Visceral Aorta Electrocautery Septotomy to Allow Branched Endovascular Aortic Repair in Ruptured Chronic Post-Dissection Thoraco-Abdominal Aneurysm.

PURPOSE: Endovascular repair of chronic post-dissection thoraco-abdominal aortic aneurysms (PD-TAAA) presents specific technical challenges due to the presence of chronic septum. Small true lumen diameter and false lumen visceral vessel origin can make branched endograft prohibitive. Septotomy may allow to overcome these challenges in cases of high complex anatomy. TECHNIQUE: We describe the application of electrocautery septotomy to the visceral aorta segment to deploy an off-the-shelf branched endograft in a chronic PD-TAAA rupture with true lumen collapse. CONCLUSIONS: Electrocautery septotomy can be an effective adjunctive technique to facilitate branched endograft, overcoming technical challenges associated with the endovascular treatment of chronic PD-TAAA. CLINICAL IMPACT: Electrocautery septotomy is an adjunctive technique that can facilitate endovascular treatment of post-dissection thoraco-abdominal aneurysm. By creating a common lumen, this technique might reduce the number of re-interventions associated with PD-TAAA endovascular exclusion.

Impact of Universal Use of the McGrath Videolaryngoscope as a Device for All Intubations in the Cardiac Operating Room. A Prospective Before-After VIDEOLAR-CAR Study.

OBJECTIVE: Tracheal intubation in cardiac surgery patients has a higher incidence of difficult laryngoscopic views compared with patients undergoing other types of surgery. The authors hypothesized that using the McGrath Mac videolaryngoscope as the first intubation option for cardiac surgery patients improves the percentage of patients with "easy intubation" compared with using a direct Macintosh laryngoscope. DESIGN: A prospective, observational, before-after study. SETTING: At a tertiary-care hospital. PARTICIPANTS: One thousand one hundred nine patients undergoing cardiac surgery. INTERVENTION: Consecutive patients undergoing cardiac surgery were intubated using, as the first option, a Macintosh laryngoscope (preinterventional phase) or a McGrath Mac videolaryngoscope (interventional phase). MEASUREMENTS AND MAIN RESULTS: The main objective was to assess whether the use of the McGrath videolaryngoscope, as the first intubation option, improves the percentage of patients with "easy intubation," defined as successful intubation on the first attempt, modified Cormack-Lehane grades of I or IIa, and the absence of the need for adjuvant airway devices. A total of 1,109 patients were included, 801 in the noninterventional phase and 308 in the interventional phase. The incidence of "easy intubation" was 93% in the interventional phase versus 78% in the noninterventional phase (p < 0.001). First-success-rate intubation was higher in the interventional phase (304/308; 98.7%) compared with the noninterventional phase (754/801, 94.1%; p = 0.005). Intubation in the interventional phase showed decreases in the incidence of difficult laryngoscopy (12/308 [3.9%] v 157/801 [19.6%]; p < 0.001), as well as moderate or difficult intubation (5/308 [1.6%] v 57/801 [7.1%]; p < 0.001). CONCLUSIONS: The use of the McGrath videolaryngoscope as the first intubation option for tracheal intubation in cardiac surgery improves the percentage of patients with "easy" intubation," increasing glottic view and first-success-rate intubation and decreasing the incidence of moderate or difficult intubation.

Rationalizing the Design of Pluronics-Surfactant Mixed Micelles through Molecular Simulations and Experiments.

Aqueous systems comprising polymers and surfactants are technologically important complex fluids with tunable features dependent on the chemical nature of each constituent, overall composition in mixed systems, and solution conditions. The phase behavior and self-assembly of amphiphilic polymers can be changed drastically in the presence of conventional ionic surfactants and need to be clearly understood. Here, the self-aggregation dynamics of a triblock copolymer (Pluronics L81, EO3PO43EO3) in the presence of three cationic surfactants (with a 12C long alkyl chain but with different structural features), viz., dodecyltrimethylammonium bromide (DTAB), didodecyldimethylammonium bromide (DDAB), and ethanediyl-1,2-bis(dimethyldodecylammonium bromide) (12-2-12), were investigated in an aqueous solution environment. The nanoscale micellar size expressed as hydrodynamic diameter (Dh) of copolymer-surfactant mixed aggregates was evaluated using dynamic light scattering, while the presence of a varied micellar geometry of L81-cationic surfactant mixed micelles were probed using small-angle neutron scattering. The obtained findings were further validated from molecular dynamics (MD) simulations, employing a simple and transferable coarse-grained molecular model based on the MARTINI force field. L81 remained molecularly dissolved up to ∼20 °C but phase separated, forming turbid/translucent dispersion, close to its cloud point (CP) and existed as unstable vesicles. However, it exhibited interesting solution behavior expressed in terms of the blue point (BP) and the double CP in the presence of different surfactants, leading to mixed micellar systems with a triggered morphology transition from unstable vesicles to polymer-rich micelles and cationic surfactant-rich micelles. Such an amendment in the morphology of copolymer nanoaggregates in the presence of cationic surfactants has been well observed from scattering data. This is further rationalized employing the MD approach, which validated the effective interactions between Pluronics-cationic surfactant mixed micelles. Thus, our experimental results integrated with MD yield a deep insight into the nanoscale interactions controlling the micellar aggregation (Pluronics-rich micelles and surfactant-rich micelles) in the investigated mixed system.

Early Experience of Inner Branch Retrograde Cannulation With E-nside Branch Stent Graft for Thoracoabdominal Aortic Aneurysms.

PURPOSE: The aim of our study is to investigate the feasibility of retrograde cannulation using devices with inner branches (IB) for the endovascular treatment of thoracoabdominal aortic aneurysms (TAAAs). MATERIALS AND METHODS: A retrospective analysis using IB configuration with retrograde cannulation was carried out on TAAAs patients undergoing endovascular treatment. RESULTS: Seven patients underwent IB endovascular treatment with retrograde cannulation between September 2020 and November 2021. The mean age was 80.4 years and 4 patients were male. A total of 26 of 28 target vessels were cannulated by retrograde access with a technical success of 93% (2 of 26 target vessels). Two intra-procedural complications were observed (1 renal artery dissection and 1 collateral renal artery rupture). In total, 26 of 28 treated vessels were retrograde cannulated with a technical success of 93%. A total of 39 stent bridges were used (all Viabahn VBX devices). The mean duration of the procedure was 321±102 minutes, and the mean scan time was 134±62 minutes. Mortality at 30 days was observed in 1 case. During the follow-up, 1 stent bridge occlusion was observed without the need for reintervention. CONCLUSION: Retrograde cannulation can also be successfully performed in the case of inner branches. CLINICAL IMPACT: In inner branched cases, retrograde cannulation should be taken into consideration in particular cases or it could become the option of choice. Dedicated endovascular material available such as steerable catheters and latest generation covered stents is fundamental for the success of the treatment.

Microdosing Sprint Distribution as an Alternative to Achieve Better Sprint Performance in Field Hockey Players.

Introduction: The implementation of optimal sprint training volume is a relevant component of team sport performance. This study aimed to compare the efficiency and effectiveness of two different configurations of within-season training load distribution on sprint performance over 6 weeks. Methods: Twenty male professional FH players participated in the study. Players were conveniently assigned to two groups: the experimental group (MG; n = 11; applying the microdosing training methodology) and the control group (TG; n = 9; traditional training, with players being selected by the national team). Sprint performance was evaluated through 20 m sprint time (T20) m and horizontal force−velocity profile (HFVP) tests before (Pre) and after (Post) intervention. Both measurements were separated by a period of 6 weeks. The specific sprint training program was performed for each group (for vs. two weekly sessions for MG and TG, respectively) attempting to influence the full spectrum of the F-V relationship. Results: Conditional demands analysis (matches and training sessions) showed no significant differences between the groups during the intervention period (p > 0.05). No significant between-group differences were found at Pre or Post for any sprint-related performance (p > 0.05). Nevertheless, intra-group analysis revealed significant differences in F0, Pmax, RFmean at 10 m and every achieved time for distances ranging from 5 to 25 m for MG (p < 0.05). Such changes in mechanical capabilities and sprint performance were characterized by an increase in stride length and a decrease in stride frequency during the maximal velocity phase (p < 0.05). Conclusion: Implementing strategies such as microdosed training load distribution appears to be an effective and efficient alternative for sprint training in team sports such as hockey.

Intensity Ratio of Kß/Kα in Selected Elements from Mg to Cu, and the Chemical Effects of Cr Kα1,2 Diagram Lines and Cr Kß/Kα Intensity Ratio in Cr Compounds.

Kα,ß X-ray lines from photon excitation were measured in selected elements from Mg to Cu using a high-resolution double-crystal X-ray spectrometer with a proportional counter, and the Kß/Kα intensity ratio for each element was obtained, after correcting for self-absorption, detection efficiency, and crystal reflectance. This intensity ratio increases rapidly from Mg to Ca but, in the 3d elements region, the increase becomes slower. This is related to the intensity of the Kß line involving valence electrons. The slow increase of this ratio in the 3d elements region is thought to be due to the correlation between 3d and 4s electrons. Moreover, the chemical shifts, FWHM, asymmetry indices, and Kß/Kα intensity ratios of the Cr compounds, due to different valences, were also investigated using the same double-crystal X-ray spectrometer. The chemical effects were clearly observed, and the Kß/Kα intensity ratio was found to be compound-dependent for Cr.

Effect of Traditional, Cluster, and Rest Redistribution Set Configurations on Neuromuscular and Perceptual Responses During Strength-Oriented Resistance Training.

ABSTRACT: Cuevas-Aburto, J, Jukic, I, Chirosa-Ríos, LJ, González-Hernández, JM, Janicijevic, D, Barboza-González, P, Guede-Rojas, F, and García-Ramos, A. Effect of traditional, cluster, and rest redistribution set configurations on neuromuscular and perceptual responses during strength-oriented resistance training. J Strength Cond Res 36(6): 1490-1497, 2022-This study aimed to compare the acute effect of traditional (TR), cluster (CL), and rest redistribution (RR) set configurations on neuromuscular and perceptual measures of fatigue. Thirty-one resistance-trained men randomly performed a Control session and 3 experimental sessions consisting of the squat (SQ) and bench press (BP) exercises performed against the 10 repetition maximum load using TR (3 sets of 6 repetitions; 3 minutes of interset rest), CL (3 sets of 6 repetitions; 30 seconds of intraset rest every 2 repetitions; 3 minutes of interset rest), and RR (9 sets of 2 repetitions; 45 seconds of interset rest) set configurations. A significant effect of "set configuration" (p = 0.002) was observed for barbell velocity. The average velocity of the training session was lower for TR compared with CL (% difference = 5.09% in SQ and 5.68% in BP) and RR (% difference = 5.92% in SQ and 2.71% in BP). The 3 set configurations induced comparable decrements in countermovement jump height (% difference from -6.0% to -8.1%) and throwing velocity (% difference from -0.6% to -1.2%). Ratings of perceived exertion (RPE-10) values collected after the sets were higher for TR (SQ: 6.9 ± 0.7 a.u.; BP: 6.8 ± 0.8 a.u.) compared with CL (SQ: 6.2 ± 0.8 a.u.; BP: 6.4 ± 0.7 a.u.) and RR (SQ: 6.2 ± 0.8 a.u.; BP: 6.6 ± 0.9 a.u.), while the session RPE did not differ between the set configurations (p = 0.595). CL and RR set configurations allow for higher velocities and lower RPE values during resistance training sessions not performed to failure in comparison with a TR set configuration.

COVID-19 Impact on Vascular Surgery Practice: Experience From an Italian University Regional Hub Center for Vascular Pathology.

BACKGROUND: The aim of the study is to evaluate the impact of COVID-19 pandemic on vascular surgery practice in a regional hub center for complex vascular disease. METHODS: This is an observational single-center study in which we collected clinical and surgical data during (P1) and after (P2) the COVID-19 outbreak and the lockdown measures implemented in Northern Italy. We compared those data with the two-month period before the pandemic (P0). RESULTS: Compared to P0, ambulatory activities were severely reduced during P1 and limited to hospitalized patients and outpatients with urgent criteria. We performed 61 operations (18 urgent and 43 elective), with a decrease in both aortic (-17.8%), cerebrovascular (-53.3%), and peripheral artery (-42.6%) disease treatments. We also observed a greater drop in open procedures (-53.2%) than in endovascular ones (-22%). All the elective patients were treated for notdeferrable conditions and they were COVID-19 negative at the ward admission screening; despite this one of them developed COVID19 during the hospital stay. Four COVID-19 positive patients were treated in urgent setting for acute limb ischemia. Throughout P2 we gradually rescheduled elective ambulatory (+155.5%) and surgical (+18%) activities, while remaining substantially lower than during P0 (respectively -45.6% and -25.7%). CONCLUSIONS: Despite COVID-19 pandemic, our experience shows that with careful patient's selection, dedicated prehospitalization protocol and proper use of personal protective equipment it is possible to guarantee continuity of care.

Diabetes is not associated with an increased risk of hepatocellular carcinoma in patients with alcoholic or hepatitis C virus cirrhosis.

BACKGROUND AND AIMS: diabetes has been reported as a risk factor for hepatocellular carcinoma (HCC) in population-based studies but there are controversial data in patients with cirrhosis. Metformin could have a protective role in HCC development. The aim of this study was to determine the influence of diabetes on the risk of developing HCC in patients with alcohol- and hepatitis C virus (HCV)-related cirrhosis. METHODS: a cohort of 982 Caucasian patients were analyzed with alcoholic or HCV cirrhosis, included from 1992 to 2014 in a HCC surveillance program and prospectively followed. The influence of diabetes on the development of HCC was analyzed by Kaplan Meier analysis and adjusted with a Cox regression for relevant co-factors. RESULTS: after a median follow-up of 49.5 (24.0-96.0) months, 156 patients (15.8 %) developed HCC. There were no differences in the cumulative incidences of HCC after 20 years between diabetic and non-diabetic patients in the global (53.5 % vs 45.4 %; p = 0.26), alcoholic (50.4 % vs 45.4 %; p = 0.21) or HCV (60 % vs 43.1 %; p = 0.57) cirrhosis series. Diabetes did not constitute a risk factor after adjusting for other potential co-factors, neither in the whole series (hazard ratio [HR]: 1.12, 95 % CI: 0.78-1.51; p = 0.26), alcoholic (HR: 1.160, 95 % CI: 0.74-1.82; p = 0.50) or HCV cirrhosis cohort (HR: 1.17, 95 % CI: 0.63-2.19; p = 0.60). These figures did not change after excluding patients treated with metformin. CONCLUSIONS: in Caucasian patients with alcoholic or HCV cirrhosis, diabetes is not a risk factor for developing HCC. This lack of an association does not seem to be a consequence of the protective effect of metformin.

Novel Disease Risk Model for Patients with Acute Myeloid Leukemia Receiving Allogeneic Hematopoietic Cell Transplantation.

Molecular data and minimal residual disease (MRD) have been shown to influence outcomes in acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic cell transplantation (AHCT). Here we developed and validated a novel AML-specific disease risk group (AML-DRG) and revised our previously developed hematopoietic cell transplant-composite risk (HCT-CR) model by incorporating molecular data and MRD status to predict outcomes of patients with AML. The study included 1414 consecutively treated adult AML patients who received a first AHCT. Patients were randomly assigned into training (n = 944) and validation (n = 470) sets. To develop the AML-DRG model, the coefficient of all significant AML-related variables in multivariable Cox regression analysis in a training dataset was converted into scores, whereas the AML-HCT-CR was the sum of disease-related factors assessed by the AML-DRG model with the addition of weighted scores from patient-related factors. The AML-DRG was developed by assigning the following scores: 1 point to secondary AML, 1 point to the European LeukaemiaNet adverse genetic risk, 2 points to complete remission with MRD positive/unknown, and 4 points to active disease. These scores were used to generate 3 risk groups of the AML-DRG with significantly different overall survivals. By adding the score for significant patient-related factors (HCT-specific comorbidity index/age), we created 4 risk groups of AML-HCT-CR with distinct survival outcomes. Both the AML-DRG and AML-HCT-CR provided significantly better discriminative capacity compared with the disease risk index, European LeukaemiaNet genetic risk model, and cytogenetic risk model. Prognostic models incorporating molecular data and MRD status allow better stratification and improved survival estimates of AML patients post-transplant.

Triosephosphate isomerase deficiency: Effect of F240L mutation on enzyme structure.

Eleven missense mutations have been describe in human triosephosphate isomerase (TPI), affecting its catalytic function. Several of these mutations generate triosephosphate isomerase deficiency, the consequences of which can in some cases be lethal. The missense F240L mutation was found in a Hungarian patient showing symptoms of chronic hemolytic anemia and neuromuscular dysfunction. In vitro studies using a recombinant version of this mutant showed that it affects kinetic parameters, thermal stability and dimeric stability. Using X-ray crystal structures, the present paper describes how this mutation affected the flexibility of catalytic residues K13 and part of the (ß/α) 8-barrel fold facing the dimeric interface in the TPI.

A Polarization-Consistent Model for Alcohols to Predict Solvation Free Energies.

Classical nonpolarizable models, normally based on a combination of Lennard-Jones sites and point charges, are extensively used to model thermodynamic properties of fluids, including solvation. An important shortcoming of these models is that they do not explicitly account for polarization effects, i.e., a description of how the electron density responds to changes in the molecular environment. Instead, polarization is implicitly included, in a mean-field sense, into the parameters of the model, usually by fitting to pure liquid properties (e.g., density). This causes problems when trying to describe thermodynamic properties that involve a change of phase (e.g., enthalpy of vaporization), that directly depend on the electronic response of the medium (e.g., dielectric constant), and that require mixing or solvation in different media (e.g., solvation free energies). Fully polarizable models present a natural route for addressing these limitations but at the price of a much higher computational cost. In this work, we combine the best of those two approaches by running fast simulations using nonpolarizable models and applying post facto corrections to the computed properties in order to account for the effects of polarization. By applying this new paradigm, a new united-atom force field for alcohols is developed that is able to predict both pure liquid properties, including dielectric constant, and solvation free energies in different solvents with a high degree of accuracy. This paves the way for the development of a generic classical nonpolarizable force field that can predict solvation of drug-like molecules in a variety of solvents.

Simple corrections for the static dielectric constant of liquid mixtures from model force fields.

Pair-wise additive force fields provide fairly accurate predictions, through classical molecular simulations, for a wide range of structural, thermodynamic, and dynamical properties of many materials. However, one key property that has not been well captured is the static dielectric constant, which characterizes the response of a system to an applied electric field and is important in determining the screening of electrostatic interactions through a system. A simple correction has been found to provide a relatively robust method to improve the estimate of the static dielectric constant from molecular simulations for a broad range of compounds. This approach accounts for the electronic contribution to molecular polarizability and assumes that the charges that couple a molecule to an applied electric field are proportional to the effective force field charges. In this work, we examine how this correction performs for systems at different temperatures and for binary mixtures. Using a value for the electronic polarizability, based on the experimental index of refraction, and a charge scaling factor, determined at a single temperature, we find that the static dielectric constant can be predicted remarkably well, in comparison to the experimentally measured values. This provides good evidence that the effective charges that appear in pair-wise additive force fields developed to reproduce the potential energy surface of a system are not the same as those that determine the static dielectric constant; however, they can be captured in a relatively simple manner, which is dependent on the particular force field.

The dielectric constant: Reconciling simulation and experiment.

In this paper, we present a simple correction scheme to improve predictions of dielectric constants by classical non-polarisable models. This scheme takes into account electronic polarisation effects, through the experimental refractive index of the liquid, and a possible mismatch between the potential energy surface and the dipole moment surface. We have described the latter effect by an empirical scaling factor on the point charges, the value of which was determined by fitting the dielectric constant of methanol. Application of the same scaling factor to existing benchmark datasets, comprising four different models and a wide range of compounds, led to remarkable improvements in the quality of the predictions. In particular, the observed systematic underestimation of the dielectric constant was eliminated by accounting for the two missing terms in standard models. We propose that this correction term be included in future development and validation efforts of classical non-polarisable models.

Characterization of human triosephosphate isomerase S-nitrosylation.

Triosephosphate isomerase (TPI), the glycolytic enzyme that catalyzes the isomerization of dihydroxyacetone phosphate (DHAP) to glyceraldehyde-3-phosphate (G3P), has been frequently identified as a target of S-nitrosylation by proteomic studies. However, the effect of S-nitrosylation on its activity has only been explored in plants and algae. Here, we describe the in vitro S-nitrosylation of human TPI (hTPI), and the effect of the modification on its enzymatic parameters. NO-incorporation into the enzyme cysteine residues occurred by a time-dependent S-transnitrosylation from both, S-nitrosocysteine (CySNO) and S-nitrosoglutathione (GSNO), with CySNO being the more efficient NO-donor. Both X-ray crystal structure and mass spectrometry analyses showed that only Cys217 was S-nitrosylated. hTPI S-nitrosylation produced a 30% inhibition of the Vmax of the DHAP conversion to G3P, without affecting the Km for DHAP. This is the first study describing features of human TPI S-nitrosylation.

Controlled searching in reversibly de-identified medical imaging archives.

Nowadays, digital medical imaging in healthcare has become a fundamental tool for medical diagnosis. This growth has been accompanied by the development of technologies and standards, such as the DICOM standard and PACS. This environment led to the creation of collaborative projects where there is a need to share medical data between different institutions for research and educational purposes. In this context, it is necessary to maintain patient data privacy and provide an easy and secure mechanism for authorized personnel access. This paper presents a solution that fully de-identifies standard medical imaging objects, including metadata and pixel data, providing at the same time a reversible de-identifier mechanism that retains search capabilities from the original data. The last feature is important in some scenarios, for instance, in collaborative platforms where data is anonymized when shared with the community but searchable for data custodians or authorized entities. The solution was integrated into an open source PACS archive and validated in a multidisciplinary collaborative scenario.

Apnea in infants hospitalized with pertussis: Incidence and gestational smoking association.

BACKGROUND: Apnea is a life-threatening complication of pertussis, now a re-emerging cause of infant hospitalization worldwide. The incidence of apnea during pertussis ranges widely. The aim of this study was therefore to determine the incidence of apnea in hospitalized infants diagnosed with pertussis and to identify relevant risk factors for apnea. METHODS: This was a retrospective analytical study. We included children hospitalized with pertussis at a tertiary hospital during a 5 year period from 2010 to 2015. Nasopharyngeal aspirates (NPA) were obtained in all subjects. Real-time polymerase chain reaction was used to test NPA samples for Bordetella pertussis. The daily charts were assessed to identify inpatients with apnea. Multivariable logistic regression was performed to identify independent risk factors for inpatient apnea. RESULTS: Inpatient apnea was identified in 51 of 147 infants with pertussis confirmation (34.7%: 95%CI: 27-42%). Maternal smoking during pregnancy was the only statistically significant, independent predictor of inpatient apnea (OR: 4.48; 95%CI: 1.35-14.8). No statistically significant association was found with gender, corrected age; birthweight, caregiver smoking; lactation, weight at admission <3rd percentile, or hematological parameters. CONCLUSIONS: The incidence of pertussis apnea was nearly one in three hospitalized infants, and was fourfold more frequent in infants whose mothers smoked during pregnancy.

Stigmatizing attitudes of primary care professionals towards people with mental disorders: A systematic review.

Objective To examine stigmatizing attitudes towards people with mental disorders among primary care professionals and to identify potential factors related to stigmatizing attitudes through a systematic review. Methods A systematic literature search was conducted in Medline, Lilacs, IBECS, Index Psicologia, CUMED, MedCarib, Sec. Est. Saúde SP, WHOLIS, Hanseníase, LIS-Localizador de Informação em Saúde, PAHO, CVSO-Regional, and Latindex, through the Virtual Health Library portal ( http://www.bireme.br website) through to June 2017. The articles included in the review were summarized through a narrative synthesis. Results After applying eligibility criteria, 11 articles, out of 19.109 references identified, were included in the review. Primary care physicians do present stigmatizing attitudes towards patients with mental disorders and show more negative attitudes towards patients with schizophrenia than towards those with depression. Older and more experience doctors have more stigmatizing attitudes towards people with mental illness compared with younger and less-experienced doctors. Health-care providers who endorse more stigmatizing attitudes towards mental illness were likely to be more pessimistic about the patient's adherence to treatment. Conclusions Stigmatizing attitudes towards people with mental disorders are common among physicians in primary care settings, particularly among older and more experienced doctors. Stigmatizing attitudes can act as an important barrier for patients to receive the treatment they need. The primary care physicians feel they need better preparation, training, and information to deal with and to treat mental illness, such as a user friendly and pragmatic classification system that addresses the high prevalence of mental disorders in primary care and community settings.

Predicting hydrophobic solvation by molecular simulation: 2. New united-atom model for alkanes, alkenes, and alkynes.

Existing united-atom models for non-polar hydrocarbons lead to systematic deviations in predicted solvation free energies in hydrophobic solvents. In this article, an improved set of parameters is proposed for alkane molecules that corrects this systematic deviation and accurately predicts solvation free energies in hydrophobic media, while simultaneously providing a very good description of pure liquid densities. The model is then extended to alkenes and alkynes, again yielding very accurate predictions of solvation free energies and densities for these classes of compounds. For alkynes in particular, this work represents the first attempt at a systematic parameterization using the united-atom approach. Averaging over all 95 solute/solvent pairs tested, the mean signed deviation from experimental data is very close to zero, indicating no systematic error in the predictions. The fact that predictions are robust even for relatively large molecules suggests that the new model may be applicable to solvation of non-polar macromolecules without accumulation of errors. The root mean squared deviation of the simulations is only 0.6 kJ/mol, which is lower than the estimated uncertainty in the experimental measurements. This excellent performance constitutes a solid basis on which a more general model can be parameterized to describe solvation in both polar and non-polar environments. © 2016 Wiley Periodicals, Inc.

Predicting hydrophobic solvation by molecular simulation: 1. Testing united-atom alkane models.

We present a systematic test of the performance of three popular united-atom force fields-OPLS-UA, GROMOS and TraPPE-at predicting hydrophobic solvation, more precisely at describing the solvation of alkanes in alkanes. Gibbs free energies of solvation were calculated for 52 solute/solvent pairs from Molecular Dynamics simulations and thermodynamic integration making use of the IBERCIVIS volunteer computing platform. Our results show that all force fields yield good predictions when both solute and solvent are small linear or branched alkanes (up to pentane). However, as the size of the alkanes increases, all models tend to increasingly deviate from experimental data in a systematic fashion. Furthermore, our results confirm that specific interaction parameters for cyclic alkanes in the united-atom representation are required to account for the additional excluded volume within the ring. Overall, the TraPPE model performs best for all alkanes, but systematically underpredicts the magnitude of solvation free energies by about 6% (RMSD of 1.2 kJ/mol). Conversely, both GROMOS and OPLS-UA systematically overpredict solvation free energies (by ∼13% and 15%, respectively). The systematic trends suggest that all models can be improved by a slight adjustment of their Lennard-Jones parameters. © 2016 Wiley Periodicals, Inc.