The emergency department evaluation and outcomes of elderly fallers

BACKGROUND: Approximately one-third of community dwelling elderly people (age ≥65 years) falls each year contributing to over 2 million elderly emergency department (ED) visits for falls annually. The cost of care for fatal falls by elderly patients in the US was $179 million in 2000, and was$19 billion for non-fatal falls. The risk of falling increases with various risk factors including advancing age. Despite the frequency and costs associated with elderly falls, it is not clear what evaluation elderly fallers receive in the ED, after the ED, and the outcomes of the care provided. OBJECTIVES: We sought to examine the ED and post-ED workup of elderly fallers, and to compare this evaluation to that recommended by published ED fall evaluation and treatment guidelines. We also examined the disposition of these patients and the rate of adverse events which occurred within 1 year of discharge. METHODS: This study was a retrospective chart review of elderly ED fall patients from one urban teaching hospital with >90,000 visits per year. Patients aged ≥65 years who had an ED visit in 2012 with fall related ICD-9 codes E880-886, E888 and who had been seen by a primary care physician (PCP) within our hospital network during the past 3 years were included. We excluded patients who were transferred to our hospital and subsequent visits related to the original fall. We randomly selected 350 eligible patients for chart review. We adapted our data collection instrument from published fall evaluation recommendations including the American Geriatric Society. Categorical data were presented as percentages and continuous data were recorded as mean with standard deviation (SD) if normally distributed or medians with inter-quartile ranges (IQR) if non-normally distributed. RESULTS: A random sample of 450 charts were taken, 100 were subsequently excluded for erroneous identification. The average age was 80 (SD±9) years; 124 (35%) were male, with an average Charlson comorbidity index of 7.6 (SD 2.9). In terms of history, 251/350 (72%) took 5 or more medications, 144/350 (41%) had their visual acuity checked in the past 12 months, and 34/350 (10%) had fallen two or more times in the past 3 months. In the physical exam, only 43/350 (12%) had orthostatics done. 168/350 (48%) patients had their extremity strength recorded, of these 16/168 (10%) had decreased muscle strength. Only 128/350 (37%) patients had their gait recorded, of which 108/128 (84%) were noted to have an abnormal gait. Basic chemistry laboratory tests and hematology were sent on 199/350 (57%) of patients in the ED. X-rays were taken of 275/350 (79%) patients, and CTs were taken of 184/350 (53%) patients in the ED. 277/350 (79%) patients were discharged to their place of preadmission residence from the ED, ED observation unit, or hospital while 70/350 (20%) were discharged to a skilled rehab facility, all after being admitted to the hospital. 196/350 (56%) patients returned to the ED for any reason within 1 year of discharge, averaging 2.4 ± 1.9 visits. 161/350 (46%) patients were hospitalized within 1 year after discharge, averaging 2 ± 1.4 hospital admissions. 23 (7%) of patients died within 1 year after discharge. CONCLUSION: The comprehensive evaluation of falls for well-established risk factors and causes appears to be poor in this academic medical center ED. While results may not be generalizable to other EDs, the results suggest that standardized evaluation and treatment guidelines are needed

Concluding remarks: The importance of polymer science for biological systems

The 139th Faraday Discussion covered many interesting subjects, divided into four sections: Cell Interactions; Membranes & Walls; Proteins and Polysaccharides; and Natural & Synthetic Polymers. Here, the meeting is summarised and future prospects are explored

Toxic Misogyny and the Limits of Counterspeech

Gender equality, across all the ways that we humans are engendered, is an unrealized ideal of many contemporary Americans. It is not enshrined in the U.S. Constitution, unless one interprets “men” to include women, which the Framers did not. Although passed by Congress in 1972, the Equal Rights Amendment (ERA) failed to gain the necessary thirty-eight state ratifications, and it has never become law. Thirty-five states initially ratified it between 1972 and 1977, then two more in 2017 and 2018. It remains one state short. These ratifications indicate significant social progress for women, but the progress is uneven, even within states that have supported the ERA. Offering a glimmer of hope, the Senate of Virginia voted to ratify the ERA in February 2019, but the measure was killed in committee by the Republican-controlled House of Delegates. Women remain constitutionally unequal. For anyone concerned with justice, the question is not whether something should be done about the misogynist onslaught girls and women encounter; the question is: What should be done, and who should do it? Supreme Court doctrine may favor counterspeech to tort remedies or criminalization, but to justify this we need a robust conception of what sorts of speech might have the power to counter oppressive speech, who can achieve it, and under what circumstances. In setting policy, we cannot assume a speech encounter between equally powerful adults, each fully free to speak their minds and each with the backing of deep and broad social norms. Where inequality reigns, the odds are not in favor of someone who tries to combat the bad speech of the powerful with the more speech of the vulnerable. This paper explores the mechanisms of counterspeech and the limits of the remedies counterspeech can provide. By understanding the very concept of misogyny and considering some mechanics of the ways language works, we can gain a better picture of the prospect of creating normative change through counterspeech

Analogical Truth-Conditions for Metaphors

It has often been said that metaphors are based on analogies, but the nature of this relation has never been made precise. This article rigorously and formally specifies two semantic relations that do obtain between some metaphors and analogies. We argue that analogies often provide conditions of meaningfulness and truth for metaphors. An analogy is treated as an isomorphism from a source to topic domain. Metaphors are thought of as surface structures. Formal analogical conditions of meaningfulness and truth are fully and rigorously worked out for several grammatical classes of metaphors. By providing analogical meaningfulness and truth conditions for metaphors, this article shows that truth-conditional semantics can be extended to metaphors

Cell response to RGD density in cross-linked artificial extracellular matrix protein films

This study examines the adhesion, spreading, and migration of human umbilical vein endothelial cells on cross-linked films of artificial extracellular matrix (aECM) proteins. The aECM proteins described here were designed for application in small-diameter grafts and are composed of elastin-like structural repeats and fibronectin cell-binding domains. aECM-RGD contains the RGD sequence derived from fibronectin; the negative control protein aECM-RDG contains a scrambled cell-binding domain. The covalent attachment of poly(ethylene glycol) (PEG) to aECM substrates reduced nonspecific cell adhesion to aECM-RDG-PEG but did not preclude sequence-specific adhesion of endothelial cells to aECM-RGD-PEG. Variation in ligand density was accomplished by the mixing of aECM-RGD-PEG and aECM-RDG-PEG prior to cross-linking. Increasing the density of RGD domains in cross-linked films resulted in more robust cell adhesion and spreading but did not affect cell migration speed. Control of cell-binding domain density in aECM proteins can thus be used to modulate cell adhesion and spreading and will serve as an important design tool as these materials are further developed for use in surgery, tissue engineering, and regenerative medicine

Noncanonical Amino Acids in the Interrogation of Cellular Protein Synthesis

Proteins in living cells can be made receptive to bioorthogonal chemistries through metabolic labeling with appropriately designed noncanonical amino acids (ncAAs). In the simplest approach to metabolic labeling, an amino acid analog replaces one of the natural amino acids specified by the protein’s gene (or genes) of interest. Through manipulation of experimental conditions, the extent of the replacement can be adjusted. This approach, often termed residue-specific incorporation, allows the ncAA to be incorporated in controlled proportions into positions normally occupied by the natural amino acid residue. For a protein to be labeled in this way with an ncAA, it must fulfill just two requirements: (i) the corresponding natural amino acid must be encoded within the sequence of the protein at the genetic level, and (ii) the protein must be expressed while the ncAA is in the cell. Because this approach permits labeling of proteins throughout the cell, it has enabled us to develop strategies to track cellular protein synthesis by tagging proteins with reactive ncAAs. In procedures similar to isotopic labeling, translationally active ncAAs are incorporated into proteins during a “pulse” in which newly synthesized proteins are tagged. The set of tagged proteins can be distinguished from those made before the pulse by bioorthogonally ligating the ncAA side chain to probes that permit detection, isolation, and visualization of the labeled proteins. Noncanonical amino acids with side chains containing azide, alkyne, or alkene groups have been especially useful in experiments of this kind. They have been incorporated into proteins in the form of methionine analogs that are substrates for the natural translational machinery. The selectivity of the method can be enhanced through the use of mutant aminoacyl tRNA synthetases (aaRSs) that permit incorporation of ncAAs not used by the endogenous biomachinery. Through expression of mutant aaRSs, proteins can be tagged with other useful ncAAs, including analogs that contain ketones or aryl halides. High-throughput screening strategies can identify aaRS variants that activate a wide range of ncAAs. Controlled expression of mutant synthetases has been combined with ncAA tagging to permit cell-selective metabolic labeling of proteins. Expression of a mutant synthetase in a portion of cells within a complex cellular mixture restricts labeling to that subset of cells. Proteins synthesized in cells not expressing the synthetase are neither labeled nor detected. In multicellular environments, this approach permits the identification of the cellular origins of labeled proteins. In this Account, we summarize the tools and strategies that have been developed for interrogating cellular protein synthesis through residue-specific tagging with ncAAs. We describe the chemical and genetic components of ncAA-tagging strategies and discuss how these methods are being used in chemical biology

Protein-based materials, toward a new level of structural control

Through billions of years of evolution nature has created and refined structural proteins for a wide variety of specific purposes. Amino acid sequences and their associated folding patterns combine to create elastic, rigid or tough materials. In many respects, nature’s intricately designed products provide challenging examples for materials scientists, but translation of natural structural concepts into bio-inspired materials requires a level of control of macromolecular architecture far higher than that afforded by conventional polymerization processes. An increasingly important approach to this problem has been to use biological systems for production of materials. Through protein engineering, artificial genes can be developed that encode protein-based materials with desired features. Structural elements found in nature, such as β-sheets and α-helices, can be combined with great flexibility, and can be outfitted with functional elements such as cell binding sites or enzymatic domains. The possibility of incorporating non-natural amino acids increases the versatility of protein engineering still further. It is expected that such methods will have large impact in the field of materials science, and especially in biomedical materials science, in the future

Structure and mechanical properties of artificial protein hydrogels assembled through aggregation of leucine zipper peptide domains

Artificial protein hydrogels made from a triblock protein (designated AC10A, where A is an acidic zipper domain and C10 comprises 10 repeats of the nonapeptide sequence exhibit normalized plateau storage moduli (G/nkT) less than 0.13 at all concentrations, pH values, and ionic strengths examined. These gels are surprisingly soft due to loop formation at the expense of bridges between physical junctions. Molecular-level evidence of loop formation is provided by strong fluorescence energy transfer (FRET) between distinct chromophores placed at the C- and N-termini of labelled chains diluted in an excess of unlabelled chains. The tendency to form loops originates from the compact size of the random coil midblock (mean RH(C10) 20 Å, determined from quasi-elastic light scattering of C10), and is facilitated by the ability of the leucine zipper domains to form antiparallel aggregates. Although the aggregation number of the leucine zipper domains is small (tetrameric, determined from multi-angle static light scattering of AC10 diblock), the average center-to-center distance between aggregates is roughly 1.5 times the average end-to-end distance of the C10 domain in a 7% w/v network. To avoid stretching the C10 domain, the chains tend to form loops. Changes in pH or ionic strength that expand the polyelectrolyte midblock favor bridging, leading to greater G as long as leucine zipper endblocks do not dissociate. Understanding of the network structure provided successful design strategies to increase the rigidity of these hydrogels. In contrast to intuitive design concepts for rubber and gel materials, it was shown that increasing either the length or the charge density of the midblock increases rigidity, because fewer chains are wasted in loop formation