The aim of the study is to evaluate the long-term near-transfer effects of computerized working memory (WM) training on standard WM tasks in children with Attention-Deficit/Hyperactivity Disorder (ADHD).
Sixty-seven children aged 10–12 years in Vestfold/Telemark counties (Norway) diagnosed with F90.0 Hyperkinetic disorder (ICD-10) were randomly assigned to training or control group. The training group participated in a 25-day training program at school, while the control group received treatment-as-usual. Participants were tested one week before intervention, immediately after and eight months later. Based on a component analysis, six measures of WM were grouped into composites representing Visual, Auditory and Manipulation WM.
The training group had significant long-term differential gains compared to the control group on all outcome measures. Performance gains for the training group were significantly higher in the visual domain than in the auditory domain. The differential gain in Manipulation WM persisted after controlling for an increase in simple storage capacity.
Systematic training resulted in a long-term positive gain in performance on similar tasks, indicating the viability of training interventions for children with ADHD. The results provide evidence for both domain-general and domain-specific models. Far-transfer effects were not investigated in this article.
Trial Registration: Controlled-Trials.com ISRCTN19133620
Childhood trauma exposure has been associated with deficits in cognitive functioning. The influence of timing of exposure on the magnitude and persistence of deficits is not well understood. The impact of exposure in early development has been especially under-investigated. This study examined the impact of interpersonal trauma exposure (IPT) in the first years of life on childhood cognitive functioning.
Children (N = 206) participating in a longitudinal birth cohort study were assessed prospectively for exposure to IPT (physical or emotional abuse or neglect, sexual abuse, witnessing maternal partner violence) between birth and 64 months. Child intelligent quotient scores (IQ) were assessed at 24, 64, and 96 months of age. Race/ethnicity, gender, socioeconomic status, maternal IQ, birth complications, birthweight, and cognitive stimulation in the home were also assessed.
IPT was significantly associated with decreased cognitive scores at all time points, even after controlling for sociodemographic factors, maternal IQ, birth complications, birthweight, and cognitive stimulation in the home. IPT in the first two years appeared to be especially detrimental. On average, compared to children not exposed to IPT in the first two years, exposed children scored one-half standard deviation lower across cognitive assessments.
IPT in early life may have adverse effects on cognitive development. IPT during the first two years may have particular impact, with effects persisting at least into later childhood.
cognitive development; IQ; trauma; child abuse; domestic violence
Studies have shown that children with ADHD profit from working memory training, although few studies have investigated transfer effects comprehensively. The current Randomized Controlled Trial analyzes transfer to other neuropsychological (NP) domains, academic performance and everyday functioning at home and school.
Sixty-seven children with ADHD were randomized into a control group or a training group. The training group underwent Cogmed’s RoboMemo program. All participants were assessed pre-training, immediately after and eight months later with a battery of NP tests, measures of mathematical and reading skills, as well as rating scales filled out by parents and teachers.
There was a significant training effect in psychomotor speed, but not to any other NP measures. Reading and mathematics were improved. There were no training induced changes in symptom rating scales either at home or at school. The increased reading scores remained significant eight months later.
The study is the most comprehensive study of transfer effects to date, and with mixed results compared to previous research. More research is needed regarding how to improve the training program and the conditions and thresholds for successful training.
Bifidobacteria are a major microbial component of infant gut microbiota, which is believed to promote health benefits for the host and stimulate maturation of the immune system. Despite their perceived importance, very little is known about the natural development of and possible correlations between bifidobacteria in human populations. To address this knowledge gap, we analyzed stool samples from a randomly selected healthy cohort of 87 infants and their mothers with >90% of vaginal delivery and nearly 100% breast-feeding at 4 months. Fecal material was sampled during pregnancy, at 3 and 10 days, at 4 months, and at 1 and 2 years after birth. Stool samples were predicted to be rich in the species Bifidobacterium adolescentis, B. bifidum, B. dentium, B. breve, and B. longum. Due to high variation, we did not identify a clear age-related structure at the individual level. Within the population as a whole, however, there were clear age-related successions. Negative correlations between the B. longum group and B. adolescentis were detected in adults and in 1- and 2-year-old children, whereas negative correlations between B. longum and B. breve were characteristic for newborns and 4-month-old infants. The highly structured age-related development of and correlation networks between bifidobacterial species during the first 2 years of life mirrors their different or competing nutritional requirements, which in turn may be associated with specific biological functions in the development of healthy gut.
Despite animal and in vitro studies demonstrating pro-oxidative effects of Hg, previous human work showed no relationship between tissue Hg and plasma levels of F2-isoprostanes (IsoPs), a whole-body oxidative stress marker. We hypothesized that another IsoP species, isofurans (IsoFs), was a more sensitive indicator of Hg-mediated oxidative stress, which can be modified by tissue Se status. A cross-sectional study was carried out involving individuals from a random subset (n = 233) of Inuit adults from a population-based survey (n = 2,595) of 36 Canadian Arctic Inuit communities to assess the relationships of plasma IsoPs to Se and Hg status indicators. F2-IsoPs were inversely correlated with blood Se (r = −0.186, P = 0.005) and toenail Se (r = −0.146, P = 0.044), but not correlated with Hg. IsoFs were inversely correlated with blood Se (r = −0.164, P = 0.014) and positively correlated with Hg (r = 0.228, P < 0.001) and Hg:Se (r = 0.340, P < 0.001). The strength of the correlations remained unchanged after multivariate adjustments. Multivariate analysis showed that F2-IsoPs were not positively associated with Hg but with Hg:Se (β = 0.148, P = 0.021). We conclude that Se and Hg status and their interactions are important factors modulating F2-IsoP and IsoF levels such that the Inuit may be protected from Hg-induced oxidative stress because of their high Se status.
isoprostane; isofuran; C-reactive protein; mercury; selenium
Symptoms similar to those found in Attention-Deficit/Hyperactivity Disorder (ADHD) often occur in children with Autism Spectrum Disorders (ASD). The objective of the current study was to compare verbal working memory, acquisition and delayed recall in children with High-Functioning Autism (HFA) to children with ADHD and typically developing children (TDC). Thirty-eight children with HFA, 79 with ADHD and 50 TDC (age 8–17) were assessed with a letter/number sequencing task and a verbal list-learning task. To investigate the possible influence of attention problems in children with HFA, we divided the HFA group into children with (HFA+) or without (HFA−) “attention problems” according to the Child Behaviour Checklist 6–18. The children with HFA+ displayed significant impairment compared to TDC on all three neurocognitive measures, while the children with HFA− were significantly impaired compared to TDC only on the working memory and acquisition measures. In addition, the HFA+ group scored significantly below the HFA− group and the ADHD group on the verbal working memory and delayed recall measures. The results support the proposition that children with HFA+, HFA−, and ADHD differ not only on a clinical level but also on a neurocognitive level which may have implications for treatment.
High rates of iron deficiency and anemia are common among Inuit and Arctic women despite a traditional diet based on animal source foods. However, representative data on iron status and relevant determinants for this population are lacking. The objectives were to determine the prevalence of anemia and depletion of iron stores, then to identify correlates of iron status in non-pregnant Canadian Inuit women.
In a cross-sectional survey of 1550 women in the International Polar Year Inuit Health Survey, 2007-2008, hemoglobin, serum ferritin, soluble transferrin receptor (on a subset), C-reactive protein (CRP), RBC fatty acid composition, and H pylori serology were analyzed on fasting venous blood. Sociodemographic, food security status, anthropometric, dietary, and health data were collected. Correlates of iron status were assessed with multivariate linear and logistic models.
Anemia was observed in 21.7% and iron deficient erythropoiesis in 3.3% of women. For women with CRP ≤ 10 mg/L (n = 1260) 29.4% had depleted iron stores. Inadequate iron intakes were observed in 16% of premenopausal and <1% of postmenopausal women. Among food insecure women, higher long-chain (n-3) polyunsaturated fatty acid (LC-PUFA) status, which reflects a more traditional food pattern, was associated with reduced risk of iron depletion.
Iron depletion and anemia are a concern for Inuit women despite adequate total dietary iron intake primarily from heme sources. The high prevalence of H. pylori exposure, together with dietary iron adequacy, suggests an inflammation-driven iron deficiency and mild anemia. The anti-inflammatory properties of LC-PUFA may be important for iron status in this population.
Next-generation sequencing (NGS) techniques have already shown their potential in the identification of mutations underlying rare inherited disorders. We report here the application of linkage analysis in combination with targeted DNA capture and NGS to a Norwegian family affected by an undiagnosed mental retardation disorder with an autosomal recessive inheritance pattern. Linkage analysis identified two loci on chromosomes 9 and 17 which were subject to target enrichment by hybridization to a custom microarray. NGS achieved 20-fold or greater sequence coverage of 83% of all protein-coding exons in the target regions. This led to the identification of compound heterozygous mutations in NAGLU, compatible with the diagnosis of Mucopolysaccharidosis IIIB (MPS IIIB or Sanfilippo Syndrome type B). This diagnosis was confirmed by demonstrating elevated levels of heparan sulphate in urine and low activity of α-N-acetyl-glucosaminidase in cultured fibroblasts. Our findings describe a mild form of MPS IIIB and illustrate the diagnostic potential of targeted NGS in Mendelian disease with unknown aetiology.
next-generation sequencing; DNA target enrichment; sequence capture; Sanfilippo Syndrome type B; mucopolysaccharidosis; NAGLU
The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders.
In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice.
More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders.
The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar spectrum. This association may reflect an etiological relationship or diagnostic overlapping criteria.
The statistical interpretation of the forensic genetic evidence requires the use of allelic frequency estimates in the reference population for the studied markers. Differences in the genetic make up of the populations can be reflected in statistically different allelic frequency distributions. One can easily figure out that collecting such information for any given population is not always possible. Therefore, alternative approaches are needed in these cases in order to compensate for the lack of information. A number of statistics have been proposed to control for population stratification in paternity testing and forensic casework, Fst correction being the only one recommended by the forensic community. In this study we aimed to evaluate the performance of Fst to correct for population stratification in forensics. By way of simulations, we first tested the dependence of Fst on the relative sizes of the sub-populations, and second, we measured the effect of the Fst corrections on the Paternity Index (PI) values compared to the ones obtained when using the local reference database. The results provide clear-cut evidence that (i) Fst values are strongly dependent on the sampling scheme, and therefore, for most situations it would be almost impossible to estimate real values of Fst; and (ii) Fst corrections might unfairly correct PI values for stratification, suggesting the use of local databases whenever possible to estimate the frequencies of genetic profiles and PI values.
Our goal is to develop a peripheral nerve electrode with long-term stability and fidelity for use in nerve-machine interfaces. Microelectromechanical systems (MEMS) use silicon probes that contain multi-channel actuators, sensors, and electronics. We tested the null hypothesis that implantation of MEMS probes do not have a detrimental effect on peripheral nerve function or regeneration.
A rat hindlimb, peroneal nerve model was utilized in all experimental groups: a) intact nerve (Control, n= 10); b) nerve division and repair (Repair, n= 9); and c) Nerve division, insertion of MEMS probe, and repair (Repair + Probe, n=9). Nerve morphology, nerve to muscle compound action potential (CMAP) studies, walking tracks, and extensor digitorum longus (EDL) muscle function tests were evaluated following an 80 day recovery.
Repair and Repair + Probe showed no differences in axon count, axon size, percent non-neural area, CMAP amplitude, latency, muscle mass, muscle force, or walking track scores. Though there was some local fibrosis around each MEMS probe, this did not lead to measurable detrimental effects in any anatomic or functional outcome measurements.
The lack of a significant difference between Repair and Repair + Probe groups in histology, CMAP, walking tracks, and muscle force suggests that MEMS electrodes are compatible with regenerating axons and show promise for establishing chemical and electrical interfaces with peripheral nerves.
peripheral nerve; electrode; MEMS; skeletal muscle; regeneration; nerve tissue
The study’s objective was to investigate the dietary correlates of an at-risk body mass index (BMI) among Inuit adults from thirty-six communities across the Canadian Arctic using data from the cross-sectional International Polar Year Inuit Health Survey, conducted in 2007–2008.
The survey included assessments of 24-hr dietary recall, sociodemographics, physical activity, and anthropometry. Dietary characteristics of overweight and obesity were similar and therefore combined into one at- risk BMI category (≥25 kg/m2) for analyses. The relationship between an at-risk BMI and energy intake from macronutrients, high sugar drinks, high-fat foods, saturated fatty acids, and traditional foods were examined entering each dietary variable separately into a logistic regression model as an independent variable. Analyses were adjusted for age, sex, region, kcalories, walking, smoking and alcohol consumption. Further multivariable models considered selected dietary variables together in one model.
An at-risk BMI was present for 64% with a prevalence of overweight and obesity of 28% and 36%, respectively. Consumption of high-sugar drinks (>15.5% E) was significantly related with having an at-risk BMI (OR = 1.6; 95% CI 1.2; 2.2), whereas the % E from total carbohydrate evaluated as a continuous variable and as quartiles was inversely related to an at-risk BMI (P -trend < 0.05) in multivariable analyses. While % E from high-fat foods was positively related to an at-risk BMI, the findings were not significant in a model controlling for high-sugar drinks and % E from carbohydrates.
The prevalence of overweight and obesity is of public health concern among Inuit. The current findings highlight the obesogenic potential of high-sugar drink consumption in an ethnically distinct population undergoing rapid cultural changes and raises concerns regarding carbohydrate restricted diets. Health promotion programs aimed at preventing the development of an unhealthy body weight should focus on physical activity and the promotion of healthy diets with reduced intake of sugar drinks.
Obesity; High-sugar drinks; Inuit
In a number of applications there is a need to determine the most likely pedigree for a group of persons based on genetic markers. Adequate models are needed to reach this goal. The markers used to perform the statistical calculations can be linked and there may also be linkage disequilibrium (LD) in the population. The purpose of this paper is to present a graphical Bayesian Network framework to deal with such data. Potential LD is normally ignored and it is important to verify that the resulting calculations are not biased. Even if linkage does not influence results for regular paternity cases, it may have substantial impact on likelihood ratios involving other, more extended pedigrees. Models for LD influence likelihoods for all pedigrees to some degree and an initial estimate of the impact of ignoring LD and/or linkage is desirable, going beyond mere rules of thumb based on marker distance. Furthermore, we show how one can readily include a mutation model in the Bayesian Network; extending other programs or formulas to include such models may require considerable amounts of work and will in many case not be practical. As an example, we consider the two STR markers vWa and D12S391. We estimate probabilities for population haplotypes to account for LD using a method based on data from trios, while an estimate for the degree of linkage is taken from the literature. The results show that accounting for haplotype frequencies is unnecessary in most cases for this specific pair of markers. When doing calculations on regular paternity cases, the markers can be considered statistically independent. In more complex cases of disputed relatedness, for instance cases involving siblings or so-called deficient cases, or when small differences in the LR matter, independence should not be assumed. (The networks are freely available at http://arken.umb.no/~dakl/BayesianNetworks.)
Premature ventricular complexes (PVC) predict cardiovascular mortality among several adult populations. Increased arrhythmia prevalence has been reported during controlled magnesium (Mg) depletion studies in adults. We thus hypothesized that serum magnesium (sMg) concentrations are inversely associated with the prevalence of PVC in adults at high cardiovascular risk.
Anthropometric, demographic and lifestyle characteristics were assessed in 750 Cree adults, aged > 18 yrs, who participated in an age-stratified, cross-sectional health survey in Quebec, Canada. Holter electrocardiograms recorded heart rate variability and cardiac arrhythmias for two consecutive hours. Multivariate logistic regression was used to evaluate the associations between sMg and PVC.
PVC prevalence in adults with hypomagnesemia (sMg ≤ 0.70 mmol/L) was more than twice that of adults without hypomagnesemia (50% vs. 21%, p = 0.015); results were similar when adults with cardiovascular disease history were excluded. All hypomagnesemic adults with PVC had type 2 diabetes (T2DM). Prevalence of PVC declined across the sMg concentration gradient in adults with T2DM only (p < 0.001 for linear trend). In multivariate logistic regressions adjusted for age, sex, community, body mass index, smoking, physical activity, alcohol consumption, kidney disease, antihypertensive and cholesterol lowering drug use, and blood docosahexaenoic acid concentrations, the odds ratio of PVC among T2DM subjects with sMg > 0.70 mmol/L was 0.24 (95% CI: 0.06-0.98) p = 0.046 compared to those with sMg ≤ 0.70 mmol/L.
sMg concentrations were inversely associated with the prevalence of PVC in patients with T2DM in a dose response manner, indicating that suboptimal sMg may be a contributor to arrhythmias among patients with T2DM.
Magnesium; Hypomagnesemia; Premature ventricular complexes; Premature ventricular beats; Ectopic beats; Arrhythmia; Type 2 diabetes
Investigate the effects of selected factors associated with quantitative ultrasound parameters among Inuit preschoolers living in Arctic communities (56° 32′–72° 40′N).
Materials and methods
Children were selected randomly in summer and early fall (n=296). Dietary intake was assessed through the administration of a 24-h dietary recall (24-h recall) and a food frequency questionnaire (FFQ). Anthropometry was measured using standardized procedures. Plasma 25-hydroxy vitamin D (25(OH)D) and parathyroid hormone (PTH) were measured using a chemiluminescent assay (Liaison, Diasorin). Quantitative ultrasound parameters were measured using Sahara Sonometer, (Hologic Inc.).
Children divided by speed of sound (SoS) and broadband ultrasound attenuation (BUA) quartiles were not different for age (years), sex (M/F), calcium (mg/d) and vitamin D intake (µg/d) and plasma 25(OH)D concentration (nmol/L). However, children in the highest BUA and SoS quartile had higher body mass index (BMI) compared to those in quartile 1. Using multivariate linear regression, higher BMI, older age and monounsaturated fatty acids (MUFA) intake were predictors of BUA while only BMI was a predictor of SoS.
Further investigation assessing intakes of traditional foods (TF) and nutrients affecting bone parameters along with assessment of vitamin D status of Inuit children across seasons is required.
speed of sound; broadband ultrasound attenuation; preschoolers; Inuit; vitamin D
To evaluate the socio-economic correlates of overweight and obesity among Inuit undergoing rapid cultural changes.
A cross-sectional health survey of 2,592 Inuit adults from 36 communities in the Canadian Arctic.
Main outcome measures were overweight and obesity (BMI>25 kg/m2 and >30 kg/m2, respectively) and as characteristics were similar, groups were combined into an at-risk BMI category (BMI>25 kg/m2). Logistic regression was used to determine the association between various sociodemographic characteristics and physical activity with overweight and obesity.
The prevalence of overweight and obesity was 28 and 36%, respectively, with a total prevalence of overweight and obesity of 64%. In analyses of sociodemographic variables adjusted for age, gender and region, higher education, any employment, personal income, and private housing were all significantly positively correlated with an at-risk BMI (p≤0.001). Smoking, Inuit language as primary language spoken at home, and walking were inversely associated with overweight and obesity.
The current findings highlight the social disparities in overweight and obesity prevalence in an ethnically distinct population undergoing rapid cultural changes.
obesity; socioeconomic status; Inuit
To determine the extent to which demographic characteristics, clinical measurements and biomarkers were associated with poor self-reported health (SRH) among Inuit adults in the Canadian Arctic.
Cross-sectional survey was adopted as the study design.
The International Polar Year Inuit Health Survey carried out in 36 Canadian Arctic communities in 2007 and 2008 included Inuit men and women, aged 18 years or older, recruited from randomly selected households. The main outcome measure was SRH, which was dichotomized into good health (excellent, very good and good responses) and poor health (fair and poor responses).
Of the 2,796 eligible households, 1,901 (68%) households and 2,595 participants took part in the survey. The weighted prevalence of poor SRH was 27.8%. Increasing age was significantly associated with poor SRH. The relative risk ratios for poor SRH was 2.0 (95% confidence interval [CI] 1.3–3.1) for men aged 50 years or older and 2.3 (95% CI 1.7–3.0) for women aged 50 years or older, compared with men and women aged 29 years or younger. After adjusting for age, gender and body mass index, poor SRH was significantly associated with smoking status (odds ratio [OR]=1.5; CI 1.1–2.0), at-risk fasting glucose levels (≥6.1 mmol/L) (OR=2.5; 95%; CI 1.5–4.2) and elevated hs C-reactive protein levels (>3–≤10 mg/L) (OR=2.1; 95% CI 1.4–3.1). Poor SRH was also significantly associated with a hypertriglyceridemic waist phenotype (high-risk waist circumference ≥102 cm for men and ≥88 cm for women with high triglyceride levels, ≥1.7 mmol/L), adjusted for age and gender, OR=1.6; 95% CI 1.1–2.3.
Clinically relevant indicators of chronic disease risk were related to subjective assessment of SRH among Inuit.
Inuit; health research; self-reported health; biomarkers
The Canadian International Polar Year (IPY) program made it possible to undertake much needed health research in 3 jurisdictions within the Canadian Inuit Nunangat (homeland) over a 2-year period: Inuvialuit Settlement Region (ISR), Nunavut Territory, and Nunatsiavut.
The Adult Inuit Health Survey (IHS) was a cross-sectional survey and provides baseline data upon which future comparisons can be made for prospectively assessing factors leading to the progression of chronic diseases among Canadian Inuit. With the help of the Canadian Coast Guard Ship Amundsen, which was equipped with research and laboratory facilities, 33 coastal communities were visited; land survey teams visited 3 inland communities.
The Adult IHS succeeded in obtaining important baseline information concerning the health status and living conditions of 2,595 adults living in ISR, Nunavut and Nunatsiavut.
Information from this survey will be useful for future comparisons and the opportunity to link with the International Inuit Cohort, a follow-up evaluation, and for the development of future health policies and public health interventions.
International Polar Year; Inuit; health research; survey; Canadian Arctic
Mitochondrial DNA (mtDNA) variation is commonly analyzed in a wide range of different biomedical applications. Cases where more than one individual contribute to a stain genotyped from some biological material give rise to a mixture. Most forensic mixture cases are analyzed using autosomal markers. In rape cases, Y-chromosome markers typically add useful information. However, there are important cases where autosomal and Y-chromosome markers fail to provide useful profiles. In some instances, usually involving small amounts or degraded DNA, mtDNA may be the only useful genetic evidence available. Mitochondrial DNA mixtures also arise in studies dealing with the role of mtDNA variation in tumorigenesis. Such mixtures may be generated by the tumor, but they could also originate in vitro due to inadvertent contamination or a sample mix-up.
We present the statistical methods needed for mixture interpretation and emphasize the modifications required for the more well-known methods based on conventional markers to generalize to mtDNA mixtures. Two scenarios are considered. Firstly, only categorical mtDNA data is assumed available, that is, the variants contributing to the mixture. Secondly, quantitative data (peak heights or areas) on the allelic variants are also accessible. In cases where quantitative information is available in addition to allele designation, it is possible to extract more precise information by using regression models. More precisely, using quantitative information may lead to a unique solution in cases where the qualitative approach points to several possibilities. Importantly, these methods also apply to clinical cases where contamination is a potential alternative explanation for the data.
We argue that clinical and forensic scientists should give greater consideration to mtDNA for mixture interpretation. The results and examples show that the analysis of mtDNA mixtures contributes substantially to forensic casework and may also clarify erroneous claims made in clinical genetics regarding tumorigenesis.
The purpose of this study is to optimize poly(3,4,-ethylenedioxythiophene) (PEDOT) polymerization into decellular nerve scaffolding for interfacing to peripheral nerves. Our ultimate aim is to permanently implant highly conductive peripheral nerve interfaces between amputee, stump, nerve fascicles and prosthetic electronics. Decellular nerve (DN) scaffolds are an FDA approved biomaterial (Axogen ) with the flexible tensile properties needed for successful permanent coaptation to peripheral nerves. Biocompatible, electroconductive, PEDOT facilitates electrical conduction through PEDOT coated acellular muscle. New electrochemical methods were used to polymerize various PEDOT concentrations into DN scaffolds without the need for a final dehydration step. DN scaffolds were then tested for electrical impedance and charge density. PEDOT coated DN scaffold materials were also implanted as 15–20mm peripheral nerve grafts. Measurement of in-situ nerve conduction immediately followed grafting. DN showed significant improvements in impedance for dehydrated and hydrated, DN, polymerized with moderate and low PEDOT concentrations when they were compared with DN alone (a ≤ 0.05). These measurements were equivalent to those for DN with maximal PEDOT concentrations. In-situ, nerve conduction measurements demonstrated that DN alone is a poor electro-conductor while the addition of PEDOT allows DN scaffold grafts to compare favorably with the “gold standard”, autograft (Table 1). Surgical handling characteristics for conductive hydrated PEDOT DN scaffolds were rated 3 (pliable) while the dehydrated models were rated 1 (very stiff) when compared with autograft ratings of 4 (normal). Low concentrations of PEDOT on DN scaffolds provided significant increases in electro active properties which were comparable to the densest PEDOT coatings. DN pliability was closely maintained by continued hydration during PEDOT electrochemical polymerization without compromising electroconductivity.
poly(3,4,-ethylenedioxythiophene); peripheral nerve; decellular nerve; nerve conduction
Inuit have not experienced an epidemic in type 2 diabetes mellitus, and it has been speculated that they may be protected from obesity’s metabolic consequences. We conducted a population-based screening for diabetes among Inuit in the Canadian Arctic and evaluated the association of visceral adiposity with diabetes.
A total of 36 communities participated in the International Polar Year Inuit Health Survey. Of the 2796 Inuit households approached, 1901 (68%) participated, with 2595 participants. Households were randomly selected, and adult residents were invited to participate. Assessments included anthropometry and fasting plasma lipids and glucose, and, because of survey logistics, only 32% of participants underwent a 75 g oral glucose tolerance test. We calculated weighted prevalence estimates of metabolic risk factors for all participants.
Participants’ mean age was 43.3 years; 35% were obese, 43.8% had an at-risk waist, and 25% had an elevated triglyceride level. Diabetes was identified in 12.2% of participants aged 50 years and older and in 1.9% of those younger than 50 years. A hypertriglyceridemic-waist phenotype was a strong predictor of diabetes (odds ratio [OR] 8.6, 95% confidence interval [CI] 2.1–34.6) in analyses adjusted for age, sex, region, family history of diabetes, education and use of lipid-lowering medications.
Metabolic risk factors were prevalent among Inuit. Our results suggest that Inuit are not protected from the metabolic consequences of obesity, and that their rate of diabetes prevalence is now comparable to that observed in the general Canadian population. Assessment of waist circumference and fasting triglyceride levels could represent an efficient means for identifying Inuit at high risk for diabetes.
Depression and anxiety are common symptoms in Parkinson's disease for which there are no optimal treatments. Sarizotan, an agonist at serotonin receptors and partial agonist at dopamine D2-like receptors, has shown antidyskinetic effects in Parkinson's disease. Based on its pharmacological profile, we hypothesized that sarizotan could also have antidepressant-like properties.
Examine effects of sarizotan on behavioral and histological measures known to be regulated by established antidepressants in normal and unilaterally 6-hydroxydopamine-lesioned rats.
Sarizotan was found to significantly reduce immobility in the modified forced swim test, a measure of antidepressant-like activity, but had no effects on thigmotaxis or corner time, measures of anxiety-like behavior, in the unilaterally 6-hydroxydopamine-lesioned rats. At the same dose, sarizotan counteracted l-DOPA/benserazide-induced supersentitized rotational behavior and dyskinesias without significantly affecting l-DOPA/benserazide-induced locomotion. At the histological level, sarizotan alone or in combination with l-DOPA/benserazide stimulated cell proliferation, measured by bromodeoxyuridine incorporation or Ki-67 staining, both in the subgranular zone of the dentate gyrus and in the subventricular zone of the striatum in the 6-hydroxydopamine-lesioned hemisphere. Likewise, combined sarizotan and l-DOPA/benserazide treatment stimulated doublecortin levels in the subgranular zone of the dentate gyrus.
These significant effects of sarizotan in the modified forced swim test and on cell proliferation are reminiscent of those found after various antidepressant therapies. These data suggest that sarizotan may have some antidepressant-like and restorative properties in Parkinsonism.
6-hydroxydopamine; Parkinson's disease; Bromodeoxyuridine; Ki-67; Doublecortin; Serotonin; Modified forced swim test
The Inuit are commonly portrayed to be somehow protected from cardiovascular diseases (CVDs) through their traditional lifestyle and diet. However, actual sociocultural transition and related major, modifiable risk factors have scarcely been quantified in the Inuit population. Such knowledge is extremely valuable in terms of public health intervention.
A total of 887 Inuit residents from Nunavik, Quebec, participated in a cohort study. The estimates presented were derived from anthropometric and biological measurements gathered at the time of recruitment and enhanced by information collected in the medical file of each participant. All estimates were corrected for a complex sampling strategy and bootstrapped to ensure the representativeness of the general Nunavik population.
Overall, 19% of Inuit had a disease of the circulatory system according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision. Among all disorders, peripheral circulatory system disease was the most prevalent (9%). Prevalences of ischemic heart disease and cerebrovascular disease were of similar magnitude (2.5%). No significant difference in disease prevalence was noted between sexes. The major modifiable CVD risk factors were smoking (84%), obesity (49%) (body mass index of greater than 30 kg/m2) and elevated blood pressure (130/85 mmHg or greater) (18%). Prevalences were globally higher among women.
The current belief that the Inuit are protected from CVD is seriously questioned by the results of the present study. Considering the extremely high prevalence of CVD risk factors, a population-based intervention reinforced for women is urgently needed to reduce their risk.
Epidemiology; Health outcomes; Hypertension; Ischemia; Morbidity; Myocardial infarction; Obesity; Prevalence; Risk factors; Stroke
Mutation models are important in many areas of genetics including forensics. This letter criticizes the model of the paper 'DNA identification by pedigree likelihood ratio accommodating population substructure and mutations' by Ge et al. (2010). Furthermore, we argue that the paper in some cases misrepresents previously published papers.
Please see related letter: http://www.investigativegenetics.com/content/2/1/8.
Variants in CLEC16A have conferred susceptibility to autoimmune diseases in genome-wide association studies. The present work aimed to investigate the locus' involvements in juvenile idiopathic arthritis (JIA) and further explore the association with rheumatoid arthritis (RA), type 1 diabetes (T1D) and Addison's disease (AD) in the Norwegian population.
Three single nucleotide polymorphisms (SNPs) were genotyped in patients with RA (n=809), JIA (n=509), T1D (n=1211) and AD (n=414) and in healthy controls (n=2149).
All diseases were associated with CLEC16A, but with different SNPs. The intron 22 SNP, rs6498169, was associated with RA (p=0.006) and JIA (p=0.016) and the intron 19 SNPs, rs12708716/rs12917716, with T1D (p=1×10−5) and AD (p=2×10−4). The RA association was confined to the anti-cyclic citrullinated peptide antibody (anti-CCP) negative subgroup (p=2×10−4).
This is the first report of a CLEC16A association with JIA and a split of the RA association according to anti-CCP status. Different causative variants underlie the rheumatic versus the organ specific diseases.