Effect of the integration method on the accuracy and computational efficiency of free energy calculations using thermodynamic integration

Although calculations of free energy using molecular dynamics simulations have gained significant importance in the chemical and biochemical fields, they still remain quite computationally intensive. Furthermore, when using thermodynamic integration, numerical evaluation of the integral of the Hamiltonian with respect to the coupling parameter may introduce unwanted errors in the free energy. In this paper, we compare the performance of two numerical integration techniques-the trapezoidal and Simpson's rules and propose a new method, based on the analytic integration of physically based fitting functions that are able to accurately describe the behavior of the data. We develop and test our methodology by performing detailed studies on two prototype systems, hydrated methane and hydrated methanol, and treat Lennard-Jones and electrostatic contributions separately. We conclude that the widely used trapezoidal rule may introduce systematic errors in the calculation, but these errors are reduced if Simpson's rule is employed, at least for the electrostatic component. Furthermore, by fitting thermodynamic integration data, we are able to obtain precise free energy estimates using significantly fewer data points (5 intermediate states for the electrostatic component and 11 for the Lennard-Jones term), thus significantly decreasing the associated computational cost. Our method and improved protocol were successfully validated by computing the free energy of more complex systems hydration of 2-methylbutanol and of 4-nitrophenol-thus paving the way for widespread use in solvation free energy calculations of drug molecules

Translation and initial validation of the Medication Adherence Report Scale (MARS) in Italian patients with Crohn's Disease

The MARS-5 (Medication Adherence Report Scale) was developed in English. The aim of this project was to analyse the MARS-5I (© Prof Rob Horne) psychometric properties and to identify whether its Italian translation is suitable for assessing medication adherence in Crohn Disease (CD) Italian patients. The MARS was translated and linguistically validated in Italian. The MARS-5I was used for evaluating medication adherence in the SOLE study, conducted in Italy on 552 subjects with CD. In order to un-bias the questionnaire results from the effects of treatment change and/or effectiveness, the analyses were performed on the 277 patients whose disease activity remained stable, selected among the 371 patients who maintained the same treatment between two consecutive visits. Internal consistency was high (Cronbach's alpha of 0.86). Pearson's correlation coefficient was 0.50 (p < 0.001) and 0.86 (p < 0.001- outliers removed), indicating satisfactory test-retest. MARS 5I scores were not correlated with Treatment Satisfaction Questionnaire for Medication but a small and statistically significant correlation was shown with physician-evaluated medication adherence, indicating convergent validity. MARS-5I, the Italian translation of the English MARS, showed satisfactory internal consistency and test-retest, and a low but statistically significant convergent validity. We confirmed the utility of this tool in patients with CD

A two-step target binding and selectivity support vector machines approach for virtual screening of dopamine receptor subtype-selective ligands

10.1371/journal.pone.0039076PLoS ONE76

Comparison between the invasive PSV and The helmet-NPPV for weaning from mechanical ventilation of patient with ARF

S.I.A.A.R.T.I. 60\ub0Congresso Nazional

Effects of tracheal intubation on ventilation with LMA Classic (TM) for percutaneous dilation tracheostomy

Aim. The classic laryngeal mask airway (cLMATM) can be used in place of an endotracheal tube (ETT) as the ventilatory device during percutaneous dilational tracheostomy (PDT). We aimed to investigate the possible loss of effica- cy of cLMATM after tracheal intubation. Methods. Severity of laryngeal lesions and efficacy of cLMATM were determined in two groups of thirty patients each who were switched from ETT ventilation to cLMA ventilation for PDT after a short (12 days) tracheal intubation. Results. cLMATM allowed us to carry out PDT in all patients. Short tracheal intubations resulted in mild lesions of the larynx and mild gas leaks during cLMATM ventilation. Longer intubations caused moderate-to-severe (P<0.05) lesions of the larynx and larger gas leaks. A single complication occurred in one patient post-procedurally and in no patient at 6-month follow-up. Conclusion. Efficacy of cLMATM was maintained after short tracheal intubation and decreased after long intubation

Mechanisms of post-prandial protein accretion in human skeletal muscle: insight from leucine and phenylalanine forearm kinetics.

none5IF: 12.015noneP. TESSARI; M. ZANETTI; R. BARAZZONI; M. VETTORE; F. MICHIELAN.Tessari, Paolo; M., Zanetti; R., Barazzoni; Vettore, Monica; F., Michiela

Occurrence of pneumothorax during noninvasive positive pressure ventilation through a helmet

A 79-year-old woman presented with hypoxemic acute respiratory failure secondary to pneumonia and was started on continuous noninvasive positive pressure ventilation (NPPV) by helmet. Patient improved over first two days of NPPV, but worsened suddenly on the third day because of development of a pneumothorax. Pneumothorax may have been caused by barotrauma from desynchronization between patient and ventilator

Protein C concentrate to restore physiological values in adult septic patients

To describe the efficacy and safety of protein C (PC) concentrate to restore physio- logical values in adult septic patients having clinical contraindications to activated PC. Design: Case series (pilot study). Setting: Three adult ICUs of a University Hospital. Patients and participants: Twenty adult patients affected by severe sep- sis or septic shock with plasma values of PC \ 50%. Interven- tions: Patients were treated with PC concentrate (Ceprotin 2\u2013\u2013Baxter) with a starting bolus followed by a continuous infusion for 72 h [3 IU/ (kg h)]. Measurements and results: PC activity, WBC, platelets, D-Dimer, fibrinogen, PT, aPTT, AT III, lactate, Sepsis-related Organ Failure Assess- ment (SOFA), Disseminated Intravascular Coagulation (DIC) score, adverse events, and mortality were measured. Baseline plasma PC activity was 34.5 \ub1 9.1%. PC con- centrate normalized the PC activity in all patients within 48 h, and then remained stable for the following days. At baseline, several patients showed abnormal PT, aPTT, platelets values, and lactate levels. During the study period, there was a significant increase of platelets, fibrinogen, PT, AT III, and a significant decrease of D-Dimer, aPTT, DIC score, and lac- tate. No adverse reactions (hemorrhage or thrombosis) were observed. Mortality at 28 days was 35%. Conclusions: Our pilot study shows that the administration of PC concentrate to patients having con- traindications to the treatment with activated PC was safe and possibly useful to control the coagulopathy triggered and sustained by sepsis. A randomized, double blind study in patients with severe sepsis and con- traindications to activated PC administration would be advisable to state the safety and the possible role of this product in the treatment of severe sepsis