Osteocytes are considered to be the major mechanosensory cells of bone, but how osteocytes in vivo process, perceive, and respond to mechanical loading remains poorly understood. Intracellular calcium (Ca) signaling resulting from mechanical stimulation has been widely studied in osteocytes in vitro and in bone explants, but has yet to be examined in vivo. This is achieved herein by using a three-point bending device which is capable of delivering well-defined mechanical loads to metatarsal bones of living mice while simultaneously monitoring the intracellular Ca responses of individual osteocytes by using a genetically encoded fluorescent Ca indicator. Osteocyte responses are imaged by using multiphoton fluorescence microscopy. We investigated the in vivo responses of osteocytes to strains ranging from 250 to 3,000 [Formula: see text] and frequencies from 0.5 to 2 Hz, which are characteristic of physiological conditions reported for bone. At all loading frequencies examined, the number of responding osteocytes increased strongly with applied strain magnitude. However, Ca intensity within responding osteocytes did not change significantly with physiological loading magnitudes. Our studies offer a glimpse into how these critical bone cells respond to mechanical load in vivo, as well as provide a technique to determine how the cells encode magnitude and frequency of loading.
The findings in rheumatic mitral stenosis appear to have undergone changes, probably in association with improved socioeconomic conditions, in developing countries. The objective of this study was to assess such changes and to adapt strategies of management. The clinical and pathologic features, mortality rate, long-term functional class and restenosis rate in 168 children and 62 pregnant women who underwent closed transventricular mitral valvotomy in the first 14-year period (June 1964 to May 1978) were compared and correlated with those of 140 children and 106 pregnant women in the following 7-year period (June 1978 to May 1985). During the late period, there were attenuated severity of the disease, emergence of a mild pathologic type of valve involvement confined to the commissures (commissural band stenosis), decreased mortality (1.2%) and restenosis rates (p less than 0.001) and increased long-term improvement (p less than 0.001) during childhood. The best results of closed valvotomy were obtained in simple commissural and commissural band stenosis, the latter forming the predominant group in children and pregnant women in the late period (p less than 0.001). Poor results were observed in patients with the subtype of combined stenosis characterized by commissural rigidity, cuspal stenosis and chordal fusion, demonstrating the inapplicability of closed valvotomy. Closed valvotomy is safe in all stages of pregnancy, as evidenced by the zero mortality rate and rate (1.8%) of fetal death, and offers good long-term palliation. However, in pregnant women with pure mitral stenosis characterized by simple commissural or commissural band stenosis, balloon valvuloplasty is an acceptable alternative, especially in light of the risks associated with surgery. The choice of the procedure for the relief of stenosis is determined by the pathologic anatomy of the valve stenosis.
Purpose of reviewMultiple biochemical and biophysical approaches have been broadly used for detection and quantitation of posttranslational protein modifications associated with diabetic bone, yet these techniques present a variety of challenges. In this review, we discuss recent advancements and complementary roles of analytical (UPLC/UPLC-MS/MS and ELISA) and biophysical (Raman and FTIR) techniques used for characterization of glycation products, measured from bone matrix and serum, and provide recommendations regarding the selection of a technique for specific study of diabetic bone. Recent findingsHyperglycemia and oxidative stress in diabetes contribute to the formation of a large subgroup of advanced glycation end products (AGEs) known as glycoxidation end products (AGOEs). AGEs/AGOEs have various adverse effects on bone health. Commonly, accumulation of AGEs/AGOEs leads to increased bone fragility. For example, recent studies show that carboxymethyllysine (CML) and pentosidine (PEN) are formed in bone at higher levels in certain diseases and metabolic conditions, in particular, in diabetes and aging. Detection and quantitation of AGEs/AGOEs in rare and/or precious samples is feasible because of a number of technological advancements of the past decade. SummaryRecent technological advancements have led to a significant improvement of several key analytical biochemistry and biophysics techniques used for detection and characterization of AGEs/AGOEs in bone and serum. Their principles and applications to skeletal tissue studies as well as limitations are discussed in this review.
The recent enhanced sophistication of non-invasive mapping of the human motor cortex using MRI-guided Transcranial Magnetic Stimulation (TMS) techniques, has not been matched by refinement of methods for generating maps from motor evoked potential (MEP) data, or in quantifying map features. This is despite continued interest in understanding cortical reorganization for natural adaptive processes such as skill learning, or in the case of motor recovery, such as after lesion affecting the corticospinal system. With the observation that TMS-MEP map calculation and quantification methods vary, and that no readily available commercial or free software exists, we sought to establish and make freely available a comprehensive software package that advances existing methods, and could be helpful to scientists and clinician-researchers. Therefore, we developed NeuroMeasure , an open source interactive software application for the analysis of TMS motor cortex mapping data collected from Nexstim® and BrainSight®, two commonly used neuronavigation platforms. NeuroMeasure features four key innovations designed to improve motor mapping analysis: de-dimensionalization of the mapping data, fitting a predictive model, reporting measurements to characterize the motor map, and comparing those measurements between datasets. This software provides a powerful and easy to use workflow for characterizing and comparing motor maps generated with neuronavigated TMS. The software can be downloaded on our github page: https://github.com/EdwardsLabNeuroSci/NeuroMeasure Aim This paper aims to describe a software platform for quantifying and comparing maps of the human primary motor cortex, using neuronavigated transcranial magnetic stimulation, for the purpose of studying brain plasticity in health and disease.
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