mass density (aBMD) and distal tibia structural components at maturity. This study underscores the importance of pubertal timing in age-related fragility fracture risk. Introduction: Recent data point to a relationship between BMI change during childhood and hip fracture risk in later life. We hypothesized that BMI development is linked to variation in pubertal timing as assessed by menarcheal age (MENA) which in turn, is related to peak bone mass (PBM) and hip fracture risk in elderly. Methods: We studied in a 124 healthy female cohort the relationship between MENA and BMI from birth to maturity, and DXA-measured femoral neck (FN) aBMD at 20.4year. At this age, we also measured bone strength related microstructure components of distal tibia by HR-pQCT. Results: At 20.4 ± 0.6year, FN aBMD (mg/cm2), cortical thickness (μm), and trabecular density (mgHA/cm3) of distal tibia were inversely related to MENA (P = 0.023, 0.015, and 0.041, respectively) and positively to BMI changes from 1.0 to 12.4years (P = 0.031, 0.089, 0.016, respectively). Significant inverse (P < 0.022 to <0.001) correlations (R = −0.21 to -0.42) were found between MENA and BMI from 7.9 to 20.4years, but neither at birth nor at 1.0year. Linear regression indicated that MENA Z-score was inversely related to BMI changes not only from 1.0 to 12.4years (R = −0.35, P = 0.001), but also from 1.0 to 8.9years, (R = −0.24, P = 0.017), i.e., before pubertal maturation. Conclusion: BMI gain during childhood is associated with pubertal timing, which in turn, is correlated with several bone traits measured at PBM including FN aBMD, cortical thickness, and volumetric trabecular density of distal tibia. These data complement the reported relationship between childhood BMI gain and hip fracture risk in later lif

Harmonizing Software Standards with a Semantic Model

The application of standards in the software development process supports interoperability between systems. Maintenance of standards must be guaranteed on the organisational and technical level. The use of semantic technologies can contribute to the standard maintenance process by providing a harmonizing bridge between standards of different knowledge domains and languages and by providing a single point of administration for standard domain concepts. This paper describes a case study of the creation of a semantic layer between software standards for water management systems in The Netherland

Zinc increases the effects of essential amino acids-whey protein supplements in frail elderly

Abstract: Protein undernutrition is frequent in the elderly. It contributes to the development of osteoporosis, possibly via lower IGF-I. Dietary zinc can influence IGF-I production. Objectives: To determine the influence of dietary zinc addition on IGF-I and bone turnover responses to essential amino acids-whey (EAA-W) protein supplements in frail elderly. Design and setting: A daily oral protein supplement was given to hospitalized patients for 4 weeks. On a randomized, double-blind basis, patients received either an additional 30 mg/day of zinc or control. Participants: Sixty-one hospitalized elderly aged 66.7 to 105.8, with a mini-nutritional assessment score between 17 and 24 were enrolled. Measurements: Activities of daily living; dietary intakes; serum IGF-I, IGF-BP3, CrossLaps™, osteocalcin and zinc were measured before and after 1, 2 and 4 weeks of protein supplementation. Results: Serum IGF-I rapidly increased in both groups. Zinc accelerated this increase with changes of +48.2±14.3 and +22.4±4.7% (p<.05) by 1 week, in the zinc-supplemented and control groups, respectively. Zinc significantly decreased the serum bone resorption marker CrossLaps™ by already 1 week. Activities of daily living improved by +27.0±3.1 and +18.3±4.5% in zinc-supplemented and control groups, respectively. Conclusion: In the elderly, zinc supplementation accelerated the serum IGF-I response to EAA-W protein by 1 week and decreased a biochemical marker of bone resorptio

Memory-based immigrants for ant colony optimization in changing environments

Copyright @ 2011 SpringerAnt colony optimization (ACO) algorithms have proved that they can adapt to dynamic optimization problems (DOPs) when they are enhanced to maintain diversity. DOPs are important due to their similarities to many real-world applications. Several approaches have been integrated with ACO to improve their performance in DOPs, where memory-based approaches and immigrants schemes have shown good results on different variations of the dynamic travelling salesman problem (DTSP). In this paper, we consider a novel variation of DTSP where traffic jams occur in a cyclic pattern. This means that old environments will re-appear in the future. A hybrid method that combines memory and immigrants schemes is proposed into ACO to address this kind of DTSPs. The memory-based approach is useful to directly move the population to promising areas in the new environment by using solutions stored in the memory. The immigrants scheme is useful to maintain the diversity within the population. The experimental results based on different test cases of the DTSP show that the memory based immigrants scheme enhances the performance of ACO in cyclic dynamic environments.This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) of UK under Grant EP/E060722/2

Pubertal timing and body mass index gain from birth to maturity in relation with femoral neck BMD and distal tibia microstructure in healthy female subjects

Childhood body mass index (BMI) gain is linked to hip fracture risk in elderly. In healthy girls, menarcheal age is inversely related to BMI gain during childhood and to femoral neck areal bone mass density (aBMD) and distal tibia structural components at maturity. This study underscores the importance of pubertal timing in age-related fragility fracture risk

Effect of a multifactorial fall-and-fracture risk assessment and management program on gait and balance performances and disability in hospitalized older adults: a controlled study

Summary: This controlled intervention study in hospitalized oldest old adults showed that a multifactorial fall-and-fracture risk assessment and management program, applied in a dedicated geriatric hospital unit, was effective in improving fall-related physical and functional performances and the level of independence in activities of daily living in high-risk patients. Introduction: Hospitalization affords a major opportunity for interdisciplinary cooperation to manage fall-and-fracture risk factors in older adults. This study aimed at assessing the effects on physical performances and the level of independence in activities of daily living (ADL) of a multifactorial fall-and-fracture risk assessment and management program applied in a geriatric hospital setting. Methods: A controlled intervention study was conducted among 122 geriatric inpatients (mean ± SD age, 84 ± 7years) admitted with a fall-related diagnosis. Among them, 92 were admitted to a dedicated unit and enrolled into a multifactorial intervention program, including intensive targeted exercise. Thirty patients who received standard usual care in a general geriatric unit formed the control group. Primary outcomes included gait and balance performances and the level of independence in ADL measured 12 ± 6days apart. Secondary outcomes included length of stay, incidence of in-hospital falls, hospital readmission, and mortality rates. Results: Compared to the usual care group, the intervention group had significant improvements in Timed Up and Go (adjusted mean difference [AMD] = −3.7s; 95% CI = −6.8 to −0.7; P = 0.017), Tinetti (AMD = −1.4; 95% CI = −2.1 to −0.8; P < 0.001), and Functional Independence Measure (AMD = 6.5; 95%CI = 0.7-12.3; P = 0.027) test performances, as well as in several gait parameters (P < 0.05). Furthermore, this program favorably impacted adverse outcomes including hospital readmission (hazard ratio = 0.3; 95% CI = 0.1-0.9; P = 0.02). Conclusions: A multifactorial fall-and-fracture risk-based intervention program, applied in a dedicated geriatric hospital unit, was effective and more beneficial than usual care in improving physical parameters related to the risk of fall and disability among high-risk oldest old patient

The predictability of large-scale wind-driven flows

International audienceThe singular values associated with optimally growing perturbations to stationary and time-dependent solutions for the general circulation in an ocean basin provide a measure of the rate at which solutions with nearby initial conditions begin to diverge, and hence, a measure of the predictability of the flow. In this paper, the singular vectors and singular values of stationary and evolving examples of wind-driven, double-gyre circulations in different flow regimes are explored. By changing the Reynolds number in simple quasi-geostrophic models of the wind-driven circulation, steady, weakly aperiodic and chaotic states may be examined. The singular vectors of the steady state reveal some of the physical mechanisms responsible for optimally growing perturbations. In time-dependent cases, the dominant singular values show significant variability in time, indicating strong variations in the predictability of the flow. When the underlying flow is weakly aperiodic, the dominant singular values co-vary with integral measures of the large-scale flow, such as the basin-integrated upper ocean kinetic energy and the transport in the western boundary current extension. Furthermore, in a reduced gravity quasi-geostrophic model of a weakly aperiodic, double-gyre flow, the behaviour of the dominant singular values may be used to predict a change in the large-scale flow, a feature not shared by an analogous two-layer model. When the circulation is in a strongly aperiodic state, the dominant singular values no longer vary coherently with integral measures of the flow. Instead, they fluctuate in a very aperiodic fashion on mesoscale time scales. The dominant singular vectors then depend strongly on the arrangement of mesoscale features in the flow and the evolved forms of the associated singular vectors have relatively short spatial scales. These results have several implications. In weakly aperiodic, periodic, and stationary regimes, the mesoscale energy content is usually relatively low and the predictability of the wind-driven circulation is determined by the large-scale structure of the flow. In the more realistic, strongly chaotic regime, in which energetic mesoscale eddies are produced by the meandering of the separated western boundary current extension, the predictability of the flow locally tends to be a stronger function of the local mesoscale eddy structure than of the larger scale structure of the circulation. This has a broader implication for the effectiveness of different approaches to forecasting the ocean with models which sequentially assimilate new observations