The transcriptional transactivator Tat selectively regulates viral splicing

HIV-1 gene expression requires both viral and cellular factors to control and coordinate transcription. While the viral factor Tat is known for its transcriptional transactivator properties, we present evidence for an unexpected function of Tat in viral splicing regulation. We used a series of HIV-1 reporter minigenes to demonstrate that Tat’s role in splicing is dependent on the cellular co-transcriptional splicing activators Tat-SF1 and CA150. Surprisingly, we show that this Tat-mediated splicing function is independent from transcriptional activation. In the context of the full-length viral genome, this mechanism promotes an autoregulatory feedback that decreases expression of tat and favors expression of the env-specific mRNA. Our data demonstrate that Tat-mediated regulation of transcription and splicing can be uncoupled and suggest a mechanism for the involvement of specific transcriptional activators in splicing

Procalcitonin Reveals Early Dehiscence in Colorectal Surgery: The PREDICS Study

Objectives: We designed a multicentric, observational study to test if Procalcitonin (PCT) might be an early and reliable marker of anastomotic leak (AL) after colorectal surgery (ClinicalTrials.govIdentifier:NCT01817647). Background: Procalcitonin is a biomarker used to monitor bacterial infections and guide antibiotic therapy. Anastomotic leak after colorectal surgery is a severe complication associated with relevant short and long-term sequelae. Methods: Between January 2013 and September 2014, 504 patients underwent colorectal surgery, for malignant colorectal diseases, in elective setting. White blood count (WBC), C-reactive protein (CRP) and PCT levels were measured in 3rd and 5th postoperative day (POD). AL and all postoperative complications were recorded. Results: We registered 28 (5.6%) anastomotic leaks. Specificity and negative predictive value for AL with PCT less than 2.7 and 2.3 ng/mL were, respectively, 91.7% and 96.9% in 3rd POD and 93% and 98.3% in 5th POD. Receiver operating characteristic curve for biomarkers shows that in 3rd POD, PCTand CRP have similar area under the curve (AUC) (0.775 vs 0.772), both better than WBC (0.601); in 5th POD, PCT has a better AUC than CRP and WBC (0.862 vs 0.806 vs 0.611). Measuring together PCT and CRP significantly improves AL diagnosis in 5th POD (AUC: 0.901). Conclusions: PCTand CRP demonstrated to have a good negative predictive value for AL, both in 3rd and in 5th POD. Low levels of PCT, together with low CRP values, seem to be early and reliable markers of AL after colorectal surgery. These biomarkers might be safely added as additional criteria of discharge protocols after colorectal surgery

State of the art and perspectives of gene therapy in heart failure. A scientific statement of the Heart Failure Association of the ESC, the ESC Council on Cardiovascular Genomics and the ESC Working Group on Myocardial & Pericardial Diseases

Gene therapy has recently become a reality in the treatment of cardiovascular diseases. Strategies to modulate gene expression using antisense oligonucleotides or small interfering RNA are proving to be safe and effective in the clinic. Adeno-associated viral vector-based gene delivery and CRISPR-Cas9-based genome editing have emerged as efficient strategies for gene delivery and repair in humans. Overall, gene therapy holds the promise not only of expanding current treatment options, but also of intervening in previously untackled causal disease mechanisms with little side effects. This scientific statement provides a comprehensive overview of the various modalities of gene therapy used to treat heart failure and some of its risk factors, and their application in the clinical setting. It discusses specifically the possibilities of gene therapy for hereditary heart diseases and (non)-genetic heart failure. Furthermore, it addresses safety and clinical trial design issues and challenges for future regulatory strategies

Laparoscopic liver resection for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) represents the most common indication of laparoscopic liver resection (LLR). It must be acknowledged that most series concern minor hepatectomies for peripheral lesions located in favorable segments, and such procedures are now performed in the majority of HPB centers. However, there are growing reports concerning major hepatectomies (i.e., 3 segments or more) and complex resections such as anatomical resections in difficult segments (i.e., postero-superior). Retrospective comparative studies, including some with propensity score matching, and meta-analyses showed that LLR is associated with short-term benefits including reduced blood loss, length of stay and morbidity with identical oncological results and survival rates. In addition, laparoscopy leads to less post-operative abdominal adhesions, improving operative outcomes in case of repeat hepatectomy or secondary liver transplantation. Despite the lack of results of randomized-controlled trials in HCC, a consensus exists that the laparoscopic approach can improve the outcome of major liver resections, provided it is performed in experienced centers. This requires specific high-quality training

Surgical Strategy: Indications

This chapter relates about surgical strategies in rectal cancer. Laparotomy, laparoscopy, SILS and robotics are detailed as the respective indications for all them. Then are described the different approaches to early cancers, to cancers requiring operation at the first diagnosis, and finally for cancer that are considered as nonresectable at the first evaluation, suggesting multidisiplinar treatments. Downstaging and downsizing are described

Laparoscopic ileocolic iterative resection with fluorescence-guided lymphatic mapping - video vignette

We assessed the correct pathway of lymphatic drainage during ileocolic iterative resection by the use of Indocyanine green (ICG) in a patient with a previous laparoscopic right hemicolectomy. A 63 years old man underwent laparoscopic right ileocolic re-resection for a high grade dysplasia of a large polyp close to the ileocolic anastomosis performed 8 years ago during a laparoscopic right hemicolectomy for a Tis of cecum. The peritumoral injection of ICG was performed at the beginning of the operation in order to correctly visualize the lymphatic pathway and then a lateral to medial approach dissection was carried out. This article is protected by copyright. All rights reserved