Outer-Sphere Contributions to the Electronic Structure of Type Zero Copper Proteins

Bioinorganic canon states that active-site thiolate coordination promotes rapid electron transfer (ET) to and from type 1 copper proteins. In recent work, we have found that copper ET sites in proteins also can be constructed without thiolate ligation (called “type zero” sites). Here we report multifrequency electron paramagnetic resonance (EPR), magnetic circular dichroism (MCD), and nuclear magnetic resonance (NMR) spectroscopic data together with density functional theory (DFT) and spectroscopy-oriented configuration interaction (SORCI) calculations for type zero Pseudomonas aeruginosa azurin variants. Wild-type (type 1) and type zero copper centers experience virtually identical ligand fields. Moreover, O-donor covalency is enhanced in type zero centers relative that in the C112D (type 2) protein. At the same time, N-donor covalency is reduced in a similar fashion to type 1 centers. QM/MM and SORCI calculations show that the electronic structures of type zero and type 2 are intimately linked to the orientation and coordination mode of the carboxylate ligand, which in turn is influenced by outer-sphere hydrogen bonding

β-Blockers and Mortality After Acute Myocardial Infarction in Patients Without Heart Failure or Ventricular Dysfunction

Background: For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if β-blockers are associated with reduced mortality. Objectives: The goal of this study was to determine the association between β-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD). Methods: This cohort study used national English and Welsh registry data from the Myocardial Ischaemia National Audit Project. A total of 179,810 survivors of hospitalization with AMI without HF or LVSD, between January 1, 2007, and June 30, 2013 (final follow-up: December 31, 2013), were assessed. Survival-time inverse probability weighting propensity scores and instrumental variable analyses were used to investigate the association between the use of β-blockers and 1-year mortality. Results: Of 91,895 patients with ST-segment elevation myocardial infarction and 87,915 patients with non–ST-segment elevation myocardial infarction, 88,542 (96.4%) and 81,933 (93.2%) received β-blockers, respectively. For the entire cohort, with >163,772 person-years of observation, there were 9,373 deaths (5.2%). Unadjusted 1-year mortality was lower for patients who received β-blockers compared with those who did not (4.9% vs. 11.2%; p < 0.001). However, after weighting and adjustment, there was no significant difference in mortality between those with and without β-blocker use (average treatment effect [ATE] coefficient: 0.07; 95% confidence interval [CI]: −0.60 to 0.75; p = 0.827). Findings were similar for ST-segment elevation myocardial infarction (ATE coefficient: 0.30; 95% CI: −0.98 to 1.58; p = 0.637) and non–ST-segment elevation myocardial infarction (ATE coefficient: −0.07; 95% CI: −0.68 to 0.54; p = 0.819). Conclusions: Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of β-blockers was not associated with a lower risk of death at any time point up to 1 year. (β-Blocker Use and Mortality in Hospital Survivors of Acute Myocardial Infarction Without Heart Failure; NCT02786654)

Long-term outcomes of oesophageal atresia without or with proximal tracheooesophageal fistula - Gross types A and B

Purpose: Because of an extended gap between esophageal pouches a variety of methods are employed to treat oesophageal atresia (OA) without (type A) or with (type B) proximal tracheooesophageal fistula. This retrospective observational study describes their single centre long-term outcomes from 1947 to 2014. Methods: Of 693 patients treated for OA 68 (9.7%) had type A (n = 58, 8.3%) or B (n = 10, 1.4%). Hospital records were reviewed. Main outcome measures were survival and oral intake. Results: Nine (13%) patients had early and 10 (15%) delayed primary anastomosis, 30 (44%) underwent reconstruction including colonic interposition (n = 13), reversed gastric tube (n = 11) and jejunum interposition (n = 6), whereas19 (28%) had died without a definite repair. Median follow up was 35 (interquartile range, 7.4-40) years. Thirty-one (63%) of 49 patients with definitive repair survived long term. Survival was 22% for early and 80% for delayed primary anastomosis, 57% for colon interposition, 82% for gastric tube and 84% for jejunum interposition. Gastrooesophageal reflux was most common after gastric tube (80%), dysphagia after colon interposition (50%), and 3 (60%) of 5 survivors with jejunum interposition had permanent feeding ostomy because of neurological disorder. Endoscopic follow-up disclosed no oesophageal cancer or dysplasia. Repair in the most recent patients from 1985 to 2014 (n = 14) included delayed primary anastomosis (n = 7), jejunum interposition (n = 6) and gastric tube (n = 1) with 93% long-term survival. Conclusion: Morbidity among long-term survivors of type A or B OA is high. With modern management survival is, however, excellent and patients without neurological disorder achieve full oral intake either after primary anastomosis or reconstruction. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Airway hyperresponsiveness, remodeling and inflammation in infants with wheeze

Abstract Background The relationship of airway hyperresponsiveness to airway remodeling and inflammation in infants with wheeze is unclear. Objective To investigate airway hyperresponsiveness, remodeling and inflammation in infants with wheeze and troublesome breathing. Methods Inclusion criteria: full-term, 3-23 months of age; doctor diagnosed wheeze and persistent recurrent troublesome breathing; without obvious structural defect, suspicion of ciliary dyskinesia, cystic fibrosis, immune deficiency or specified use of corticosteroids. Airway hyperresponsiveness (AHR) was evaluated by performing a methacholine bronchial challenge test combined with whole body pletysmography and rapid thoracoabdominal compression. Endobronchial biopsies were analyzed for remodeling (thickness of reticular basement membrane and amount of airway smooth muscle) and for inflammation (numbers of inflammatory cells). Correlation analyses were performed. Results Forty-nine infants fulfilled the inclusion criteria for the present study. Median age was 1.06 years (IQR 0.6; 1.5). Lung function was impaired in 39/49 (80%) children, at the median age of 1.1 years. Methacholine challenge was successfully performed in 38/49 children. Impaired baseline lung function correlated with AHR (p=0.047, Spearman). In children with the most sensitive quartile of AHR, the percentage of median bronchial airway smooth muscle % and the number of bronchial mast cells in airway smooth muscle were not significantly higher compared to others (p=0.057 and 0.056 respectively). No association was found between AHR and thickness of reticular basement membrane or inflammatory cells. Only a small group of children with both atopy and AHR (the most reactive quartile) had thicker airway smooth muscle area than non-atopics with AHR (p=0.031). Conclusions & Clinical Relevance These findings don not support the concept that AHR in very young children with wheeze is determined by eosinophilic inflammation or clear-cut remodeling although it is associated with impaired baseline lung function. The possible association of increased airway smooth muscle area among atopic children with AHR remains to be confirmed.Peer reviewe

EMU - A Swedish Perspective

Provides a comprehensive survey of the EMU project. Evaluates the main advantages and disadvantages of a single currency, integrating the economic and political aspects. This volume is a revised version of the report by the Swedish Government Commission on the EMU

Sverige och EMU : betänkande

Abstract is not availabl