Clock drawing performance in cognitively normal elderly

The Clock Drawing Test (CDT) is a common neuropsychological measure sensitive to cognitive changes and functional skills (e.g., driving test performance) among older adults. However, normative data have not been adequately developed. We report the distribution of CDT scores using three common scoring systems [Mendez, M. F., Ala, T., & Underwood, K. L. (1992). Development of scoring criteria for the Clock Drawing Task in Alzheimer's Disease. Journal of the American Geriatrics Society, 40, 1095-1099; Cahn, D. A., Salmon, D. P., Monsch, A. U., Butters, N., Wiederholt, W. C., & Corey-Bloom, J. (1996). Screening for dementia of the Alzheimer type in the community: The utility of the Clock Drawing Test. Archives of Clinical Neuropsychology, 11(6), 529-539], among 207 cognitively normal elderly. The systems were well correlated, took little time to use, and had high inter-rater reliability. We found statistically significant differences in CDT scores based on age and WRAT-3 Reading score, a marker of education quality. We present means, standard deviations, and t- and z-scores based on these subgroups. We found that "normal" CDT performance includes a wider distribution of scores than previously reported. Our results may serve as useful comparisons for clinicians wishing to know whether their patients perform in the general range of cognitively normal elderly. © 2007 National Academy of Neuropsychology

Striatal mRNA expression patterns underlying peak dose L-DOPA-induced dyskinesia in the 6-OHDA hemiparkinsonian rat

L-DOPA is the primary pharmacological treatment for relief of the motor symptoms of Parkinson’s disease (PD). With prolonged treatment (⩾5 years) the majority of patients will develop abnormal involuntary movements as a result of L-DOPA treatment, known as L-DOPA-induced dyskinesia. Understanding the underlying mechanisms of dyskinesia is a crucial step toward developing treatments for this debilitating side effect. We used the 6-hydroxydopamine (6-OHDA) rat model of PD treated with a three-week dosing regimen of L-DOPA plus the dopa decarboxylase inhibitor benserazide (4 mg/kg and 7.5 mg/kg s.c., respectively) to induce dyskinesia in 50% of individuals. We then used RNA-seq to investigate the differences in mRNA expression in the striatum of dyskinetic animals, non-dyskinetic animals, and untreated parkinsonian controls at the peak of dyskinesia expression, 60 min after L-DOPA administration. Overall, 255 genes were differentially expressed; with significant differences in mRNA expression observed between all three groups. In dyskinetic animals 129 genes were more highly expressed and 14 less highly expressed when compared with non-dyskinetic and untreated parkinsonian controls. In L-DOPA treated animals 42 genes were more highly expressed and 95 less highly expressed when compared with untreated parkinsonian controls. Gene set cluster analysis revealed an increase in expression of genes associated with the cytoskeleton and phosphoproteins in dyskinetic animals compared with non-dyskinetic animals, which is consistent with recent studies documenting an increase in synapses in dyskinetic animals. These genes may be potential targets for drugs to ameliorate L-DOPA-induced dyskinesia or as an adjunct treatment to prevent their occurrence

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Functional diversification enabled grassy biomes to fill global climate space

Global change impacts on the Earth System are typically evaluated using biome classifications based on trees and forests. However, during the Cenozoic, many terrestrial biomes were transformed through the displacement of trees and shrubs by grasses. While grasses comprise 3% of vascular plant species, they are responsible for more than 25% of terrestrial photosynthesis. Critically, grass dominance alters ecosystem dynamics and function by introducing new ecological processes, especially surface fires and grazing. However, the large grassy component of many global biomes is often neglected in their descriptions, thereby ignoring these important ecosystem processes. Furthermore, the functional diversity of grasses in vegetation models is usually reduced to C3 and C4 photosynthetic plant functional types, omitting other relevant traits. Here, we compile available data to determine the global distribution of grassy vegetation and key traits related to grass dominance. Grassy biomes (where > 50% of the ground layer is covered by grasses) occupy almost every part of Earth’s vegetated climate space, characterising over 40% of the land surface. Major evolutionary lineages of grasses have specialised in different environments, but species from only three grass lineages occupy 88% of the land area of grassy vegetation, segregating along gradients of temperature, rainfall and fire. The environment occupied by each lineage is associated with unique plant trait combinations, including C3 and C4 photosynthesis, maximum plant height, and adaptations to fire and aridity. There is no single global climatic limit where C4 grasses replace C3 grasses. Instead this ecological transition varies biogeographically, with continental disjunctions arising through contrasting evolutionary histories

Characterization of gene polymorphisms related to immune system physiology in Mangalarga horses

The objectives of this study were to standardize a PCR-RFLP genotyping method for the AY_731081:g.1900T>C SNP of the equine CD14 gene, and to characterize this SNP and two other polymorphisms (AY_005808: c.1530A>G of the TLR4 gene and AX_463789: g.133T>C of the Cε gene) in Mangalarga horses, in order to contribute to future studies investigating the association between DNA markers and traits related to immune system physiology in this breed. A total of 151 Mangalarga horses of both sexes and variable ages, representative of the population of São Paulo State, were used. PCR-RFLP was found to be adequate for genotyping of the AY_731081: g.1900T>C SNP of the equine CD14 gene. However, this polymorphism is probably not present in Mangalarga horses, thus impairing association studies using this marker in the breed. The population genetic parameters obtained for the TLR4 AY_005808:c.1530A>G and Cε AX_463789:g.133T>C polymorphisms suggest the use of these markers in association studies with immune system-related traits in Mangalarga horses

Eficiência do CCB na resistência da madeira de algaroba (Prosopis juliflora (Sw.) D.C.) em ensaio de apodrecimento acelerado Efficiency of CCB on resistance of Prosopis juliflora (Sw.) D.C. wood in accelerated laboratory test decay

O objetivo da pesquisa foi avaliar o efeito do preservativo "Osmose CCB" na resistência da madeira de algaroba (Prosopis juliflora (Sw) D.C.) ao fungo Postia placenta, em condições de laboratório. Peças roliças de algaroba foram tratadas pelo método de substituição da seiva por transpiração radial, em soluções de 1, 2 e 3% de ingredientes ativos de CCB, durante 3, 6, 9, 12 e 15 dias. Das peças tratadas foram retirados discos em três posições (50 cm da base, meio do comprimento e topo da peça), em que foram analisadas a penetração e retenção do CCB, bem como a resistência ao fungo Postia placenta. Observou-se melhor penetração e retenção nas peças submetidas a 2% de ingredientes ativos. A penetração e retenção do CCB, assim como a resistência conferida à madeira, de modo geral, decresceram da base para o topo das peças. O tratamento preservativo conferiu às peças de algaroba uma alta resistência ao fungo P. placenta. Isso não ocorreu apenas nas amostras provenientes do topo (submetidas a 1% de CCB e 15 dias de tratamento; 2% e 9 dias; 3% e 3, 12 e 15 dias) e meio das peças (3% de CCB e 3 e 12 dias de tratamento), que foram classificadas como resistentes.<br>The objective of research was to analyze the "Osmose CCB" preservative efficiency to improve the wood Prosopis juliflora (Sw) D.C. resistance to Postia placenta fungus. In order to meet the objectives proposed, round pieces of P. juliflora were treated by sap displaced method in 1; 2 and 3% of active ingredients of CCB solutions, by 3, 6, 9, 12 and 15 days. Wood disks were obtained at three positions (50 cm from the base, middle and top) of the treated pieces. CCB penetration and retention were analyzed at these positions, as well as the resistance to P. placenta fungus (accelerated laboratory test decay) It was found better penetration and retention in pieces submitted to 2% of CCB solutions. The CCB penetration and retention, as well as the resistance of treated wood, in general, decreased from base to top of pieces. The preservative treatment conferred high-level resistance against P. placenta fungus to P. juliflora pieces. This has not occurred only for samples from the top (1% CCB and 15-day treatment; 2% and 9 days; 3% and 3, 12 and 15 days) and from the middle of pieces (3% CCB and 3 and 12-day treatment), which were classified as resistant