Keep Your Differential Broad This Back Pain Season Penetrating Aortic Ulceration: A Case Report

Abstract: Keep Your Differential Broad this Back Pain Season, Kyle Diaz D.O., Anthony Colucci D.O. The chief complaint of back pain is a common occurrence in the emergency department. Our departments can often be inundated with this complaint especially now that the season of slips and falls is upon us. We are not only seeing traumatic back pain but chronic back pain and atraumatic acute back pain frequent the halls of the emergency department as well. While wading through the morass of these nonspecific and often menial complaints it may become difficult for a provider to maintain a broad differential. This case will serve as a reminder to remain vigilant while working up back pain. Additionally, information on an interesting diagnosis of aortic ulceration will be gleaned throughout the case review.The case is that of a 65 year old female with significant medical history including hypertension and remote history of smoking who presents to the emergency department complaining of back pain. The patient reports that she has been having mid thoracic back pain for the past 2-3 weeks. This pain is described as aching and is sharp with movement. Patient reports pain radiating to both sides with movement. Patient denies associated chest pain, shortness of breath, nausea, vomiting, neck pain, low back pain, sciatica, incontinence of stool, urinary retention. Patient does report that symptoms improve significantly with leaning forward.A thorough examination demonstrated Para spinal tenderness throughout the mid thoracic spine. Patient’s examination was otherwise normal save her vitals which showed hypertension to the degree of 180/95. Initial evaluation included AP chest, thoracic XR and basic lab work. Pain control was provided as well.On repeat examination patient’s back pain was well controlled however she remained hypertensive and was now having bilateral flank discomfort. At this point advanced imaging was obtained and a CTA of the chest was ordered. This demonstrate a broad based aortic ulceration about the ascending portion of the thoracic aorta.Immediate measures were taken to control patient\u27s elevated blood pressure and consultation was made to vascular surgery. Patient was admitted to the ICU for further management and evaluation. With strict impulse control repeat CTA was ordered at 48 hours. There was no progression of the disease and as such patient was discharged home with conservative medical management as she was not amenable to surgery at time of initial presentation.One month later the patient represented due to continued pain and was found to have a type B thoracic aortic dissection. At this time she underwent TEVAR and after an uncomplicated operation and post-operative course has followed with both family practice and vascular and is progressing well. As a conclusion of the case I would like to discuss the treatment and management of this finding of Aortic ulceration and the morbidity associated with this rare diagnosis. I believe that this interesting case will both add to the expansion of our differential when caring for back pain in addition to providing helpful information for diagnosis that does not have a mass of readily available data.https://scholarlycommons.henryford.com/merf2019caserpt/1087/thumbnail.jp

The effect of fingolimod on regulatory T cells in a mouse model of brain ischaemia

Background: The role of the immune system in stroke is well-recognised. Fingolimod, an immunomodulatory agent licensed for the management of relapsing-remitting multiple sclerosis, has been shown to provide benefit in rodent models of stroke. Its mechanism of action, however, remains unclear. We hypothesised fingolimod increases the number and/or function of regulatory T cells (Treg), a lymphocyte population which promotes stroke recovery. The primary aim of this study was to rigorously investigate the effect of fingolimod on Tregs in a mouse model of brain ischaemia. The effect of fingolimod in mice with common stroke-related comorbidities (ageing and hypercholesteremia) was also investigated. Methods: Young (15–17 weeks), aged C57BL/6 mice (72–73 weeks), and ApoE?/? mice fed a high-fat diet (20–21 weeks) underwent permanent electrocoagulation of the left middle cerebral artery. Mice received either saline or fingolimod (0.5 mg/kg or 1 mg/kg) at 2, 24, and 48 h post-ischaemia via intraperitoneal injection. Another cohort of young mice (8–9, 17–19 weeks) received short-term (5 days) or long-term (10 days) fingolimod (0.5 mg/kg) treatment. Flow cytometry was used to quantify Tregs in blood, spleen, and lymph nodes. Immunohistochemistry was used to quantify FoxP3+ cell infiltration into the ischaemic brain. Results: Fingolimod significantly increased the frequency of Tregs within the CD4+ T cell population in blood and spleen post-ischaemia in all three mouse cohorts compared to untreated ischemic mice. The highest splenic Treg frequency in fingolimod-treated mice was observed in ApoE?/? mice (9.32 ± 1.73% vs. 7.8 ± 3.01% in young, 6.09 ± 1.64% in aged mice). The highest circulating Treg frequency was also noted in ApoE?/? mice (8.39 ± 3.26% vs. 5.43 ± 2.74% in young, 4.56 ± 1.60% in aged mice). Fingolimod significantly increased the number of FoxP3+ cells in the infarct core of all mice. The most pronounced effects were seen when mice were treated for 10 days post-ischaemia. Conclusions: Fingolimod increases Treg frequency in spleen and blood post-ischaemia and enhances the number of FoxP3+ cells in the ischaemic brain. The effect of fingolimod on this regulatory cell population may underlie its neuroprotective activity and could be exploited as part of future stroke therapy

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This project was developed in response to the following challenge: create messaging to promote a more welcoming and inclusive climate on campus while branding the Jackie Gaughan Multicultural Center

CBR driven interactive explainable AI.

Explainable AI (XAI) can greatly enhance user trust and satisfaction in AI-assisted decision-making processes. Numerous explanation techniques (explainers) exist in the literature, and recent findings suggest that addressing multiple user needs requires employing a combination of these explainers. We refer to such combinations as explanation strategies. This paper introduces iSee - Intelligent Sharing of Explanation Experience, an interactive platform that facilitates the reuse of explanation strategies and promotes best practices in XAI by employing the Case-based Reasoning (CBR) paradigm. iSee uses an ontology-guided approach to effectively capture explanation requirements, while a behaviour tree-driven conversational chatbot captures user experiences of interacting with the explanations and provides feedback. In a case study, we illustrate the iSee CBR system capabilities by formalising a realworld radiograph fracture detection system and demonstrating how each interactive tools facilitate the CBR processes

The architecture of amyloid-like peptide fibrils revealed by X-ray scattering, diffraction and electron microscopy

Structural analysis of protein fibrillation is inherently challenging. Given the crucial role of fibrils in amyloid diseases, method advancement is urgently needed. A hybrid modelling approach is presented enabling detailed analysis of a highly ordered and hierarchically organized fibril of the GNNQQNY peptide fragment of a yeast prion protein. Data from small-angle X-ray solution scattering, fibre diffraction and electron microscopy are combined with existing high-resolution X-ray crystallographic structures to investigate the fibrillation process and the hierarchical fibril structure of the peptide fragment. The elongation of these fibrils proceeds without the accumulation of any detectable amount of intermediate oligomeric species, as is otherwise reported for, for example, glucagon, insulin and [alpha]-synuclein. Ribbons constituted of linearly arranged protofilaments are formed. An additional hierarchical layer is generated via the pairing of ribbons during fibril maturation. Based on the complementary data, a quasi-atomic resolution model of the protofilament peptide arrangement is suggested. The peptide structure appears in a [beta]-sheet arrangement reminiscent of the [beta]-zipper structures evident from high-resolution crystal structures, with specific differences in the relative peptide orientation. The complexity of protein fibrillation and structure emphasizes the need to use multiple complementary methods

Functionalised peptide hydrogel for the delivery of cardiac progenitor cells.

Heart failure (HF) remains one of the leading causes of death worldwide; most commonly developing after myocardial infarction (MI). Since adult cardiomyocytes characteristically do not proliferate, cells lost during MI are not replaced. As a result, the heart has a limited regenerative capacity. There is, therefore, a need to develop novel cell-based therapies to promote the regeneration of the heart after MI. The delivery and retention of cells at the injury site remains a significant challenge. In this context, we explored the potential of using an injectable, RGDSP-functionalised self-assembling peptide - FEFEFKFK - hydrogel as scaffold for the delivery and retention of rat cardiac progenitor cells (CPCs) into the heart. Our results show that culturing CPCs in vitro within the hydrogel for one-week promoted their spontaneous differentiation towards adult cardiac phenotypes. Injection of the hydrogel on its own, or loaded with CPCs, into the rat after injury resulted in a significant reduction in myocardial damage and left ventricular dilation

Increased hydralic risk in assemblages of woody plant species predicts spatial patterns of drought-induced mortality

Predicting drought-induced mortality (DIM) of woody plants remains a key research challenge under climate change. Here, we integrate information on the edaphoclimatic niches, phylogeny and hydraulic traits of species to model the hydraulic risk of woody plants globally. We combine these models with species distribution records to estimate the hydraulic risk faced by local woody plant species assemblages. Thus, we produce global maps of hydraulic risk and test for its relationship with observed DIM. Our results show that local assemblages modelled as having higher hydraulic risk present a higher probability of DIM. Metrics characterizing this hydraulic risk improve DIM predictions globally, relative to models accounting only for edaphoclimatic predictors or broad functional groupings. The methodology we present here allows mapping of functional trait distributions and elucidation of global macro-evolutionary and biogeographical patterns, improving our ability to predict potential global change impacts on vegetation

Inhalation frequency controls reformatting of mitral/tufted cell odor representations in the olfactory bulb

In mammals, olfactory sensation depends on inhalation, which controls activation of sensory neurons and temporal patterning of central activity. Odor representations by mitral and tufted (MT) cells, the main output from the olfactory bulb (OB), reflect sensory input as well as excitation and inhibition from OB circuits, which may change as sniff frequency increases. To test the impact of sampling frequency on MT cell odor responses, we obtained whole-cell recordings from MT cells in anesthetized male and female mice while varying inhalation frequency via tracheotomy, allowing comparison of inhalation-linked responses across cells. We characterized frequency effects on MT cell responses during inhalation of air and odorants using inhalation pulses and also "playback" of sniffing recorded from awake mice. Inhalation-linked changes in membrane potential were well predicted across frequency from linear convolution of 1 Hz responses; and, as frequency increased, near-identical temporal responses could emerge from depolarizing, hyperpolarizing, or multiphasic MT responses. However, net excitation was not well predicted from 1 Hz responses and varied substantially across MT cells, with some cells increasing and others decreasing in spike rate. As a result, sustained odorant sampling at higher frequencies led to increasing decorrelation of the MT cell population response pattern over time. Bulk activation of sensory inputs by optogenetic stimulation affected MT cells more uniformly across frequency, suggesting that frequency-dependent decorrelation emerges from odor-specific patterns of activity in the OB network. These results suggest that sampling behavior alone can reformat early sensory representations, possibly to optimize sensory perception during repeated sampling.SIGNIFICANCE STATEMENT Olfactory sensation in mammals depends on inhalation, which increases in frequency during active sampling of olfactory stimuli. We asked how inhalation frequency can shape the neural coding of odor information by recording from projection neurons of the olfactory bulb while artificially varying odor sampling frequency in the anesthetized mouse. We found that sampling an odor at higher frequencies led to diverse changes in net responsiveness, as measured by action potential output, that were not predicted from low-frequency responses. These changes led to a reorganization of the pattern of neural activity evoked by a given odorant that occurred preferentially during sustained, high-frequency inhalation. These results point to a novel mechanism for modulating early sensory representations solely as a function of sampling behavior.This work was supported by National Institutes of Health Grants DC06441 and DC013076. We thank C. Zabawa and J. Ball for technical support; J. Fernandez, J. White, and A. Schaefer for advice on recordings; M.W. laboratory members for helpful comments on the manuscript; and D. Wesson for collecting the intranasal pressure data from awake mice. (DC06441 - National Institutes of Health; DC013076 - National Institutes of Health)Published versio