Prior test experience produces changes of t-patterns spatial distribution in the elevated plus maze test

Aim of present research was to investigate in male Wistar rats whether a prior elevated plus maze experience modifies the temporal structure of the behavioral response following a retest applied after 24h. Video files were coded by means of a software coder and event log files generated for each subject were analyzed by means of a specific software for temporal pattern analysis (Theme). Present research shows a clear reduction of the number of t-patterns from trial one to trial two. This reduction is provoked by the disappearance of t-patterns consisting of behavioral elements occurring in the unprotected zones of the maze. The results suggest that the previous experience in the maze causes learning-dependent behavioral changes inducing a more clear-cut response to environmental anxiogenic conditions

Lower Prevalence of Chronic Pain in Manifest Huntington’s Disease: A Pilot Observational Study

Pain is a minor problem compared with other Huntington Disease (HD) symptoms. Nevertheless, in HD it is poorly recognized and underestimated. So far, no study evaluated the presence of chronic pain in HD. The aim of this pilot study was to evaluate the presence and features of chronic pain in a cohort of HD gene carriers. An observational cross-sectional study was conducted in a cohort of HD gene carriers compared to not gene carriers (n.134 HD subjects, n.74 not gene mutation carriers). A specific pain interview, alongside a neurological, cognitive and behavioural examination, was performed in order to classify the type of pain, subjective intensity. A significant prevalence of “no Pain” in HD was found, which tended to increase with HD progression and a reduced frequency of pain in the last 3 months. A clear difference was found between manifest and premanifest HD in terms of intensity of pain, which did not change significantly with HD progression; however, a tendency emerges to a progressive reduction. No significant group difference was present in analgesic use, type and the site of pain. These findings could support a lower prevalence of chronic pain in manifest HD. Prevalence and intensity of chronic pain seem directly influenced by the process of neurodegeneration rather than by an incorrect cognitive and emotional functioning.</jats:p

Big Data Analytics for Earth Sciences: the EarthServer approach

Big Data Analytics is an emerging field since massive storage and computing capabilities have been made available by advanced e-infrastructures. Earth and Environmental sciences are likely to benefit from Big Data Analytics techniques supporting the processing of the large number of Earth Observation datasets currently acquired and generated through observations and simulations. However, Earth Science data and applications present specificities in terms of relevance of the geospatial information, wide heterogeneity of data models and formats, and complexity of processing. Therefore, Big Earth Data Analytics requires specifically tailored techniques and tools. The EarthServer Big Earth Data Analytics engine offers a solution for coverage-type datasets, built around a high performance array database technology, and the adoption and enhancement of standards for service interaction (OGC WCS and WCPS). The EarthServer solution, led by the collection of requirements from scientific communities and international initiatives, provides a holistic approach that ranges from query languages and scalability up to mobile access and visualization. The result is demonstrated and validated through the development of lighthouse applications in the Marine, Geology, Atmospheric, Planetary and Cryospheric science domains

Slow Roll Reconstruction: Constraints on Inflation from the 3 Year WMAP Dataset

We study the constraints on the inflationary parameter space derived from the 3 year WMAP dataset using ``slow roll reconstruction'', using the SDSS galaxy power spectrum to gain further leverage where appropriate. This approach inserts the inflationary slow roll parameters directly into a Monte Carlo Markov chain estimate of the cosmological parameters, and uses the inflationary flow hierarchy to compute the parameters' scale-dependence. We work with the first three parameters (epsilon, eta and xi) and pay close attention to the possibility that the 3 year WMAP dataset contains evidence for a ``running'' spectral index, which is dominated by the xi term. Mirroring the WMAP team's analysis we find that the permitted distribution of xi is broad, and centered away from zero. However, when we require that inflationary parameters yield at least 30 additional e-folds of inflation after the largest observable scales leave the horizon, the bounds on xi tighten dramatically. We make use of the absence of an explicit pivot scale in the slow roll reconstruction formalism to determine the dependence of the computed parameter distributions on the pivot. We show that the choice of pivot has a significant effect on the inferred constraints on the inflationary variables, and the spectral index and running derived from them. Finally, we argue that the next round of cosmological data can be expected to place very stringent constraints on the region of parameter space open to single field models of slow roll inflation.Comment: 26 pages, 11 figures, JHEP format. v2: version accepted by JCAP: minor clarifications and references added, 1 figure added, v3: 1 reference adde

New Synthetic Thrombin Inhibitors: Molecular Design and Experimental Verification

BACKGROUND: The development of new anticoagulants is an important goal for the improvement of thromboses treatments. OBJECTIVES: The design, synthesis and experimental testing of new safe and effective small molecule direct thrombin inhibitors for intravenous administration. METHODS: Computer-aided molecular design of new thrombin inhibitors was performed using our original docking program SOL, which is based on the genetic algorithm of global energy minimization in the framework of a Merck Molecular Force Field. This program takes into account the effects of solvent. The designed molecules with the best scoring functions (calculated binding energies) were synthesized and their thrombin inhibitory activity evaluated experimentally in vitro using a chromogenic substrate in a buffer system and using a thrombin generation test in isolated plasma and in vivo using the newly developed model of hemodilution-induced hypercoagulation in rats. The acute toxicities of the most promising new thrombin inhibitors were evaluated in mice, and their stabilities in aqueous solutions were measured. RESULTS: New compounds that are both effective direct thrombin inhibitors (the best K(I) was <1 nM) and strong anticoagulants in plasma (an IC(50) in the thrombin generation assay of approximately 100 nM) were discovered. These compounds contain one of the following new residues as the basic fragment: isothiuronium, 4-aminopyridinium, or 2-aminothiazolinium. LD(50) values for the best new inhibitors ranged from 166.7 to >1111.1 mg/kg. A plasma-substituting solution supplemented with one of the new inhibitors prevented hypercoagulation in the rat model of hemodilution-induced hypercoagulation. Activities of the best new inhibitors in physiological saline (1 µM solutions) were stable after sterilization by autoclaving, and the inhibitors remained stable at long-term storage over more than 1.5 years at room temperature and at 4°C. CONCLUSIONS: The high efficacy, stability and low acute toxicity reveal that the inhibitors that were developed may be promising for potential medical applications

Levodopa–carbidopa intrajejunal infusion in Parkinson’s disease: untangling the role of age

Objectives Levodopa–Carbidopa Intrajejunal gel (LCIG) infusion is an effective intervention for people with advanced Parkinson’s disease (PD). Although age may not be a limiting factor for LCIG implant, no data are available on late elderly PD (LE-PD) subjects. In this cross-sectional, we aimed to demonstrate if older age may impact on quality of life (QoL), motor and non-motor symptoms severity, and profile of side effects in PD treated with LCIG. Methods Out of 512 PD subjects treated with LCIG at 9 Italian PD centers, we selected 25 LE-PD defined as age ≥ 80 years at last follow-up who were available to attend the study visit. Twenty-five PD patients (Control-PD, defined as age < 75 years at last follow-up) matched to LE-PD by disease and LCIG duration served as control group. The following motor and non-motor variables were ascertained: quality of life (PDQ-8), time spent in ON, wearing-off Questionnaire, Unified PD Rating Scale, freezing of gait questionnaire, Parkinson’s disease sleep scale-2, Non Motor Symptoms Scale (NMSS), and MOCA. Results No statistically significant differences were found between LE-PD and Control-PD on PDQ-8 and several motor and non-motor variables. LE-PD had less frequent and milder impulsive–compulsive behaviors and milder dyskinesia. At multivariable regression, worse quality of life was associated with UPDRS-III and NMSS scores but not to age at study visit and age at LICG implant. Rate of adverse effects was similar in both groups. Drop-out rate calculated in the whole PD cohort was comparable between the two groups. Conclusion Our data provide evidence that valuable LCIG infusion might be achieved in late elderly PD

Large Non-Gaussianities in Single Field Inflation

We compute the 3-point correlation function for a general model of inflation driven by a single, minimally coupled scalar field. Our approach is based on the numerical evaluation of both the perturbation equations and the integrals which contribute to the 3-point function. Consequently, we can analyze models where the potential has a "feature", in the vicinity of which the slow roll parameters may take on large, transient values. This introduces both scale and shape dependent non-Gaussianities into the primordial perturbations. As an example of our methodology, we examine the ``step'' potentials which have been invoked to improve the fit to the glitch in the $$ $C_l$ for $l \sim 30$, present in both the one and three year WMAP data sets. We show that for the typical parameter values, the non-Gaussianities associated with the step are far larger than those in standard slow roll inflation, and may even be within reach of a next generation CMB experiment such as Planck. More generally, we use this example to explain that while adding features to potential can improve the fit to the 2-point function, these are generically associated with a greatly enhanced signal at the 3-point level. Moreover, this 3-point signal will have a very nontrivial shape and scale dependence, which is correlated with the form of the 2-point function, and may thus lead to a consistency check on the models of inflation with non-smooth potentials.Comment: 23 pages JHEP-style, 7 Figures. Updated with improved results. Accepted for publication by JCA

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

Levodopa Equivalent Dose of Safinamide: A Multicenter, Longitudinal, Case-Control Study

Background Effects of dopaminergic medications used to treat Parkinson's disease (PD) may be compared with each other by using conversion factors, calculated as Levodopa equivalent dose (LED). However, current LED proposals on MAO-B inhibitors (iMAO-B) safinamide and rasagiline are still based on empirical approaches. Objectives To estimate LED of safinamide 50 and 100 mg. Methods In this multicenter, longitudinal, case–control study, we retrospectively reviewed clinical charts of 500 consecutive PD patients with motor complications and treated with (i) safinamide 100 mg (N = 130), safinamide 50 mg (N = 144), or rasagiline 1 mg (N = 97) for 9 ± 3 months and a control group of patients never treated with any iMAO-B (N = 129). Results Major baseline features (age, sex, disease duration and stage, severity of motor signs and motor complications) were similar among the groups. Patients on rasagiline had lower UPDRS-II scores and Levodopa dose than control subjects. After a mean follow-up of 8.8-to-10.1 months, patients on Safinamide 50 mg and 100 mg had lower UPDRS-III and OFF-related UPDRS-IV scores than control subjects, who in turn had larger increase in total LED than the three iMAO-B groups. After adjusting for age, disease duration, duration of follow-up, baseline values and taking change in UPDRS-III scores into account (sensitivity analysis), safinamide 100 mg corresponded to 125 mg LED, whereas safinamide 50 mg and rasagiline 1 mg equally corresponded to 100 mg LED. Conclusions We used a rigorous approach to calculate LED of safinamide 50 and 100 mg. Large prospective pragmatic trials are needed to replicate our findings

Elevated International Normalized Ratio in a Patient Taking Warfarin and Mauby: A Case Report.

We describe a 70-year-old Haitian man who had been taking warfarin for 5 years for atrial fibrillation and pulmonary hypertension. This patient had his international normalized ratio (INR) checked in the pharmacist-run anticoagulation clinic and was followed monthly. Prior to the interaction, his INR was therapeutic for 5 months while taking warfarin 10.5 mg/d. The patient presented with an INR \u3e 8.0. Patient held 4 days of warfarin and restarted on warfarin 8.5 mg/d. Two weeks later, his INR was 2.5. After continuing dose, patient presented 2 weeks later and INR was 4.8. Upon further questioning, the patient stated he recently began ingesting mauby. Mauby is a bitter dark liquid extracted from the bark of the mauby tree that is commonly used in the Caribbean population as a folk remedy with many health benefits. This case report illustrates that mauby may have a probable drug-herb interaction (Naranjo Algorithm Score of 6) when given with warfarin. There is a lack of published literature and unclear information on the Internet describing the interaction of mauby and warfarin. Health professionals should be cautious regarding interactions between warfarin and mauby until the interaction is fully elucidated