Disease Severity and Progression in Progressive Supranuclear Palsy and Multiple System Atrophy: Validation of the NNIPPS – PARKINSON PLUS SCALE

BACKGROUND The Natural History and Neuroprotection in Parkinson Plus Syndromes (NNIPPS) study was a large phase III randomized placebo-controlled trial of riluzole in Progressive Supranuclear Palsy (PSP, n = 362) and Multiple System Atrophy (MSA, n = 398). To assess disease severity and progression, we constructed and validated a new clinical rating scale as an ancillary study. METHODS AND FINDINGS Patients were assessed at entry and 6-montly for up to 3 years. Evaluation of the scale's psychometric properties included reliability (n = 116), validity (n = 760), and responsiveness (n = 642). Among the 85 items of the initial scale, factor analysis revealed 83 items contributing to 15 clinically relevant dimensions, including Activity of daily Living/Mobility, Axial bradykinesia, Limb bradykinesia, Rigidity, Oculomotor, Cerebellar, Bulbar/Pseudo-bulbar, Mental, Orthostatic, Urinary, Limb dystonia, Axial dystonia, Pyramidal, Myoclonus and Tremor. All but the Pyramidal dimension demonstrated good internal consistency (Cronbach α ≥ 0.70). Inter-rater reliability was high for the total score (Intra-class coefficient = 0.94) and 9 dimensions (Intra-class coefficient = 0.80-0.93), and moderate (Intra-class coefficient = 0.54-0.77) for 6. Correlations of the total score with other clinical measures of severity were good (rho ≥ 0.70). The total score was significantly and linearly related to survival (p<0.0001). Responsiveness expressed as the Standardized Response Mean was high for the total score slope of change (SRM = 1.10), though higher in PSP (SRM = 1.25) than in MSA (SRM = 1.0), indicating a more rapid progression of PSP. The slope of change was constant with increasing disease severity demonstrating good linearity of the scale throughout disease stages. Although MSA and PSP differed quantitatively on the total score at entry and on rate of progression, the relative contribution of clinical dimensions to overall severity and progression was similar. CONCLUSIONS The NNIPPS-PPS has suitable validity, is reliable and sensitive, and therefore is appropriate for use in clinical studies with PSP or MSA. TRIAL REGISTRATION ClinicalTrials.gov NCT00211224

Temporal progression in migratory status and sexual maturation in European silver eels during downstream migration

The onset of downstream migration of European eels is accompanied by a cessation of feeding and the start of sexual maturation which stresses the link between metabolism and sexual maturation, also suggesting an important role for exercise. Exercise has been tested with eels in swim tunnels and was found to stimulate the onset of sexual maturation. In this study, we have investigated the interplay between migration and maturation in the field during the downstream migration of female silver eels. Temporal changes in migratory status and sexual maturation among silver eels of the upstream Rhine River system over 3 months of the migration season (August, September and October) were determined in biometrical parameters, plasma 17β-estradiol and calcium levels, oocyte histology and gonadal fat levels. Furthermore, the ecological relevant parameters age as determined by otolithometry and health aspects indicated by haematocrit, haemoglobin and swim-bladder parasite load were measured. Silver eels were estimated to be 14 years old. A strong temporal progression in migratory stage was shown over the months of downstream migration. Catches probably represented a mix of reproductive migrants and feeding migrants of which the ratio increased over time. Furthermore, this study confirmed our hypothesis linking the migratory stage to early maturation as indicated by enlargement of the eyes, oocyte growth and fat deposition in the oocytes, exactly the same changes as found induced by exercise but not ruling out environmental influences. Migrants show extensive fat uptake by the oocytes, probably stimulated by the swimming exercise. In addition, at least 83% of the silver eels in this spawning run may have suffered from negative effects of swim-bladder parasites on their swimming performance

Can inorganic elements affect herpesvirus infections in European eels?

SHORT RESEARCH AND DISCUSSION ARTICLEIn combination, pollution and pathogens represent a serious threat to the health of European eels that has been increasingly recognized. Thus, the impact of contaminants, cadmium, lead,mercury, and selenium, on anguillid herpesvirus 1 infection inwild European eels has been evaluated. Despite the small sample size, results indicate that selenium and mercury concentrations may compromise the European eel immune system as herpesvirus infection was more prevalent in specimens with higher Hg and Se hepatic concentrations.Versión del editor2,65

Reference procedures for the measurement of gaseous emissions from livestock houses and stores of animal manure.

In the ten years before the EMILI 2012 symposium, gaseous losses from animal farms became increasingly important in the m edia. The paradox of this tendency was the great number of publications, scientific or not, even though the emissions of most animal farms had never been measured. Therefor e, the development of reference tools to measure greenhouse gas and ammonia emissio ns was important. Such tools allow recognition and remuneration of the best pract ices and equipment. Accordingly, ADEME funded an international project associating several research and development organizations involved with the animal production chain. The project proposed an initial set of 18 procedures to measure ammonia and greenho use gas emissions from animal houses and manure stores. These were adapted to the diversity of animal farms found throughout the world. Some methods were compared duri ng a ?building? and a ?liquid manure? experiment. Results showed a high difference among methods (ca. 80%), much higher than the estimated uncertainty. Associat ing independent emission measurements, together with a mass balance of the system, is necessary for the reliability of further results. However, previously published references lack uncertainty estimates of measurements that conform to GUM 2008. In the coming years, this is one of the major concerns for measuring emission factor s. Uncertainty estimates should depend on the measurand (temporal: hourly, per batch, yearly; spatial: animal, house, national) and include the uncertainties associated with system representativity and temporal interpolation.Edited by Mélynda Hassouna and Nadine Guingand

The swimming kinematics of larval Atlantic cod, Gadus morhua L., are resilient to elevated seawater pCO2

Kinematics of swimming behavior of larval Atlantic cod, aged 12 and 27 days post-hatch (dph) and cultured under three pCO2 conditions (control-370, medium-1800, and high-4200 μatm) from March to May 2010, were extracted from swim path recordings obtained using silhouette video photography. The swim paths were analyzed for swim duration, distance and speed, stop duration, and horizontal and vertical turn angles to determine whether elevated seawater pCO2—at beyond near-future ocean acidification levels—affects the swimming kinematics of Atlantic cod larvae. There were no significant differences in most of the variables tested: the swimming kinematics of Atlantic cod larvae at 12 and 27 dph were highly resilient to extremely elevated pCO2 levels. Nonetheless, cod larvae cultured at the highest pCO2 concentration displayed vertical turn angles that were more restricted (median turn angle, 15°) than larvae in the control (19°) and medium (19°) treatments at 12 dph (but not at 27 dph). Significant reduction in the stop duration of cod larvae from the high treatment (median stop duration, 0.28 s) was also observed compared to the larvae from the control group (0.32 s) at 27 dph (but not at 12 dph). The functional and ecological significance of these subtle differences are unclear and, therefore, require further investigation in order to determine whether they are ecologically relevant or spurious

The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson's disease with a sexual dimorphism

The catechol-O-methyltranferase (COMT) is one of the main enzymes that metabolise dopamine in the brain. The Val158Met polymorphism in the COMT gene (rs4680) causes a trimodal distribution of high (Val/Val), intermediate (Val/Met) and low (Met/Met) enzyme activity. We tested whether the Val158Met polymorphism is a modifier of the age at onset (AAO) in Parkinson's disease (PD). The rs4680 was genotyped in a total of 16 609 subjects from five independent cohorts of European and North American origin (5886 patients with PD and 10 723 healthy controls). The multivariate analysis for comparing PD and control groups was based on a stepwise logistic regression, with gender, age and cohort origin included in the initial model. The multivariate analysis of the AAO was a mixed linear model, with COMT genotype and gender considered as fixed effects and cohort and cohort-gender interaction as random effects. COMT genotype was coded as a quantitative variable, assuming a codominant genetic effect. The distribution of the COMT polymorphism was not significantly different in patients and controls (p=0.22). The Val allele had a significant effect on the AAO with a younger AAO in patients with the Val/Val (57.1±13.9, p=0.03) than the Val/Met (57.4±13.9) and the Met/Met genotypes (58.3±13.5). The difference was greater in men (1.9 years between Val/Val and Met/Met, p=0.007) than in women (0.2 years, p=0.81). Thus, the Val158Met COMT polymorphism is not associated with PD in the Caucasian population but acts as a modifier of the AAO in PD with a sexual dimorphism: the Val allele is associated with a younger AAO in men with idiopathic PD

Swimming physiology of European silver eels (Anguilla anguilla L.): energetic costs and effects on sexual maturation and reproduction

The European eel migrates 5,000–6,000 km to the Sargasso Sea to reproduce. Because they venture into the ocean in a pre-pubertal state and reproduce after swimming for months, a strong interaction between swimming and sexual maturation is expected. Many swimming trials have been performed in 22 swim tunnels to elucidate their performance and the impact on maturation. European eels are able to swim long distances at a cost of 10–12 mg fat/km which is 4–6 times more efficient than salmonids. The total energy costs of reproduction correspond to 67% of the fat stores. During long distance swimming, the body composition stays the same showing that energy consumption calculations cannot be based on fat alone but need to be compensated for protein oxidation. The optimal swimming speed is 0.61–0.67 m s−1, which is ~60% higher than the generally assumed cruise speed of 0.4 m s−1 and implies that female eels may reach the Sargasso Sea within 3.5 months instead of the assumed 6 months. Swimming trials showed lipid deposition and oocyte growth, which are the first steps of sexual maturation. To investigate effects of oceanic migration on maturation, we simulated group-wise migration in a large swim-gutter with seawater. These trials showed suppressed gonadotropin expression and vitellogenesis in females, while in contrast continued sexual maturation was observed in silver males. The induction of lipid deposition in the oocytes and the inhibition of vitellogenesis by swimming in females suggest a natural sequence of events quite different from artificial maturation protocols

A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p<5x10(-10), PARK16/1q32, STX1B/16p11, FGF20/8p22, STBD1/4q21, and GPNMB/7p15). Two of these five loci have been suggested by previous association studies (PARK16/1q32, FGF20/8p22), and this study provides further support for these findings. Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci