Altered Inflammatory State and Mitochondrial Function Identified by Transcriptomics in Paediatric Congenital Heart Patients Prior to Surgical Repair.

Congenital heart disease (CHD) remains the most common birth defect, with surgical intervention required in complex cases. Right ventricle (RV) function is known to be a major predictor of sustained cardiac health in these patients; thus, by elucidating the divergent profiles between CHD and the control through tissue analysis, this study aims to identify new avenues of investigation into the mechanisms surrounding reduced RV function. Transcriptomic profiling, in-silico deconvolution and functional network analysis were conducted on RV biopsies, identifying an increase in the mitochondrial dysfunction genes and (padj = 4.

Challenges and solutions to recruitment of neonates and children having cardiac surgery into a study using a novel sampling device.

Objective: To narratively describe the challenges and solutions required in delivering a non-commercial study of children undergoing cardiac surgery using a novel subcutaneous hormone collection device.

Results: The challenges faced by the research team are divided into those of conducting healthcare research in children and those specific to this study. Many of the issues of conducting healthcare research in children can and have been overcome by structural and institutional culture change-normalising and embedding research as part of good clinical care.

A pre-registered, multi-lab non-replication of the action-sentence compatibility effect (ACE).

The Action-sentence Compatibility Effect (ACE) is a well-known demonstration of the role of motor activity in the comprehension of language. Participants are asked to make sensibility judgments on sentences by producing movements toward the body or away from the body. The ACE is the finding that movements are faster when the direction of the movement (e.

CUL5 is required for thalidomide-dependent inhibition of cellular proliferation.

Angiogenesis is essential for cancer metastasis, thus the discovery and characterization of molecules that inhibit this process is important. Thalidomide is a teratogenic drug which is known to inhibit angiogenesis and effectively inhibit cancer metastasis, yet the specific cellular targets for its effect are not well known. We discovered that CUL5 (previously identified as VACM-1), a scaffold protein in E3 ligase complexes, is involved in thalidomide-dependent inhibition of endothelial cell growth.

Heterogeneity of Human Breast Stem and Progenitor Cells as Revealed by Transcriptional Profiling.

During development, the mammary gland undergoes extensive remodeling driven by stem cells. Breast cancers are also hierarchically organized and driven by cancer stem cells characterized by CD44CD24 or aldehyde dehydrogenase (ALDH) expression. These markers identify mesenchymal and epithelial populations both capable of tumor initiation.

Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling.

Inflammatory breast cancer (IBC) is the most lethal form of breast cancer. All IBC patients have lymph node involvement and one-third of patients already have distant metastasis at diagnosis. This propensity for metastasis is a hallmark of IBC distinguishing it from less lethal non-inflammatory breast cancers (nIBC).

Abrogating phosphorylation of eIF4B is required for EGFR and mTOR inhibitor synergy in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) patients suffer from a highly malignant and aggressive disease. They have a high rate of relapse and often develop resistance to standard chemotherapy. Many TNBCs have elevated epidermal growth factor receptor (EGFR) but are resistant to EGFR inhibitors as monotherapy.

EGFR Tyrosine 845 Phosphorylation-Dependent Proliferation and Transformation of Breast Cancer Cells Require Activation of p38 MAPK.

Phosphorylation of epidermal growth factor receptor (EGFR) on tyrosine 845 by c-Src has been shown to be important for cell proliferation and migration in several model systems. This cross talk between EGFR and Src family kinases (SFKs) is one mechanism for resistance to EGFR inhibitors both in cell models and in the clinic. Here, we show that phosphorylation of tyrosine 845 on EGFR is required for proliferation and transformation using several cell models of breast cancer.

Fibroblast-secreted hepatocyte growth factor mediates epidermal growth factor receptor tyrosine kinase inhibitor resistance in triple-negative breast cancers through paracrine activation of Met.

Introduction: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown clinical efficacy in lung, colon, and pancreatic cancers. In lung cancer, resistance to EGFR TKIs correlates with amplification of the hepatocyte growth factor (HGF) receptor tyrosine kinase Met. Breast cancers do not respond to EGFR TKIs, even though EGFR is overexpressed.

Reduced-dose rituximab in rheumatoid arthritis: efficacy depends on degree of B cell depletion.

Objective: Studies comparing 500 mg rituximab and 1,000 mg rituximab doses in rheumatoid arthritis have yielded conflicting data on clinical outcomes, but in all of these studies a subgroup of patients has had excellent responses at the lower dose. Historically, it was considered that rituximab uniformly depleted B cells at both doses. Using highly sensitive assays, we have shown that B cell depletion is variable and predictive of clinical response.

Ligament and bone pathologic abnormalities more frequent in neuropathic joint disease in comparison with degenerative arthritis of the foot and ankle: implications for understanding rapidly progressive joint degeneration.

Objective: The variable disease progression of osteoarthritis (OA) and the basis for rapid joint deterioration in some subgroups of patients are poorly understood. To explore an anatomic basis for rapidly progressive OA, this observational study compared the magnetic resonance imaging (MRI) patterns of disease between patients with neuropathic joint disease (NJD) and patients with degenerative arthritis of the ankle and foot.

Methods: MR images of the foot and ankle of patients with early NJD (n = 7) and patients with OA (n = 15) were assessed.

Managing patients with resistant rheumatoid arthritis.

This article describes the management of patients with difficult to treat rheumatoid arthritis. Pharmacological treatment of patients using disease-modifying and biologic drugs is discussed. Clinical measures of disease activity are also described.

Successful treatment of resistant pseudogout with anakinra.

We describe herein the case of a 63-year-old man with pseudogout affecting multiple joints that was resistant to treatment with allopurinol, steroids, and antiinflammatory drugs. Based on recent data on the molecular mechanism of pseudogout that demonstrated overproduction of interleukin-1 (IL-1), we treated the patient with anakinra, an IL-1 receptor antagonist. The patient responded to treatment with anakinra within 2 weeks, with resolution of the signs and symptoms of pseudogout and normalization of levels of inflammation markers.