Developmental SMAD6 loss leads to blood vessel hemorrhage and disrupted endothelial cell junctions.

The BMP pathway regulates developmental processes including angiogenesis, yet its signaling outputs are complex and context-dependent. Recently, we showed that SMAD6, an intracellular BMP inhibitor expressed in endothelial cells, decreases vessel sprouting and branching both in vitro and in zebrafish. Genetic deletion of SMAD6 in mice results in poorly characterized cardiovascular defects and lethality.

Novel in vitro method for measuring the mass fraction of bioaccessible atmospheric polycyclic aromatic hydrocarbons using simulated human lung fluids.

The bioaccessibility of organic pollutants is a key factor in human health risk assessments. We developed a novel in vitro method for determining the mass fraction of bioaccessible atmospheric polycyclic aromatic hydrocarbons (PAHs) using an air-washing device containing simulated human lung fluid. The experimental parameters were optimized based on the deposition fractions (DFs) of PAHs in human lung fluids.

Rapid gastrointestinal loss of Clostridial Clusters IV and XIVa in the ICU associates with an expansion of gut pathogens.

Commensal gastrointestinal bacteria resist the expansion of pathogens and are lost during critical illness, facilitating pathogen colonization and infection. We performed a prospective, ICU-based study to determine risk factors for loss of gut colonization resistance during the initial period of critical illness. Rectal swabs were taken from adult ICU patients within 4 hours of admission and 72 hours later, and analyzed using 16S rRNA gene sequencing and selective culture for vancomycin-resistant Enterococcus (VRE).

Ultrasound Measurement of Vascular Density to Evaluate Response to Anti-Angiogenic Therapy in Renal Cell Carcinoma.

Background: Functional and molecular changes often precede gross anatomical changes, so early assessment of a tumor's functional and molecular response to therapy can help reduce a patient's exposure to the side effects of ineffective chemotherapeutics or other treatment strategies.

Objective: Our intent was to test the hypothesis that an ultrasound microvascular imaging approach might provide indications of response to therapy prior to assessment of tumor size.

Methods: Mice bearing clear-cell renal cell carcinoma xenograft tumors were treated with antiangiogenic and Notch inhibition therapies.

Identification of an I-dependent and I-mediated proarrhythmic mechanism in cardiomyocytes derived from pluripotent stem cells of a Brugada syndrome patient.

Brugada syndrome (BrS) is an inherited cardiac arrhythmia commonly associated with SCN5A mutations, yet its ionic mechanisms remain unclear due to a lack of cellular models. Here, we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a BrS patient (BrS1) to evaluate the roles of Na currents (I) and transient outward K currents (I) in BrS induced action potential (AP) changes. To understand the role of these current changes in repolarization we employed dynamic clamp to "electronically express" I and restore normal resting membrane potentials and allow normal recovery of the inactivating currents, I, I and I.

A novel three base-pair deletion in domain two of the cardiac sodium channel causes Brugada syndrome.

Introduction: Mutations within SCN5A are found in a significant proportion (15-30%) of Brugada syndrome (BrS) cases and impair sodium transport across excitable cardiac cells that mediate ventricular contractions. Genetic testing offers a means to clinically assess and manage affected individuals and their family members.

Methods And Results: The proband at age 44 years old exhibited a syncopal event during exercise, and presented later with a spontaneous type-I BrS pattern on 12‑lead resting electrocardiogram (ECG).

Integrin α2β1 Expression Regulates Matrix Metalloproteinase-1-Dependent Bronchial Epithelial Repair in Pulmonary Tuberculosis.

Pulmonary tuberculosis (TB) is caused by inhalation of , which damages the bronchial epithelial barrier to establish local infection. Matrix metalloproteinase-1 plays a crucial role in the immunopathology of TB, causing breakdown of type I collagen and cavitation, but this collagenase is also potentially involved in bronchial epithelial repair. We hypothesized that the extracellular matrix (ECM) modulates driven matrix metalloproteinase-1 expression by human bronchial epithelial cells (HBECs), regulating respiratory epithelial cell migration and repair.

Morphology Evolution of Stimuli-Responsive Triblock Copolymer Modulated by Polyoxometalates.

Polyoxometalate (POM) HPMoO was coassembled with stimuli-responsive triblock copolymer poly(ethylene oxide)- block-polystyrene- block-poly(2-(dimethylamino)ethyl methacrylate) (PEO- b-PS- b-PDMAEMA) by electrostatic interactions. Depending on the POM contents, the hybrid complexes can self-assemble into a series of morphologies: micelles, rods, toroids, and vesicles. Unlike traditional morphology transition of amphiphilic block copolymer derived from a broad range of hydrophobic volume fractions, POM-induced morphology transitions just occurred in a narrow range of volume fractions.

Dual electrical switching permeability of vesicles via redox-responsive self-assembly of amphiphilic block copolymers and polyoxometalates.

Electro-responsive vesicles were demonstrated based on an amphiphilic block copolymer PEO114-b-P(DCH-Ru)n and an inorganic nanoparticle polyoxometalate H3PMo12O40 (PMo12) via electrostatic interactions. After undergoing electrochemical reactions, vesicle membranes allow the migration of electrolyte ions and release of loaded cargos.

Pathogen colonization of the gastrointestinal microbiome at intensive care unit admission and risk for subsequent death or infection.

Purpose: Loss of colonization resistance within the gastrointestinal microbiome facilitates the expansion of pathogens and has been associated with death and infection in select populations. We tested whether gut microbiome features at the time of intensive care unit (ICU) admission predict death or infection.

Methods: This was a prospective cohort study of medical ICU adults.

The influence of bilateral sagittal split ramus osteotomy on the stress distributions in the temporomandibular joints of the patients with facial asymmetry under symmetric occlusions.

The aim of this study is to compare the differences in the stress distributions in the temporomandibular joints (TMJs) of the patients with facial asymmetry before and after bilateral sagittal split ramus osteotomy (BSSRO) under the symmetric occlusions using the three-dimensional (3D) finite element method.Ten facial asymmetry patients (Preoperative group, age 24.6 ± 4.

What Raises Troponins in the Paediatric Population?

Troponin I is a cardiac enzyme that is released during myocardial injury. However, cardiac enzymes are non-specific and can occur in many cardiac and non-cardiac pathologies. We aim to (1) describe the range of acute conditions that were associated with raised troponins in the paediatric population in our institution and (2) quantify the extent of troponin elevation and correlate it with the underlying aetiology.

Accuracy of implementing principles of fusion imaging in the follow up and surveillance of complex aneurysm repair.

Fusion imaging is standard for the endovascular treatment of complex aortic aneurysms, but its role in follow up has not been explored. A critical issue is renal function deterioration over time. Renal volume has been used as a marker of renal impairment; however, it is not reproducible and remains a complex and resource-intensive procedure.

A prospective observational trial of fusion imaging in infrarenal aneurysms.

Objective: Use of three-dimensional fusion has been shown to significantly reduce radiation exposure and contrast material use in complex (fenestrated and branched) endovascular aneurysm repair (EVAR). Cydar software (CYDAR Medical, Cambridge, United Kingdom) is a cloud-based technology that can provide imaging guidance by overlaying preoperative three-dimensional vessel anatomy from computed tomography scans onto live fluoroscopy images both in hybrid operating rooms and on mobile C-arms. The aim of this study was to determine whether radiation dose reduction would occur with the addition of fusion imaging to infrarenal repair in all imaging environments.

Unexplained absence resulting in deaths of nursing home residents in Australia-A 13-year retrospective study.

Objectives: To examine deaths of Australian nursing home (NH) residents following an unexplained absence.

Methods: Population based cross-sectional study was conducted using coronial data from the National Coronial Information System. Participants are residents of accredited NHs if death followed an unexplained absence and was reported to the Coroner between July 1, 2000 and June 30, 2013.

Allometric Relationships for Cardiac Size and Longitudinal Function in Healthy Chinese Adults - Normal Ranges and Clinical Correlates.

Background: Cardiac size measurements require indexing to body size. Allometric indexing has been investigated in Caucasian populations but a range of different values for the so-called allometric power exponent () have been proposed, with uncertainty as to whether allometry offers clinical utility above body surface area (BSA)-based indexing. We derived optimal values for in normal echocardiograms and validated them externally in cardiac patients.

Application of RNS in refractory epilepsy: Targeting insula.

Although responsive neurostimulation (RNS) is approved for treatment of resistant focal epilepsy in adults, little is known about response to treatment of specific cortical targets. We describe the experience of RNS targeting the insular lobe. We identified patients who had RNS implantation with at least one electrode within the insula between April 2014 and October 2015.

Association of family history and survival in patients with colorectal cancer: a pooled analysis of eight epidemiologic studies.

A family history of colorectal cancer (CRC) in first-degree relatives (FDRs) increases the risk of CRC. However, the influence of family history on survival among CRC patients remains unclear. We conducted a pooled analysis of survival in 5010 incident CRC cases.

Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity.

Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project.

Background: While tobacco and alcohol are established risk factors for hepatocellular carcinoma (HCC), the most common type of primary liver cancer, it is unknown whether they also increase the risk of intrahepatic cholangiocarcinoma (ICC). Thus, we examined the association between tobacco and alcohol use by primary liver cancer type.

Methods: The Liver Cancer Pooling Project is a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC n = 1423, ICC n = 410).