A metabolomic approach to animal vitreous humor topographical composition: A pilot study

The purpose of this study was to evaluate the feasibility of a 1H-NMR-based metabolomic approach to explore the metabolomic signature of different topographical areas of vitreous humor (VH) in an animal model. Five ocular globes were enucleated from five goats and immediately frozen at 280uC. Once frozen, three of them were sectioned, and four samples corresponding to four different VH areas were collected: the cortical, core, and basal, which was further divided into a superior and an inferior fraction. An additional two samples were collected that were representative of the whole vitreous body. 1H-NMR spectra were acquired for twenty-three goat vitreous samples with the aim of characterizing the metabolomic signature of this biofluid and identifying whether any site-specific patterns were present. Multivariate statistical analysis (MVA) of the spectral data were carried out, including Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), and Partial Least Squares Discriminant Analysis (PLS-DA). A unique metabolomic signature belonging to each area was observed. The cortical area was characterized by lactate, glutamine, choline, and its derivatives, N-acetyl groups, creatine, and glycerol; the core area was characterized by glucose, acetate, and scyllo-inositol; and the basal area was characterized by branched-chain amino acids (BCAA), betaine, alanine, ascorbate, lysine, and myo-inositol. We propose a speculative approach on the topographic role of these molecules that are mainly responsible for metabolic differences among the as-identified areas. 1H-NMR-based metabolomic analysis has shown to be an important tool for investigating the VH. In particular, this approach was able to assess in the samples here analyzed the presence of different functional areas on the basis of a different metabolite distribution.The purpose of this study was to evaluate the feasibility of a 1H-NMR-based metabolomic approach to explore the metabolomic signature of different topographical areas of vitreous humor (VH) in an animal model. Five ocular globes were enucleated from five goats and immediately frozen at -80°C. Once frozen, three of them were sectioned, and four samples corresponding to four different VH areas were collected: the cortical, core, and basal, which was further divided into a superior and an inferior fraction. An additional two samples were collected that were representative of the whole vitreous body. 1H-NMR spectra were acquired for twenty-three goat vitreous samples with the aim of characterizing the metabolomic signature of this biofluid and identifying whether any site-specific patterns were present. Multivariate statistical analysis (MVA) of the spectral data were carried out, including Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), and Partial Least Squares Discriminant Analysis (PLS-DA). A unique metabolomic signature belonging to each area was observed. The cortical area was characterized by lactate, glutamine, choline, and its derivatives, N-acetyl groups, creatine, and glycerol; the core area was characterized by glucose, acetate, and scyllo-inositol; and the basal area was characterized by branched-chain amino acids (BCAA), betaine, alanine, ascorbate, lysine, and myo-inositol. We propose a speculative approach on the topographic role of these molecules that are mainly responsible for metabolic differences among the as-identified areas. 1H-NMR-based metabolomic analysis has shown to be an important tool for investigating the VH. In particular, this approach was able to assess in the samples here analyzed the presence of different functional areas on the basis of a different metabolite distribution. © 2014 Locci et al

Levetiracetam in patients with epilepsy and chronic liver disease: observations in a case series.

OBJECTIVES: To evaluate levetiracetam (LEV) tolerability in patients with epilepsy and liver disease. METHODS: Fourteen patients with epilepsy and concomitant liver disease were treated with LEV in an open prospective investigation mimicking the daily clinical practice. All patients were stabilized (ie, for at least 1 year) on traditional antiepileptic drugs with complete or partial control of seizures. In the 6-month pre-LEV baseline period, seizure frequency ranged from 3 to 300. Levetiracetam was added on to the basal treatment at a starting daily dose of 250 mg, and the dose was adjusted according to the tolerability and the therapeutic response. Four patients discontinued the drug within the first 3 months because of intolerable side effects. The remaining 10 continued LEV treatment, and the present follow-up is 12 to 38 months. RESULTS: In the last 6 months of observation, none of the patients showed worsening of liver function on the basis of blood chemistry, and in 4 patients, a complete normalization or a trend toward physiological values of transaminase and/or gamma-glutamyltransferase activity was observed. A greater than 50% reduction in seizure frequency occurred in all uncontrolled patients, 2 of whom achieved seizure freedom during LEV treatment. CONCLUSIONS: Based on these observations, LEV seems to be an attractive therapeutic option in epileptic patients with chronic liver diseases

Field Representations of Vector Supersymmetry

We study some field representations of vector supersymmetry with superspin Y=0 and Y=1/2 and nonvanishing central charges. For Y=0, we present two multiplets composed of four spinor fields, two even and two odd, and we provide a free action for them. The main differences between these two multiplets are the way the central charge operators act and the compatibility with the Majorana reality condition on the spinors. One of the two is related to a previously studied spinning particle model. For Y=1/2, we present a multiplet composed of one even scalar, one odd vector and one even selfdual two-form, which is a truncation of a known representation of the tensor supersymmetry algebra in Euclidean spacetime. We discuss its rotation to Minkowski spacetime and provide a set of dynamical equations for it, which are however not derived from a Lagrangian. We develop a superspace formalism for vector supersymmetry with central charges and we derive our multiplets by superspace techniques. Finally, we discuss some representations with vanishing central charges.Comment: 37 page

Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study.

ObjectiveTo assess the efficacy and safety of enzyme replacement therapy (ERT) with BMN 110 (elosulfase alfa) in patients with Morquio A syndrome (mucopolysaccharidosis IVA).MethodsPatients with Morquio A aged ≥5 years (N = 176) were randomised (1:1:1) to receive elosulfase alfa 2.0 mg/kg/every other week (qow), elosulfase alfa 2.0 mg/kg/week (weekly) or placebo for 24 weeks in this phase 3, double-blind, randomised study. The primary efficacy measure was 6-min walk test (6MWT) distance. Secondary efficacy measures were 3-min stair climb test (3MSCT) followed by change in urine keratan sulfate (KS). Various exploratory measures included respiratory function tests. Patient safety was also evaluated.ResultsAt week 24, the estimated mean effect on the 6MWT versus placebo was 22.5 m (95 % CI 4.0, 40.9; P = 0.017) for weekly and 0.5 m (95 % CI -17.8, 18.9; P = 0.954) for qow. The estimated mean effect on 3MSCT was 1.1 stairs/min (95 % CI -2.1, 4.4; P = 0.494) for weekly and -0.5 stairs/min (95 % CI -3.7, 2.8; P = 0.778) for qow. Normalised urine KS was reduced at 24 weeks in both regimens. In the weekly dose group, 22.4 % of patients had adverse events leading to an infusion interruption/discontinuation requiring medical intervention (only 1.3 % of all infusions in this group) over 6 months. No adverse events led to permanent treatment discontinuation.ConclusionsElosulfase alfa improved endurance as measured by the 6MWT in the weekly but not qow dose group, did not improve endurance on the 3MSCT, reduced urine KS, and had an acceptable safety profile

Genetic parameters and selection strategies for soybean genotypes resistant to the stink bug-complex

Soybean genotypes resistant to stink bugs are derived from complex breeding processes obtained through indirect selection. The aim of the present work was to estimate genetic parameters for guiding selection strategies towards resistant genotypes, based on those traits associated with responses to pod-attacking stink bugs, such as the grain filling period (GFP), leaf retention (LR), percentage index of pod damage (PIPD) and percentage of spotted seeds (PSS). We assessed the parental lines IAC-100 (resistant) and FT-Estrela (susceptible), the progenies F2 and F 4 , 30 progenies F 2:3 , 30 progenies BC 1 F 2:3 and 30 progenies BC 2 F 2:3 , besides the cultivars BRS Celeste and MGBR-46 (Conquista). Three field experiments, using randomized complete block design with three replications, were installed in Goiânia-GO, in the 2002/03 season. Each experiment consisted of 36 treatments (6 common and 30 regular). Heritability estimates were: 74.6 and 36.1 (GFP); 51.9 and 19.9 (LR); 49.6 and 49.6 (PIPD) and 55.8 and 20.3 (PSS), in both the broad and narrow senses, respectively. Based on these results, we concluded that the best strategy for obtaining stink bug-resistant genotypes consists of selecting the PIPD trait in early generations (F 3 or F 4 ), followed by selection for the GFP, LR and PSS traits in generations with higher endogamy levels

Influenza and pneumococcal vaccine uptake among nursing home residents in Nottingham, England: a postal questionnaire survey

<p>Abstract</p> <p>Background</p> <p>Previous studies have shown influenza vaccine uptake in UK nursing home residents to be low. Very little information exists regarding the uptake of pneumococcal vaccine in this population. The formulation of policies relating to the vaccination of residents has been proposed as a simple step that may help improve vaccine uptake in care homes.</p> <p>Methods</p> <p>A postal questionnaire was sent to matrons of all care homes with nursing within the Greater Nottingham area in January 2006. Non respondents were followed up with up to 3 phone calls.</p> <p>Results</p> <p>30% (16/53) of respondents reported having a policy addressing influenza vaccination and 15% (8/53) had a policy addressing pneumococcal vaccination. Seasonal influenza vaccine coverage in care homes with a vaccination policy was 87% compared with 84% in care homes without a policy (p = 0.47). The uptake of pneumococcal vaccination was found to be low, particularly in care homes with no vaccination policy. Coverage was 60% and 32% in care homes with and without a vaccination policy respectively (p = 0.06). This result was found to be statistically significant on multivariate analysis (p = 0.03, R = 0.46)</p> <p>Conclusion</p> <p>The uptake of influenza vaccine among care home residents in the Nottingham region is relatively high, although pneumococcal vaccine uptake is low. This study shows that there is an association between pneumococcal vaccine uptake and the existence of a vaccination policy in care homes, and highlights that few care homes have vaccination policies in place.</p

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

Effect of a mixed reality-based intervention on arm, hand, and finger function on chronic stroke

[EN] Background: Virtual and mixed reality systems have been suggested to promote motor recovery after stroke. Basing on the existing evidence on motor learning, we have developed a portable and low-cost mixed reality tabletop system that transforms a conventional table in a virtual environment for upper limb rehabilitation. The system allows intensive and customized training of a wide range of arm, hand, and finger movements and enables interaction with tangible objects, while providing audiovisual feedback of the participants' performance in gamified tasks. This study evaluates the clinical effectiveness and the acceptance of an experimental intervention with the system in chronic stroke survivors. Methods: Thirty individuals with stroke were included in a reversal (A-B-A) study. Phase A consisted of 30 sessions of conventional physical therapy. Phase B consisted of 30 training sessions with the experimental system. Both interventions involved flexion and extension of the elbow, wrist, and fingers, and grasping of different objects. Sessions were 45-min long and were administered three to five days a week. The body structures (Modified Ashworth Scale), functions (Motricity Index, Fugl-Meyer Assessment Scale), activities (Manual Function Test, Wolf Motor Function Test, Box and Blocks Test, Nine Hole Peg Test), and participation (Motor Activity Log) were assessed before and after each phase. Acceptance of the system was also assessed after phase B (System Usability Scale, Intrinsic Motivation Inventory). Results: Significant improvement was detected after the intervention with the system in the activity, both in arm function measured by the Wolf Motor Function Test (p < 0.01) and finger dexterity measured by the Box and Blocks Test (p < 0.01) and the Nine Hole Peg Test (p < 0.01); and participation (p < 0.01), which was maintained to the end of the study. The experimental system was reported as highly usable, enjoyable, and motivating. Conclusions: Our results support the clinical effectiveness of mixed reality interventions that satisfy the motor learning principles for upper limb rehabilitation in chronic stroke survivors. This characteristic, together with the low cost of the system, its portability, and its acceptance could promote the integration of these systems in the clinical practice as an alternative to more expensive systems, such as robotic instruments.The authors wish to thank the staff and patients of the Servicio de Neurorrehabilitación y Daño Cerebral de los Hospitales NISA for their involvement in the study. The authors also wish to thank the staff of LabHuman for their support in this project, especially Francisco Toledo and José Roda for their assistance. This study was funded in part by the Project TEREHA (IDI-20110844) and Project NeuroVR (TIN2013-44741-R) of the Ministerio de Economia y Competitividad of Spain, the Project Consolider-C (SEJ2006-14301/PSIC) of the Ministerio de Educacion y Ciencia of Spain, the "CIBER of Physiopathology of Obesity and Nutrition, an initiative of ISCIII", and the Excellence Research Program PROMETEO of the Conselleria de Educacion of Generalitat Valenciana (2008-157).Colomer Font, C.; Llorens Rodríguez, R.; Noé Sebastián, E.; Alcañiz Raya, ML. (2016). Effect of a mixed reality-based intervention on arm, hand, and finger function on chronic stroke. Journal of NeuroEngineering and Rehabilitation. 13:1-10. https://doi.org/10.1186/s12984-016-0153-6S11013Fregni F, Pascual-Leone A. Hand motor recovery after stroke: tuning the orchestra to improve hand motor function. Cogn Behav Neurol. 2006;19(1):21–33.Patten C, Condliffe EG, Dairaghi CA, Lum PS. 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