Trabecular bone volume and osteoprotegerin expression in uremic rats given high calcium

Calcium (Ca)-containing phosphate binders have been recommended for the treatment of hyperphosphatemia in children with chronic kidney disease. To study the effects of high Ca levels on trabecular bone volume (BV) and osteoprotegerin (OPG) expression in uremic young rats, a model of marked overcorrection of secondary hyperparathyroidism was created by providing a diet of high Ca to 5/6 nephrectomized young rats (Nx-Ca) for 4 weeks. The results of chondrocyte proliferation and apoptosis, osteoclastic activity, OPG expression and BV were compared among intact rats given the control diet, intact rats given a high Ca diet and 5/6 nephrectomized rats given the control diet (Nx-Control) and the high Ca diet (Nx-Ca). Ionized Ca levels were higher and parathyroid hormone levels were lower in Nx-Ca rats than in the other groups. Final weight, final length and final tibial length of Nx-Ca rats were significantly less than those of the other groups, although the length gain did not differ among the groups. The hypertrophic zone width was markedly enlarged in Nx-Ca rats. Chondrocyte proliferation rates did not differ among the groups, whereas osteoclastic activity was decreased in Nx-Ca rats compared with the Nx-Control animals. The OPG expression and BV were increased in Nx-Ca rats compared with the Nx-Control rats. Increased BV should improve bone strength, whereas disturbance of osteoclastogenesis interferes with bone remodeling. Bone quality has yet to be determined in high Ca-fed uremic young rats

Strontium ranelate and alendronate have differing effects on distal tibia bone microstructure in women with osteoporosis

The structural basis of the antifracture efficacy of strontium ranelate and alendronate is incompletely understood. We compared the effects of strontium ranelate and alendronate on distal tibia microstructure over 2 years using HR-pQCT. In this pre-planned, interim, intention-to-treat analysis at 12 months, 88 osteoporotic postmenopausal women (mean age 63.7 ± 7.4) were randomized to strontium ranelate 2 g/day or alendronate 70 mg/week in a double-placebo design. Primary endpoints were changes in microstructure. Secondary endpoints included lumbar and hip areal bone mineral density (aBMD), and bone turnover markers. This trial is registered with http://www.controlled-trials.com, number ISRCTN82719233. Baseline characteristics of the two groups were similar. Treatment with strontium ranelate was associated with increases in mean cortical thickness (CTh, 5.3%), cortical area (4.9%) and trabecular density (2.1%) (all P < 0.001, except cortical area P = 0.013). No significant changes were observed with alendronate. Between-group differences in favor of strontium ranelate were observed for CTh, cortical area, BV/TV and trabecular density (P = 0.045, 0.041, 0.048 and 0.035, respectively). aBMD increased to a similar extent with strontium ranelate and alendronate at the spine (5.7% versus 5.1%, respectively) and total hip (3.3% versus 2.2%, respectively). No significant changes were observed in remodeling markers with strontium ranelate, while suppression was observed with alendronate. Within the methodological constraints of HR-pQCT through its possible sensitivity to X-ray attenuation of different minerals, strontium ranelate had greater effects than alendronate on distal tibia cortical thickness and trabecular volumetric density

Efficacy of Synaptic Inhibition Depends on Multiple, Dynamically Interacting Mechanisms Implicated in Chloride Homeostasis

Chloride homeostasis is a critical determinant of the strength and robustness of inhibition mediated by GABAA receptors (GABAARs). The impact of changes in steady state Cl− gradient is relatively straightforward to understand, but how dynamic interplay between Cl− influx, diffusion, extrusion and interaction with other ion species affects synaptic signaling remains uncertain. Here we used electrodiffusion modeling to investigate the nonlinear interactions between these processes. Results demonstrate that diffusion is crucial for redistributing intracellular Cl− load on a fast time scale, whereas Cl−extrusion controls steady state levels. Interaction between diffusion and extrusion can result in a somato-dendritic Cl− gradient even when KCC2 is distributed uniformly across the cell. Reducing KCC2 activity led to decreased efficacy of GABAAR-mediated inhibition, but increasing GABAAR input failed to fully compensate for this form of disinhibition because of activity-dependent accumulation of Cl−. Furthermore, if spiking persisted despite the presence of GABAAR input, Cl− accumulation became accelerated because of the large Cl− driving force that occurs during spikes. The resulting positive feedback loop caused catastrophic failure of inhibition. Simulations also revealed other feedback loops, such as competition between Cl− and pH regulation. Several model predictions were tested and confirmed by [Cl−]i imaging experiments. Our study has thus uncovered how Cl− regulation depends on a multiplicity of dynamically interacting mechanisms. Furthermore, the model revealed that enhancing KCC2 activity beyond normal levels did not negatively impact firing frequency or cause overt extracellular K− accumulation, demonstrating that enhancing KCC2 activity is a valid strategy for therapeutic intervention

Efeitos de polímeros hidrorretentores nas propriedades físico-hídricas de dois meios porosos

Com o propósito de avaliar os efeitos de polímeros hidrorretentores nas propriedades físicas e hidráulicas de dois meios porosos, realizou-se um experimento no Laboratório de Física do Solo da Universidade Federal do Paraná, entre 18/03 e 30/10/97. O polímero hidrorretentor usado foi produzido na Bélgica e os meios porosos foram um Latossolo Vermelho textura argilosa e uma Areia Quartzosa Marinha, ambos na forma de TFSA. Os polímeros foram aplicados na forma de grãos passados em peneira de 0,5 e 1 mm de diâmetro, nas seguintes concentrações: 0, 2, 4, 8, 16 e 32 kg m-3. Foram elaboradas as curvas de retenção a baixas tensões (0; 0,025; 0,045; 0,10; 0,20; 0,60; 1,5 e 3,0 mH2O), medidas as condutividades hidráulicas saturadas e estimados os diâmetros médios de poros. O processo da evaporação de água do solo foi simulado por modelagem numérica. As curvas de retenção de água medidas e os perfis de umidade simulados da evaporação afastaram-se consideravelmente da origem (testemunhas) pela adição de polímeros, particularmente na Areia Quartzosa Marinha. O diâmetro médio de poros também aumentou progressivamente com o aumento da concentração de polímeros. Foi verificado que, nas concentrações de polímeros acima de 8 kg m-3, as propriedades físico-hídricas dos meios porosos foram dominadas pela ação dos polímeros hidrorretentores

On the death of 100 + Italian doctors from COVID-19

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Integrating supervised classification in social participation systems for disaster response. A pilot study

The recent evolution of Information and Communication Technology (ICT) and mobile devices has strongly encouraged social participation as a tool for decision-support systems. These social participation tools are labelled as Participatory Geographic Information System (PGIS). The use of these tools has also extended to several domains – such as natural disasters, humanitarian crises, political conflicts – with the main aim to help affected populations and provide useful information for survival. Nonetheless, social participation tools present some drawbacks for managing non-structured information retrieved from large databases and Social Networks. The limitations concern either the need to understand knowledge in (almost) real time or data classification according to a specific domain. The present work aims at understanding the use of supervised classification models in situations of emergencies (i.e. disaster response) to classify message requests asking for/offering to help. To achieve the above aim we use machine learning techniques to compare classification models and evaluate their effectiveness and potentials to integrate them into existing PGIS systems. Main results suggest the existence of a relatively high accuracy of test and training classification by employing Random Forest, Neural Networks and Support Vector Machine (SVM) models. We argue in favour of supervised classification for its usefulness as a tool to be integrated in social participation for disaster response