Coronary Artery Calcification and Risk of Cardiac Complication in Geriatric Trauma Population.

BACKGROUND: Better means of identifying patients with increased cardiac complication (CC) risk is needed. Coronary artery calcification (CAC) is reported on routine chest CT scans. We assessed the correlation of CAC and CCs in the geriatric trauma population. STUDY DESIGN: A prospective, observational study of patients 55 years and older who had chest CT scan from May to September 2022 at a level 1 trauma center. Radiologists scored CAC as none, mild, moderate, or severe. None-to-mild CAC (NM-CAC) and moderate-to-severe CAC (MS-CAC) were grouped and in-hospital CCs assessed (arrhythmia, ST elevation myocardial infarction [STEMI], non-STEMI, congestive heart failure, pulmonary edema, cardiac arrest, cardiogenic shock, and cardiac mortality). Univariate and bivariate analyses were performed. RESULTS: Five hundred sixty-nine patients had a chest CT, of them 12 were excluded due to missing CAC severity. Of 557 patients, 442 (79.3%) had none-to-mild CAC and 115 (20.7%) has MS-CAC; the MS-CAC group was older (73.3 vs 67.4 years) with fewer male patients (48.7% vs 54.5%), had higher cardiac-related comorbidities, and had higher abbreviated injury scale chest injury scores. The MS-CAC group had an increased rate of CC (odds ratio [OR] 1.81, p = 0.016). Cardiac complications statistically more common in MS-CAC were congestive heart failure (OR 3.41, p = 0.003); cardiogenic shock (OR 3.3, p = 0.006); non-STEMI I or II (OR 2.8, p = 0.017); STEMI (OR 5.9, p = 0.029); and cardiac-caused mortality (OR 5.27, p = 0.036). No statistical significance between pulmonary edema (p = 0.6), new-onset arrhythmia (p = 0.74), or cardiac arrest (p = 0.193). CONCLUSIONS: CAC as reported on chest CT scans demonstrates a significant correlation with CC and should warrant additional cardiac monitoring.

An ethological analysis of close-contact inter-cat interactions determining if cats are playing, fighting, or something in between.

Intraspecific social interactions in domestic cats are often categorised as affiliative or agonistic. However, public or professional assessment of encounters can have difficulty distinguishing rough-and-tumble play from true agonism. One possible issue is the potential occurrence of elements of both, play and agonism, within inter-cat play, for example when one cat wants to terminate a bout of play but the other seeks to continue the interaction, which subsequently may provoke more overt agonistic behaviour. To test this hypothesis, we conducted behavioural observations of 105 unique dyadic interactions of domestic cats (N = 210) captured on videos collected from owners and YouTube. We assessed cats for the frequency and duration of six behavioural elements. The dataset was reduced using PCA with a varimax rotation and factor scores were used to classify the population using hierarchical cluster analysis. To validate the identified clusters, the average scores of the constituent factors were compared and the data on interactions were labelled by four cat behaviour experts as "playful", "intermediate" or "agonistic". In addition, to evaluate properties of expert-labelled categories we used linear discriminant analysis followed by an ordinal regression. The results showed considerable convergent validity in factor distributions between clusters and expert-labelled groups: reciprocal wrestling was most closely associated with a group of playfully interacting cats, while vocalisation and chasing were associated with the agonistic group. The intermediate group, while having characteristics of both, was more closely related to the playful group than the agonistic group, with prolonged exchanges of interactive behaviours being a predominant feature. Thus, our findings support the suggestion of there being an intermediate category between mutual social play and agonism. This might escalate into a fully agonistic encounter, but does not necessarily reflect a break down in their social relationship but rather a short-term disagreement in social priorities.

3-Nitrotyrosine-dependent dopaminergic neurotoxicity following direct nigral administration of a peroxynitrite but not a nitric oxide donor.

The presence of 3-nitrotyrosine (3-NT) adducts in Lewy bodies in Parkinson's disease suggests a role for nitrative stress in dopaminergic cell death. Whether this is a direct effect of increased nitric oxide (NO) formation or requires its reaction with superoxide to form peroxynitrite is not clear. In the present study, we show that direct nigral administration of a NO donor, SNOG, in the rat produced only local toxicity to dopaminergic neurones pre-labeled with fluorogold with no 3-NT formation. However, administration of a peroxynitrite donor, SIN-1, caused widespread damage to dopaminergic neurones and marked expression of 3-NT immunoreactivity. Importantly, dopaminergic cell loss and the expression of 3-NT were completely prevented when SIN-1 was co-administered with the NO/peroxynitrite scavenger, carboxy-PTIO. The results suggest that increased NO formation is not inherently toxic to dopaminergic neurons, but when both oxidative and nitrative stress combine to cause peroxynitrite formation, neurotoxicity occurs.

Notch signalling and the synchronization of the somite segmentation clock.

In vertebrates with mutations in the Notch cell-cell communication pathway, segmentation fails: the boundaries demarcating somites, the segments of the embryonic body axis, are absent or irregular. This phenotype has prompted many investigations, but the role of Notch signalling in somitogenesis remains mysterious. Somite patterning is thought to be governed by a "clock-and-wavefront" mechanism: a biochemical oscillator (the segmentation clock) operates in the cells of the presomitic mesoderm, the immature tissue from which the somites are sequentially produced, and a wavefront of maturation sweeps back through this tissue, arresting oscillation and initiating somite differentiation. Cells arrested in different phases of their cycle express different genes, defining the spatially periodic pattern of somites and controlling the physical process of segmentation. Notch signalling, one might think, must be necessary for oscillation, or to organize subsequent events that create the somite boundaries. Here we analyse a set of zebrafish mutants and arrive at a different interpretation: the essential function of Notch signalling in somite segmentation is to keep the oscillations of neighbouring presomitic mesoderm cells synchronized.

Sequence and embryonic expression of deltaC in the zebrafish.

Four genes - deltaA, deltaB, deltaC and deltaD - coding for homologues of the Notch ligand Delta have been discovered in zebrafish (Haddon et al., 1998b). We report here the cDNA sequence and expression pattern of deltaC. Its closest relatives are deltaB and Xenopus X-Delta-2. Unlike deltaA, deltaB, and deltaD, deltaC is not expressed in the majority of nascent primary neurons; but it is strongly expressed in the early retina, where it precedes other delta genes. It is also expressed in cranial ganglia, in sensory epithelia including ear and lateral line, and in scattered epidermal cells. In the mesoderm, expression is visible by 50% epiboly; it is seen subsequently in the tail bud, in stripes in the presomitic mesoderm and in the posterior half of each somite. There is expression also in notochord, blood vessels and pronephros.

Hair cells without supporting cells: further studies in the ear of the zebrafish mind bomb mutant.

Each sensory hair cell in the ear is normally surrounded by supporting cells, which separate it from the next hair cell. In the mind bomb mutant, as a result of a failure of lateral inhibition, cells that would normally become supporting cells differentiate as hair cells instead, creating sensory patches that consist of hair cells only. This provides a unique opportunity to pinpoint the functions for which supporting cells are required in normal hair cell development. We find that hair cells in the mutant develop an essentially normal cytoskeleton, with a correctly structured hair bundle and well-defined planar polarity, and form apical junctional complexes with one another in standard epithelial fashion. They fail, however, to form a basal lamina or to adhere properly to the adjacent non-sensory epithelial cells, which overgrow them. The hair cells are eventually expelled from the ear epithelium into the underlying mesenchyme, losing their hair bundles in the process. It is not clear whether they undergo apoptosis: many cells staining strongly with the TUNEL procedure are seen but do not appear apoptotic by other criteria. Supporting cells, therefore, are needed to hold hair cells in the otic epithelium and, perhaps, to keep them alive, but are not needed for the construction of normal hair bundles or to give the hair bundles a predictable polarity. Moreover, supporting cells are not absolutely required as a source of materials for otoliths, which, though small and deformed, still develop in their absence.

Delta-Notch signalling and the patterning of sensory cell differentiation in the zebrafish ear: evidence from the mind bomb mutant.

Mechanosensory hair cells in the sensory patches of the vertebrate ear are interspersed among supporting cells, forming a fine-grained pattern of alternating cell types. Analogies with Drosophila mechanosensory bristle development suggest that this pattern could be generated through lateral inhibition mediated by Notch signalling. In the zebrafish ear rudiment, homologues of Notch are widely expressed, while the Delta homologues deltaA, deltaB and deltaD, coding for Notch ligands, are expressed in small numbers of cells in regions where hair cells are soon to differentiate. This suggests that the delta-expressing cells are nascent hair cells, in agreement with findings for Delta1 in the chick. According to the lateral inhibition hypothesis, the nascent hair cells, by expressing Delta protein, would inhibit their neighbours from becoming hair cells, forcing them to be supporting cells instead. The zebrafish mind bomb mutant has abnormalities in the central nervous system, somites, and elsewhere, diagnostic of a failure of Delta-Notch signalling: in the CNS, it shows a neurogenic phenotype accompanied by misregulated delta gene expression. Similar misregulation of delta ; genes is seen in the ear, along with misregulation of a Serrate homologue, serrateB, coding for an alternative Notch ligand. Most dramatically, the sensory patches in the mind bomb ear consist solely of hair cells, which are produced in great excess and prematurely; at 36 hours post fertilization, there are more than ten times as many as normal, while supporting cells are absent. A twofold increase is seen in the number of otic neurons also. The findings are strong evidence that lateral inhibition mediated by Delta-Notch signalling controls the pattern of sensory cell differentiation in the ear.

Multiple delta genes and lateral inhibition in zebrafish primary neurogenesis.

In Drosophila, cells are thought to be singled out for a neural fate through a competitive mechanism based on lateral inhibition mediated by Delta-Notch signalling. In tetrapod vertebrates, nascent neurons express the Delta1 gene and thereby deliver lateral inhibition to their neighbours, but it is not clear how these cells are singled out within the neurectoderm in the first place. We have found four Delta homologues in the zebrafish--twice as many as reported in any tetrapod vertebrate. Three of these--deltaA, deltaB and deltaD--are involved in primary neurogenesis, while two--deltaC and deltaD--appear to be involved in somite development. In the neural plate, deltaA and deltaD, unlike Delta1 in tetrapods, are expressed in large patches of contiguous cells, within which scattered individuals expressing deltaB become singled out as primary neurons. By gene misexpression experiments, we show: (1) that the singling-out of primary neurons, including the unique Mauthner cell on each side of the hindbrain, depends on Delta-Notch-mediated lateral inhibition, (2) that deltaA, deltaB and deltaD all have products that can deliver lateral inhibition and (3) that all three of these genes are themselves subject to negative regulation by lateral inhibition. These properties imply that competitive lateral inhibition, mediated by coordinated activities of deltaA, deltaB and deltaD, is sufficient to explain how primary neurons emerge from proneural clusters of neuroepithelial cells in the zebrafish.

Intercellular signals and cell-fate choices in the developing inner ear: origins of global and of fine-grained pattern.

The major regions of the inner ear begin to be distinguishable by their patterns of gene expression very early, before the otocyst has closed. Later, individual cells within a neurogenic or sensory patch become committed to specific pathways of differentiation. Insights gained from homologies with invertebrates and from studies of tissues other than the ear, combined with discoveries from screens for mutations affecting development in the zebrafish, are beginning to reveal the genes and signalling mechanisms that control these cell-fate choices in the developing inner ear.

Early ear development in the embryo of the zebrafish, Danio rerio.

The zebrafish provides an important model for vertebrate inner ear development. The otic placode becomes visible at approximately 16 hours (at 28.5 degrees C) and forms a vesicle with a lumen by cavitation at approximately 18 hours. Two otoliths appear in the lumen by 19.5 hours, and at about 24 hours the first sensory hair cells are seen, grouped in two small patches, one beneath each otolith, corresponding to future maculae. Staining with fluorescent phalloidin reveals 10-20 hair cells in each macula by 42 hours; between 3 days and 7 days the numbers grow to approximately 80 per macula. Neurons of the statoacoustic ganglion are first visible by staining with HNK-1 antibody at about 24 hours. Serial sections and time-lapse films show that the neuronal precursors originate by delamination from the ventral face of the otocyst; the peak period of delamination is from 22 hours to 30 hours. The system of semicircular canals forms between 42 hours and 72 hours by outgrowth of protrusions from the walls of the otocyst to form pillars of tissue spanning the lumen. Three further clusters of hair cells also become visible in this period, forming the three cristae. Thus, by the end of the first week, all key components of the ear are present. Subsequent growth produces thousands more hair cells; additional neurons probably derive from proliferation of neuronal precursors within the ganglion. Although the timetable is species-specific, the principles of inner ear development in the zebrafish seem to be the same as in other vertebrates.

Hyaluronan as a propellant for epithelial movement: the development of semicircular canals in the inner ear of Xenopus.

The membranous labyrinth of the inner ear, with its three semicircular canals, originates from a simple spheroidal otic vesicle. The process is easily observed in Xenopus. The vesicle develops three dorsal outpocketings; from the two opposite faces of each outpocketing pillars of tissue are protruded into the lumen; and these paired 'axial protrusions' eventually meet and fuse, to form a column of tissue spanning the lumen of the outpocketing like the hub of a wheel, with a tube of epithelium forming the semicircular canal around the periphery. Each axial protrusion consists of epithelium encasing a core of largely cell-free extracellular matrix that stains strongly with alcian blue. In sections, at least 60% of the stainable material is removed by treatment with Streptomyces hyaluronidase. When Streptomyces hyaluronidase is microinjected into the core of a protrusion in vivo, the protrusion collapses and the corresponding semicircular canal fails to form. Hyaluronan (hyaluronic acid) in the core of the protrusion therefore seems to be essential in driving the extension of the protrusion. Autoradiography with tritiated glucosamine indicates that the hyaluronan-rich matrix is synthesised by the epithelium covering the tip of the protrusion; the basal lamina here appears to be discontinuous. These findings indicate that the epithelium of the axial protrusion propels itself into the lumen of the otocyst by localised synthesis of hyaluronan. Hyaluronan may be used in a similar way in the development of other organs, such as the heart and the secondary palate.