Incidence of post myocardial infarction left ventricular thrombus formation in the era of primary percutaneous intervention and glycoprotein IIb/IIIa inhibitors. A prospective observational study

BACKGROUND: Before the widespread use of primary percutaneous coronary intervention (PCI) and glycoprotein IIb/IIIa inhibitors (GP IIb/IIIa) left ventricular (LV) thrombus formation had been reported to complicate up to 20% of acute myocardial infarctions (AMI). The incidence of LV thrombus formation with these treatment modalities is not well known. METHODS: 92 consecutive patients with ST-elevation AMI treated with PCI and GP IIb/IIIa inhibitors underwent 2-D echocardiograms, with and without echo contrast agent, within 24–72 hours. RESULTS: Only 4/92 (4.3%) had an LV thrombus, representing a significantly lower incidence than that reported in the pre-PCI era. Use of contrast agents did not improve detection of LV thrombi in our study. CONCLUSION: The incidence of LV thrombus formation after acute MI, in the current era of rapid reperfusion, is lower than what has been historically reported

Collagen I but not Matrigel matrices provide an MMP-dependent barrier to ovarian cancer cell penetration

Abstract Background The invasive potential of cancer cells is usually assessed in vitro using Matrigel as a surrogate basement membrane. Yet cancer cell interaction with collagen I matrices is critical, particularly for the peritoneal metastatic route undertaken by several cancer types including ovarian. Matrix metalloprotease (MMP) activity is important to enable cells to overcome the barrier constraints imposed by basement membranes and stromal matrices in vivo. Our objective was to compare matrices reconstituted from collagen I and Matrigel as representative barriers for ovarian cancer cell invasion. Methods The requirement of MMP activity for ovarian cancer cell penetration of Matrigel and collagen matrices was assessed in 2D transwell and 3D spheroid culture systems. Results The broad range MMP inhibitor GM6001 completely prevented cell perforation of polymerised collagen I-coated transwell membranes. In contrast, GM6001 decreased ES-2 cell penetration of Matrigel by only ~30% and had no effect on HEY cell Matrigel penetration. In 3D culture, ovarian cancer cells grown as spheroids also migrated into surrounding Matrigel matrices despite MMP blockade. In contrast, MMP activity was required for invasion into 3D matrices of collagen I reconstituted from acid-soluble rat-tail collagen I, but not from pepsin-extracted collagen I (Vitrogen/Purecol), which lacks telopeptide regions. Conclusion Matrigel does not form representative barriers to ovarian cancer cells in either 2D or 3D culture systems. Our findings support the use of collagen I rather than Matrigel as a matrix barrier for invasion studies to better approximate critical interactions and events associated with peritoneal metastasis

Mindful Parenting in Mental Health Care

Mindfulness is a form of meditation based on the Buddhist tradition, which has been used over the last two decades to successfully treat a multitude of mental health problems. Bringing mindfulness into parenting (“mindful parenting”) is one of the applications of mindfulness. Mindful parenting interventions are increasingly being used to help prevent and treat mental disorders in children, parenting problems, and prevent intergenerational transmission of mental disorders from parents to children. However, to date, few studies have examined the hypothesized mechanisms of change brought about by mindful parenting. We discuss six possible mechanisms through which mindful parenting may bring about change in parent–child interactions in the context of child and parent mental health problems. These mechanisms are hypothesized to be mediated by the effects of mindfulness on parental attention by: (1) reducing parental stress and resulting parental reactivity; (2) reducing parental preoccupation resulting from parental and/or child psychopathology; (3) improving parental executive functioning in impulsive parents; (4) breaking the cycle of intergenerational transmission of dysfunctional parenting schemas and habits; (5) increasing self-nourishing attention; and (6) improving marital functioning and co-parenting. We review research that has applied mindful parenting in mental health settings, with a focus on evidence for these six mechanisms. Finally, we discuss directions for future research into mindful parenting and the crucial questions that this research should strive to answer

Comparative Oncogenomic Analysis of Copy Number Alterations in Human and Zebrafish Tumors Enables Cancer Driver Discovery

The identification of cancer drivers is a major goal of current cancer research. Finding driver genes within large chromosomal events is especially challenging because such alterations encompass many genes. Previously, we demonstrated that zebrafish malignant peripheral nerve sheath tumors (MPNSTs) are highly aneuploid, much like human tumors. In this study, we examined 147 zebrafish MPNSTs by massively parallel sequencing and identified both large and focal copy number alterations (CNAs). Given the low degree of conserved synteny between fish and mammals, we reasoned that comparative analyses of CNAs from fish versus human MPNSTs would enable elimination of a large proportion of passenger mutations, especially on large CNAs. We established a list of orthologous genes between human and zebrafish, which includes approximately two-thirds of human protein-coding genes. For the subset of these genes found in human MPNST CNAs, only one quarter of their orthologues were co-gained or co-lost in zebrafish, dramatically narrowing the list of candidate cancer drivers for both focal and large CNAs. We conclude that zebrafish-human comparative analysis represents a powerful, and broadly applicable, tool to enrich for evolutionarily conserved cancer drivers.Kathy and Curt Marble Cancer Research FundArthur C. MerrillNational Institutes of Health (U.S.) (Grant CA106416)National Institutes of Health (U.S.) (Grant ROI RR020833)National Institutes of Health (U.S.) (Grant 1F32GM095213-01

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe