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Peripheral artery disease (PAD) affects millions of people worldwide, presenting with varying symptom severity, including chronic total occlusion of arteries, and occasionally, limb amputation. There are various interventions, such as atherectomy and the use of drug-coated balloons and stents, which have been developed to revascularize affected ischemic regions. However, each interventional approach must be individualized due to a patient's unique underlying conditions. Comorbid conditions, especially diabetes, play a significant role in PAD, as poorly controlled diabetes can accelerate PAD progression. For this reason, an early and accurate diagnosis of PAD is crucial, especially when symptoms may present dissimilar to classic PAD symptoms, often leading to misdiagnosis. The presented cases highlight the tailored interventions to revascularize arteries in patients with diabetic foot wounds utilizing catheters, stents, guidewires, and balloons, made possible after early angiogram. These interventions have been promising in treating PAD patients, and highlight the need for early diagnosis and timely and customized interventions to prevent limb amputation and mitigate potential complications., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tran et al.)

Penetrating brain injury (PBI) is a subtype of traumatic brain injury (TBI) that has been steadily increasing in prevalence and causing significant mortality in trauma patients. In an emergent setting, it is important to determine the mechanism of injury and decide whether a PBI or a blunt TBI has occurred in order to guide diagnostic imaging and subsequent treatment. In cases where a PBI has been likely or has occurred, it is important to initiate treatment expeditiously as rapid interventions have been shown to lead to better outcomes. However, in cases of unwitnessed pediatric trauma, it can be difficult to ascertain the specific method of injury due to a lack of reliable sources. In such cases of unwitnessed trauma, PBI should be included in the differential of any orbitocranial injury. In this series, we present two cases of unwitnessed pediatric orbitocranial injury that highlight the importance of gathering a detailed history, obtaining appropriate imaging studies, and using physician intuition., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic commonly called COVID-19 brought new changes to healthcare delivery in the US. The purpose of this study is to identify the impact of COVID-19 on the delivery of acute surgical care for patients at a Level 1 trauma center during the lockdown period of the pandemic from March 13-May 1 2020., Methods: All trauma admission to the University Medical Center Level 1 Trauma Center from March 13 to May 13, 2020, were retrospectively abstracted and compared to the same period during 2019. Analysis focused on the lockdown period of March 13-May 1, 2020, and compared to the same dates in 2019. Abstracted data included demographics, care timeframes, length of stay, and mortality. The data were analyzed using Chi-Square, Fisher Exact, and the Mann-Whitney U test., Results: A total of 305 (2019) vs. 220 (2020) procedures were analyzed. No significant differences were seen in mean BMI, Injury Severity Score, American Society of Anesthesia Score, and Charlson Comorbidity Index between the two groups. Diagnosis time, interval to surgery, anesthesia time, surgical preparation time, operation time, transit time, mean hospital stay, and mortality were similar., Conclusion: The results of this study demonstrate that the lockdown period of the COVID-19 pandemic did not significantly affect the trauma surgery service line, aside from case volume, at a Level 1 trauma center in West Texas during the lockdown period. Despite changes to healthcare delivery during the pandemic, care of surgical patients was conserved as timely and of high quality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Systemic lupus erythematosus (SLE) is an autoimmune disease with varying dermatological findings. We review a unique presentation of SLE with a literature review. A previously healthy early adolescent female presented with painful, oral mucosal bullae filled with sanguineous fluid. She endorsed a tender right knee, but examination revealed no additional abnormalities. CBC demonstrated severe pancytopaenia. Further workup, including Coombs positive RBCs and positive ANA, anti-Smith, and anti-dsDNA antibodies, confirmed Lupus as the aetiology of this patient's presentation. A form of blistering SLE and resultant thrombocytopaenia was likely responsible for the patient's oral manifestations. After receiving 60 g intravenous immunoglobulin and 3 days high-dose pulse corticosteroids, her dermatological symptoms resolved. Although cases of blistering SLE with mucosal bullae have been described in the literature, this is the first documented case of haemorrhagic mucosal bullae as the presenting symptom of thrombocytopaenia in SLE in a paediatric patient., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Extracellular vesicles (EVs) are released by nearly every cell type and have attracted much attention for their ability to transfer protein and diverse RNA species from donor to recipient cells. Much attention has been given so far to the features of EV short RNAs such as miRNAs. However, while the presence of mRNA and long noncoding RNA (lncRNA) transcripts in EVs has also been reported by multiple different groups, the properties and function of these longer transcripts have been less thoroughly explored than EV miRNA. Additionally, the impact of EV export on the transcriptome of exporting cells has remained almost completely unexamined. Here, we globally investigate mRNA and lncRNA transcripts in endothelial EVs in multiple different conditions., Results: In basal conditions, long RNA transcripts enriched in EVs have longer than average half-lives and distinctive stability-related sequence and structure characteristics including shorter transcript length, higher exon density, and fewer 3' UTR A/U-rich elements. EV-enriched long RNA transcripts are also enriched in HNRNPA2B1 binding motifs and are impacted by HNRNPA2B1 depletion, implicating this RNA-binding protein in the sorting of long RNA to EVs. After signaling-dependent modification of the cellular transcriptome, we observed that, unexpectedly, the rate of EV enrichment relative to cells was altered for many mRNA and lncRNA transcripts. This change in EV enrichment was negatively correlated with intracellular abundance, with transcripts whose export to EVs increased showing decreased abundance in cells and vice versa. Correspondingly, after treatment with inhibitors of EV secretion, levels of mRNA and lncRNA transcripts that are normally highly exported to EVs increased in cells, indicating a measurable impact of EV export on the long RNA transcriptome of the exporting cells. Compounds with different mechanisms of inhibition of EV secretion affected the cellular transcriptome differently, suggesting the existence of multiple EV subtypes with different long RNA profiles., Conclusions: We present evidence for an impact of EV physiology on the characteristics of EV-producing cell transcriptomes. Our work suggests a new paradigm in which the sorting and packaging of transcripts into EVs participate, together with transcription and RNA decay, in controlling RNA homeostasis and shape the cellular long RNA abundance profile., (© 2022. The Author(s).)

Viral infections are known to hijack the transcription and translation of the host cell. However, the extent to which viral proteins coordinate these perturbations remains unclear. Here we used a model system, the human T-cell leukemia virus type 1 (HTLV-1), and systematically analyzed the transcriptome and interactome of key effectors oncoviral proteins Tax and HBZ. We showed that Tax and HBZ target distinct but also common transcription factors. Unexpectedly, we also uncovered a large set of interactions with RNA-binding proteins, including the U2 auxiliary factor large subunit (U2AF2), a key cellular regulator of pre-mRNA splicing. We discovered that Tax and HBZ perturb the splicing landscape by altering cassette exons in opposing manners, with Tax inducing exon inclusion while HBZ induces exon exclusion. Among Tax- and HBZ-dependent splicing changes, we identify events that are also altered in Adult T cell leukemia/lymphoma (ATLL) samples from two independent patient cohorts, and in well-known cancer census genes. Our interactome mapping approach, applicable to other viral oncogenes, has identified spliceosome perturbation as a novel mechanism coordinated by Tax and HBZ to reprogram the transcriptome., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The negative correlation between BPH-size and incidence of prostate cancer (PCa) is well-documented in the literature, however the exact mechanism is not well-understood. The present study uses histo-anatomical imaging to study prostate volume in correlation to prostate capsule thickness, and glandular epithelial cell density within the peripheral zone (PZ)., Materials and Methods: Specimens were selected from radical prostatectomies ranging from 20 to 160 mL based on ease of anatomical reconstruction by the slides. A total of 60 patients were selected and underwent quantitative measurements of prostate capsule thickness and glandular epithelial density within the PZ using computer-based imaging software. Pearson's correlation and a stepwise multiple linear regression analysis was conducted to determine the relationship between these measured parameters and the clinical characteristic of these patients., Results: Pearson's correlation analysis revealed a strongly significant, negative correlation between prostate volume and glandular epithelial cell density (r(58)=-0.554, p<0.001), and a strongly significant, positive correlation between prostate volume and average capsule thickness (r(58)=0.462, p<0.001). Results of multiple regression analysis showed that average glandular epithelial cell density added statistically to this prediction (p<0.05)., Conclusions: The results suggest that growth of the transition zone in BPH causes increased fibrosis of the PZ, leading to atrophy and fibrosis of glandular cells. As 80% of PCa originates from the glandular epithelium within the PZ, this observed phenomenon may explain the inverse correlation between BPH and PCa that is well-documented in the literature., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

ERG family proteins (ERG, FLI1 and FEV) are a subfamily of ETS transcription factors with key roles in physiology and development. In Ewing sarcoma, the oncogenic fusion protein EWS-FLI1 regulates both transcription and alternative splicing of pre-messenger RNAs. However, whether wild-type ERG family proteins might regulate splicing is unknown. Here, we show that wild-type ERG proteins associate with spliceosomal components, are found on nascent RNAs, and induce alternative splicing when recruited onto a reporter minigene. Transcriptomic analysis revealed that ERG and FLI1 regulate large numbers of alternative spliced exons (ASEs) enriched with RBFOX2 motifs and co-regulated by this splicing factor. ERG and FLI1 are associated with RBFOX2 via their conserved carboxy-terminal domain, which is present in EWS-FLI1. Accordingly, EWS-FLI1 is also associated with RBFOX2 and regulates ASEs enriched in RBFOX2 motifs. However, in contrast to wild-type ERG and FLI1, EWS-FLI1 often antagonizes RBFOX2 effects on exon inclusion. In particular, EWS-FLI1 reduces RBFOX2 binding to the ADD3 pre-mRNA, thus increasing its long isoform, which represses the mesenchymal phenotype of Ewing sarcoma cells. Our findings reveal a RBFOX2-mediated splicing regulatory function of wild-type ERG family proteins, that is altered in EWS-FLI1 and contributes to the Ewing sarcoma cell phenotype., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Introduction: The inverse relationship between benign prostate hypertrophy and incidence/severity of prostate cancer is well documented in the clinical literature. However, this phenomenon is not well understood. The purpose of this review is to offer an update in the evolving hypothesis of how benign prostate hypertrophy may be protective in prostate cancer., Methods: A literature search was conducted on PubMed limited to articles published within the past 10 years with the search criteria of "interaction" AND "benign prostate hypertrophy" AND "prostate cancer" as well as the key words of this paper., Results: Nine articles from the literature search met inclusion criteria. The articles analyze the prostate on parameters of peripheral zone volume, glandular tissue density and prostate capsule thickness. All 9 articles described peripheral zone atrophy and transition zone hypertrophy in benign prostate hypertrophy patients., Conclusions: As the transition zone grows in benign prostate hypertrophy, volume and glandular density of the peripheral zone as well as the prostate capsule undergo significant changes. The disease processes outlined in this review support the hypothesis that the growing transition zone compresses the peripheral zone against the prostatic capsule causing secondary atrophy, apoptosis, and necrosis of the peripheral zone's glandular tissue. If this hypertrophy-induced disease process of glandular tissue atrophy within the peripheral zone is confirmed in future studies, it will have relevant clinical implications on the diagnosis and treatment of benign prostate hypertrophy and prostate cancer.