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General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

Objective: To evaluate the impact of an extruded muesli product based on [beta]-glucan-rich oat bran on postprandial glycaemia and insulinaemia. Subject/Design: The study is divided in two series. Blood glucose [...]

Eight crossbred, ovariectomized gilts (Swedish Landrace x Swedish Yorkshire x Hampshire), with a mean age of 7.5 mo, were studied during anesthesia and surgery, control-sampling, relocation, and grouping during a period of 3 wk. Acute treatment with a hydrocortisone injection (5 mg, i.v.) was also given. Blood samples were taken frequently (every 10 min) during the intensive part of the experimental days. The blood samples were analyzed for catecholamines (CA), adrenaline (A) and noradrenaline (NA), cortisol, and corticosteroid-binding globulin (CBG). The surgical period with anesthesia and surgery showed significant effects on CA, cortisol, and CBG. The A level increased immediately after the surgery. A biphasic increase in the cortisol level was observed on the day of surgery; the greatest increase was seen when the animals had regained consciousness after surgery but still were drowsy and staggering. The CBG level decreased on the day after the surgery. The study showed that the levels of the analyzed substances were back to normal 2 d after surgery. During relocation and grouping there was a short, significant increase in CA and cortisol levels, whereas the CBG level was not affected. Treatment with hydrocortisone significantly increased the cortisol level, but no change was seen in plasma CA or CBG levels. In conclusion, anesthesia and surgery induced significant effects on the levels of CA, cortisol, and CBG in gilts and the animals needed 2 d to recover before regaining their normal condition. During relocation and a limited grouping period, the significant increases in CA and cortisol levels were of short duration and CBG did not change. The animals returned to their normal condition again a few hours later.

Traumatic brain injury (TBI) is clinically divided into a spectrum of severities, with mild TBI being the least severe form and a frequent occurrence in contact sports, such as ice hockey, American football, rugby, horse riding and boxing. Mild TBI is caused by blunt nonpenetrating head trauma that causes movement of the brain and stretching and tearing of axons, with diffuse axonal injury being a central pathogenic mechanism. Mild TBI is in principle synonymous with concussion; both have similar criteria in which the most important elements are acute alteration or loss of consciousness and/or post-traumatic amnesia following head trauma and no apparent brain changes on standard neuroimaging. Symptoms in mild TBI are highly variable and there are no validated imaging or fluid biomarkers to determine whether or not a patient with a normal computerized tomography scan of the brain has neuronal damage. Mild TBI typically resolves within a few weeks but 10-15% of concussion patients develop postconcussive syndrome. Repetitive mild TBI, which is frequent in contact sports, is a risk factor for a complicated recovery process. This overview paper discusses the relationships between repetitive head impacts in contact sports, mild TBI and chronic neurological symptoms. What are these conditions, how common are they, how are they linked and can they be objectified using imaging or fluid-based biomarkers? It gives an update on the current state of research on these questions with a specific focus on clinical characteristics, epidemiology and biomarkers. [ABSTRACT FROM AUTHOR]

Objective: Depression is associated with accelerated aging and age‐related diseases. However, mechanisms underlying this relationship remain unclear. The aim of this study was to longitudinally assess the link between depressive symptoms, brain atrophy, and cortisol levels. Method: Participants from the Betula prospective cohort study (mean age = 59 years, SD = 13.4 years) underwent clinical, neuropsychological and brain 3T MRI assessments at baseline and a 4‐year follow‐up. Cortisol levels were measured at baseline in four saliva samples. Cortical and hippocampal atrophy rates were estimated and compared between participants with and without depressive symptoms (n = 81) and correlated with cortisol levels (n = 49). Results: Atrophy in the left superior frontal gyrus and right lingual gyrus developed in parallel with depressive symptoms, and in the left temporal pole, superior temporal cortex, and supramarginal cortex after the onset of depressive symptom. Depression‐related atrophy was significantly associated with elevated cortisol levels. Elevated cortisol levels were also associated with widespread prefrontal, parietal, lateral, and medial temporal atrophy. Conclusion: Depressive symptoms and elevated cortisol levels are associated with atrophy of the prefrontal and limbic areas of the brain. [ABSTRACT FROM AUTHOR]

Background: Web-based interventions for pain management are increasingly used with possible benefits, but never used in addition to multimodal rehabilitation (MMR). MMR is recommended treatment for persistent pain in Sweden. The aim was to evaluate the effects of a self-guided, web-based programme added to MMR for work ability, pain, disability and health-related quality of life.Methods: We included 99 participants with persistent musculoskeletal pain in a randomized study with two intervention arms: (1) MMR and web-based intervention, and (2) MMR. Data was collected at baseline, 4 and 12 months. Outcome measures were work ability, working percentage, average pain intensity, pain-related disability, and health-related quality of life.Results: There were no significant effects of adding the web-based intervention to MMR regarding any of the outcome variables.Conclusions: This trial provides no support for adding a self-guided, web-based activity programme to MMR for patients with persistent musculoskeletal pain.Significance: The comprehensive self-guided, web-based programme for activity, Web-BCPA, added to multimodal treatment in primary health care had no effect on work ability, pain, disability or health-related quality of life. Future web-based interventions should be tailored to patients' individual needs and expectations. [ABSTRACT FROM AUTHOR]

The episodic long-term memory system supports remembering of events. It is considered to be the most age-sensitive system, with an average onset of decline around 60 years of age. However, there is marked interindividual variability, such that some individuals show faster than average change and others show no or very little change. This variability may be related to the risk of developing dementia, with elevated risk for individuals with accelerated episodic memory decline. Brain imaging with functional magnetic resonance imaging (MRI) of blood oxygen level-dependent (BOLD) signalling or positron emission tomography (PET) has been used to reveal the brain bases of declining episodic memory in ageing. Several studies have demonstrated a link between age-related episodic memory decline and the hippocampus during active mnemonic processing, which is further supported by studies of hippocampal functional connectivity in the resting state. The hippocampus interacts with anterior and posterior neocortical regions to support episodic memory, and alterations in hippocampus-neocortex connectivity have been shown to contribute to impaired episodic memory. Multimodal MRI studies and more recently hybrid MRI/PET studies allow consideration of various factors that can influence the association between the hippocampal BOLD signal and memory performance. These include neurovascular factors, grey and white matter structural alterations, dopaminergic neurotransmission, amyloid-Β and glucose metabolism. Knowledge about the brain bases of episodic memory decline can guide interventions to strengthen memory in older adults, particularly in those with an elevated risk of developing dementia, with promising results for combinations of cognitive and physical stimulation. [ABSTRACT FROM AUTHOR]

Background: The epsilon4 allele of apolipoprotein E (APOE) and head injury are risk factors for dementia diseases, and may act synergistically to further increase the risk. The aim of this study was to examine the association between mild head injury, APOE and dementia.Methods: Data were obtained from the Betula prospective population-based study of aging, memory, and health. The study included 543 participants in the age range 40-85 years, free of dementia at baseline, who were followed up within a 5-year interval. Dementia was classified using DSM-IV criteria. Information on previous head injury was obtained through screening of the participants' answers to health questionnaires at baseline and at follow-up.Results: Subjects with head injury but without APOE epsilon4 had no increased risk of dementia. Subjects with APOE epsilon4 had an increased risk and those with both APOE epsilon4 and head injury had the highest risk of dementia (odds ratio = 5.2).Conclusions: APOE epsilon4 constitutes a risk factor for dementia, mild injury in isolation does not increase the risk, but head injury in combination with the APOE epsilon4 leads to increased risk of dementia. [ABSTRACT FROM AUTHOR]

In spite of the great abundance and ecological importance of headwater streams, managers are usually limited by a lack of information about water chemistry in these headwaters. In this study we test whether river outlet chemistry can be used as an additional source of information to improve the prediction of the chemistry of upstream headwaters (size < 2 km²), relative to models based on map information alone. We use the concentration of total organic carbon (TOC), an important stream ecosystem parameter, as the target for our study. Between 2000 and 2008, we carried out 17 synoptic surveys in 9 mesoscale catchments (size 32-235 km2). Over 900 water samples were collected in total, primarily from headwater streams but also including each catchment's river outlet during every survey. First we used partial least square regression (PLS) to model the distribution (median, interquartile range (IQR)) of headwater stream TOC for a given catchment, based on a large number of candidate variables including sub-catchment characteristics from GIS, and measured river chemistry at the catchment outlet. The best candidate variables from the PLS models were then used in hierarchical linear mixed models (MM) to model TOC in individual headwater streams. Three predictor variables were consistently selected for the MM calibration sets: (1) proportion of forested wetlands in the sub-catchment (positively correlated with headwater stream TOC), (2) proportion of lake surface cover in the sub-catchment (negatively correlated with headwater stream TOC), and (3) river outlet TOC (positively correlated with headwater stream TOC). Including river outlet TOC improved predictions, with 5-15% lower prediction errors than when using map information alone. Thus, data on water chemistry measured at river outlets offer information which can complement GIS-based modelling of headwater stream chemistry. [ABSTRACT FROM AUTHOR]

In spite of the great abundance and ecological importance of headwater streams, managers are usually limited by a lack of information about water chemistry in these headwaters. In this study we test whether river outlet chemistry can be used as an additional source of information to improve the prediction of the chemistry of upstream headwaters (size < 2 km²), relative to models based on map information alone. Between 2000 and 2008, we conducted 17 synoptic surveys of streams within 9 mesoscale catchments (size 32-235 km²). Over 900 water samples were collected from catchments ranging in size from 0.03 to 235 km². First we used partial least square regression (PLS) to model headwater stream total organic carbon (TOC) median and interquartile values for a given catchment, based on a large number of candidate variables including catchment characteristics from GIS, and measured chemistry at the catchment outlet. The best candidate variables from the PLS models were then used in hierarchical linear mixed models (MM) to model TOC in individual headwater streams. Three predictor variables were consistently selected for the MM calibration sets: (1) proportion of forested wetlands in the sub-catchment (positively correlated with headwater stream TOC), (2) proportion of lake surface cover in the sub-catchment (negatively correlated with headwater stream TOC), and (3) whole-catchment river outlet TOC (positively correlated with headwater stream TOC). Including river outlet TOC as a predictor in the models gave 5-15% lower prediction errors than using map information alone. Thus, data on water chemistry measured at river outlets offers information which can complement GIS-based modelling of headwater stream chemistry. [ABSTRACT FROM AUTHOR]

We demonstrate how nanofluidic channels can be used as a tool to rapidly determine the number and sizes of plasmids in bacterial isolates. Each step can be automated at low cost, opening up opportunities for general use in microbiology labs. [ABSTRACT FROM AUTHOR]