The ß-hairpin from the Thermus thermophilus HB27 laccase works as a pH-dependent switch to regulate laccase activity.

The multi-copper oxidase from the hyper-thermophilic bacteria Thermus thermophilus (Tth-MCO), has been previously characterized and described as an example of a laccase with low catalytic properties, especially when it is compared with the activity of fungal laccases, but it is active at high temperatures. Structurally, Tth-MCO has a unique feature: a ß-hairpin near the T1Cu site, which is not present in any other laccases deposited at the PDB. This ß-hairpin has an expected crystallographic behavior in solvent-exposed areas of a crystallized protein: lack of electron density, high B-values and several crystalline contacts with neighboring crystallographic copies; however, its dynamical behavior in solution and its biological implications have not been described. Here, we describe four new Tth-MCO crystallographic structures, and the ß-hairpin behavior has been analyzed by molecular dynamics simulations, considering the effect of pH and temperature. The ß-hairpin new crystallographic conformations described here, together with their dynamics, were used to understand the pH-restrained laccase activity of Tth-MCO against substrates as syringaldazine. Remarkably, there are insertions in laccases from Thermus and Meiothermus genus, sharing the same position and a methionine-rich composition of the Tth-MCO ß-hairpin. This unique high methionine content of the Tth-MCO ß-hairpin is responsible to coordinate, Ag+1 and Hg+1 in oxidative conditions, but Cu+1 and Cu+2 are not coordinated in crystallographic experiments, regardless of the redox conditions; however, Ag+1 addition does not affect Tth-MCO laccase activity against syringaldazine. Here, we propose that the pH-dependent ß-hairpin dynamical behavior could explain, at least in part, the inefficient laccase activity displayed by Tth-MCO in acidic pH values.

Current and research therapies for the prevention and treatment of delayed neurological syndrome associated with carbon monoxide poisoning: A narrative review.

Severe carbon monoxide (CO) poisoning causes fulminant deaths in common environment as well as neurological sequelae to survivors. Prevention of delayed neurological syndrome (DNS) after exposure to CO, the most important sequela, is based up to date on hyperbaric oxygen administration. Nevertheless, its use remains controversial due to the lack of evidence regarding its efficacy. The aim of this review is to report therapies under investigation for preventing or improving DNS, some of them with promising results in humans.

Lack of correlation between left ventricular outflow tract velocity time integral and stroke volume index in mechanically ventilated patients.

OBJECTIVE: To assess the correlation between left ventricular outflow tract velocity time integral (LVOT VTI) and stroke volume index (SVI) calculated by thermodilution methods in ventilated critically ill patients. DESIGN: A prospective, descriptive, multicenter study was performed. SETTING: Five intensive care units from university hospitals. PATIENTS: Patients older than 17 years needing mechanical ventilation and invasive hemodynamic monitoring were included. INTERVENTIONS: LVOT VTI was measured by pulsatile Doppler echocardiography. Calculations of SVI were performed through a floating pulmonary artery catheter (PAC) or a Pulse index Contour Cardiac Output (PiCCO®) thermodilution methods. MAIN VARIABLES: The relation between LVOT VTI and SVI was tested by linear regression analysis. RESULTS: One hundred and fifty-six paired measurements were compared. Mean LVOT VTI was 20.83±4.86cm and mean SVI was 41.55±9.55mL/m2. Pearson correlation index for these variables was r=0.644, p<0.001; ICC was 0.52 (CI 95% 0.4-0.63). When maximum LVOT VTI was correlated with SVI, Pearson correlation index was r=0.62, p<0.001. Correlation worsened for extreme values, especially for those with higher LVOT VTI. CONCLUSIONS: LVOT VTI could be a complementary hemodynamic evaluation in selected patients, but does not eliminate the need for invasive monitoring at the present time. The weak correlation between LVOT VTI and invasive monitoring deserves additional assessment to identify the factors affecting this disagreement.

[Characteristics of deep sedation in gastrointestinal endoscopic procedures performed by intensivists]. / Características de la sedación profunda en procesos endoscópicos gastrointestinales, realizada por médicos intensivistas.

OBJECTIVE: To determine tolerance, pain intensity, percentage of tests completed successfully and complications of deep sedation controlled by intensivists during gastrointestinal endoscopic procedures. DESIGN: A one-year, prospective observational study was carried out. SETTING: Department of Intensive Care intervention in the Endoscopy Unit of Hospital Universitario del Tajo (Spain). PATIENTS: Subjects over 15 years of age subjected to endoscopic procedures under deep sedation. RESULTS: A total of 868 patients were sedated during the study period, with the conduction of 1010 endoscopic procedures. The degree of tolerance was considered adequate («Very good¼/«Good¼) in 96.9% of the patients (95%CI: 95.7-98.1%), with a median score of 0 on the pain visual analog scale. A total of 988 endoscopic procedures were successfully completed (97.8%; 95%CI: 96.9-98.8%): 675 colonoscopies (97.1%) and 305 endoscopies (99.7%). Complications were recorded in 106 patients (12.2%; 95%CI: 10.0-14.5%). The most frequent being desaturation (6.1%), rhythm disturbances (5.1%) and hypotension (2.4%). CONCLUSION: Gastrointestinal endoscopic procedures under sedation controlled by intensivists are well tolerated and satisfactory for the patient, and are successfully completed in a very large percentage of cases. The procedures are associated with frequent minor complications that are resolved successfully.

Alveolar-interstitial pneumopathy after gold-salts compounds administration, requiring mechanical ventilation.

The pulmonary toxicity of gold salts is an uncommon cause of life-threatening respiratory failure. Currently, patients who suffer from this do not need mechanical ventilation, and the toxicity can be difficult to diagnose when it occurs in patient with an illness producing pulmonary manifestations. We report a case of severe respiratory failure due to gold salt toxicity in a patient suffering from rheumatoid arthritis requiring mechanical ventilation. At such a time, the poor respiratory function makes some diagnostic procedures harmful. The diagnosis can be made after the exclusion of other causes of rheumatoid lung when the patient's poor respiratory status precludes invasive exploration. The clinical findings, radiological features, and results of pulmonary function tests may be enough to diagnose gold-related pneumopathy. This avoids the need for bronchoscopic examination or transfer of the patient for computed tomography. Attention must be paid to this complication because the outcome and functional prognosis are better when pulmonary involvement is gold related: in our case steroid therapy was life-saving and induced complete recovery of the lung damage.

Early vs conventional extubation after cardiac surgery with cardiopulmonary bypass.

OBJECTIVES: Sedation and ventilation overnight after cardiac surgery is common practice. However, early extubation may be feasible with no increase in postoperative complications. This study examines (1) if early extubation is possible in a significant number of patients, (2) if it reduces ICU stay, and (3) if this practice increases postoperative complications. DESIGN: Prospective, controlled, randomized clinical trial. PATIENTS AND METHODS: We randomized 404 consecutive patients to early extubation (7 to 11 h postoperatively) (group A, 201 patients) or conventional extubation (between 8 and 12 AM the following day) (group B, 203 patients). Variables included type and severity of the disease, surgical risk, type of operation, operative incidences, postoperative complications, duration of mechanical ventilation, intubation and ICU stay, bleeding, reoperation, vasoactive drugs, and mortality. RESULTS: Groups were comparable. Extubation within the preestablished time was successful in 60.2% of patients in group A and 74.4% in group B. Median ICU stay was 27 h in group A and 44 h in group B (p=0.008). Discharge from ICU within the first 24 h postoperatively was 44.3% in group A and 30.5% in group B (p=0.006). There was no significant difference in complications between groups. Successfully extubated patients in group A had more reintubation and prolonged ventilation than in group B. CONCLUSIONS: (1) Sixty percent of our patients were extubated within 11 h of operation. (2) As a result, the length of stay in ICU was reduced and the percentage of patients discharged within 24 h was increased. (3) There was no increase in clinically important postoperative complications.