Development of rhesus macaque astrocyte cell lines supporting infection with a panel of viruses.

Non-human primate (NHP)-based model systems are highly relevant for biomedical research. However, only few NHP cell lines are available and the generation of additional cell lines is an urgent need to help in the refinement and replacement of these models. Using lentiviral transduction of c-Fos, we established cell lines from the brain of rhesus macaques (Macaca mulatta). Transcriptome analysis revealed that these cell lines are closely related to astrocytes, which was confirmed by immunoblot and immunofluorescence microscopy detecting expression of the astrocyte marker glial fibrillary acidic protein (GFAP). Quantitative real-time PCR (qRT-PCR) demonstrated that major pathways of the interferon (IFN) system are intact. Using retroviral pseudotypes we found that the cell lines are susceptible to entry driven by the glycoproteins of vesicular stomatitis virus (VSV), lymphocytic choriomeningitis virus (LCMV) and to a lesser extent influenza A virus (IAV). Finally, these cells supported growth of Zika virus (ZIKV) and Papiine alphaherpesvirus 2 (PaHV2). In summary, we developed IFN-responsive cell lines from the rhesus macaque brain that allowed entry driven by several viral glycoproteins and were permissive to infection with ZIKV and a primate simplexvirus. These cell lines will be useful for efforts to analyze neurotropic viral infections in rhesus macaque models.

A Lost Bullet in the Coronary Sinus: A Cautionary Tale.

We present a case of venous bullet embolism to the right atrium following a gunshot wound (GSW) to the abdomen. A 53-year-old male presented after a GSW to the abdomen. His workup included a computed tomography (CT) scan demonstrating an aortic injury with aortocaval fistula. A radio-opaque object consistent with a bullet was visualized in the right atrium. First, this case details an important decision, choice of surgery versus an interventional approach. After repair of the aortocaval fistula, the patient underwent a planned attempt to extract the bullet through a right lateral thoracotomy approach utilizing cardiopulmonary bypass to facilitate a right atriotomy. Intraoperatively, the team was not able to localize the bullet in the right atrium despite fluoroscopic evaluation. A postoperative CT scan demonstrated that the bullet had migrated into the coronary sinus. Lastly, this case demonstrates successful positioning maneuvers to dislodge the bullet out of the heart and into the inferior vena cava, allowing for the endovascular extraction of the bullet.

Development of immortalized rhesus macaque kidney cells supporting infection with a panel of viruses.

Non-human primate (NHP)-based model systems faithfully reproduce various viral diseases including Ebola, influenza, AIDS and Zika. However, only a small number of NHP cell lines are available and generation of additional cell lines could help to refine these models. We immortalized rhesus macaque kidney cells by lentiviral transduction with a vector encoding telomerase reverse transcriptase (TERT) and report the generation of three TERT-immortalized cell lines derived from rhesus macaque kidney. Expression of the kidney podocyte marker podoplanin on these cells was demonstrated by flow cytometry. Quantitative real-time PCR (qRT-PCR) was employed to demonstrate induction of MX1 expression upon stimulation with interferon (IFN) or viral infection, suggesting a functional IFN system. Further, the cell lines were susceptible to entry driven by the glycoproteins of vesicular stomatitis virus, influenza A virus, Ebola virus, Nipah virus and Lassa virus as assessed by infection with retroviral pseudotypes. Finally, these cells supported growth of Zika virus and the primate simplexviruses Cercopithecine alphaherpesvirus 2 and Papiine alphaherpesvirus 2. In summary, we developed IFN-responsive rhesus macaque kidney cell lines that allowed entry driven by diverse viral glycoproteins and were permissive to infection with Zika virus and primate simplexviruses. These cell lines will be useful for efforts to analyze viral infections of the kidney in macaque models.

A Comprehensive Research Schema for the Characterization of Aortic Aneurysms.

A robust, accurate, and standardized approach to measurement of the aorta is critical to improve the predictive accuracy of these aortic measurements, and to investigate other aortic imaging biomarkers. Developing a comprehensive and generic schema for characterization of the aorta to enable investigators to standardize data that are collected across all aorta research. A systematic review of the literature was conducted to identify and assess schemata of aortic measurement and description. The schemata were reported and discussed to guide the synthesis of a comprehensive schema. We propose the International College of Angiology Aortic Research Schema as a comprehensive design that fills the gaps left behind by previously reported schemata. It is intended to be applicable for all clinically relevant purposes, including endograft development for aneurysm repair and for the accurate characterization of the aortic anatomy. This schema divides the aorta into 14 segments and 2 sections (thoracic and abdominal aortas). The segmentation proposed can be used in addition to specific measurements taken for any aneurysm including the neck, and maximal and minimal diameters of the aneurysm.

Clinical significance of the hemodynamic gain index in patients undergoing exercise stress testing and coronary computed tomography angiography.

BACKGROUND: Many hemodynamic parameters provide limited information regarding obstructive coronary artery disease (CAD) during exercise stress testing particularly when exercise is suboptimal. Hemodynamic gain index (HGI) is a recent sensitive indicator of ischemia and has been associated with increased mortality. This study evaluated the clinical impact of HGI in patients who underwent concomitant exercise stress testing and coronary computed tomography angiography (CCTA). METHODS: A total of 284 consecutive patients from the executive health program between 2010 and 2018 were identified. Resting and peak heart rate (HR) as well as systolic blood pressure (SBP) measurements were recorded. Framingham risk score (FRS), Duke treadmill score (DTS) and HGI [Formula: see text] were calculated. The latter was divided into quartiles. CCTA was used as a reference test to detect any CAD. Multivariate analysis and artificial neural network were used to determine the independent predictors of obstructive CAD. RESULTS: Mean age was 53 ± 12 years with 83% male. Mean HGI was 1.74 ± 0.67, with cut-off value of severely blunted HGI ≤ 1.25 (Quartile 4). Patients with severely blunted HGI were older, had higher FRS, and worse DTS. Patients with obstructive CAD had lower HGI when compared to those with normal CCTA/non-obstructive CAD (1.36 ± 0.53 vs. 1.77 ± 0.67, P = 0.005), and showed a higher prevalence of severely blunted HGI (44% vs. 22%, P = 0.019). After adjusting for traditional risk factors, HGI remained an independent predictor of obstructive CAD while severely blunted HGI was associated with threefold increased odds of having obstructive CAD (P = 0.05). Using artificial intelligence analysis, severely blunted HGI independently predicted obstructive CAD with an area under the curve of 0.83 and 0.96, and normalized importance of HGI of 100% and 63%, respectively for different models. CONCLUSIONS: Among patients who underwent concomitant exercise stress testing and CCTA, severely blunted HGI independently predicted obstructive CAD after multivariate adjustment for traditional risk factors.

Impact of intravenous access site on attenuation for thoracic computed tomographic angiography: A time-matched, nested, case-control study.

BACKGROUND: The objective of this study was to evaluate whether the choice of intravenous access (IVA) site affects aortic attenuation during thoracic computed tomographic angiography (T-CTA) and any associated risks with intravenous device placement. METHODS: All T-CTA exams performed between 1/1/2013 and 8/14/2015 were retrospectively reviewed to identify those performed with contrast media injection via alternative (i.e. non-antecubital) IVA (n = 1769). Using time matching, antecubital IVA exams (n = 1769) were selected as controls. For each exam, attenuation was measured in the ascending aorta. Patient and technical data was subsequently collected from all 3538 patients included in this study. Multiple linear regression was used to determine if IVA site affected attenuation. Lastly, data related to extravasations for the entire T-CTA cohort were collected and compared. RESULTS: Hand/wrist, arm, and central venous access device IVA were all equivalent to antecubital IVA in terms of attenuation (P = 0.579, P = 0.599, and P = 0.522 respectively). Forearm and intraosseous IVA had significantly higher attenuation (P = 0.010 and P = 0.002, respectively) than antecubital IVA. Right-sided IVA was associated with a small attenuation increase of 11 Hounsfield Units (P < 0.001) compared to left-sided IVA. In terms of extravasation, antecubital IVA was equivalent to hand/wrist, forearm, and upper arm IVA (P = 0.778, P = 0.060, and P = 0.090 respectively). CONCLUSIONS: Satisfactory aortic attenuation achieved with non-antecubital IVA is equivalent to attenuation achieved with antecubital IVA for T-CTA imaging. The risk of contrast media extravasation in peripheral IVA devices was relatively low, however, appropriate IVA site selection should be considered an important factor for successful administration of contrast media for future imaging studies. This prevents undue harm to patients through preventable device failures when using a peripheral IV device in areas of high flexion/range of movements undergoing pressure injection for contrast media.

Perivascular adipose tissue in autoimmune rheumatic diseases.

Perivascular adipose tissue (PVAT) resides at the outermost boundary of the vascular wall, surrounding most conduit blood vessels, except for the cerebral vessels, in humans. A growing body of evidence suggests that inflammation localized within PVAT may contribute to the pathogenesis of cardiovascular disease (CVD). Patients with autoimmune rheumatic diseases (ARDs), e.g., systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriasis, etc., exhibit heightened systemic inflammation and are at increased risk for CVD. Data from clinical studies in patients with ARDs support a linkage between dysfunctional adipose tissue, and PVAT in particular, in disease pathogenesis. Here, we review the data linking PVAT to the pathogenesis of CVD in patients with ARDs, focusing on the role of novel PVAT imaging techniques in defining disease risk and responses to biological therapies.

Low Turnover Renal Osteodystrophy With Abnormal Bone Quality and Vascular Calcification in Patients With Mild-to-Moderate CKD.

Introduction: Limited information is available on renal osteodystrophy (ROD) and vascular calcification (VC) during early chronic kidney disease (CKD). This study was designed to evaluate ROD and VC in 32 patients with CKD stages II to IV. Methods: Patients underwent dual-energy X-ray absorptiometry (DXA) for assessment of bone mineral density (BMD) and trabecular bone score (TBS), thoracic computed tomography for VC scoring using the Agatston method, and anterior iliac crest bone biopsy for mineralized bone histology, histomorphometry, and Fourier transform infrared spectroscopy (FTIR). Classical and novel bone markers were determined in the blood. Results: Mean estimated glomerular filtration rate (eGFR) was 44 ± 16 ml/min per 1.73 m2. Of the patients, 84% had low bone turnover. In Whites, eGFR correlated negatively with the turnover parameter activation frequency (Ac.f) (r -0.48, P = 0.019) and with parameters of bone formation. Most patients had VC (>80%) which correlated positively with levels of phosphorus, c-terminal fibroblast growth factor-23, and activin. Aortic calcifications (ACs) correlated negatively with bone formation rate (BFR) and Ac.f (rho -0.62, -0.61, P < 0.001). TBS correlated negatively with coronary calcification (rho -0.42, P = 0.019) and AC (rho -0.57, P = 0.001). These relationships remained after adjustment of age. The mineral-to-matrix ratio, an FTIR metric reflecting bone quality, was negatively related to Ac.f and positively related to AC. Conclusion: Low bone turnover and VC are predominant in early stages of CKD. This is the first study demonstrating mineral abnormalities indicating reduced bone quality in these stages of CKD.

Complete postsurgical left ventricular-aortic discontinuity and pseudoaneurysm formation.

BACKGROUND: Left ventricular outflow tract pseudoaneurysm is a rare but potentially fatal complication of aortic valve replacement, infective endocarditis (IE), and suture dehiscence. Left ventricular-aortic discontinuity is a severe and uncommon manifestation of IE. For patients who have a long-standing history of endocarditis, periannular lesions in the aortic valve may rupture, leading to the rare occurrence of complete, or total, left ventricular-aortic discontinuity. METHODS: We present a case of complete postoperative left ventricular-aortic discontinuity and massive circumferential left ventricular outflow tract pseudoaneurysm discovered during a 3-month follow-up visit. Appropriate consent was obtained from all parties before submission of this case report. RESULTS: Postoperative cardiac computed tomography of a patient demonstrated dehiscence of a recently placed surgical aortic valve from the left ventricular outflow tract, with massive circumferential pseudoaneurysm formation. Only a small remnant of the membranous interventricular septum connected the aortic root to the heart, informing the diagnosis of complete left ventricular-aortic discontinuity. CONCLUSION: The clinical presentation of a left ventricular outflow tract pseudoaneurysm with concomitant left ventricular-aortic discontinuity is commonly nonspecific or clinically silent; thus, it requires a high index of suspicion and use of multimodality imaging for diagnosis and management.

Impact of pixel value truncation on image quality of low dose chest CT.

PURPOSE: In some noisy low dose CT lung cancer screening images, we noticed that the CT density values of air were increased and the visibility of emphysema was distinctly decreased. By examining histograms of these images, we found that the CT density values were truncated at -1024 HU. The purpose of this study was to investigate the effect of pixel value truncation on the visibility of emphysema using mathematical models. METHODS AND MATERIALS: Assuming CT noise follows a normal distribution, we derived the relationship between the mean CT density value and the standard deviation (SD) when the pixel values below -1024 HU are truncated and replaced by -1024 HU. To validate our mathematical model, 20 untruncated phantom CT images were truncated by simulation, and the mean CT density values and SD of air in the images were measured and compared with the theoretical values. In addition, the mean CT density values and SD of air were measured in 100 cases of real clinical images obtained by GE, Siemens, and Philips scanners, respectively, and the agreement with the theoretical values was examined. Next, the contrast-to-noise ratio (CNR) between air (-1000 HU) and lung parenchyma (-850 HU) was derived from the mathematical model in the presence and absence of truncation as a measure of the visibility of emphysema. In addition, the radiation dose ratios required to obtain the same CNR in the case with and without truncation were also calculated. RESULTS: The mathematical model revealed that when the pixel values are truncated, the mean CT density values are proportional to the noise magnitude when the magnitude exceeds a certain level. The mean CT density values and SD measured in the images with pixel values truncated by simulation and in the real clinical images acquired by GE and Philips scanners agreed well with the theoretical values from our mathematical model. In the Siemens images, the measured and theoretical values agreed well when a portion of the truncated values were replaced by random values instead of simply replacing by -1024 HU. The CNR of air and lung parenchyma was lowered by truncating CT density values compared to that of no truncation. Furthermore, it was found that higher radiation dose was required to obtain the same CNR with truncation as without. As an example, when the noise SD was 60 HU, the radiation dose required for the GE and Philips truncation method was about 1.2 times higher than that without truncation, and that for the Siemens truncation method was about 1.4 times higher. CONCLUSIONS: It was demonstrated mathematically that pixel value truncation causes a brightening of the mean CT density value and decreases the CNR of emphysema. Our results indicate that it is advisable to turn off truncation at -1024 HU, especially when scanning at low and ultra-low radiation doses in the thorax.

Characterisation of an Anti-Vaccinia Virus F13 Single Chain Fragment Variable from a Human Anti-Vaccinia Virus-Specific Recombinant Immunoglobulin Library.

Vaccinia virus (VACV) belongs to the genus Orthopoxvirus of the family Poxviridae. There are four different forms of infectious virus particles: intracellular mature virus (IMV), intracellular en-veloped virus (IEV), cell-associated enveloped virus (CEV) and extracellular enveloped virus (EEV). The F13 protein occupies the inner side of the CEV- and EEV-membranes and the outer side of the IEV-membranes. It plays an important role in wrapping progress and EEV production. We constructed a human single-chain fragment variable (scFv) library with a diversity of ≥4 × 108 independent colonies using peripheral blood from four vaccinated donors. One anti-F13 scFv was isolated and characterised after three rounds of panning. In Western blotting assays, the scFv 3E2 reacted with the recombinant F13VACV protein with a reduction of binding under denatured and reduced conditions. Two antigenic binding sites (139-GSIHTIKTLGVYSDY-153 and 169-AFNSAKNSWLNL-188) of scFv 3E2 were mapped using a cellulose membrane encompassing 372 15-mere peptides with 12 overlaps covering the whole F13 protein. No neutralisation capa-bilities were observed either in the presence or absence of complement. In conclusion, the con-struction of recombinant immunoglobulin libraries is a promising strategy to isolate specific scFvs to enable the study of the host-pathogen interaction.

CT-guided microwave ablation of hepatic malignancies via transpulmonary approach without ancillary techniques.

OBJECTIVES: The objectives of the study were to determine the safety and efficacy of computed tomography (CT)-guided transpulmonary percutaneous microwave ablation (MWA) for hepatic malignancies without the use of ancillary techniques. MATERIAL AND METHODS: A retrospective review was performed on patients who underwent MWA for hepatic malignancy between January 2014 and February 2020 at a single tertiary center. Imaging was reviewed for each procedure to identify MWA showing transpleural transgression on CT scans. For these patients, demographics, ablation data, pulmonary complication rate, and predictors of pneumothorax were analyzed. RESULTS: A total of 71 consecutive sessions (62.1 ± 11.3 years, 79% of males) of MWA were performed to treat 71 tumors (1.90 ± 0.96 cm) via transpulmonary approach under CT guidance. Technical success was achieved in all cases immediately after the procedure. At 1-month follow-up, 65/69 (94.2%) patients had no residual disease (two patients were lost to follow-up). Pulmonary complications occurred in 26/71 (36.6%) sessions, and 15/26 (57.7%) were minor requiring no intervention. Pneumothorax occurred in 14/71 (19.7%) sessions, and the rate of major pneumothorax requiring chest tube was 8/71 (11.3%). Lesions on the left side of the liver (segments I-IV) and intraprocedural probe adjustment were found to be independent predictors of developing major pneumothorax (P = 0.007 and 0.028, respectively). There were no reported pulmonary complications at the 1-month follow-up. CONCLUSION: CT-guided transpulmonary MWA is safe and effective in treating hepatic malignancies. Although it is associated with the risk of developing pulmonary complications, patients underwent successful ablation of their hepatic malignancies without life-threatening complications and mortality.

Swiss cheese interventricular septum presenting with catastrophic stroke: the potential role of ECG-gated CTA.

Ventricular septal defect is a common congenital cardiac condition that presents in a variety of morphologies. Less commonly, when an individual patient is found to have multiple ventricular septal defects, the term "Swiss cheese ventricular septal defect" is applied. Although not routinely utilized in clinical practice, electrocardiogram (ECG)-gated computed tomographic angiography (CTA) has been shown to provide utility in detecting intracardiac shunts, demonstrating promise in preventing acute strokes secondary to a paradoxical embolus from occurring; this is especially important when atypical cardiac septa are suspected. This case seeks to illustrate how usage of ECG-gated CTA can assist in early detection and prevention of adverse outcomes resulting from an atypical presentation of a ventricular septal defect.

Role of prostaglandin D2 receptors in the pathogenesis of abdominal aortic aneurysm formation.

Prostaglandin D2 (PGD2) released from immune cells or other cell types activates its receptors, D prostanoid receptor (DP)1 and 2 (DP1 and DP2), to promote inflammatory responses in allergic and lung diseases. Prostaglandin-mediated inflammation may also contribute to vascular diseases such as abdominal aortic aneurysm (AAA). However, the role of DP receptors in the pathogenesis of AAA has not been systematically investigated. In the present study, DP1-deficient mice and pharmacological inhibitors of either DP1 or DP2 were tested in two distinct mouse models of AAA formation: angiotensin II (AngII) infusion and calcium chloride (CaCl2) application. DP1-deficient mice [both heterozygous (DP1+/-) and homozygous (DP1-/-)] were protected against CaCl2-induced AAA formation, in conjunction with decreased matrix metallopeptidase (MMP) activity and adventitial inflammatory cell infiltration. In the AngII infusion model, DP1+/- mice, but not DP1-/- mice, exhibited reduced AAA formation. Interestingly, compensatory up-regulation of the DP2 receptor was detected in DP1-/- mice in response to AngII infusion, suggesting a potential role for DP2 receptors in AAA. Treatment with selective antagonists of DP1 (laropiprant) or DP2 (fevipiprant) protected against AAA formation, in conjunction with reduced elastin degradation and aortic inflammatory responses. In conclusion, PGD2 signaling contributes to AAA formation in mice, suggesting that antagonists of DP receptors, which have been extensively tested in allergic and lung diseases, may be promising candidates to ameliorate AAA.

A Recombinant System and Reporter Viruses for Papiine Alphaherpesvirus 2.

Primate simplex viruses, including Herpes simplex viruses 1 and 2, form a group of closely related herpesviruses, which establish latent infections in neurons of their respective host species. While neuropathogenic infections in their natural hosts are rare, zoonotic transmission of Macacine alphaherpesvirus 1 (McHV1) from macaques to humans is associated with severe disease. Human infections with baboon-derived Papiine alphaherpesvirus 2 (PaHV2) have not been reported, although PaHV2 and McHV1 share several biological properties, including neuropathogenicity in mice. The reasons for potential differences in PaHV2 and McHV1 pathogenicity are presently not understood, and answering these questions will require mutagenic analysis. Here, we report the development of a recombinant system, which allows rescue of recombinant PaHV2. In addition, we used recombineering to generate viruses carrying reporter genes (Gaussia luciferase or enhanced green fluorescent protein), which replicate with similar efficiency as wild-type PaHV2. We demonstrate that these viruses can be used to analyze susceptibility of cells to infection and inhibition of infection by neutralizing antibodies and antiviral compounds. In summary, we created a recombinant system for PaHV2, which in the future will be invaluable for molecular analyses of neuropathogenicity of PaHV2.

Primate Simplexviruses Differ in Tropism for Macaque Cells.

Primate simplexviruses are closely related neurotropic herpesviruses, which are largely apathogenic in their respective host species. However, cross-species transmission of Macacine alphaherpesvirus 1 (McHV1, also termed herpes B virus) from rhesus macaques to humans can cause fatal encephalomyelitis. In contrast, closely related viruses, such as Cercopithecine alphaherpesvirus 2 (CeHV2, also termed simian agent 8) or Papiine alphaherpesvirus 2 (PaHV2, also termed herpesvirus papio 2), have not been linked to human disease and are believed to be largely apathogenic in humans. Here, we investigated whether McHV1, PaHV2 and CeHV2 differ in their capacity to infect human and non-human primate (NHP) cells. For comparison, we included the human simplexviruses HSV1 and HSV2 in our analyses. All five viruses replicated efficiently in cell lines of human and African green monkey origin, and McHV1 and PaHV2 also showed robust replication in rhesus macaque cell lines. In contrast, the replication of CeHV2 and particularly HSV1 and HSV2 in cell lines of rhesus macaque origin were reduced or inefficient. Similarly, McHV1, but not CeHV2, efficiently infected rhesus macaque brain organoids. These results point towards the previously unappreciated partial resistance of certain rhesus macaque cells to HSV1/HSV2/CeHV2 infection and reveal similarities between the cell tropism of McHV1 and PaHV2 that might be relevant for risk assessment.

Three Technologies That Will Guide Revascularization of Chronic Coronary Syndrome Patients into the 21st Century: A Review.

Although medical therapy is the preferred first-line treatment for patients with chronic coronary syndrome (CCS), revascularization remains an important consideration. We present a review that identifies the three diagnostic technologies most important to guiding the decision to revascularize patients with CCS: (1) cardiac computed tomography, (2) intracoronary imaging, and (3) lesion-specific physiological guidance.

Clinical experience with a chlorhexidine-coated PICC: A prospective, multicenter, observational study.

INTRODUCTION: This study evaluated a chlorhexidine-coated peripherally inserted central catheter (PICC) and the incidence of associated complications within both inpatient and outpatient populations. METHODS: This IRB-approved, multicenter, prospective observational study was performed at three large teaching hospitals in the US. All adults who required a PICC for ⩾14 days were considered. Patients were monitored throughout entire catheter dwell. Duplex venous ultrasounds were performed before insertion, after 10 to 14 days of dwell time, and upon removal. Data was collected from the hospital, outpatient clinic, and patient PICC diary records. RESULTS: A total of 103 patients, 56% male, with mean BMI 29 ± 8.8, were enrolled. The majority (79%) of patients were from high-risk groups-cancer, infectious diseases, transplant, and trauma. Primary treatment indications were antibiotics (66.99%) and chemotherapy (25.24%). Double lumen PICCs (59.2%) were favored clinically, as was basilic vein placement (71.84%). Mean catheter dwell was 47.01 ± 25.82 days. Three (3, 2.9%) central line-associated bloodstream infections (CLABSI) were reported. Four patients (4.6%) reported symptomatic catheter-related thrombosis (CRT), confirmed with ultrasound. Three patients (3.4%) had ultrasound-confirmed fibroblastic sleeve (FS). Eight patients (9.2%) who entered the study with pre-existing superficial thrombosis, had complete resolution at the time of catheter removal. The incidence of CLABSI was 0.82/1000 days. The combined CRT and FS rate was 6.9%. CONCLUSION: Based upon the observational findings of this study, chlorhexidine-coated PICC technology may be considered for use in patient populations who are at moderate to high-risk for catheter-related complications in both inpatient and outpatient settings.

Evidence that two instead of one defective interfering RNA in influenza A virus-derived defective interfering particles (DIPs) does not enhance antiviral activity.

Influenza A virus (IAV) infection constitutes a significant health threat. Defective interfering particles (DIPs) can arise during IAV infection and inhibit spread of wild type (WT) IAV. DIPs harbor defective RNA segments, termed DI RNAs, that usually contain internal deletions and interfere with replication of WT viral RNA segments. Here, we asked whether DIPs harboring two instead of one DI RNA exert increased antiviral activity. For this, we focused on DI RNAs derived from segments 1 and 3, which encode the polymerase subunits PB2 and PA, respectively. We demonstrate the successful production of DIPs harboring deletions in segments 1 and/or 3, using cell lines that co-express PB2 and PA. Further, we demonstrate that DIPs harboring two instead of one DI RNA do not exhibit increased ability to inhibit replication of a WT RNA segment. Similarly, the presence of two DI RNAs did not augment the induction of the interferon-stimulated gene MxA and the inhibition of IAV infection. Collectively, our findings suggest that the presence of multiple DI RNAs derived from genomic segments encoding polymerase subunits might not result in increased antiviral activity.

Rapid 3D reconstruction guided embolization for catastrophic bleeding following vacuum assisted breast biopsy; A case report and review of the literature.

The most clinically significant complication associated with stereotactic core needle biopsy of the breast is hematoma formation, which only occurs in less than 1% of biopsies and may require treatment. Cases of uncontrollable bleeding, refractory to repeated compression, resulting from biopsy are exceedingly rare. We present a case of catastrophic, uncontrollable bleeding and large hematoma formation resulting from stereotactic vacuum-assisted breast biopsy of a breast mass identified in screening mammography. Percutaneous embolization was planned and guided using 3D reconstructions from computed tomographic angiography, and bleeding was successfully controlled with micro-coil embolization.