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Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
Introduction: BACKGROUND: Recognition rates of delirium in older ED patients were reported between 13 to 25% in studies conducted in the U.S in the 1990's. Recently, there has been increased attention to delirium in Emergency Medicine, with the development of Geriatric curriculums in Canada specifically focused on delirium. However rates of delirium recognition have not been reassessed in Canadian ED's. OBJECTIVES: To assess the rate of delirium recognition by ED staff in a cohort of older ED patients assessed at a tertiary care Canadian ED. Methods: STUDY DESIGN: Prospective observational cohort study at a Canadian teaching ED. PARTICIPANTS: Eligible patients were aged ≥70 years and older who had stayed in the ED for a minimum of 4 hours. We excluded patients who were critically ill, visually impaired or otherwise unable to communicate. DATA COLLECTION: Trained research assistants approached clinical staff prior to approaching patients to confirm that patients were delirium free. They then assessed demographics, ED length of stay (LOS) and cognition using the validated Montreal Cognitive Assessment scale (MOCA), mini-mental status exam (MMSE), delirium index and Richardson Agitation Scale (RASS) at baseline. Delirium was assessed using the validated Confusion Assessment Method (CAM). We report descriptive statistics and 95% confidence intervals (CI) where appropriate. Results: We enrolled 203 patients of which 102 (50.3%) were female. Their mean age was 81.0 years, mean LOS was 16.3 hours, mean MOCA was 23.4 and mean MMSE was 26.7. RA's detected delirium using the CAM in 16/203 patients (7.9%, 95% CI 4.6 to 12.5%). Mean MOCA and MMSE for delirious patients was 13.4 and 18.3 and their mean DI was 6.4. All CAM positive patients were deemed to be delirium free by clinical staff. RA alerted clinical staff in all cases where patients had delirium, but 3/16 were discharged home (18.8%, 95% CI 4.1 to 45.7%). Conclusion: Our findings confirm previous low delirium recognition rates in a Canadian Tertiary ED. Future research should explore barriers and facilitators to recognizing delirium in the ED.
The goal of this study was to assess the utility of serial electrocardiograms in routine follow-up of paediatric Marfan patients.
Children ⩽18 years who met the revised Ghent criteria for Marfan syndrome and received a 12-lead electrocardiogram and echocardiogram within a 3-month period were included. Controls were matched by age, body surface area, gender, race, and ethnicity, and consisted of patients assessed in clinic with a normal cardiac evaluation. Demographic, clinical, echocardiographic, and electrocardiographic data were collected.
A total of 45 Marfan patients (10.8 [2.4–17.1] years) and 37 controls (12.8 [1.3–17.1] years) were included. Left atrial enlargement and left ventricular hypertrophy were more frequently present on 12-lead electrocardiogram of Marfan patients compared with controls (12 (27%) versus 0 (0%), p<0.001; and 8 (18%) versus 0 (0%), p=0.008, respectively); however, only two patients with left atrial enlargement on 12-lead electrocardiogram were confirmed to have left atrial enlargement by echocardiogram, and one patient had mild left ventricular hypertrophy by echocardiogram, not appreciated on 12-lead electrocardiogram. QTc interval was longer in Marfan patients compared with controls (427±16 versus 417±22 ms, p=0.03), with four Marfan patients demonstrating borderline prolonged QTc intervals for gender.
While Marfan patients exhibited a higher frequency of left atrial enlargement and left ventricular hypertrophy on 12-lead electrocardiograms compared with controls, these findings were not supported by echocardiography. Serial 12-lead electrocardiograms in routine follow-up of asymptomatic paediatric Marfan patients may be more appropriate for a subgroup of Marfan patients only, specifically those with prolonged QTc interval at their baseline visit.
From 1994 onwards, radiocarbon discharges from the Sellafield nuclear fuel reprocessing plant have been made largely to the northeast Irish Sea. They represent the largest contributor to UK and European populations of the collective dose commitment derived from the entire nuclear industry discharges. Consequently, it is important to understand the long-term fate of 14C in the marine environment. Research undertaken in 2000 suggested that the carbonate component of northeast Irish Sea sediments would increase in 14C activity as mollusk shells, which have become enriched in Sellafield-derived 14C, are broken down by physical processes including wave action and incorporated into intertidal and subtidal sediments. The current study, undertaken in 2011, tested this hypothesis. The results demonstrate significant increases in 14C enrichments found in whole mussel shells compared to those measured in 2000. Additionally, in 2000, there was an enrichment above ambient background within only the largest size fraction (>500 μm) of the intertidal inorganic sediment at Nethertown and Flimby (north of Sellafield). In comparison, the present study has demonstrated 14C enrichments above ambient background in most size fractions at sites up to 40 km north of Sellafield, confirming the hypothesis set out more than a decade ago.
Ocean sunfish from the genus Mola, family Molidae, are the world's heaviest bony fish, reaching 2500 kg, primarily on a diet of gelatinous zooplankton. Three molid species are reported to occur in the Galápagos archipelago: Mola mola, Masturus lanceolatus and Ranzania laevis. To date, no genetic analysis of any molid has been conducted in Galápagos. In October 2011, tissue samples were obtained from nine sunfish at Punta Vicente Roca, Isabela Island, genetically analysed and found to be Mola ramsayi—the southern sunfish. This marks the first record of M. ramsayi in Galápagos waters.
The target adopted by world leaders of significantly reducing the rate of biodiversity loss by 2010 was not met but this stimulated a new suite of biodiversity targets for 2020 adopted by the Parties to the Convention on Biological Diversity (CBD) in October 2010. Indicators will be essential for monitoring progress towards these targets and the CBD will be defining a suite of relevant indicators, building on those developed for the 2010 target. Here we argue that explicitly linked sets of indicators offer a more useful framework than do individual indicators because the former are easier to understand, communicate and interpret to guide policy. A Response-Pressure-State-Benefit framework for structuring and linking indicators facilitates an understanding of the relationships between policy actions, anthropogenic threats, the status of biodiversity and the benefits that people derive from it. Such an approach is appropriate at global, regional, national and local scales but for many systems it is easier to demonstrate causal linkages and use them to aid decision making at national and local scales. We outline examples of linked indicator sets for humid tropical forests and marine fisheries as illustrations of the concept and conclude that much work remains to be done in developing both the indicators and the causal links between them.
The ability to integrate electrical functionality into textile garments is becoming increasingly desired both on the battlefield and in the work environment. In order to accomplish this, the issue of compatibility of mechanical properties between dissimilar materials needs to be addressed. Textiles are typically selected for comfort while electrical materials are chosen for superior electrical properties with secondary consideration given to properties such as flexibility. As a result many attempts to integrate electrical functionality into textiles result in stiff, unwieldy garments that have difficulty gaining user acceptance.
Part of the electrotextile work done at Foster-Miller has focused on the integration of these dissimilar materials in a manner that does not degrade the wearability of the garment. Our work has included the development of textile cables that carry power and data using both electrical and optical media. In order to assess the wearability of these cables a method was needed of testing their stiffness. Several methods of measuring textile stiffness existed but did not address the many issues and material characteristics unique to conductive textiles.
Today's complex geo-political climate has forced the U.S. armed services into new operational strategies. The prevalence of international terrorism, the threat from chemical and biological weapons, and the pressure to “do more with less” has placed increasing demands on the military. This new operational environment requires highly mobile troops having enhanced decision-making capability provided through the rapid transfer and dissemination of information to each member of the squad. What is missing is the ability to process and use this information via an Intranet at the level of the individual soldier. The purpose of our work has been to develop, evaluate and implement such a wearable conductive network for the dismounted soldier.
The increasing desire to internet the soldier on the battlefield requires a new approach to outfit the soldier with communications systems capable of operating in multiple frequency domains as shown in Table 1. Outfitting the soldier with multiple unwieldy antennas often results in the equipment being left behind, used improperly or broken. The ultimate in unobtrusive antennas is one that conforms to the body and does not interfere with the normal degrees of freedom of the soldier's uniform. Conformal antennas mounted on the body must take into account the electrical properties of the body, particularly at frequencies above 30 MHz. In addition, integration into the textile structure requires that the antenna be isolated from effects of clothing usage including clothing movement, wet operation, washing, and mechanical abrasion.
Cognitive impairment precedes the diagnosis of Alzheimer's disease. It is unclear which psychometric measures predict dementia, and what cut-off points should be used. Replicable cognitive measures to provide information about differential diagnosis and prognosis would be clinically useful.
In a prospective cohort study we investigated which measures distinguish between individuals with amnestic mild cognitive impairment (aMCI) that converts to dementia and those whose impairment does not, and which combination of measures best predicts the fate of people with aMCI.
Forty-four participants with aMCI underwent extensive neuropsychological assessment at baseline and annually thereafter for an average of 4 years. Differences in baseline cognitive performance of participants who were converters and non-converters to clinically diagnosed dementia were analysed. Classification accuracy was estimated by sensitivity, specificity, positive and negative predictive values and using logistic regression.
Forty-one percent of participants had progressed to dementia by the end of study, with a mean annual conversion rate of 11%. Most (63%) showed persisting or progressive cognitive impairment, irrespective of diagnosis. The Addenbrooke's Cognitive Examination together with the discrimination index of the Hopkins Verbal Learning Test – Revised (but none of the demographic indices) differentiated the participants who were converters from the non-converters at baseline with 74% accuracy.
Targeted neuropsychological assessment, beyond simple cognitive screening, could be used in clinical practice to provide individuals with aMCI with prognostic information and aid selective early initiation of monitoring and treatment among those who progress towards a clinically diagnosable dementia.
In a sample of 18-, 30-, and 42-month-olds, the relations among parenting, effortful control (EC), and maladjustment were examined. Parenting was assessed with mothers' reports and observations; EC was measured with mothers' and caregivers' reports, as well as a behavioral task; and externalizing and internalizing symptoms were assessed with parents' and caregivers' reports. Although 18-month unsupportive (vs. supportive) parenting negatively predicted EC at 30 months, when the stability of these variables was taken into account, there was no evidence of additional potentially causal relations between these two constructs. Although EC was negatively related to both internalizing and externalizing problems within all three ages as well as across 1 year, EC did not predict maladjustment once the stability of the constructs and within time covariation between the constructs were taken into account. In addition, externalizing problems at 30 months negatively predicted EC at 42 months, and internalizing problems at 30 months positively predicted EC at 42 months, but only when the effects of externalizing on EC were controlled. The findings are discussed in terms of the reasons for the lack of causal relations over time.
Subjects with the metabolic syndrome (MetS) have enhanced oxidative stress and inflammation. Dietary fat quality has been proposed to be implicated in these conditions. We investigated the impact of four diets distinct in fat quantity and quality on 8-iso-PGF2α (a major F2-isoprostane and oxidative stress indicator), 15-keto-13,14-dihydro-PGF2α (15-keto-dihydro-PGF2α, a major PGF2α metabolite and marker of cyclooxygenase-mediated inflammation) and C-reactive protein (CRP). In a 12-week parallel multicentre dietary intervention study (LIPGENE), 417 volunteers with the MetS were randomly assigned to one of the four diets: two high-fat diets (38 % energy (%E)) rich in SFA or MUFA and two low-fat high-complex carbohydrate diets (28 %E) with (LFHCC n-3) or without (LFHCC) 1·24 g/d of very long chain n-3 fatty acid supplementation. Urinary levels of 8-iso-PGF2α and 15-keto-dihydro-PGF2α were determined by RIA and adjusted for urinary creatinine levels. Serum concentration of CRP was measured by ELISA. Neither concentrations of 8-iso-PGF2α and 15-keto-dihydro-PGF2α nor those of CRP differed between diet groups at baseline (P>0·07) or at the end of the study (P>0·44). Also, no differences in changes of the markers were observed between the diet groups (8-iso-PGF2α, P = 0·83; 15-keto-dihydro-PGF2α, P = 0·45; and CRP, P = 0·97). In conclusion, a 12-week dietary fat modification did not affect the investigated markers of oxidative stress and inflammation among subjects with the MetS in the LIPGENE study.
Hypertension is a key feature of the metabolic syndrome. Lifestyle and dietary changes may affect blood pressure (BP), but the knowledge of the effects of dietary fat modification in subjects with the metabolic syndrome is limited. The objective of the present study was to investigate the effect of an isoenergetic change in the quantity and quality of dietary fat on BP in subjects with the metabolic syndrome. In a 12-week European multi-centre, parallel, randomised controlled dietary intervention trial (LIPGENE), 486 subjects were assigned to one of the four diets distinct in fat quantity and quality: two high-fat diets rich in saturated fat or monounsaturated fat and two low-fat, high-complex carbohydrate diets with or without 1·2 g/d of very long-chain n-3 PUFA supplementation. There were no overall differences in systolic BP (SBP), diastolic BP or pulse pressure (PP) between the dietary groups after the intervention. The high-fat diet rich in saturated fat had minor unfavourable effects on SBP and PP in males.