The discovery of Rous sarcoma virus (RSV) led to the identification of cellular Src (c-Src), a non-receptor tyrosine kinase, which has since been implicated in the development of numerous human cancers. c-Src has been found to be highly activated in colon cancers, particularly in those metastatic to the liver. Studies of the mechanism of c-Src regulation have suggested that c-Src kinase activity is downregulated by phosphorylation of a critical carboxy-terminal tyrosine (Tyr 530 in human c-Src, equivalent to Tyr 527 in chicken Src) and have implied the existence of activating mutations in this C-terminal regulatory region. We report here the identification of a truncating mutation in SRC at codon 531 in 12% of cases of advanced human colon cancer tested and demonstrate that the mutation is activating, transforming, tumorigenic and promotes metastasis. These results provide, for the first time, genetic evidence that activating SRC mutations may have a role in the malignant progression of human colon cancer.

Background: Differences in cardiac remodeling after mitral valve (MV) surgery between the sexes is poorly understood. Inferior outcomes for females undergoing MV surgery compared with males have been suggested in the literature, although causative factors behind this discrepancy have not been identified. Materials and Methods: In this propensity-matched, retrospective, single-center study, we sought to identify the impact that sex may have on cardiac remodeling and long-term outcomes to better inform clinical decision-making in MV surgical intervention. Outcomes were compared between males and females undergoing MV replacement (MVR) between 2004 and 2018. The primary outcome was cardiac remodeling 1 year postoperatively. Secondary outcomes included mortality, stroke, myocardial infarction (MI), reoperation of the MV, and rehospitalization. Results: A total of 311 males and 311 females were included after propensity matching. Both groups demonstrated significant improvement in left atrial remodeling, although only males demonstrated a significant degree of improved left ventricular remodeling while their female counterparts did not. Mortality rates were relatively equivalent between the two groups, although males were more likely to develop sepsis and require rehospitalization due to MI. Conclusions: There has been little research exploring the differences in cardiac remodeling between the sexes after MVR. The results of this study have suggested that MVR is equally safe for both sexes and has demonstrated a difference in the heart's ability to remodel after MVR. The significance of this difference has the potential to result in largely different clinical outcomes for males and females. Further study is necessary to fully elucidate this relationship.

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The extract of Siegesbeckia pubescens herb and its chemical constituents were tested for the ability to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglia. The methanol extract and the 90% MeOH fraction of S. pubescens effectively attenuated lipopolysaccharide-induced nitric oxide production. Several steps of chromatography yielded eight ent-kaurane diterpenes (1-8) and one ent-pimarane diterpene (9) from the 90% MeOH fraction. Among these compounds, compounds 2-9 showed significant inhibitory effect on lipopolysaccharide-induced nitric oxide production in BV2 microglia. Compounds 3 and 9 concentration-dependently decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), supported by quantitative real time polymerase chain reaction (PCR) and Western blot analysis. These results suggest that ent-kaurane and ent-pimarane diterpenes isolated from S. pubescens are expected to be potential candidates against neuroinflammation-related disease.

Obesity has been associated with increased incidence of comorbidities and shorter life expectancy, and it has generally been assumed that patients with obesity should have inferior outcomes after surgery. Previous literature has often demonstrated equivalent or even improved rates of mortality after cardiac surgery when compared to their lower-weight counterparts, coined the obesity paradox. Herein, we aim to review the literature investigating the impact of obesity on surgical valve interventions. PubMed and Embase were systematically searched for articles published from

Purpose of review We summarize the recent developments in transcatheter mitral valve repair (TMVr) and replacement (TMVR), discuss determinants of MitraClip outcomes in various mitral regurgitation causes, and highlight newly emerging devices and randomized trials. Recent findings The discordant results published in the two recent randomized trials for MitraClip, the COAPT and the MITRA-FR trial have led to the emergence of a new conceptual framework such as the proportionate versus disproportionate mitral regurgitation and hemodynamics assessment tools like the real-time continuous left atrial pressure monitoring. Learning curve and volume-outcome analyses and studies examining the MitraClip usage in patients with degenerative mitral regurgitation are recent developments that have influenced MitraClip regulation and coverage. Several trials for TMVr devices that take an alternative approach to the edge-to-edge repair are underway and advancements in the TMVR technologies are continuing to progress to fill the unmet needs of treating high surgical risk patients whose complex valve anatomy make TMVr unfeasible. Summary Evidence supports careful analysis of the valve area and left ventricular function in addition to the left atrial hemodynamics will improve the MitraClip outcome. Operator experience plays a greater effect when achieving excellent results with 1+ or less residual mitral regurgitation whereas surgical MVr volume did not influence TMVr outcome. Interventions on the complex primary mitral regurgitation remain under the surgical domain, but MITRA high risk (HR) and REPAIR mitral regurgitation trials are underway to evaluate the role of MitraClip in high to intermediate surgical risk patients with primary mitral regurgitation. Despite the slow developments in TMVR, the results of the early trials of its devices are promising.

Purpose of review The purpose of this review is to compare outcomes of surgical valve replacement (SVR) and coronary artery bypass grafting (CABG), minimally invasive cardiac surgery (MICS) SVR and percutaneous coronary intervention (PCI), and transcatheter aortic valve replacement and PCI for the treatment of combined coronary artery disease (CAD) and valvular heart disease (VHD). Recent findings Several studies have attempted to identify key differences in outcomes with hybrid MICS SVR and PCI approaches to combined CAD and VHD. Recent studies have demonstrated that MICS SVR and PCI, when compared with conventional open SVR and CABG, demonstrate reduced or unchanged morbidity and mortality. However, the rate of bleeding in MICS SVR and PCI is consistently higher likely because of the effects of antiplatelet therapy. Summary A shift toward MICS has occurred in the preceding decades, with outcomes improving in recent years. With limited ability to perform CABG through MICS approaches, attempts have been made at hybrid procedures to address multiple presenting concerns while allowing for the benefits of MICS approaches. Hybrid MICS SVR and PCI approaches may provide suitable alternatives to traditional surgical approaches with reduced intra and postoperative morbidity and mortality, with the notable exception of bleeding complications.

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