Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

Cognitive endpoints for therapy development for neuronopathic mucopolysaccharidoses: Results of a consensus procedure

The design and conduct of clinical studies to evaluate the effects of novel therapies on central nervous system manifestations in children with neuronopathic mucopolysaccharidoses is challenging. Owing to the rarity of these disorders, multinational studies are often needed to recruit enough patients to provide meaningful data and statistical power. This can make the consistent collection of reliable data across study sites difficult. To address these challenges, an International MPS Consensus Conference for Cognitive Endpoints was convened to discuss approaches for evaluating cognitive and adaptive function in patients with mucopolysaccharidoses. The goal was to develop a consensus on best practice for the design and conduct of clinical studies investigating novel therapies for these conditions, with particular focus on the most appropriate outcome measures for cognitive function and adaptive behavior. The outcomes from the consensus panel discussion are reported here

Can current moisture responses predict soil CO2 efflux under altered precipitation regimes? A synthesis of manipulation experiments

As a key component of the carbon cycle, soil CO2 efflux (SCE) is being increasingly studied to improve our mechanistic understanding of this important carbon flux. Predicting ecosystem responses to climate change often depends on extrapolation of current relationships between ecosystem processes and their climatic drivers to conditions not yet experienced by the ecosystem. This raises the question of to what extent these relationships remain unaltered beyond the current climatic window for which observations are available to constrain the relationships. Here, we evaluate whether current responses of SCE to fluctuations in soil temperature and soil water content can be used to predict SCE under altered rainfall patterns. Of the 58 experiments for which we gathered SCE data, 20 were discarded because either too few data were available or inconsistencies precluded their incorporation in the analyses. The 38 remaining experiments were used to test the hypothesis that a model parameterized with data from the control plots (using soil temperature and water content as predictor variables) could adequately predict SCE measured in the manipulated treatment. Only for 7 of these 38 experiments was this hypothesis rejected. Importantly, these were the experiments with the most reliable data sets, i.e., those providing high-frequency measurements of SCE. Regression tree analysis demonstrated that our hypothesis could be rejected only for experiments with measurement intervals of less than 11 days, and was not rejected for any of the 24 experiments with larger measurement intervals. This highlights the importance of high-frequency measurements when studying effects of altered precipitation on SCE, probably because infrequent measurement schemes have insufficient capacity to detect shifts in the climate dependencies of SCE. Hence, the most justified answer to the question of whether current moisture responses of SCE can be extrapolated to predict SCE under altered precipitation regimes is 'no' - as based on the most reliable data sets available. We strongly recommend that future experiments focus more strongly on establishing response functions across a broader range of precipitation regimes and soil moisture conditions. Such experiments should make accurate measurements of water availability, should conduct high-frequency SCE measurements, and should consider both instantaneous responses and the potential legacy effects of climate extremes. This is important, because with the novel approach presented here, we demonstrated that, at least for some ecosystems, current moisture responses could not be extrapolated to predict SCE under altered rainfall conditions

Crystalline Composition of Equine Urinary Sabulous Deposits

The composition and crystal morphology of 141 equine sabulous deposits were determined by infrared spectroscopy (IR), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX). The IR analysis revealed that all investigated deposits contained calcium carbonates (calcite, CaCO3, and/or vaterite, CaCO3) as major constituents; 42 samples were composed of calcite and vaterite, 33 of calcite, 18 of calcite/vaterite and calcium oxalate, and 17 of vaterite. The remaining specimens contained calcite/vaterite and other compounds (calcium phosphates, sulphate and/or oxalates and/or silica). The examination of 44 selected samples by means of SEM/EDX, revealed the characteristic morphology and elemental composition of the constituents of the sabulous deposits. Calcite crystals showed a typical spherical shape, as well as other less common rhombohedral habit. Vaterite displayed a flower or star appearance and also a mulberry shape. Less frequent was a spherular habit for vaterite resembling that of calcite. Elemental analysis of both calcite and vaterite crystals showed, besides calcium, varying proportions of magnesium and potassium. It is concluded that calcite and vaterite were mainly present in a substituted form. Calcium oxalate dihydrate crystals showed their characteristic bi pyramidal morphology. Calcium oxalate monohydrate crystals, which were less frequent, exhibited dumbbell or hour-glass shape

Can current moisture responses predict soil CO2 efflux under altered precipitation regimes? A synthesis of manipulation experiments.

As a key component of the carbon cycle, soil CO2 efflux (SCE) is being increasingly studied to improve our mechanistic understanding of this important carbon flux. Predicting ecosystem responses to climate change often depends on extrapolation of current relationships between ecosystem processes and their climatic drivers to conditions not yet experienced by the ecosystem. This raises the question of to what extent these relationships remain unaltered beyond the current climatic window for which observations are available to constrain the relationships. Here, we evaluate whether current responses of SCE to fluctuations in soil temperature and soil water content can be used to predict SCE under altered rainfall patterns. Of the 58 experiments for which we gathered SCE data, 20 were discarded because either too few data were available or inconsistencies precluded their incorporation in the analyses. The 38 remaining experiments were used to test the hypothesis that a model parameterized with data from the control plots (using soil temperature and water content as predictor variables) could adequately predict SCE measured in the manipulated treatment. Only for 7 of these 38 experiments was this hypothesis rejected. Importantly, these were the experiments with the most reliable data sets, i.e., those providing high-frequency measurements of SCE. Regression tree analysis demonstrated that our hypothesis could be rejected only for experiments with measurement intervals of less than 11 days, and was not rejected for any of the 24 experiments with larger measurement intervals. This highlights the importance of high-frequency measurements when studying effects of altered precipitation on SCE, probably because infrequent measurement schemes have insufficient capacity to detect shifts in the climate dependencies of SCE. Hence, the most justified answer to the question of whether current moisture responses of SCE can be extrapolated to predict SCE under altered precipitation regimes is ?no? ? as based on the most reliable data sets available. We strongly recommend that future experiments focus more strongly on establishing response functions across a broader range of precipitation regimes and soil moisture conditions. Such experiments should make accurate measurements of water availability, should conduct high-frequency SCE measurements, and should consider both instantaneous responses and the potential legacy effects of climate extremes. This is important, because with the novel approach presented here, we demonstrated that, at least for some ecosystems, current moisture responses could not be extrapolated to predict SCE under altered rainfall conditions

Ribonucleotide reductases of Salmonella Typhimurium : transcriptional regulation and differential role in pathogenesis

Ribonucleotide reductases (RNRs) are essential enzymes that carry out the de novo synthesis of deoxyribonucleotides by reducing ribonucleotides. There are three different classes of RNRs (I, II and III), all having different oxygen dependency and biochemical characteristics. Salmonella enterica serovar Typhimurium (S. Typhimurium) harbors class Ia, class Ib and class III RNRs in its genome. We have studied the transcriptional regulation of these three RNR classes in S. Typhimurium as well as their differential function during infection of macrophage and epithelial cells. Deletion of both NrdR and Fur, two main transcriptional regulators, indicates that Fur specifically represses the class Ib enzyme and that NrdR acts as a global repressor of all three classes. A Fur recognition sequence within the nrdHIEF promoter has also been described and confirmed by electrophoretic mobility shift assays (EMSA). In order to elucidate the role of each RNR class during infection, S. Typhimurium single and double RNR mutants (as well as Fur and NrdR mutants) were used in infection assays with macrophage and epithelial cell lines. Our results indicate class Ia to be mainly responsible for deoxyribonucleotide production during invasion and proliferation inside macrophages and epithelial cells. Neither class Ib nor class III seem to be essential for growth under these conditions. However, class Ib is able to maintain certain growth in an nrdAB mutant during the first hours of macrophage infection. Our results suggest that, during the early stages of macrophage infection, class Ib may contribute to deoxyribonucleotide synthesis by means of both an NrdR and a Fur-dependent derepression of nrdHIEF due to hydrogen peroxide production and DNA damage associated with the oxidative burst, thus helping to overcome the host defenses

A review of wearable motion tracking systems used in rehabilitation following hip and knee replacement

Clinical teams are under increasing pressure to facilitate early hospital discharge for total hip replacement and total knee replacement patients following surgery. A wide variety of wearable devices are being marketed to assist with rehabilitation following surgery. A review of wearable devices was undertaken to assess the evidence supporting their efficacy in assisting rehabilitation following total hip replacement and total knee replacement. A search was conducted using the electronic databases including Medline, CINAHL, Cochrane, PsycARTICLES, and PubMed of studies from January 2000 to October 2017. Five studies met the eligibility criteria, and all used an accelerometer and a gyroscope for their technology. A review of the studies found very little evidence to support the efficacy of the technology, although they show that the use of the technology is feasible. Future work should establish which wearable technology is most valuable to patients, which ones improve patient outcomes, and the most economical model for deploying the technolog

Study of the polycarbonate-urethane/metal contact in different positions during gait cycle

Nowadays, a growing number of young andmore active patients receive hip replacement.More strenuous activities in such patients involve higher friction and wear rates, with friction on the bearing surface being crucial to ensure arthroplasty survival in the long term. Over the last years, the polycarbonate-urethane has offered a feasible alternative to conventional bearings. A finite element model of a healthy hip joint was developed and adjusted to three gait phases (heel strike, mid-stance, and toe-off), serving as a benchmark for the assessment of the results of joint replacement model. Three equivalent models were made with the polycarbonate-urethane Tribofit system implanted, one for each of the three gait phases, after reproducing a virtual surgery over the respective healthy models. Standard body-weight loads were considered: 230% body-weight toe-off, 275% body-weight mid-stance, and 350% body-weight heel strike. Contact pressures were obtained for the different models. When comparing the results corresponding to the healthy model to polycarbonate-urethane joint, contact areas are similar and so contact pressures are within a narrower value range. In conclusion, polycarbonate-urethane characteristics are similar to those of the joint cartilage. So, it is a favorable alternative to traditional bearing surfaces in total hip arthroplasty, especially in young patients

Educação e Leitura

Suscitar o debate sobre educação e leitura, os desafios que se colocam a educadores e profissionais de bibliotecas na promoção da leitura, na formação de leitores e na relação com a escola e os sistemas de ensino formal e não formal.Comunidades envolvidas: profissionais trabalhando em/com escolas, bibliotecas de leitura pública, bibliotecas universitárias (áreas científicas relacionadas), outros serviços relacionados com a educação