Hepatic insulin resistance is a major risk factor for the development of type 2 diabetes and is associated with the accumulation of lipids, including diacylglycerol (DAG), triacylglycerols (TAG) and ceramide. There is evidence that enzymes involved in ceramide or sphingolipid metabolism may have a role in regulating concentrations of glycerolipids such as DAG and TAG. Here we have investigated ...

A unique two-step modular system for site-specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase A for incorporation of strained cyclooctyne functional groups. The second step of this modular approach involves the azide-alkyne cycloaddition click reaction. The versatility of the two-step approach ...

Activated platelets provide a promising target for imaging inflammatory and thrombotic events along with site-specific delivery of a variety of therapeutic agents. Multifunctional protein micelles bearing targeting and therapeutic proteins were now obtained by one-pot transpeptidation using an evolved sortase A. Conjugation to the corona of a single-chain antibody (scFv), which binds to the lig...

The enzyme-mediated site-specific bioconjugation of a radioactive metal complex to a single-chain antibody using the transpeptidase sortase A is reported. Cage amine sarcophagine ligands that were designed to function as substrates for the sortase A mediated bioconjugation to antibodies were synthesized and enzymatically conjugated to a single-chain variable fragment. The antibody fragment scFv...

Metal-organic coordination materials are of widespread interest because of the coupled benefits of inorganic and organic building blocks. These materials can be assembled into hollow capsules with a range of properties, which include selective permeability, enhanced mechanical/thermal stability, and stimuli-responsiveness. Previous studies have primarily focused on the assembly aspects of metal...

This study tested the hypothesis that varying degrees of hemodynamic fluctuations seen after birth following immediate cord clamping were related to development of asphyxia with longer cord clamp-to-ventilation intervals, resulting in higher perinatal circulating levels of the catecholamines norepinephrine (NE) and epinephrine (Epi), and thus increased heart rate, blood pressures, and cardiac c...

Cognitive decline leading to dementia represents a global health burden. In the absence of targeted pharmacotherapy, lifestyle approaches remain the best option for slowing the onset of dementia. However, older adults spend very little time doing moderate to vigorous exercise and spend a majority of time in sedentary behavior. Sedentary behavior has been linked to poor glycemic control and ...

BACKGROUND: The appropriateness of repeat transthoracic echocardiography (TTE) for stable heart failure (HF) is based on timing of the follow-up examination, but this lacks scientific support. We sought the association of routine follow-up TTE on survival and readmission in stable HF. METHODS: Patients with HF were selected from consecutive HF admissions from 2008 to 2012. Groups were di...

OBJECTIVES: This study sought to show the degree to which experience and training affect the precision and validity of global longitudinal strain (GLS) measurement and to evaluate the variability of strain measurement after feedback. BACKGROUND: The application of GLS for the detection of subclinical dysfunction has been recommended in an expert consensus document and is being used with ...

OBJECTIVES: The authors have compared exercise echocardiography and exercise cardiac magnetic resonance imaging with simultaneous invasive pressure registration (ExCMRip) for the assessment of pulmonary vascular and right ventricular (RV) function. BACKGROUND: Exercise echocardiography may enable early diagnosis of pulmonary vascular disease, but its accuracy is untested. METHODS: Ex...

OBJECTIVES: This study sought to investigate the association of exercise intolerance in type 2 diabetes (T2DM) with skeletal muscle capillary blood flow (CBF) reserve. BACKGROUND: Exercise intolerance in T2DM strongly predicts adverse prognosis, but associations with muscle blood flow independent of cardiac dysfunction are undefined. METHODS: In 134 T2DM patients without cardiovascul...

OBJECTIVES: The aim of this study was to assess clinical safety and efficacy outcomes of renal denervation executed by an externally delivered, completely noninvasive focused therapeutic ultrasound device. BACKGROUND: Renal denervation has emerged as a potential treatment approach for resistant hypertension. METHODS: Sixty-nine subjects received renal denervation with externally deli...

OBJECTIVES: This study sought to describe the development of a multicenter, transcatheter aortic valve replacement program and regional systems of care intended to optimize coordinated, efficient, and appropriate delivery of this new therapy. BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become an accepted treatment option for patients with severe aortic stenosis who are ...

OBJECTIVES: The aim of this study was to determine the contemporary profile, clinical characteristics, and intrahospital outcomes of acute heart failure (AHF) in an African urban community. BACKGROUND: There are limited data on the current burden and characteristics of AHF in Nigerian Africans. METHODS: Comprehensive and detailed clinical and sociodemographic data were prospectively collec...

Objectives This study aimed to determine the spatiotemporal stability of rotors and other atrial activation patterns over 10 min in longstanding, persistent AF, along with the relationship of rotors to short cycle-length (CL) activity. Background The prevalence, stability, and mechanistic importance of rotors in human atrial fibrillation (AF) remain unclear. Methods Epicardial mappin...

Rationale The early detection of primary tumours and metastatic disease is vital for successful therapy and is contingent upon highly specific molecular markers and sensitive, non-invasive imaging techniques. We hypothesized that the accumulation of activated platelets within tumours is a general phenomenon and thus represents a novel means for the molecular imaging of cancer. Here we investiga...

One of the major hurdles in intravenous regenerative cell therapy is the low homing efficiency to the area where these cells are needed. To increase cell homing toward areas of myocardial damage, we developed a bispecific tandem single-chain antibody (Tand-scFvSca-1+GPIIb/IIIa) that binds with high affinity to activated platelets via the activated glycoprotein (GP)IIb/IIIa receptor, and to a su...

Progress in pharmaceutical development is highly-dependent on preclinical in vivo animal studies. Small animal imaging is invaluable for the identification of new disease markers and the evaluation of drug efficacy. Here, we report for the first time the use of a three-dimensional fluorescence bioimager called FLuorescence Emission Computed Tomography (FLECT) for the detection of a novel recomb...

RATIONALE: Myocardial infarction and stroke are leading causes of morbidity/mortality. The typical underlying pathology is the formation of thrombi/emboli and subsequent vessel occlusion. Systemically administered fibrinolytic drugs are the most effective pharmacological therapy. However, bleeding complications are relatively common and this risk as such limits their broader use. Furthermore...

Rationale: Genetic therapy using modified mRNA for specific therapeutic protein expression for disease treatment and vaccination represents a new field of therapeutic and diagnostic medicine. Non-viral vectors transfection using biocompatible nanoliposomes enables safe and efficient delivery of therapeutic mRNA. Objective: Generation of non-toxic, cell-compatible cationic nanoliposomes as nanot...