Arginase II Promotes Macrophage Inflammatory Responses Through Mitochondrial Reactive Oxygen Species, Contributing to Insulin Resistance and Atherogenesis

Macrophage-mediated chronic inflammation is mechanistically linked to insulin resistance and atherosclerosis. Although arginase I is considered antiinflammatory, the role of arginase II (Arg-II) in macrophage function remains elusive. This study characterizes the role of Arg-II in macrophage inflammatory responses and its impact on obesity-linked type II diabetes mellitus and atherosclerosis.

Persistent Left Superior Vena Cava in Cardiac Congenital Surgery

Persistent left superior vena cava (LSVC) is a relatively frequent finding in congenital cardiac malformation. The scope of the study was to analyze the timing of diagnosis of persistent LSVC, the timing of diagnosis of associated anomalies of the coronary sinus, and the global impact on morbidity and mortality of persistent LSVC in children with congenital heart disease after cardiac surgery. Retrospective analysis of a cohort of children after cardiac surgery on bypass for congenital heart disease. Three hundred seventy-one patients were included in the study, and their median age was 2.75 years (IQR 0.65-6.63). Forty-seven children had persistent LSVC (12.7 %), and persistent LSVC was identified on echocardiography before surgery in 39 patients (83 %). In three patients (6.4 %) with persistent LSVC, significant inflow obstruction of the left ventricle developed after surgery leading to low output syndrome or secondary pulmonary hypertension. In eight patients (17 %), persistent LSVC was associated with a partially or completely unroofed coronary sinus and in two cases (4 %) with coronary sinus ostial atresia. Duration of mechanical ventilation was significantly shorter in the control group (1.2 vs. 3.0 days, p = 0.04), whereas length of stay in intensive care did not differ. Mortality was also significantly lower in the control group (2.5 vs. 10.6 %, p = 0.004). The results of study show that persistent LSVC in association with congenital cardiac malformation increases the risk of mortality in children with cardiac surgery on cardiopulmonary bypass. Recognition of a persistent LSVC and its associated anomalies is mandatory to avoid complications during or after cardiac surgery.

Thoraxschmerzen bei Kindern und Jugendlichen - das Herz?

Chest pain in children and adolescents is a frequent observation, although potentially relevant disease is rather rare and then found in situations with acute presentation. In children with an inflammatory/infectious clinical context the differential diagnosis is oesophagitis, pleuropneumonia or pericarditis. Potentially dangerous complications may be found in youth with predisposing conditions for aortic dissection, pneumothorax or pulmonary embolism, or even in rare instances for an acute coronary complication. In these cases aggressive diagnostic work-up is mandatory. In the frequent elective outpatient evaluation of teenagers with long-lasting episodes of chest pain, relevant underlying cardiovascular disease only rarely can be found as the cause. In the elective outpatient evaluation for chest pain, usually patient history and clinical examination may be enough to track the problem, the main role of the physician is to provide reassurance with minimal but appropriate testing.

On supercurrent superfields and Fayet–Iliopoulos terms in N=1N=1 gauge theories

We revisit the supermultiplet structure of Noether currents for N=1 supersymmetric gauge theories. Using superfield identities and the field equations we show how to derive a superfield equation for the divergences of the Noether currents in terms of the supercurrent and anomaly superfields containing 16_B+16_F components. We refer to this as the natural supercurrent structure as it is invariant under all local symmetries of the theory. It corresponds to the S-multiplet of Komargodski and Seiberg. We clarify the on/off-shell nature of the currents appearing in this multiplet and we study in detail the effect of specific improvement transformations leading to 1) a Ferrara-Zumino multiplet and to 2) a multiplet containing the new improved energy-momentum tensor of Callan, Coleman and Jackiw. Our methods also apply to supersymmetric gauge theories with a Fayet-Iliopoulos term. We construct the natural supercurrent multiplet for such a theory and show how to improve this to a formally gauge-invariant Ferrara-Zumino multiplet by introducing a non-dynamical chiral superfield S to ensure superfield gauge invariance. Finally we study the coupling of this theory to supergravity and show that S remains non-dynamical if the theory is R-symmetric and that S becomes propagating if the theory is not R-symmetric, leading to non-minimal 16_B+16_F supergravity

A high-resolution soil erosion risk map of Switzerland as strategic policy support system

Soil erosion models and soil erosion risk maps are often used as indicators to assess potential soil erosion in order to assist policy decisions. This paper shows the scientific basis of the soil erosion risk map of Switzerland and its application in policy and practice. Linking a USLE/RUSLE-based model approach (AVErosion) founded on multiple flow algorithms and the unit contributing area concept with an extremely precise and high-resolution digital terrain model (2 m × 2 m grid) using GIS allows for a realistic assessment of the potential soil erosion risk, on single plots, i.e. uniform and comprehensive for the agricultural area of Switzerland (862,579 ha in the valley area and the lower mountain regions). The national or small-scale soil erosion prognosis has thus reached a level heretofore possible only in smaller catchment areas or single plots. Validation was carried out using soil loss data from soil erosion damage mappings in the field from long-term monitoring in different test areas. 45% of the evaluated agricultural area of Switzerland was classified as low potential erosion risk, 12% as moderate potential erosion risk, and 43% as high potential erosion risk. However, many of the areas classified as high potential erosion risk are located at the transition from valley to mountain zone, where many areas are used as permanent grassland, which drastically lowers their current erosion risk. The present soil erosion risk map serves on the one hand to identify and prioritise the high-erosion risk areas, and on the other hand to promote awareness amongst farmers and authorities. It was published on the internet and will be made available to the authorities in digital form. It is intended as a tool for simplifying and standardising enforcement of the legal framework for soil erosion prevention in Switzerland. The work therefore provides a successful example of cooperation between science, policy and practice.

Glucagon-like peptide-1 is involved in sodium and water homeostasis in humans

In previous studies with glucagon-like peptide-1 (GLP-1) we have observed that this peptide modulates fluid intake and increases renal sodium excretion in healthy volunteers and in patients with diabetes mellitus type 2. The effect of GLP-1 on thirst, water intake and on osmoregulation has, however, not been examined in detail in humans.

Interferon-inducible expression of APOBEC3 editing enzymes in human hepatocytes and inhibition of hepatitis B virus replication

Hypermutations in hepatitis B virus (HBV) DNA by APOBEC3 cytidine deaminases have been detected in vitro and in vivo, and APOBEC3G (A3G) and APOBEC3F (A3F) have been shown to inhibit the replication of HBV in vitro, but the presumably low or even absent hepatic expression of these enzymes has raised the question as to their physiological impact on HBV replication. We show that normal human liver expresses the mRNAs of APOBEC3B (A3B), APOBEC3C (A3C), A3F, and A3G. In primary human hepatocytes, interferon alpha (IFN-alpha) stimulated the expression of these cytidine deaminases up to 14-fold, and the mRNAs of A3G, A3F, and A3B reached expression levels of 10%, 3%, and 3%, respectively, relative to GAPDH mRNA abundance. On transfection, the full-length protein A3B(L) inhibited HBV replication in vitro as efficiently as A3G or A3F, whereas the truncated splice variant A3B(S) and A3C had no effect. A3B(L) and A3B(S) were detected predominantly in the nucleus of uninfected cells; however, in HBV-expressing cells both proteins were found also in the cytoplasm and were associated with HBV viral particles, similarly to A3G and A3F. Moreover, A3G, A3F, and A3B(L), but not A3B(S), induced extensive G-to-A hypermutations in a fraction of the replicated HBV genomes. In conclusion, the editing enzymes A3B(L), A3F, and most markedly A3G, which are expressed in liver and up-regulated by IFN-alpha in hepatocytes, are candidates to contribute to the noncytolytic clearance of HBV.

Sodium pump reduction correlates with aortic clamp time in pediatric heart surgery

Myocardial depression after cardiac surgery is modulated by cardiopulmonary bypass (CPB) and the underlying heart disease. The sodium pump is a key component for myocardial function. We hypothesized that the change in sodium pump expression during CPB correlates with intraoperative and postoperative laboratory and clinical parameters in neonates and children with various congenital heart defects. Sodium pump isoforms alpha1 (ATP1A1) and alpha3 (ATP1A3) mRNA expression in right atrial myocardium, excised before and after CPB, was quantified. Groups were assigned according to presence (VO group, n = 8) or absence (NO group, n = 8) of right atrial volume overload. CPB and aortic clamp time correlated with postoperative troponin-I values and ICU stay. ATP1A1 (P = 0.008) and ATP1A3 (P = 0.038) mRNA expression were significantly reduced during CPB. Longer aortic clamp times were associated with lower postoperative ATP1A1 (P = 0.045) and ATP1A3 (P = 0.002) mRNA expression. Low postoperative ATP1A1 (P = 0.043) and ATP1A3 (P = 0.002) expressions were associated with high troponin-I values. These results were restricted to the VO group. No correlation of sodium pump mRNA expression was found with the duration of ICU stay or ventilation. The postoperative troponin-I and clinical parameters correlated with the length of CPB, regardless of volume overload. In contrast, only dilated right atrium seemed to be susceptible to CPB in terms of sodium pump expression, showing a reduction during the operation and a correlation of sodium pump with postoperative troponin-I values.

Important excess morbidity due to upper airway anomalies in the perioperative course in infant cardiac surgery

BACKGROUND: The study aimed at defining the excess morbidity or mortality caused by an additional airway malformation in children with congenital heart disease requiring surgery. METHODS: All patients requiring surgery for heart disease during an 8-year period ending in 2003 who had an associated upper airway malformation were retrospectively studied. All patients were seen in 2004 for a prospective follow-up examination. RESULTS: Eleven patients with upper airway anomalies were identified (tracheobronchial malacia in 6 patients, long-segment tracheal stenosis in 3, and bilateral vocal cord paralysis and tracheal hemangioma in 1 patient each). They accounted for 1.5% of the entire cardiac surgical load of 764 patients. In 5 infants, the airway anomaly was diagnosed before cardiac repair, in 6 patients thereafter. Diagnosis was made by bronchoscopy in all patients, by additional bronchography in 2. Failure of rapid postoperative extubation was the most common finding. Airway management was surgical in 2 and conservative in 8 patients, 1 newborn having been denied therapy because of the severity of airway hypoplasia. Compared with patients with isolated cardiac disease, those with additional airway anomalies had significantly longer duration of postoperative mechanical ventilation (median, 24 days versus 3), perioperative hospitalization (median, 72 days versus 11) and total number of days of hospitalization during the first year of life (median, 104 days versus 14). After a maximum follow-up of 8 years (median, 37 months) only 3 of 10 surviving patients remained symptomatic owing to the airway malformation. CONCLUSIONS: Upper airway anomalies accompanying heart disease in infancy resulted in a significant prolongation of perioperative intensive care and hospital stay, as well as duration of mechanical ventilation. Failure of early postoperative extubation was the leading symptom.

Reduced atrial connexin43 expression after pediatric heart surgery

Myocardial dysfunction and arrhythmias may be induced by congenital heart defects, but also be the result of heart surgery with cardiopulmonary bypass (CPB), potentially caused by differential expression of connexin40 (Cx40) and connexin43 (Cx43). In 16 pediatric patients undergoing corrective heart surgery, connexin mRNA expression was studied in volume overloaded (VO group, n=8) and not overloaded (NO group, n=8) right atrial myocardium, excised before and after CPB. Additionally, in eight of these patients ventricular specimens were investigated. The atrial Cx43 expression decreased during CPB, which was restricted to the VO group (p=0.008). In contrast, atrial Cx40 mRNA did not change during CPB. In ventricular myocardium compared to atrial mRNA levels, Cx40 was lower (p=0.006) and Cx43 higher (p=0.017) expressed, without significant change during CPB. This study revealed a significant influence of CPB and the underlying heart defect on Cx43 expression.