Modulated optical nanoprobes (MOONs) are microscopic (spherical and aspherical) fluorescent particles designed to emit varying intensities of light in a manner that depends on particle orientation. MOONs can be prepared over a broad size range, allowing them to be tailored to applications including intracellular sensors, using submicrometer MOONs, and immunoassays, using 1−10 μm MOONs. When particle orientation is controlled remotely, using magnetic fields (MagMOONs), it allows modulation of fluorescence intensity in a selected temporal pattern. In the absence of external fields, or material that responds to external fields, the particles tumble erratically due to Brownian thermal forces (Brownian MOONs). These erratic changes in orientation cause the MOONs to blink. The temporal pattern of blinking reveals information about the local rheological environment and any forces and torques acting on the MOONs, including biomechanical forces as observed in macrophages. The rotational diffusion rate of Brownian MOONs is inversely proportional to the particle volume and hydrodynamic shape factor, for constant temperature and viscosity. Changes in the particle volume and shape due to binding, deformation, or aggregation can be studied using the temporal time pattern from the probes. The small size and the large number of MOONs that can be viewed simultaneously provide local measurements of physical properties, in both homogeneous and inhomogeneous media, as well as global statistical ensemble properties.
This paper presents the development and characterization of a highly selective magnesium fluorescent optical nanosensor, made possible by PEBBLE (probe encapsulated by biologically localized embedding) technology. A ratiometric sensor has been developed by co-immobilizing a dye that is sensitive to and highly selective for magnesium, with a reference dye in a matrix. The sensors are prepared via a microemulsion polymerization process, which entraps the sensing components inside a polymer matrix. The resultant spherical sensors are approximately 40 nm in diameter. The Coumarin 343 (C343) dye, which by itself does not enter the cell, when immobilized in a PEBBLE is used as the magnesium-selective agent that provides the high and necessary selectivity over other intracellular ions, such as Ca2+, Na+, and K+. The dynamic range of these sensors was 1-30 mM, with a linear range from 1 to 10 mM, with a response time of <4 s. In contrast to free dye, these nano-optodes are not perturbed by proteins. They are fully reversible and exhibit minimal leaching and photobleaching over extended periods of time. In vitro intracellular changes in Mg2+ concentration were monitored in C6 glioma cells, which remained viable after PEBBLE delivery via gene gun injection. The selectivity for Mg2+ along with the biocompatibility of the matrix provides a new and reliable tool for intracellular magnesium measurements.
Introduction Readmission to the hospital following a hip fracture is common, often involves an adverse event, and strains an already overburdened health care system. Objectives To assess the rate of 30-day readmission to the hospital after discharge for care of hip fracture. A secondary objective was measurement of the 30-day mortality rate for those patients readmitted versus those patients not readmitted to the hospital after discharge. Materials and methods Study design was a retrospective review of registry data comparing readmitted patients to those not readmitted after hip fracture. Setting was a university affiliated level 3 trauma center. Participants: 1,081 patients aged 65 and older. Measurements: rate of readmission, rate of mortality, predictors of readmission. Results 129 patients (11.9 %) were readmitted to the hospital within 30 days of their initial discharge date. The primary causes of readmission were surgical in nature for 24/129 (18.6 %) patients and 105/129 (81.4 %) were readmitted for medical or other reasons. Twenty-four (18.6 %) patients who were readmitted died during readmission. The one-year mortality rate for patients readmitted within 30 days was 56.2 vs. a 21.8 % 1-year mortality rate for those patients not readmitted (p \ 0.0001). Independent predictors of readmission were age [85 (OR = 1.52; p = 0.03), time to surgery [24 h (OR = 1.50; p = 0.05), Charlson score C4 (OR = 1.70; p = 0.04), delirium (OR = 1.65; p = 0.01), dementia (OR = 1.61; p = 0.01), history of arrhythmia with pacemaker placement (OR = 1.75; p = 0.02), and presence of a pre-op arrhythmia (OR = 1.62; p = 0.02).Conclusion Readmission after hip fracture is harmful and undesirable-18.6 % of readmitted patients died during their readmission and the average length of stay was 8.7 days. Approximately one of every six readmissions was identified as potentially preventable with interventions.
Brownian modulated optical nanoprobes (Brownian MOONs) are fluorescent micro- and nanoparticles that resemble moons: one hemisphere emits a bright fluorescent signal, while an opaque metal darkens the other hemisphere. Brownian motion causes the particles to tumble and blink erratically as they rotate literally through the phases of the moon. The fluctuating probe signals are separated from optical and electronic backgrounds using principal components analysis or images analysis. Brownian MOONs enable microrheological measurements on size scales and timescales that are difficult to study with other methods. Local chemical concentrations can be measured simultaneously, using spectral characteristics of indicator dyes embedded within the MOONs.
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