Emergency department imaging utilization post-transcatheter aortic valve replacement: single institution 7-year experience.

PURPOSE: This study aims to highlight presentations, acute findings and imaging phenotypes of patients presenting to the emergency department (ED) within 30 days of a transcatheter aortic valve replacement (TAVR). METHODS: A retrospective review of patients diagnosed with aortic valve disease who underwent a TAVR between Jan 2015 and Nov 2021 at a large academic medical center was completed. From an initial 1271 patients, 146 were included based on their presentation to the ED within 30 days post-TAVR procedure. Patient data, including ED presentation details and imaging results, were recorded and de-identified. RESULTS: Of the 146 post-TAVR patients, there were 168 ED visits within 30 days. The median time to ED after TAVR was 12 days. Respiratory symptoms were the most common complaint (27%). Neurological (23%) and cardiovascular symptoms (18%) followed. Cross-sectional imaging was conducted 250 times across visits, with an average of 1.7 scans per patient. CTs were most frequently used, followed by ultrasounds, especially echocardiograms and duplex extremity vasculature ultrasounds. 30.1% of patients had acute findings from imaging. Specific findings included heart failure (5.5%), access site complications (5.5%), pneumonia (5.5%), intracranial pathologies (3.4% for strokes and 0.7% for hematoma), and pleural effusion (3.4%). Echocardiograms and CTA chest were most associated with significant acute findings. CONCLUSION: Our study highlights the vital role of early and accurate imaging in post-TAVR patients within 30 days post-procedure. As transcatheter approaches rise in popularity, emergency radiologists become instrumental in diagnosing common post-procedural presentations. Continued research is essential to devise post-discharge strategies to curtail readmissions and related costs. Proper imaging ensures prompt, effective care, enhancing overall patient outcomes.

A hybrid energy harvester inspired by bionic flapping wing structure based on magnetic levitation.

A hybrid energy harvester based on magnetic levitation is inspired by the structure of the flapping wing, which consists of two parts: one is a flapping wing structure mounted with a piezoelectric sheet, which can achieve piezoelectric energy harvesting; the other is an intermediate muscle unit, which is vertically arranged by three groups of permanent magnets to achieve magnetic levitation electromagnetic energy harvesting. An electromechanical-electromagnetic coupling model of this harvester is established based on electromechanical coupling characteristics. The simulation analysis can evaluate the magnetic field distribution and nonlinear magnetic properties and also analyze its effects on the output performance. Several experiments are designed to verify the effectiveness of the hybrid energy harvesting structure and to check the influence of the number of magnets on the output power. The maximum output power of the proposed structure can generate 13.61 mW at 4.5 Hz excitation.

Analysis of ChatGPT publications in radiology: Literature so far.

OBJECTIVE: To perform a detailed qualitative and quantitative analysis of the published literature on ChatGPT and radiology in the nine months since its public release, detailing the scope of the work in the short timeframe. METHODS: A systematic literature search was carried out of the MEDLINE, EMBASE databases through August 15, 2023 for articles that were focused on ChatGPT and imaging/radiology. Articles were classified into original research and reviews/perspectives. Quantitative analysis was carried out by two experienced radiologists using objective scoring systems for evaluating original and non-original research. RESULTS: 51 articles were published involving ChatGPT and radiology/imaging dating from 26 Jan 2023 to the last article published on 14 Aug 2023. 23 articles were original research while the rest included reviews/perspectives or brief communications. For quantitative analysis scored by two readers, we included 23 original research and 17 non-original research articles (after excluding 11 letters as responses to previous articles). Mean score for original research was 3.20 out of 5 (across five questions), while mean score for non-original research was 1.17 out of 2 (across six questions). Mean score grading performance of ChatGPT in original research was 3.20 out of five (across two questions). DISCUSSION: While it is early days for ChatGPT and its impact in radiology, there has already been a plethora of articles talking about the multifaceted nature of the tool and how it can impact every aspect of radiology from patient education, pre-authorization, protocol selection, generating differentials, to structuring radiology reports. Most articles show impressive performance of ChatGPT which can only improve with more research and improvements in the tool itself. There have also been several articles which have highlighted the limitations of ChatGPT in its current iteration, which will allow radiologists and researchers to improve these areas.

Radiology Reading Room for the Future: Harnessing the Power of Large Language Models Like ChatGPT.

Radiology has usually been the field of medicine that has been at the forefront of technological advances, often being the first to wholeheartedly embrace them. Whether it's from digitization to cloud side architecture, radiology has led the way for adopting the latest advances. With the advent of large language models (LLMs), especially with the unprecedented explosion of freely available ChatGPT, time is ripe for radiology and radiologists to find novel ways to use the technology to improve their workflow. Towards this, we believe these LLMs have a key role in the radiology reading room not only to expedite processes, simplify mundane and archaic tasks, but also to increase the radiologist's and radiologist trainee's knowledge base at a far faster pace. In this article, we discuss some of the ways we believe ChatGPT, and the likes can be harnessed in the reading room.

Psychological Safety as a New ACGME Requirement: A Comprehensive All-in-One Guide to Radiology Residency Programs.

RATIONALE AND OBJECTIVES: With the Accreditation Council for Graduate Medical Education recently updating their common program requirements to include components of psychological safety as a core principle, radiology training programs and academic radiology institutions will need to evaluate psychological safety within their residency programs and implement practices to sustain a safety culture. This article reviews current literature to present a concise guide for radiology programs on best practices for implementing psychological safety, considering the plethora of literature that is available. MATERIALS AND METHODS: We searched PubMed for published studies evaluating safety culture in medical education and residency. The key words used were Psychological Safety, Education, Radiology, Workplace Culture, and Leadership. RESULTS: Ninety two studies were reviewed that contributed to the topics examined throughout this manuscript, including a brief history of psychological safety, evolving challenges, and a summation of best practices at the institutional, interpersonal, and individual levels that can result in a sustainable psychologically safe culture for radiology residents. CONCLUSION: This article will highlight unique considerations pertinent to a radiology residency program, including suggestions for creating a less stressful environment during case conferences, fostering and supporting residents who are struggling, and inclusive psychological safety practices that also consider non-resident contributors to a residency program, such as attending physician faculty and non-physician radiology technicians.

Intraoperative Diagnosis of Serosal Invasion in Gastric Cancer by Magnifying Endoscopy with Narrow-Band Imaging for Intraoperative Measurement Decision.

Purpose: To establish a precise diagnostic method for serosal invasion in gastric cancer (GC) during surgery using therapeutic measures, and facilitate quick decision-making. Methods: A total of 19 GC patients treated in the department of gastrointestinal surgery of Fujian Provincial Hospital between April 2019 and December 2020 were enrolled. An electronic gastroscopy with a magnifying endoscope with narrow-band imaging was used to photograph the serosal surface of the GC lesion site and the normal gastric wall around the lesion during surgery. The endoscopic diagnosis was confirmed on the basis of the microvascular phenotype of the serosal surface and validated by comparison with the pathological diagnosis. Results: Under the specific endoscopy, serosal invasion, including subserosal tissue invasion and serosal layer invasion, was diagnosed by observing the capillary morphology change, and capillary diameter and density increase. According to the pathological diagnosis, the accuracy of serosal invasion diagnosis was 94.7%, the sensitivity was 100%, the specificity was 75%, the positive predictive value was 93.8%, and the negative predictive value was 100%. To further distinguish the subserosal tissue invasion and serosal layer invasion, the magnifying endoscope with narrow-band imaging possessed a 78.9% accuracy by distinguishing irregular changes in microvessels. Conclusions: Magnifying endoscope with narrow-band imaging is less time-consuming than pathological diagnosis. Intraoperative diagnosis using microvascular observation can accurately detect serosal invasion. It is of value for the intraoperative diagnosis in GC patients.

Dynamin-like protein 1 cleavage by calpain in Alzheimer's disease.

Abnormal mitochondrial dynamics contributes to mitochondrial dysfunction in Alzheimer's disease (AD), yet the underlying mechanism remains elusive. In the current study, we reported that DLP1, the key mitochondrial fission GTPase, is a substrate of calpain which produced specific N-terminal DLP1 cleavage fragments. In addition, various AD-related insults such as exposure to glutamate, soluble amyloid-ß oligomers, or reagents inducing tau hyperphosphorylation (i.e., okadaic acid) led to calpain-dependent cleavage of DLP1 in primary cortical neurons. DLP1 cleavage fragments were found in cortical neurons of CRND8 APP transgenic mice which can be inhibited by calpeptin, a potent small molecule inhibitor of calpain. Importantly, these N-terminal DLP1 fragments were also present in the human brains, and the levels of both full-length and N-terminal fragments of DLP1 and the full-length and calpain-specific cleavage product of spectrin were significantly reduced in AD brains along with significantly increased calpain. These results suggest that calpain-dependent cleavage is at least one of the posttranscriptional mechanisms that contribute to the dysregulation of mitochondrial dynamics in AD.

Mfn2 ablation causes an oxidative stress response and eventual neuronal death in the hippocampus and cortex.

BACKGROUND: Mitochondria are the organelles responsible for energy metabolism and have a direct impact on neuronal function and survival. Mitochondrial abnormalities have been well characterized in Alzheimer Disease (AD). It is believed that mitochondrial fragmentation, due to impaired fission and fusion balance, likely causes mitochondrial dysfunction that underlies many aspects of neurodegenerative changes in AD. Mitochondrial fission and fusion proteins play a major role in maintaining the health and function of these important organelles. Mitofusion 2 (Mfn2) is one such protein that regulates mitochondrial fusion in which mutations lead to the neurological disease. METHODS: To examine whether and how impaired mitochondrial fission/fusion balance causes neurodegeneration in AD, we developed a transgenic mouse model using the CAMKII promoter to knockout neuronal Mfn2 in the hippocampus and cortex, areas significantly affected in AD. RESULTS: Electron micrographs of neurons from these mice show swollen mitochondria with cristae damage and mitochondria membrane abnormalities. Over time the Mfn2 cKO model demonstrates a progression of neurodegeneration via mitochondrial morphological changes, oxidative stress response, inflammatory changes, and loss of MAP2 in dendrites, leading to severe and selective neuronal death. In this model, hippocampal CA1 neurons were affected earlier and resulted in nearly total loss, while in the cortex, progressive neuronal death was associated with decreased cortical size. CONCLUSIONS: Overall, our findings indicate that impaired mitochondrial fission and fusion balance can cause many of the neurodegenerative changes and eventual neuron loss that characterize AD in the hippocampus and cortex which makes it a potential target for treatment strategies for AD.

The inhibition of TDP-43 mitochondrial localization blocks its neuronal toxicity.

Genetic mutations in TAR DNA-binding protein 43 (TARDBP, also known as TDP-43) cause amyotrophic lateral sclerosis (ALS), and an increase in the presence of TDP-43 (encoded by TARDBP) in the cytoplasm is a prominent histopathological feature of degenerating neurons in various neurodegenerative diseases. However, the molecular mechanisms by which TDP-43 contributes to ALS pathophysiology remain elusive. Here we have found that TDP-43 accumulates in the mitochondria of neurons in subjects with ALS or frontotemporal dementia (FTD). Disease-associated mutations increase TDP-43 mitochondrial localization. In mitochondria, wild-type (WT) and mutant TDP-43 preferentially bind mitochondria-transcribed messenger RNAs (mRNAs) encoding respiratory complex I subunits ND3 and ND6, impair their expression and specifically cause complex I disassembly. The suppression of TDP-43 mitochondrial localization abolishes WT and mutant TDP-43-induced mitochondrial dysfunction and neuronal loss, and improves phenotypes of transgenic mutant TDP-43 mice. Thus, our studies link TDP-43 toxicity directly to mitochondrial bioenergetics and propose the targeting of TDP-43 mitochondrial localization as a promising therapeutic approach for neurodegeneration.

Upregulation of Glutaredoxin-1 Activates Microglia and Promotes Neurodegeneration: Implications for Parkinson's Disease.

AIMS: Neuroinflammation and redox dysfunction are recognized factors in Parkinson's disease (PD) pathogenesis, and diabetes is implicated as a potentially predisposing condition. Remarkably, upregulation of glutaredoxin-1 (Grx1) is implicated in regulation of inflammatory responses in various disease contexts, including diabetes. In this study, we investigated the potential impact of Grx1 upregulation in the central nervous system on dopaminergic (DA) viability. RESULTS: Increased GLRX copy number in PD patients was associated with earlier PD onset, and Grx1 levels correlated with levels of proinflammatory tumor necrosis factor-alpha (TNF-α) in mouse and human brain samples, prompting mechanistic in vitro studies. Grx1 content/activity in microglia was upregulated by lipopolysaccharide (LPS), or TNF-α, treatment. Adenoviral overexpression of Grx1, matching the extent of induction by LPS, increased microglial activation; Grx1 silencing diminished activation. Selective inhibitors/probes of nuclear factor κB (NF-κB) activation revealed glrx1 induction to be mediated by the Nurr1/NF-κB axis. Upregulation of Grx1 in microglia corresponded to increased death of neuronal cells in coculture. With a mouse diabetes model of diet-induced insulin resistance, we found upregulation of Grx1 in brain was associated with DA loss (decreased tyrosine hydroxylase [TH]; diminished TH-positive striatal axonal terminals); these effects were not seen with Grx1-knockout mice. INNOVATION: Our results indicate that Grx1 upregulation promotes neuroinflammation and consequent neuronal cell death in vitro, and synergizes with proinflammatory insults to promote DA loss in vivo. Our findings also suggest a genetic link between elevated Grx1 and PD development. CONCLUSION: In vitro and in vivo data suggest Grx1 upregulation promotes neurotoxic neuroinflammation, potentially contributing to PD. Antioxid. Redox Signal. 25, 967-982.

Estrogen receptor-α is localized to neurofibrillary tangles in Alzheimer's disease.

The female predominance for developing Alzheimer disease (AD) suggests the involvement of gender specific factor(s) such as a reduced estrogen-estrogen receptor signaling in the pathogenesis of AD. The potential role of ERα in AD pathogenesis has been explored by several groups with mixed results. We revisited this issue of expression and distribution of ERα in AD brain using a specific ERα antibody. Interestingly, we found that ERα co-localized with neurofibrillary pathology in AD brain and further demonstrated that ERα interacts with tau protein in vivo. Immunoprecipitaion experiments found increased ERα-tau interaction in the AD cases, which may account for ERα being sequestered in neuronal tau pathology. Indeed, tau overexpression in M17 cells leads to interruption of estrogen signaling. Our data support the idea that sequestration of ERα by tau pathology underlies the loss of estrogen neuroprotection during the course of AD.

Structure and mechanism of a nitrate transporter.

The nitrate/nitrite transporters NarK and NarU play an important role in nitrogen homeostasis in bacteria and belong to the nitrate/nitrite porter family (NNP) of the major facilitator superfamily (MFS) fold. The structure and functional mechanism of NarK and NarU remain unknown. Here, we report the crystal structure of NarU at a resolution of 3.1 Å and systematic biochemical characterization. The two molecules of NarU in an asymmetric unit exhibit two distinct conformational states: occluded and partially inward-open. The substrate molecule nitrate appears to be coordinated by four highly conserved, charged, or polar amino acids. Structural and biochemical analyses allowed the identification of key amino acids that are involved in substrate gating and transport. The observed conformational differences of NarU, together with unique sequence features of the NNP family transporters, suggest a transport mechanism that might deviate from the canonical rocker-switch model.

Polycomb group protein PHF1 regulates p53-dependent cell growth arrest and apoptosis.

Polycomb group protein PHF1 is well known as a component of a novel EED-EZH2·Polycomb repressive complex 2 complex and plays important roles in H3K27 methylation and Hox gene silencing. PHF1 is also involved in the response to DNA double-strand breaks in human cells, promotes nonhomologous end-joining processes through interaction with Ku70/Ku80. Here, we identified another function of PHF1 as a potential p53 pathway activator in a pathway screen using luminescence reporter assay. Subsequent studies showed PHF1 directly interacts with p53 proteins both in vivo and in vitro and co-localized in nucleus. PHF1 binds to the C-terminal regulatory domain of p53. Overexpression of PHF1 elevated p53 protein level and prolonged its turnover. Knockdown of PHF1 reduced p53 protein level and its target gene expression both in normal state and DNA damage response. Mechanically, PHF1 protects p53 proteins from MDM2-mediated ubiquitination and degradation. Furthermore, we showed that PHF1 regulates cell growth arrest and etoposide-induced apoptosis in a p53-dependent manner. Finally, PHF1 expression was significantly down-regulated in human breast cancer samples. Taken together, we establish PHF1 as a novel positive regulator of the p53 pathway. These data shed light on the potential roles of PHF1 in tumorigenesis and/or tumor progression.

RLIM interacts with Smurf2 and promotes TGF-ß induced U2OS cell migration.

TGF-ß (transforming growth factor-ß), a pleiotropic cytokine that regulates diverse cellular processes, has been suggested to play critical roles in cell proliferation, migration, and carcinogenesis. Here we found a novel E3 ubiquitin ligase RLIM which can directly bind to Smurf2, enhancing TGF-ß responsiveness in osteosarcoma U2OS cells. We constructed a U2OS cell line stably over-expressing RLIM and demonstrated that RLIM promoted TGF-ß-driven migration of U2OS cells as tested by wound healing assay. Our results indicated that RLIM is an important positive regulator in TGF-ß signaling pathway and cell migration.

Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex.

Mitofusins (Mfn1 and Mfn2) are outer mitochondrial membrane proteins involved in regulating mitochondrial dynamics. Mutations in Mfn2 cause Charcot-Marie-Tooth disease (CMT) type 2A, an inherited disease characterized by degeneration of long peripheral axons, but the nature of this tissue selectivity remains unknown. Here, we present evidence that Mfn2 is directly involved in and required for axonal mitochondrial transport, distinct from its role in mitochondrial fusion. Live imaging of neurons cultured from Mfn2 knock-out mice or neurons expressing Mfn2 disease mutants shows that axonal mitochondria spend more time paused and undergo slower anterograde and retrograde movements, indicating an alteration in attachment to microtubule-based transport systems. Furthermore, Mfn2 disruption altered mitochondrial movement selectively, leaving transport of other organelles intact. Importantly, both Mfn1 and Mfn2 interact with mammalian Miro (Miro1/Miro2) and Milton (OIP106/GRIF1) proteins, members of the molecular complex that links mitochondria to kinesin motors. Knockdown of Miro2 in cultured neurons produced transport deficits identical to loss of Mfn2, indicating that both proteins must be present at the outer membrane to mediate axonal mitochondrial transport. In contrast, disruption of mitochondrial fusion via knockdown of the inner mitochondrial membrane protein Opa1 had no effect on mitochondrial motility, indicating that loss of fusion does not inherently alter mitochondrial transport. These experiments identify a role for mitofusins in directly regulating mitochondrial transport and offer important insight into the cell type specificity and molecular mechanisms of axonal degeneration in CMT2A and dominant optic atrophy.