The association between physical activity and risk of neurodegenerative diseases is not well established. We therefore aimed to quantify this association using meta-analytical techniques.
We searched ...Medline, the Cochrane Database of Systematic Reviews and Web of Science databases from 1990 to 2007 for prospective epidemiological studies of physical activity and incident dementia, Alzheimer's and Parkinson's disease. We excluded studies of physical activity and cognitive decline without diagnosis of a neurodegenerative disease. Information on study design, participant characteristics, measurement of exposure and outcome variables, adjustment for potential confounding, and estimates of associations was abstracted independently by the two investigators.
We included 16 prospective studies in the overall analysis, which incorporated 163797 non-demented participants at baseline with 3,219 cases at follow-up. We calculated pooled relative risk (RR) using a random effects model. The RR of dementia in the highest physical activity category compared with the lowest was 0.72 95% confidence interval (CI) 0.60-0.86, p<0.001, for Alzheimer's, 0.55 (95% CI 0.36-0.84, p=0.006), and for Parkinson's 0.82 (95% CI 0.57-1.18, p=0.28).
Our results suggest that physical activity is inversely associated with risk of dementia. Future studies should examine the optimal dose of physical activity to induce protection, which presently remains unclear.
Summary
The risk of type 2 diabetes among obese adults who are metabolically healthy has not been established. We systematically searched Medline (1946–August 2013) and Embase (1947–August 2013) for ...prospective studies of type 2 diabetes incidence (defined by blood glucose levels or self‐report) among metabolically healthy obese adults (defined by body mass index BMI and normal cardiometabolic clustering, insulin profile or risk score) aged ≥18 years at baseline. We supplemented the analysis with an original effect estimate from the English Longitudinal Study of Ageing (ELSA), with metabolically healthy obesity defined as BMI ≥ 30 kg m−2 and <2 of hypertension, impaired glycaemic control, systemic inflammation, adverse high‐density lipoprotein cholesterol and adverse triglycerides. Estimates from seven published studies and ELSA were pooled using random effects meta‐analyses (1,770 healthy obese participants; 98 type 2 diabetes cases). The pooled adjusted relative risk (RR) for incident type 2 diabetes was 4.03 (95% confidence interval = 2.66–6.09) in healthy obese adults and 8.93 (6.86–11.62) in unhealthy obese compared with healthy normal‐weight adults. Although there was between‐study heterogeneity in the size of effects (I2 = 49.8%; P = 0.03), RR for healthy obesity exceeded one in every study, indicating a consistently increased risk across study populations. Metabolically healthy obese adults show a substantially increased risk of developing type 2 diabetes compared with metabolically healthy normal‐weight adults. Prospective evidence does not indicate that healthy obesity is a harmless condition.
► logKoc coefficients for PFOS and PFOA are similar for soils and sewage sludge. ► Field-based distribution coefficients are larger than lab-based coefficients. ► Dissipation times from soils may be ...underestimated using lab-based coefficients. ► Groundwater and surface waters are the main sinks for PFOA and PFOS.
The sorption of perfluorinated compounds (PFCs) to soils and sediments determines their fate and distribution in the environment, but there is little consensus regarding distribution coefficients that should be used for assessing the environmental fate of these compounds. Here we reviewed sorption coefficients for PFCs derived from laboratory experiments and compared these values with the gross distribution between the concentrations of PFCs in surface waters and sediments or between wastewater and sewage sludge. Sorption experiments with perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) suggest that their sorption can be described reasonably well as a partitioning-like process with an average logKoc of approximately 2.8 for PFOA and 3.0 for PFOS. However, median concentrations in sediments (PFOA, 0.27ngg−1; PFOS, 0.54ngg−1) or sewage sludge (PFOA, 37ngg−1; PFOS, 69ngg−1) in relation to median concentrations in surface water (PFOA, 3ngl−1; PFOS, 3ngl−1) or wastewater treatment effluent (PFOA, 24ngl−1; PFOS, 11ngl−1), suggest that effective logKoc distribution coefficients for the field situation may be close to 3.7 for PFOA and 4.2 for PFOS. Applying lab-based logKoc distribution coefficients can therefore result in a serious overestimation of PFC concentrations in water and in turn to an underestimation of the residence time of PFOA and PFOS in contaminated soils. Irrespective of the dissipation kinetics, the majority of PFOA and PFOS from contaminated soils will be transported to groundwater and surface water bodies.
Summary Background Temporal lobe epilepsy is a common and frequently intractable seizure disorder. Its pathogenesis is thought to involve large-scale alterations to the expression of genes ...controlling neurotransmitter signalling, ion channels, synaptic structure, neuronal death, gliosis, and inflammation. Identification of mechanisms coordinating gene networks in patients with temporal lobe epilepsy will help to identify novel therapeutic targets and biomarkers. MicroRNAs (miRNAs) are a family of small non-coding RNAs that control the expression levels of multiple proteins by decreasing mRNA stability and translation, and could therefore be key regulatory mechanisms and therapeutic targets in epilepsy. Recent developments In the past 5 years, studies have found changes in miRNA levels in the hippocampus of patients with temporal lobe epilepsy and in neural tissues from animal models of epilepsy. Early functional studies showed that silencing of brain-specific miR-134 using antisense oligonucleotides (antagomirs) had potent antiseizure effects in animal models, whereas genetic deletion of miR-128 produced fatal epilepsy in mice. Levels of certain miRNAs were also found to be altered in the blood of rodents after seizures. In the past 18 months, functional studies have identified nine novel miRNAs that appear to influence seizures or hippocampal pathology. Their targets include transcription factors, neurotransmitter signalling components, and modulators of neuroinflammation. New approaches to manipulate miRNAs have been tested, including injection of mimics (agomirs) to enhance brain levels of miRNAs. Altered miRNA expression has also been reported in other types of refractory epilepsy and our understanding of how miRNA levels are controlled has grown, with studies on DNA methylation indicating epigenetic regulation. Biofluids (blood) of patients with epilepsy have shown differences in quantity of circulating miRNAs, implying diagnostic biomarker potential. Where next? Recent functional studies need to be replicated to build a robust evidence base. The specific cell types in which miRNAs execute their functions and their primary targets have to be identified, to fully explain the phenotypic effects of modulating miRNAs. Delivery of large molecules such as antisense inhibitors or mimics to the brain poses a challenge, and the multi-targeting effects of miRNAs create additional risks of unanticipated side effects. Potential genetic variation in miRNAs should be explored as the basis for disease susceptibility. The latest findings provide a rich source of new miRNA targets, but substantial challenges remain before their role in the pathogenesis, diagnosis, and treatment of epilepsy can be translated into clinical practice.
To quantify the association between walking and the risk of cardiovascular disease (CVD) and all-cause mortality in healthy men and women.
Medline, Cochrane Database of Systematic Reviews, and Web of ...Science databases were searched to May 2007.
Prospective epidemiological studies of walking and CVD and all-cause mortality.
18 prospective studies were included in the overall analysis, which incorporated 459 833 participants free from CVD at baseline with 19 249 cases at follow-up. From the meta-analysis the pooled hazard ratio of CVD in the highest walking category compared with the lowest was 0.69, (95% CI 0.61 to 0.77, p<0.001), and 0.68 (0.59 to 0.78, p<0.001) for all-cause mortality. These effects were robust among men and women, although there was evidence of publication biases for the associations with CVD risk. Walking pace was a stronger independent predictor of overall risk compared with walking volume (48% versus 26% risk reductions, respectively). There was also evidence of a dose-response relationship across the highest, intermediate, and lowest walking categories in relation to the outcome measures.
The results suggest walking is inversely associated with clinical disease endpoints and largely support the current guidelines for physical activity. The mechanisms that mediate this relationship remain largely unknown and should be the focus of future research.
Regular physical activity is thought to be associated with better mental health, although there is a lack of consensus regarding the optimal amount and type of activity to achieve these benefits. The ...association between mental health and physical activity behaviours was examined among a representative sample of men and women from the Scottish Health Surveys.
Self-reported physical activity was measured and the General Health Questionnaire (GHQ-12) was administered in order to obtain information on current mental health. Participants were 19 842 men and women. Risk estimates per category of physical activity sessions per week were calculated using logistic regression models.
Psychological distress (based on a score of 4 or more on the GHQ-12) was evident in 3200 participants. Any form of daily physical activity was associated with a lower risk of psychological distress after adjustment for age, gender, social economic group, marital status, body mass index, long-standing illness, smoking and survey year (OR 0.59, 95% CI 0.52 to 0.66, p<0.001). A dose-response relationship was apparent, with moderate reductions in psychological distress with less frequent activity (OR 0.67, 95% CI 0.61 to 0.75). Different types of activities including domestic (housework and gardening), walking and sports were all independently associated with lower odds of psychological distress, although the strongest effects were observed for sports (OR 0.67, 95% CI 0.54 to 0.82).
Mental health benefits were observed at a minimal level of at least 20 min/week of any physical activity, although a dose-response pattern was demonstrated with greater risk reduction for activity at a higher volume and/or intensity.
Summary
Background Butyrate, a short‐chain fatty acid, is a main end‐product of intestinal microbial fermentation of mainly dietary fibre. Butyrate is an important energy source for intestinal ...epithelial cells and plays a role in the maintenance of colonic homeostasis.
Aim To provide an overview on the present knowledge of the bioactivity of butyrate, emphasizing effects and possible mechanisms of action in relation to human colonic function.
Methods A PubMed search was performed to select relevant publications using the search terms: ‘butyrate, short‐chain fatty acid, fibre, colon, inflammation, carcinogenesis, barrier, oxidative stress, permeability and satiety’.
Results Butyrate exerts potent effects on a variety of colonic mucosal functions such as inhibition of inflammation and carcinogenesis, reinforcing various components of the colonic defence barrier and decreasing oxidative stress. In addition, butyrate may promote satiety. Two important mechanisms include the inhibition of nuclear factor kappa B activation and histone deacetylation. However, the observed effects of butyrate largely depend on concentrations and models used and human data are still limited.
Conclusion Although most studies point towards beneficial effects of butyrate, more human in vivo studies are needed to contribute to our current understanding of butyrate‐mediated effects on colonic function in health and disease.
Ultralight mechanical resonators based on low-dimensional materials are well suited as exceptional transducers of minuscule forces or mass changes. However, the low dimensionality also provides a ...challenge to minimize resistive losses and heating. Here, we report on a novel approach that aims to combine different two-dimensional (2D) materials to tackle this challenge. We fabricated a heterostructure mechanical resonator consisting of few layers of niobium diselenide (NbSe2) encapsulated by two graphene sheets. The hybrid membrane shows high quality factors up to 245,000 at low temperatures, comparable to the best few-layer graphene mechanical resonators. In contrast to few-layer graphene resonators, the device shows reduced electrical losses attributed to the lower resistivity of the NbSe2 layer. The peculiar low-temperature dependence of the intrinsic quality factor points to dissipation over two-level systems which in turn relax over the electronic system. Our high sensitivity readout is enabled by coupling the membrane to a superconducting cavity which allows for the integration of the hybrid mechanical resonator as a sensitive and low loss transducer in future quantum circuits.
Very little is known about cortical development in the first years of life, a time of rapid cognitive development and risk for neurodevelopmental disorders. We studied regional cortical and ...subcortical gray matter volume growth in a group of 72 children who underwent magnetic resonance scanning after birth and at ages 1 and 2 years using a novel longitudinal registration/parcellation approach. Overall, cortical gray matter volumes increased substantially (106%) in the first year of life and less so in the second year (18%). We found marked regional differences in developmental rates, with primary motor and sensory cortices growing slower in the first year of life with association cortices growing more rapidly. In the second year of life, primary sensory regions continued to grow more slowly, while frontal and parietal regions developed relatively more quickly. The hippocampus grew less than other subcortical structures such as the amygdala and thalamus in the first year of life. It is likely that these patterns of regional gray matter growth reflect maturation and development of underlying function, as they are consistent with cognitive and functional development in the first years of life.
Cortical thickness (CT) and surface area (SA) are altered in many neuropsychiatric disorders and are correlated with cognitive functioning. Little is known about how these components of cortical gray ...matter develop in the first years of life. We studied the longitudinal development of regional CT and SA expansion in healthy infants from birth to 2 years. CT and SA have distinct and heterogeneous patterns of development that are exceptionally dynamic; overall CT increases by an average of 36.1%, while cortical SA increases 114.6%. By age 2, CT is on average 97% of adult values, compared with SA, which is 69%. This suggests that early identification, prevention, and intervention strategies for neuropsychiatric illness need to be targeted to this period of rapid postnatal brain development, and that SA expansion is the principal driving factor in cortical volume after 2 years of age.
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