Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells

The anti-diabetic drug metformin regulates T-cell responses to immune activation and is proposed to function by regulating the energy-stress-sensing adenosine-monophosphate-activated protein kinase (AMPK). However, the molecular details of how metformin controls T cell immune responses have not been studied nor is there any direct evidence that metformin acts on T cells via AMPK. Here, we report that metformin regulates cell growth and proliferation of antigen-activated T cells by modulating the metabolic reprogramming that is required for effector T cell differentiation. Metformin thus inhibits the mammalian target of rapamycin complex I signalling pathway and prevents the expression of the transcription factors c-Myc and hypoxia-inducible factor 1 alpha. However, the inhibitory effects of metformin on T cells did not depend on the expression of AMPK in T cells. Accordingly, experiments with metformin inform about the importance of metabolic reprogramming for T cell immune responses but do not inform about the importance of AMPK

Access to recreational physical activities by car and bus : an assessment of socio-spatial inequalities in mainland Scotland

Obesity and other chronic conditions linked with low levels of physical activity (PA) are associated with deprivation. One reason for this could be that it is more difficult for low-income groups to access recreational PA facilities such as swimming pools and sports centres than high-income groups. In this paper, we explore the distribution of access to PA facilities by car and bus across mainland Scotland by income deprivation at datazone level. GIS car and bus networks were created to determine the number of PA facilities accessible within travel times of 10, 20 and 30 minutes. Multilevel negative binomial regression models were then used to investigate the distribution of the number of accessible facilities, adjusting for datazone population size and local authority. Access to PA facilities by car was significantly (p<0.01) higher for the most affluent quintile of area-based income deprivation than for most other quintiles in small towns and all other quintiles in rural areas. Accessibility by bus was significantly lower for the most affluent quintile than for other quintiles in urban areas and small towns, but not in rural areas. Overall, we found that the most disadvantaged groups were those without access to a car and living in the most affluent areas or in rural areas

Risk-based early prevention in comparison with routine prevention of dental caries: a 7-year follow-up of a controlled clinical trial; clinical and economic aspects

BACKGROUND: The results in an earlier study with 2–5-year-old children indicated that, in comparison with conventional prevention, a risk-based prevention programme was effective in reducing dental caries in a low-caries community. The aim of the present study was to examine the clinical and economic findings seven years after the cessation of the targeted programme, from the perspective of public health care. METHODS: The present material was collected from the dental records of the public health care centres, and included all dental visits after the 5-year examination until the 12-year examination. The groups were compared in relation to clinically detected caries at the age of 12 years, the number of dental visits needed from 5 to 12 years of age, and the estimation of running costs during these years. Statistical analyses included univariate analysis of variance, and calculation of absolute risk reduction and number needed to treat (NNT) values. RESULTS: At the age of 12 years, DMF was significantly related to the risk category determined ten years earlier, in both study groups. In the risk-based group, the absolute risk reduction for caries in permanent dentition was 0.13 (95% confidence interval 0.06 – 0.21), and the associated NNT value was 8 (95% confidence interval 5 – 17). The total number of preventive, as well as restorative visits was lower in the risk-based than in the routine prevention group. The findings indicate that early risk-based prevention can be correctly targeted, clinically effective, and economically profitable also from the long-term point of view. CONCLUSION: Early prevention of dental caries also has long-term benefits in a 7-year follow-up perspective. This seems to hold true as regards targeting, as well as clinical and economic effectiveness. Success in risk-based prevention enables successful work division, and consequently, economic effectiveness

A hysteretic multiscale formulation for nonlinear dynamic analysis of composite materials

This article has been made available through the Brunel Open Access Publishing Fund.A new multiscale finite element formulation is presented for nonlinear dynamic analysis of heterogeneous structures. The proposed multiscale approach utilizes the hysteretic finite element method to model the microstructure. Using the proposed computational scheme, the micro-basis functions, that are used to map the microdisplacement components to the coarse mesh, are only evaluated once and remain constant throughout the analysis procedure. This is accomplished by treating inelasticity at the micro-elemental level through properly defined hysteretic evolution equations. Two types of imposed boundary conditions are considered for the derivation of the multiscale basis functions, namely the linear and periodic boundary conditions. The validity of the proposed formulation as well as its computational efficiency are verified through illustrative numerical experiments

The distribution of burden of dental caries in schoolchildren: a critique of the high-risk caries prevention strategy for populations

BACKGROUND: The 'high-risk approach' is a commonly adopted strategy recommended for the prevention of dental caries in populations. The scientific basis for the strategy has been questioned. The objective of this study is to assess the contribution that children identified at 'high-risk' made towards the total of new caries lesions over a 4-year period, by analysing the distribution of new lesions per 100 children. METHODS: Data are from the National Preventive Dentistry Demonstration Programme (NPDDP) in the United States. The analyses identified the distribution of new carious lesions over a 4-year period in four groups of 7 year-old children who received differing preventive regimes. RESULTS: The majority of new lesions occurred in those children classified at lowest caries risk at baseline. Irrespective of the preventive regime adopted and the initial caries levels, children classified as 'highest risk' contributed less than 6% of the total number of new lesions developing over 4 years. CONCLUSION: These findings challenge the basis for the adoption of a high-risk strategy

Functional near infrared spectroscopy (fNIRS) to assess cognitive function in infants in rural Africa

Cortical mapping of cognitive function during infancy is poorly understood in low-income countries due to the lack of transportable neuroimaging methods. We have successfully piloted functional near infrared spectroscopy (fNIRS) as a neuroimaging tool in rural Gambia. Four-to-eight month old infants watched videos of Gambian adults perform social movements, while haemodynamic responses were recorded using fNIRS. We found distinct regions of the posterior superior temporal and inferior frontal cortex that evidenced either visual-social activation or vocally selective activation (vocal > non-vocal). The patterns of selective cortical activation in Gambian infants replicated those observed within similar aged infants in the UK. These are the first reported data on the measurement of localized functional brain activity in young infants in Africa and demonstrate the potential that fNIRS offers for field-based neuroimaging research of cognitive function in resource-poor rural communities

Cell lineage-specific mitochondrial resilience during mammalian organogenesis

Mitochondrial activity differs markedly between organs, but it is not known how and when this arises. Here we show that cell lineage-specific expression profiles involving essential mitochondrial genes emerge at an early stage in mouse development, including tissue-specific isoforms present before organ formation. However, the nuclear transcriptional signatures were not independent of organelle function. Genetically disrupting intra-mitochondrial protein synthesis with two different mtDNA mutations induced cell lineage-specific compensatory responses, including molecular pathways not previously implicated in organellar maintenance. We saw downregulation of genes whose expression is known to exacerbate the effects of exogenous mitochondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic development. The compensatory pathways were both tissue and mutation specific and under the control of transcription factors which promote organelle resilience. These are likely to contribute to the tissue specificity which characterizes human mitochondrial diseases and are potential targets for organ-directed treatments

Functional near infrared spectroscopy (fNIRS) to assess cognitive function in infants in rural Africa

Cortical mapping of cognitive function during infancy is poorly understood in low-income countries due to the lack of transportable neuroimaging methods. We have successfully piloted functional near infrared spectroscopy (fNIRS) as a neuroimaging tool in rural Gambia. Four-to-eight month old infants watched videos of Gambian adults perform social movements, while haemodynamic responses were recorded using fNIRS. We found distinct regions of the posterior superior temporal and inferior frontal cortex that evidenced either visual-social activation or vocally selective activation (vocal > non-vocal). The patterns of selective cortical activation in Gambian infants replicated those observed within similar aged infants in the UK. These are the first reported data on the measurement of localized functional brain activity in young infants in Africa and demonstrate the potential that fNIRS offers for field-based neuroimaging research of cognitive function in resource-poor rural communities

Isolation of a wide range of minerals from a thermally treated plant: Equisetum arvense, a Mare’s tale

Silica is the second most abundant biomineral being exceeded in nature only by biogenic CaCO3. Many land plants (such as rice, cereals, cucumber, etc.) deposit silica in significant amounts to reinforce their tissues and as a systematic response to pathogen attack. One of the most ancient species of living vascular plants, Equisetum arvense is also able to take up and accumulate silica in all parts of the plant. Numerous methods have been developed for elimination of the organic material and/or metal ions present in plant material to isolate biogenic silica. However, depending on the chemical and/or physical treatment applied to branch or stem from Equisetum arvense; other mineral forms such glass-type materials (i.e. CaSiO3), salts (i.e. KCl) or luminescent materials can also be isolated from the plant material. In the current contribution, we show the chemical and/or thermal routes that lead to the formation of a number of different mineral types in addition to biogenic silica

Neighborhood fast food restaurants and fast food consumption: A national study

<p>Abstract</p> <p>Background</p> <p>Recent studies suggest that neighborhood fast food restaurant availability is related to greater obesity, yet few studies have investigated whether neighborhood fast food restaurant availability promotes fast food consumption. Our aim was to estimate the effect of neighborhood fast food availability on frequency of fast food consumption in a national sample of young adults, a population at high risk for obesity.</p> <p>Methods</p> <p>We used national data from U.S. young adults enrolled in wave III (2001-02; ages 18-28) of the National Longitudinal Study of Adolescent Health (n = 13,150). Urbanicity-stratified multivariate negative binomial regression models were used to examine cross-sectional associations between neighborhood fast food availability and individual-level self-reported fast food consumption frequency, controlling for individual and neighborhood characteristics.</p> <p>Results</p> <p>In adjusted analysis, fast food availability was not associated with weekly frequency of fast food consumption in non-urban or low- or high-density urban areas.</p> <p>Conclusions</p> <p>Policies aiming to reduce neighborhood availability as a means to reduce fast food consumption among young adults may be unsuccessful. Consideration of fast food outlets near school or workplace locations, factors specific to more or less urban settings, and the role of individual lifestyle attitudes and preferences are needed in future research.</p