Medicine

Introduction The primary challenge in the initial assessment of a patient with undifferentiated shock is to quickly identify and treat any reversible causes of shock. Bedside ultrasound provides real-time information that can assist with the achievement of this goal; as a result, it has gained widespread popularity in the field of critical care and emergency medicine. Many researchers have suggested that the use of a simple ultrasound approach to guide the management of these patients would reduce the morbidity associated with delayed or inappropriate treatment and would result in better outcomes. Purpose With the goal of optimizing early management of critically ill patients, we describe in this article an algorithm based on simple clinical questions that combines the information provided by lung, cardiac and inferior vena cava ultrasonography. Conclusions The advantages of this approach, in addition to efficiency, include easy reproducibility and standardization for teaching purposes and clinical trials.

Introduction The primary challenge in the initial assessment of a patient with undifferentiated shock is to quickly identify and treat any reversible causes of shock. Bedside ultrasound provides real-time information that can assist with the achievement of this goal; as a result, it has gained widespread popularity in the field of critical care and emergency medicine. Many researchers have suggested that the use of a simple ultrasound approach to guide the management of these patients would reduce the morbidity associated with delayed or inappropriate treatment and would result in better outcomes. Purpose With the goal of optimizing early management of critically ill patients, we describe in this article an algorithm based on simple clinical questions that combines the information provided by lung, cardiac and inferior vena cava ultrasonography. Conclusions The advantages of this approach, in addition to efficiency, include easy reproducibility and standardization for teaching purpo...

Human immunodeficiency virus type 1 (HIV-1) Gag selects for and mediates genomic RNA (vRNA) encapsidation into progeny virus particles. The host protein, Staufen1 interacts directly with Gag and is found in ribonucleoprotein (RNP) complexes containing vRNA, which provides evidence that Staufen1 plays a role in vRNA selection and encapsidation. In this work, we show that Staufen1, vRNA and Gag are found in the same RNP complex. These cellular and viral factors also colocalize in cells and constitute novel Staufen1 RNPs (SHRNPs) whose assembly is strictly dependent on HIV-1 expression. SHRNPs are distinct from stress granules and processing bodies, are preferentially formed during oxidative stress and are found to be in equilibrium with translating polysomes. Moreover, SHRNPs are stable, and the association between Staufen1 and vRNA was found to be evident in these and other types of RNPs. We demonstrate that following Staufen1 depletion, apparent supraphysiologic-sized SHRNP foci are formed in the cytoplasm and in which Gag, vRNA and the residual Staufen1 accumulate. The depletion of Staufen1 resulted in reduced Gag levels and deregulated the assembly of newly synthesized virions, which were found to contain several-fold increases in vRNA, Staufen1 and other cellular proteins. This work provides new evidence that Staufen1-containing HIV-1 RNPs preferentially form over other cellular silencing foci and are involved in assembly, localization and encapsidation of vRNA.

Translation initiation from the human immunodeficiency virus type-1 (HIV-1) mRNA can occur through a cap or an IRES dependent mechanism. Cap-dependent translation initiation of the HIV-1 mRNA can be inhibited by the instability element (INS)-1, a cis-acting regulatory element present within the gag open reading frame (ORF). In this study we evaluated the impact of the INS-1 on HIV-1 IRES-mediated translation initiation. Using heterologous bicistronic mRNAs, we show that the INS-1 negatively impact on HIV-1 IRES-driven translation in in vitro and in cell-based experiments. Additionally, our results show that the inhibitory effect of the INS-1 is not general to all IRESes since it does not hinder translation driven by the HCV IRES. The inhibition by the INS-1 was partially rescued in cells by the overexpression of the viral Rev protein or hnRNPA1. Citation: Valiente-Echeverría F, Vallejos M, Monette A, Pino K, Letelier A, et al. (2013) A cis-Acting Element Present within the gag Open Reading Frame Negatively Impacts on the Activity of the HIV-1 IRES. PLoS ONE 8(2): e56962.

The precursor group-specific antigen (pr55 Gag ) is central to HIV-1 assembly. Its expression alone is sufficient to assemble into virus-like particles. It also selects the genomic RNA for encapsidation and is involved in several important virus-host interactions for viral assembly and restriction, making its synthesis essential for aspects of viral replication. Here, we show that the initiation of translation of the HIV-1 genomic RNA is mediated through both a cap-dependent and an internal ribosome entry site (IRES)-mediated mechanisms. In support of this notion, pr55 Gag synthesis was maintained at 70% when cap-dependent translation initiation was blocked by the expression of eIF4G-and PABP targeting viral proteases in two in vitro systems and in HIV-1-expressing cells directly infected with poliovirus. While our data reveal that IRES-dependent translation of the viral genomic RNA ensures pr55 Gag expression, the synthesis of other HIV-1 proteins, including that of pr160 Gag/Pol , Vpr and Tat is suppressed early during progressive poliovirus infection. The data presented herein implies that the unspliced HIV-1 genomic RNA utilizes both cap-dependent and IRES-dependent translation initiation to supply pr55 Gag for virus assembly and production. Citation: Monette A, Valiente-Echeverría F, Rivero M, Cohen ÉA, Lopez-Lastra M, et al. (2013) Dual Mechanisms of Translation Initiation of the Full-Length HIV-1 mRNA Contribute to Gag Synthesis. PLoS ONE 8(7): e68108.

Cardiovascular complications are the second leading cause of late mortality in survivors of Hodgkin's lymphoma (HL) exposed to mediastinal radiotherapy. Symptomatic cardiac disease following classic thoracic irradiation for HL is reported in 10%-30% of patients at 5-10 years of follow-up. We present the case of a 44-year-old man with a history of left cervical nodular lymphocyte predominant HL treated at childhood with 40 Gy extended field thoracic irradiation (Mantle) who presented with mixed aortic and mitral valve disease, coronary artery stenosis, myocardial and aortic calcifications, and mediastinal fibrosis. Despite extensive cardiac surgery, the postoperative course was complicated and resulted in the patient's death. We review herein the typical cardiac involvement related to mediastinal radiotherapy and the controversies surrounding its surgical approach.

severe aortic stenosis (AS). We examined the role of transesophageal echocardiography (TEE) in PAVR. TEE was used initially to assess the native valve and aortic root, and served as a guide during PAVR. Following prosthetic valve deployment, TEE was used to assess valve function. Eleven patients aged 82 ± 10 years with NYHA III-IV underwent PAVR. Periprocedural TEE gave immediate information on prosthetic position and function, LV function, mitral regurgitation, pericardium, and thoracic aorta anatomy. There was excellent visual agreement between fluoroscopic and TEE images of prosthetic positioning and deployment. TEE facilitated the detection and management of procedurerelated complications. Compared with pre-PAVR, AV area (0.56 ± 0.19 cm 2 vs. 1.3 ± 0.4 cm 2 ; P < 0.001) and LVEF (49 ± 17% vs. 56 ± 11%; P < 0.001) increased. TEE provides key anatomical and functional information, and serves as a diagnostic guide for complications, which may arise during PAVR. (ECHOCARDIOGRAPHY, Volume 25, September 2008) transesophageal echocardiography, aortic valve prosthesis, aortic stenosis, prosthetic valve, intraoperative transesophageal echocardiography, elderly

Hemodynamic modifications induced by general anesthesia could lead to underestimation of mitral regurgitation (MR) severity in the operating department and potentially serious consequences. The intraoperative severity of MR was prospectively compared with the preoperative baseline evaluation using dynamic quantitative transesophageal echocardiography in 25 patients who were stable with MR 2/4 or greater undergoing coronary bypass, mitral valve operation, or both. Significant changes in the severity of MR using transesophageal echocardiographic criteria occurred after the induction of general anesthesia and with phenylephrine. Quantitative transesophageal echocardiographic evaluation of MR using effective orifice area and vena contracta, and the use of phenylephrine challenge, were useful to avoid underestimating MR severity in the operating department. (J Am Soc Echocardiogr 2006;19:140-146.)

Background: Chronic ischemic mitral regurgitation is associated with poor longterm survival. Despite the increasing popularity of valve repair, its durability and long-term outcome for ischemic mitral regurgitation have recently been questioned.

Methods: A total of 2,953 patients underwent valve replacement with the CarboMedics valve between 1988 and 2004 at the Montreal Heart Institute. Patients were prospectively followed at the outpatient valve clinic. Subsequently, 1,004 patients underwent echocardiographic ...

Aims: To describe the initial experience with the GORE ® septal occluder (GSO), a new septal occluder for the treatment of atrial septal defects (ASD) and patent foramen ovale (PFO). Methods and results: This was a prospective single-centre review of patients undergoing percutaneous closure for a PFO or ASD with the GSO. A clinical evaluation and follow-up echocardiography were performed at three months with transoesophageal echocardiography (TEE) in case of PFO and transthoracic echocardiography (TTE) in ASDs. Between July 2011 and February 2012, thirty-eight patients underwent PFO (n=29) or ASD (n=9) closure with the GSO using TEE (n=36, 94.7%) or intracardiac echocardiography (n=2, 5.3%) guidance. In PFOs, three-month TEE was available in 24 patients and showed no residual shunt in 18 (75%), bubble shunt in two (8.3%) and bubble shunt after Valsalva in four (16.7%). In ASDs, threemonth TTE showed no shunt in eight patients (88.8%) and residual shunt in one patient (11.2%). There was no device embolisation, air embolism, procedure-related stroke or pericardial effusion. No neurological events occurred during the follow-up period. Conclusions: This initial experience with the new GSO device has demonstrated acceptable safety with no procedural complications and acceptable efficacy with low rates of residual shunting at three-month follow-up.

OBJECTIVES: Mediastinal drainage following cardiac surgery with traditional large-bore plastic tubes can be painful and cumbersome. This study was designed to determine whether prolonged drainage (5 days) with a silastic tube decreased the incidence of significant pericardial effusion and tamponade following aortic or valvular surgery. METHODS: One hundred and fifty patients undergoing valvular or aortic surgery in a tertiary cardiac surgery institution were randomized to receive a conventional mediastinal tube plus a silastic Blake drain (n = 75), or two conventional tubes (n = 75). Conventional drains were removed on postoperative day (POD) 1, while Blake drains were removed on POD 5. The primary end-point was the combined incidence of significant pericardial effusion (≥15 mm) or tamponade through POD 5. Secondary end-points included total mediastinal drainage, postoperative atrial fibrillation (AF) and pain. RESULTS: Analysis was performed for 67 patients in the Blake group and 73 in the conventional group. There was no difference between the two groups in the combined end-point of significant effusion or tamponade (7.4 vs 8.3%, P = 0.74), or in the incidence of AF (47 vs 46%, P = 0.89). Mean 24-h drainage was greater in the Blake group than in the conventional group (749 ± 444 ml vs 645 ± 618 ml, P < 0.01). Overall incidence of significant pericardial effusion at 30 days was 12.1% (n = 17), with 5% (n = 7) requiring drainage. The Blake group had a numerically lower incidence of effusion requiring drainage at POD 30 (3.0 vs 6.8%, P = 0.44). Postoperative pain was similar between groups. CONCLUSIONS: In patients undergoing ascending aortic or valvular surgery, prolonged drainage with silastic tubes is safe and does not increase postoperative pain. There was no difference between the Blake and conventional drains with regard to significant pericardial effusion or tamponade in this cohort; however, this conclusion is limited by the low overall incidence of the primary outcome in this cohort.

Objectives This study sought to describe and compare a novel fluoroscopic method and a 2-dimensional transesophageal echocardiographic (TEE) method to localize mitral periprosthetic leaks (PPLs) for transcatheter reduction. Background Transcatheter reduction of significant regurgitation represents a modern and attractive alternative to surgery for the treatment of mitral PPL in high-risk patients. Accurate localization and precise communication between the echocardiographer and the interventional cardiologist are essential for procedural success. Methods We analyzed TEE and fluoroscopic studies of patients with mitral PPL who underwent multiplane 2-dimensional TEE-guided transcatheter reduction in our institution. Periprosthetic leaks were routinely localized using the "surgeon's-view" time-clock method during periprocedural TEE assessments. The 2-dimensional TEE examinations were later retrospectively reviewed by an echocardiographer blinded to procedural TEE findings. A corresponding surgeon's-view time-clock method was plotted for fluoroscopic PPL localization. Using this fluoroscopic method, offline fluoroscopic images were reviewed by an independent interventional cardiologist blinded to TEE results. Agreement between methods was evaluated. Results Complete imaging data were available for analysis in 20 patients who, between 2002 and 2009, underwent transcatheter reduction in which the defect was successfully crossed. There was excellent agreement between procedural TEE and retrospective TEE review for PPL localization (100%; p Ͻ 0.0001) and between fluoroscopic and procedural TEE localization (90%; 95% confidence interval [CI]: 77% to 100%; p ϭ 0.0003). In the 2 cases where there was disagreement, fluoroscopic PPL localization was adjacent to TEE localization. Conclusions The surgeon's-view time-clock method of localizing PPL using 2-dimensional TEE is highly reproducible and allows fluoroscopic localization using the same reference system with very good agreement.