Haem-regulated eIF2alpha kinase is necessary for adaptive gene expression in erythroid precursors under the stress of iron deficiency

Haem-regulated eIF2alpha kinase (HRI) is essential for the regulation of globin gene translation and the survival of erythroid precursors in iron/haem deficiency. This study found that that in iron deficiency, fetal definitive erythropoiesis is inhibited at the basophilic erythroblast stage with increased proliferation and elevated apoptosis. This hallmark of ineffective erythropoiesis is more severe in HRI deficiency. Microarray gene profiling analysis showed that HRI was required for adaptive gene expression in erythroid precursors during chronic iron deficiency. The number of genes with expression affected more than twofold increased, from 213 in iron deficiency and 73 in HRI deficiency, to 3135 in combined iron and HRI deficiencies. Many of these genes are regulated by Gata1 and Fog1. We demonstrate for the first time that Gata1 expression in developing erythroid precursors is decreased in iron deficiency, and is decreased further in combined iron and HRI deficiencies. Additionally, Fog1 expression is decreased in combined deficiencies, but not in iron or HRI deficiency alone. Our results indicate that HRI confers adaptive gene expression in developing erythroblasts during iron deficiency through maintaining Gata1/Fog1 expression.     

Contrast transesophageal echocardiographic detection of a pulmonary arteriovenous malformation draining into left lower pulmonary vein

We report the identification of a pulmonary arteriovenous malformation draining into the left lower pulmonary vein by contrast two-dimensional transesophageal echocardiography in an adult with no evidence of hereditary hemorrhagic telangiectasia. To our knowledge, this has not been reported previously. This study also emphasizes the importance of transesophageal echocardiographic examination of the left lower pulmonary vein in the detection of a pulmonary arteriovenous malformation.     

Collaborative care for the wearable cardioverter defibrillator patient: Getting the patient and medical team “vested and active”

Patients with a reduced ejection fraction of 35% or less and a history of myocardial infarction (MI) are at increased risk of sudden cardiac death (SCD). These patients have a class I indication for an implantable cardioverter‐defibrillator after allowing time for medical therapy optimization and potential cardiac recovery. The rates of SCD are highest in this “gap” period early after a cardiac event, and the wearable cardioverter‐defibrillator (WCD) is an intervention that can be used to protect against SCD during this time period. There has been a clinical trial that randomized patients with a reduced ejection fraction at the time of MI to a WCD versus control. Results of the trial showed no statistically significant difference in the primary endpoint of SCD. There are many intricacies to the interpretation of the trial, including the importance of patient adherence to WCD therapy, which is affected by the patient experience and psychological factors. Patients with a new cardiomyopathy are affected by a mix of psychological factors, including the feeling of safety and protection from a WCD contrasted by the WCD providing a reminder of awareness and fear of ventricular arrhythmias and SCD. Beyond the capabilities of a WCD to defibrillate a life‐threatening ventricular arrhythmia, the device can also provide activity and heart failure diagnostics monitoring. Patients need to be engaged in shared decision‐making conversations about a WCD, so that patients can make a decision based on their own values construct, ultimately increasing adherence among the patients that want a WCD.     

Transesophageal Three-Dimensional Echocardiographic Assessment of Left Main Coronary Artery Fistula

We describe a patient with a left main coronary artery fistula with an opening at the superior vena cava-right atrial junction in whom three-dimensional transesophageal echocardiography permitted more accurate assessment of the shape and size of the communication site than two-dimensional transesophageal echocardiography.     

Transesophageal Three-Dimensional Color Doppler Echocardiographic Reconstruction of the Left Vertebral Artery

We present a patient in whom we successfully reconstructed a long segment of the proximal left vertebral artery in three dimensions using color Doppler transesophageal echocardiography (TEE). Three-dimensional (3-D) color Doppler TEE may complement two-dimensional (2-D) TEE by its ability to view cross sections of the left vertebral artery at any desired level from the 3-D data stored in the computer.     

Recombinant hemagglutinin protein of rinderpest virus expressed in insect cells induces cytotoxic T-cell responses in cattle.

Rinderpest virus (RPV), a member of the genus Morbillivirus within the Paramyxoviridae family, causes a highly contagious and often fatal disease known as rinderpest in wild and domestic ruminants. The envelope of the virus contains two surface glycoproteins, namely the hemagglutinin (H) and the fusion (F) proteins, both of which have been shown to confer protective immunity in animals. In this paper, we demonstrate that single administration of low doses of recombinant H protein of RPV expressed in insect cells in the form of extracellular virus induces long lasting bovine leukocyte antigen class I restricted cytotoxic T-cell (CTL) responses in cattle in the absence of adjuvant. This is the first report of CTL responses in cattle against one of the protective antigens of RPV.     

An Analysis of Presentation,Pattern and Outcome of Chest Trauma Patients at an Urban Level 1 Trauma Center

Chest trauma is an important public health problem accounting for a substantial proportion of all trauma admissions and deaths. It directly account for 20–25 % of deaths due to trauma. Therefore, this study was conducted to analyze the presentation, patterns, and outcome of chest trauma in a level-1 urban trauma center. It was a prospective observational study of all patients presented with chest trauma to an urban level 1-trauma center over a period of 3 years. Demographic profile, mechanism of injury, injury severity scores (ISS), associated injuries, hospital stay, etc. were recorded. Morbidity and mortality rates were analyzed and compared with the published literature. Chest injuries comprised 30.9 % of all trauma admissions and the mechanism was blunt in majority (83.5 %) of the cases. Vehicular crashes (59.7 %) followed by assault were the most common modes of injury. Rib fracture was the most common chest injury seen in 724 of the 1258 patients while abdominal visceral injuries were the commonest associated injuries in polytrauma cases. Majority of the patients were managed non-operatively. Inter costal tube drainage (ICD) was the main stay of treatment in 75 % of the cases, whereas, thoracotomy was required only in 5.56 % of the patients. Overall mortality was 11 % and it was found to be significantly higher following blunt chest trauma. We observed that associated extra thoracic injuries resulted in higher mortality as compared to isolated chest injuries. Thoracic injuries can be readily diagnosed in the emergency department by meticulous and repeated clinical evaluation and majority require simple surgical procedures to prevent immediate mortality and long-term morbidity.     

Autonomic modulation of the u wave during sympathomimetic stimulation and vagal inhibition in normal individuals

Prolonged repolarization time, an important contributor to the pathogenesis of ventricular arrhythmias, is usually identified by a long QT interval (QT) on the ECG but is frequently confounded by the presence of a U wave. The physiological basis and clinical relevance of the U wave is unresolved. To better understand the relationship between the T and U waves, this study examined their behavior during nonresting autonomic conditions. Twenty-five healthy subjects were evaluated during sympathomimetic infusion with isoproterenol and vagal inhibition with atropine. As heart rate (HR) increased in response to isoproterenol, the QU interval (QU) decreased by an eightfold greater extent than QT. Furthermore, a marked increase in U wave amplitude and decrease in T wave amplitude were observed with T and U wave fusion at higher HRs. During atropine, QU decreased by only a threefold greater extent than QT, T and U wave amplitudes were affected only minimally, and T-U wave fusion was not observed. These results demonstrate that sympathomimetic stimulation causes striking alterations in the timing and amplitude of U waves that differ from effects on the T wave. These effects are not observed during vagal inhibition. Thus, the U wave represents a component of cardiac repolarization that is electrocardiographically and physiologically distinct from the T wave with a unique response to sympathomimetic stimulation.     

The function of heme-regulated eIF2alpha kinase in murine iron homeostasis and macrophage maturation

Heme-regulated eIF2α kinase (HRI) plays an essential protective role in anemias of iron deficiency, erythroid protoporphyria, and β-thalassemia. In this study, we report that HRI protein is present in murine macrophages, albeit at a lower level than in erythroid precursors. Hri^–/– mice exhibited impaired macrophage maturation and a weaker antiinflammatory response with reduced cytokine production upon LPS challenge. The level of production of hepcidin, an important player in the pathogenesis of the anemia of inflammation, was significantly decreased in Hri^–/– mice, accompanied by decreased splenic macrophage iron content and increased serum iron content. Hepcidin expression was also significantly lower, with a concomitant increase in serum iron in Hri^–/– mice upon LPS treatment. We also demonstrated an impairment of erythrophagocytosis by Hri^–/– macrophages both in vitro and in vivo under chronic hemolytic anemia, providing evidence for the role of HRI in recycling iron from senescent red blood cells. This work demonstrates that HRI deficiency attenuates hepcidin expression and iron homeostasis in mice, indicating a potential role for HRI in the anemia of inflammation.