"Invictus".

While attempting to thrombose a pseudoaneurysm, an interventional radiology resident provides important care to a patient beyond the procedure.

Surgeon Perspectives on Benefits and Downsides of Overlapping Surgery: In-depth, Qualitative Interviews.

OBJECTIVE: The aim of the study was to characterize surgeon perspectives regarding the benefits and downsides of conducting overlapping surgery. BACKGROUND: Although surgeons are key stakeholders in current discussions surrounding overlapping surgery, little has been published regarding their opinions on the practice. Further characterization of surgeon perspectives is needed to guide future studies and policy development regarding overlapping surgery. METHODS: Study information was sent to all members of 3 professional surgical societies. Interested individuals were eligible to participate if they identified as attending surgeons in an academic setting who work with trainees. Purposive selection was used to diversify surgeons interviewed across multiple dimensions, including subspecialty and opinion regarding appropriateness of overlapping surgery. In-depth, qualitative interviews were conducted with participants regarding their opinions on overlapping surgery. RESULTS: The 51 surgeons interviewed identified a wide array of potential benefits and disadvantages of overlapping surgery, some of which have not previously been measured, including downsides to surgeon wellness and patient experience, less surgeon control over procedures, and difficulty in scheduling cases. Interviewees often disagreed as to whether overlapping surgery negatively or positively affects each dimension discussed, particularly regarding the impact on resident training. CONCLUSIONS: The utilization of the novel perspectives presented here will allow for targeted assessment of physician perspectives in future quantitative studies and increase the likelihood that variables measured encompass the range of factors that surgeons find meaningful and relevant. Priority areas of future research should include examining effects of overlapping surgery on surgical training and surgeon wellness.

Association between Periprocedural Neutropenia and Early Infection-related Chest Port Removal.

Background Patients who require long-term central venous access can present for port placement with depressed immune function as a result of their treatment or disease process. At present, there is no consensus regarding whether neutropenia at the time of port placement confers a higher risk for early infection-related port removal. Purpose To compare the incidence of early infection-related chest port removal in adults when placed in neutropenic versus nonneutropenic patient groups. Materials and Methods This retrospective cohort study examined 2580 port placements in 1081 men (41.9%) and 1499 women (58.1%) at a single tertiary medical center between June 2007 and July 2017. Mean patient age ± standard deviation was 56 years ± 14 (range, 18-91 years). The electronic medical record was used to identify neutropenia (absolute neutrophil count <1500 cells/mm3) at the time of port placement and incidence of infection-related port removal. Electronic medical record follow-up was conducted for 30 days following port placement. End points were infection-related port removal or death related to port infection within 30 days. Statistical analysis compared the neutropenic (n = 159) and nonneutropenic (n = 2421) patient groups by using a χ2 test for categorical data and a Student t test for continuous variables, with a Fisher exact test to compare incidence of port removal and death related to port infection. Results Ports placed in patients with neutropenia had an infection-related removal rate of 3.8% (six of 159) versus 0.91% (22 of 2421) in patients without neutropenia (P = .003). Patients with neutropenia had a port infection-related death rate of 0.63% (one of 159) versus 0.12% (three of 2421) for patients without neutropenia (P = .22). Conclusion Neutropenia in adults at the time of implantable subcutaneous chest port placement was associated with a higher risk for early infection-related port removal. There was no difference in the incidence of death related to port infection in neutropenic or nonneutropenic populations. © RSNA, 2019 See also the editorial by Johnson in this issue.

MicroRNA-378-mediated suppression of Runx1 alleviates the aggressive phenotype of triple-negative MDA-MB-231 human breast cancer cells.

The Runx1 transcription factor, known for its essential role in normal hematopoiesis, was reported in limited studies to be mutated or associated with human breast tumor tissues. Runx1 increases concomitantly with disease progression in the MMTV-PyMT transgenic mouse model of breast cancer. Compelling questions relate to mechanisms that regulate Runx1 expression in breast cancer. Here, we tested the hypothesis that dysregulation of Runx1-targeting microRNAs (miRNAs) allows for pathologic increase of Runx1 during breast cancer progression. Microarray profiling of the MMTV-PyMT model revealed significant downregulation of numerous miRNAs predicted to target Runx1. One of these, miR-378, was inversely correlated with Runx1 expression during breast cancer progression in mice and in human breast cancer cell lines MCF7 and triple-negative MDA-MB-231 that represent early- and late-stage diseases, respectively. MiR-378 is nearly absent in MDA-MB-231 cells. Luciferase reporter assays revealed that miR-378 binds the Runx1 3' untranslated region (3'UTR) and inhibits Runx1 expression. Functionally, we demonstrated that ectopic expression of miR-378 in MDA-MB-231 cells inhibited Runx1 and suppressed migration and invasion, while inhibition of miR-378 in MCF7 cells increased Runx1 levels and cell migration. Depletion of Runx1 in late-stage breast cancer cells resulted in increased expression of both the miR-378 host gene PPARGC1B and pre-miR-378, suggesting a feedback loop. Taken together, our study identifies a novel and clinically relevant mechanism for regulation of Runx1 in breast cancer that is mediated by a PPARGC1B-miR-378-Runx1 regulatory pathway. Our results highlight the translational potential of miRNA replacement therapy for inhibiting Runx1 in breast cancer.

Spontaneous Formation of Melanin from Dopamine in the Presence of Iron.

Parkinson's disease is associated with degeneration of neuromelanin (NM)-containing substantia nigra dopamine (DA) neurons and subsequent decreases in striatal DA transmission. Dopamine spontaneously forms a melanin through a process called melanogenesis. The present study examines conditions that promote/prevent DA melanogenesis. The kinetics, intermediates, and products of DA conversion to melanin in vitro, and DA melanogenesis under varying levels of Fe3+, pro-oxidants, and antioxidants were examined. The rate of melanogenesis for DA was substantially greater than related catecholamines norepinephrine and epinephrine and their precursor amino acids tyrosine and l-Dopa as measured by UV-IR spectrophotometry. Dopamine melanogenesis was concentration dependent on the pro-oxidant species and Fe3+. Melanogenesis was enhanced by the pro-oxidant hydrogen peroxide (EC50 = 500 µM) and decreased by the antioxidants ascorbate (IC50 = 10 µM) and glutathione (GSH; IC50 = 5 µM). Spectrophotometric results were corroborated by tuning a fast-scan cyclic voltammetry system to monitor DA melanogenesis. Evoked DA release in striatal brain slices resulted in NM formation that was prevented by GSH. These findings suggest that DA melanogenesis occurs spontaneously under physiologically-relevant conditions of oxidative stress and that NM may act as a marker of past exposure to oxidative stress.

Life in the Year 6000 by Santiago Ramón y Cajal: A Translation of an Unpublished "Vacation Story".

In 2006, Laura Otis provided the first English translation of five short stories written by the Spanish artist, neuroscientist, and histologist Santiago Ramón y Cajal. These stories, originally published in 1905 by Cajal under the pseudonym "Dr. Bacteria," are called "Cuentos de vacaciones: narraciones seudocientíficas" or "Vacation Stories: Pseudoscientific Tales." In 1973, a version of Cajal's manuscript "La vida en el año 6000" (Life in the year 6000) was revealed. It had remained in manuscript form since the mid-1880s and appears to be a draft of one of Cajal's unpublished "Cuentos de vacaciones." The present work is a translation of this manuscript, which is archived in the Cajal Institute in Madrid. It details the protagonist's observations, especially regarding advances in science and medicine, when he suddenly awakes in the year 6000 AD.

An AML1-ETO/miR-29b-1 regulatory circuit modulates phenotypic properties of acute myeloid leukemia cells.

Acute myeloid leukemia (AML) is characterized by an aggressive clinical course and frequent cytogenetic abnormalities that include specific chromosomal translocations. The 8;21 chromosomal rearrangement disrupts the key hematopoietic RUNX1 transcription factor, and contributes to leukemia through recruitment of co-repressor complexes to RUNX1 target genes, altered subnuclear localization, and deregulation of the myeloid gene regulatory program. However, a role of non-coding microRNAs (miRs) in t(8;21)-mediated leukemogenesis is minimally understood. We present evidence of an interplay between the tumor suppressor miR-29b-1 and the AML1-ETO (also designated RUNX1-RUNX1T1) oncogene that is encoded by the t(8;21). We find that AML1-ETO and corepressor NCoR co-occupy the miR-29a/b-1 locus and downregulate its expression in leukemia cells. Conversely, re-introduction of miR-29b-1 in leukemia cells expressing AML1-ETO causes significant downregulation at the protein level through direct targeting of the 3' untranslated region of the chimeric transcript. Restoration of miR-29b-1 expression in leukemia cells results in decreased cell growth and increased apoptosis. The AML1-ETO-dependent differentiation block and transcriptional program are partially reversed by miR-29b-1. Our findings establish a novel regulatory circuit between the tumor-suppressive miR-29b-1 and the oncogenic AML1-ETO that controls the leukemic phenotype in t(8;21)-carrying acute myeloid leukemia.