Mass spectrometric study of molecular and ionic sublimation of lanthanum triiodide

The molecular and ionic composition of saturated vapor over lanthanum triiodide was studied by Knudsen effusion mass spectrometry. The (LaI3)n molecules (n = 1–3) and the [I(LaI3)n]− ions (n = 0–4) were observed. The partial pressures of the molecules were determined and the enthalpies of sublimation, ΔsH° (298.15 K) in kJ mol−1, in the form of monomers (304 ± 7), dimers (428 ± 25), and trimers (455 ± 50) were obtained by the second and third laws of thermodynamics. The enthalpy of formation, ΔfH° (298.15 K) in kJ mol−1, of the LaI3 (−376 ± 10), La2I6 (−932 ± 25), La3I9 (−1585 ± 50) molecules and the LaI4− (−841 ± 24), La2I7− (−1486 ± 32) ions were determined. The electron work function, φe = 3.5 ± 0.3 eV, for the LaI3 crystal was calculated from the thermochemical cycle.

Percutaneous screw fixation of the iliosacral joint: optimal screw pathways are frequently not completely intraosseous

INTRODUCTION In iliosacral screw fixation, the dimensions of solely intraosseous (secure) pathways, perpendicular to the ilio-sacral articulation (optimal) with corresponding entry (EP) and aiming points (AP) on lateral fluoroscopic projections, and the factors (demographic, anatomic) influencing these have not yet been described. METHODS In 100 CTs of normal pelvises, the height and width of the secure and optimal pathways were measured on axial and coronal views bilaterally (total measurements: n=200). Corresponding EP and AP were defined as either the location of the screw head or tip at the crossing of lateral innominate bones' cortices (EP) and sacral midlines (AP) within the centre of the pathway, respectively. EP and AP were transferred to the sagittal pelvic view using a coordinate system with the zero-point in the centre of the posterior cortex of the S1 vertebral body (x-axis parallel to upper S1 endplate). Distances are expressed in relation to the anteroposterior distance of the S1 upper endplate (in %). The influence of demographic (age, gender, side) and/or anatomic (PIA=pelvic incidence angle; TCA=transversal curvature angle, PID-Index=pelvic incidence distance-index; USW=unilateral sacral width-index) parameters on pathway dimensions and positions of EP and AP were assessed (multivariate analysis). RESULTS The width, height or both factors of the pathways were at least 7mm or more in 32% and 53% or 20%, respectively. The EP was on average 14±24% behind the centre of the posterior S1 cortex and 41±14% below it. The AP was on average 53±7% in the front of the centre of the posterior S1 cortex and 11±7% above it. PIA influenced the width, TCA, PID-Index the height of the pathways. PIA, PID-Index, and USW-Index significantly influenced EP and AP. Age, gender, and TCA significantly influenced EP. CONCLUSION Secure and optimal placement of screws of at least 7mm in diameter will be unfeasible in the majority of patients. Thoughtful preoperative planning of screw placement on CT scans is advisable to identify secure pathways with an optimal direction. For this purpose, the presented methodology of determining and transferring EPs and APs of corresponding pathways to the sagittal pelvic view using a coordinate system may be useful.

Murine coronavirus ubiquitin-like domain is important for papain-like protease stability and viral pathogenesis

Ubiquitin-like domains (Ubls) now are recognized as common elements adjacent to viral and cellular proteases; however, their function is unclear. Structural studies of the papain-like protease (PLP) domains of coronaviruses (CoVs) revealed an adjacent Ubl domain in severe acute respiratory syndrome CoV, Middle East respiratory syndrome CoV, and the murine CoV, mouse hepatitis virus (MHV). Here, we tested the effect of altering the Ubl adjacent to PLP2 of MHV on enzyme activity, viral replication, and pathogenesis. Using deletion and substitution approaches, we identified sites within the Ubl domain, residues 785 to 787 of nonstructural protein 3, which negatively affect protease activity, and valine residues 785 and 787, which negatively affect deubiquitinating activity. Using reverse genetics, we engineered Ubl mutant viruses and found that AM2 (V787S) and AM3 (V785S) viruses replicate efficiently at 37°C but generate smaller plaques than wild-type (WT) virus, and AM2 is defective for replication at higher temperatures. To evaluate the effect of the mutation on protease activity, we purified WT and Ubl mutant PLP2 and found that the proteases exhibit similar specific activities at 25°C. However, the thermal stability of the Ubl mutant PLP2 was significantly reduced at 30°C, thereby reducing the total enzymatic activity. To determine if the destabilizing mutation affects viral pathogenesis, we infected C57BL/6 mice with WT or AM2 virus and found that the mutant virus is highly attenuated, yet it replicates sufficiently to elicit protective immunity. These studies revealed that modulating the Ubl domain adjacent to the PLP reduces protease stability and viral pathogenesis, revealing a novel approach to coronavirus attenuation. IMPORTANCE Introducing mutations into a protein or virus can have either direct or indirect effects on function. We asked if changes in the Ubl domain, a conserved domain adjacent to the coronavirus papain-like protease, altered the viral protease activity or affected viral replication or pathogenesis. Our studies using purified wild-type and Ubl mutant proteases revealed that mutations in the viral Ubl domain destabilize and inactivate the adjacent viral protease. Furthermore, we show that a CoV encoding the mutant Ubl domain is unable to replicate at high temperature or cause lethal disease in mice. Our results identify the coronavirus Ubl domain as a novel modulator of viral protease stability and reveal manipulating the Ubl domain as a new approach for attenuating coronavirus replication and pathogenesis.

Utility of electrophysiological studies to predict arrhythmic events

AIM To evaluate the prognostic value of electrophysiological stimulation (EPS) in the risk stratification for tachyarrhythmic events and sudden cardiac death (SCD). METHODS We conducted a prospective cohort study and analyzed the long-term follow-up of 265 consecutive patients who underwent programmed ventricular stimulation at the Luzerner Kantonsspital (Lucerne, Switzerland) between October 2003 and April 2012. Patients underwent EPS for SCD risk evaluation because of structural or functional heart disease and/or electrical conduction abnormality and/or after syncope/cardiac arrest. EPS was considered abnormal, if a sustained ventricular tachycardia (VT) was inducible. The primary endpoint of the study was SCD or, in implanted patients, adequate ICD-activation. RESULTS During EPS, sustained VT was induced in 125 patients (47.2%) and non-sustained VT in 60 patients (22.6%); in 80 patients (30.2%) no arrhythmia could be induced. In our cohort, 153 patients (57.7%) underwent ICD implantation after the EPS. During follow-up (mean duration 4.8 ± 2.3 years), a primary endpoint event occurred in 49 patients (18.5%). The area under the receiver operating characteristic curve (AUROC) was 0.593 (95%CI: 0.515-0.670) for a left ventricular ejection fraction (LVEF) < 35% and 0.636 (95%CI: 0.563-0.709) for inducible sustained VT during EPS. The AUROC of EPS was higher in the subgroup of patients with LVEF ≥ 35% (0.681, 95%CI: 0.578-0.785). Cox regression analysis showed that both, sustained VT during EPS (HR: 2.26, 95%CI: 1.22-4.19, P = 0.009) and LVEF < 35% (HR: 2.00, 95%CI: 1.13-3.54, P = 0.018) were independent predictors of primary endpoint events. CONCLUSION EPS provides a benefit in risk stratification for future tachyarrhythmic events and SCD and should especially be considered in patients with LVEF ≥ 35%.

Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial

BACKGROUND Clinical trials yielded conflicting data about the benefit of adding systemic corticosteroids for treatment of community-acquired pneumonia. We assessed whether short-term corticosteroid treatment reduces time to clinical stability in patients admitted to hospital for community-acquired pneumonia. METHODS In this double-blind, multicentre, randomised, placebo-controlled trial, we recruited patients aged 18 years or older with community-acquired pneumonia from seven tertiary care hospitals in Switzerland within 24 h of presentation. Patients were randomly assigned (1:1 ratio) to receive either prednisone 50 mg daily for 7 days or placebo. The computer-generated randomisation was done with variable block sizes of four to six and stratified by study centre. The primary endpoint was time to clinical stability defined as time (days) until stable vital signs for at least 24 h, and analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00973154. FINDINGS From Dec 1, 2009, to May 21, 2014, of 2911 patients assessed for eligibility, 785 patients were randomly assigned to either the prednisone group (n=392) or the placebo group (n=393). Median time to clinical stability was shorter in the prednisone group (3·0 days, IQR 2·5-3·4) than in the placebo group (4·4 days, 4·0-5·0; hazard ratio [HR] 1·33, 95% CI 1·15-1·50, p<0·0001). Pneumonia-associated complications until day 30 did not differ between groups (11 [3%] in the prednisone group and 22 [6%] in the placebo group; odds ratio [OR] 0·49 [95% CI 0·23-1·02]; p=0·056). The prednisone group had a higher incidence of in-hospital hyperglycaemia needing insulin treatment (76 [19%] vs 43 [11%]; OR 1·96, 95% CI 1·31-2·93, p=0·0010). Other adverse events compatible with corticosteroid use were rare and similar in both groups. INTERPRETATION Prednisone treatment for 7 days in patients with community-acquired pneumonia admitted to hospital shortens time to clinical stability without an increase in complications. This finding is relevant from a patient perspective and an important determinant of hospital costs and efficiency. FUNDING Swiss National Science Foundation, Viollier AG, Nora van Meeuwen Haefliger Stiftung, Julia und Gottfried Bangerter-Rhyner Stiftung.