Bennett fracture combined with hamate fracture: carpometacarpal joint 'diagonal' fracture and dislocation: a case report.

BACKGROUND: Multiple carpometacarpal fractures and dislocations are rare. This case report describes a novel multiple carpometacarpal injury, namely, 'diagonal' carpometacarpal joint fracture and dislocation. CASE PRESENTATION: A 39-year-old male general worker sustained a compression injury to his right hand in the dorsiflexion position. Radiography indicated a Bennett fracture, hamate fracture, and fracture at the base of the second metacarpal. Subsequent computed tomography and intraoperative examination confirmed an injury to the first to fourth carpometacarpal joint along a diagonal line. The normal anatomy of the patient's hand was successfully restored via open reduction combined with Kirschner wire and steel plate fixation. CONCLUSION: Our findings highlight the importance of taking the injury mechanism into account to avoid a missed diagnosis and to choose the best treatment approach. This is the first case of 'diagonal' carpometacarpal joint fracture and dislocation to be reported in the literature.

Surgical Outcomes of Percutaneous Pinning and Open Locking Plating in Patients With Intra-articular Fractures of the Base of the Fifth Metacarpal.

PURPOSE: The purpose of the study was to demonstrate the results of surgical treatment, including percutaneous K-wire fixation after closed reduction (CRKF) or locking plate fixation after open reduction (ORPF), in patients with intra-articular fractures of the base of the fifth metacarpal. METHODS: We retrospectively reviewed data of 29 patients who received surgical treatment for closed, intra-articular fractures of the base of the fifth metacarpal and were followed up for at least 1 year after surgery. Sixteen of the 29 patients underwent CRKF, whereas 13 patients underwent ORPF. Attempts were made to address intra-articular step-off with closed reduction in all the patients; however, if inadequate, ORPF was performed. Clinical outcomes were evaluated using Disabilities of the Arm, Shoulder, and Hand scores, visual analog scale pain scores, the total active motion (TAM) of the little finger, and grip strength. Osseous union and posttraumatic arthritis of the fifth carpometacarpal joint were also evaluated. RESULTS: K-wire fixation after closed reduction was performed for 13 simple fractures and 3 comminuted fractures; ORPF was performed for 6 simple fractures and 7 comminuted fractures. All the patients had satisfactory subjective outcomes with over 90% grip strength compared with that on the contralateral side and nearly full TAM. All the patients in both the groups achieved osseous union. There were five cases of grade 1 posttraumatic arthritis after CRKF and seven cases of grade 1 posttraumatic arthritis after ORPF. CONCLUSIONS: Surgical treatment provided satisfactory results in patients with intra-articular fractures of the base of the fifth metacarpal treated with either CRKF or ORPF. Our data showed that the patients who underwent CPKF had good results, and those who underwent ORPF after attempt failure of close reduction also had good results. Our experience suggests that ORPF can be a backup plan when CRKF cannot be accomplished in a satisfactory way. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Xenotransplantation becoming reality.

To bridge the gap between organ demand and supply, xenotransplantation has long been considered as a realistic option for end-stage organ failure. Early this year this promise became reality for David Bennett Sr., the first patient whose own failing heart was replaced with a xeno-pig heart. To get here has been a rollercoaster ride of physiological hurdles seemingly impossible to overcome, technological breakthroughs and ethical and safety concerns. It started in 1984, with Stephanie Fae Beauclair, also known as baby Fae, receiving a baboon heart, which allowed her to survive for another 30 days. For ethical reasons primate work was soon abandoned in favour of the pig. But increased phylogenetic distance also brought with it an increased immunological incompatibility. It has been the development of ever more sophisticated genetic engineering tools, which brought down the physiological barriers, enabled humanisation of porcine organs and helped addressing safety concerns. This renewed the confidence in xenotransplantation, brought new funding opportunities and resulted finally in the first in human trial.

Accuracy of fluoroscopic examination in the treatment of Bennett's fracture.

BACKGROUND: Restoration of joint congruity is an important factor for the prevention of subsequent arthritis in patients with Bennett's fracture. Surgical treatment of Bennett's fracture is thus generally recommended for displaced intra-articular fractures to the proximal aspect of the thumb metacarpal. Fluoroscopic examination is used to evaluate the adequacy of closed reduction after pinning of Bennett's fracture. The purpose of this study was to determine the accuracy of fluoroscopy to determine the reduction of Bennett's fractures. METHODS: A model was created, to mimic a Bennett's fracture utilizing ten fresh-frozen cadaveric hands. An oblique cut was made in the proximal aspect of the thumb metacarpal using an oscillating saw. The small oblique fragment involved 1/4-1/3 of the joint surface was then shifted in position creating a step-off or gap at the fracture site. An anatomical reduction model, gap models (1 mm, 2 mm, 3 mm), and step-off models (1 mm, 2 mm, 3 mm) were created using percutaneous fixation with two 1.0 mm Kirschner wires for each cadaveric hand. Fluoroscopic assessment then took place and was reviewed by 2 attending hand surgeons blinded to the actual position. Their estimated fluoroscopic position was then compared to the actual displacement. RESULTS: The step-off and gap on fluoroscopic examination showed a significant difference compared to the step-off and gap from direct visualization. The frequency of underestimation for the 3 mm displacement models from the fluoroscopic examination was 60%. The frequency for overestimated was 9% for the models in which displacement was within 2 mm (0, 1, 2 mm). CONCLUSIONS: The assessment of articular gap and step-off using PA (postero-anterior), AP (antero-posterior), and lateral view of fluoroscopic examination is not accurate as compared to the examination by direct visualization. Surgeons need to be aware that PA, AP and lateral view of fluoroscopic examination alone may not be sufficient to judge the final position of a reduced Bennett's fracture. Other methods such as live fluoroscopy in multiple different planes, 3-dimensional fluoroscopy or arthroscopic examination should be considered.

The Clinical Significance of Immediate Mandibular Lateral Translation: Critically Appraised Topic (CAT).

PURPOSE: The purpose of this Critically Appraised Topic was to investigate the possible clinical relevance of recording the immediate mandibular lateral translation. MATERIALS AND METHODS: A literature search limited to Clinical trials, Randomized Controlled Trials, Systematic Reviews, Meta Analyses, and using the PICO headings revealed no citations. Using the key words dental, occlusion, immediate side shift, also received no citations. Expanding the search criteria to include Journal Articles revealed 17 citations. Using dental occlusion, Bennett movement, revealed 21 citations. RESULTS: The cited articles were reviewed for relevance and duplicates were eliminated. The resulting 10 English language in vivo studies pertinent to the question were included. Other articles were culled from the author's library and the reference list of the aforementioned articles. There is no evidence on the prevalence of IMLT in patients in need of occlusal rehabilitation. There is agreement that the recording of the IMLT is reference point and recording instrument dependent. There is agreement that IMLT is observable on some patients and is minimal in magnitude. There is no evidence of any adverse clinical events as a result of not including IMLT in a restorative occlusal scheme. CONCLUSIONS: It is justifiable to question the necessity of attempting both to record immediate mandibular lateral translation on the average patient and reproduce it on an articulator.

Prevalence of Bennett lesions based on sex, ancestry, and age in an osteologic collection of 5,662 scapulae.

BACKGROUND: Bennett lesions represent an extra-articular ossification on the posteroinferior aspect of the glenoid fossa and a potential source of posterior shoulder pain and limitation. The prevalence of Bennett lesions in the general population is unknown. MATERIALS AND METHODS: A total of 5,662 scapulae from 2,831 individual cadaveric specimens greater than 18 years of age at the time of death were examined. Matching scapulae were evaluated for Bennett lesions by two independent authors. Lesion prevalence was calculated and statistical analysis performed to evaluate differences in prevalence based on specimen sex (males vs. females), ancestry (African-American vs. Caucasian) and with increasing age at the time of death. RESULTS: Bennett lesions were observed in 3.5% (n = 98 of 2,831) of specimens and 1.8% (n = 104 of 5,662) of scapulae. Interobserver reliability was 0.83, indicating excellent agreement among authors. Males possessed significant higher odds of possessing a Bennett lesion when compared to females (p = .009) and African-American specimens when compared to Caucasian specimens (p < .001). Each additional year of age was associated with a 1.4% increase in odds of a specimen having a Bennett lesion, while no significant increase in Bennett lesion prevalence was appreciated with increasing specimen age at the time of death when comparing male to female specimens (p = .07) or African-American to Caucasian specimens (p = .73). CONCLUSIONS: Bennett lesions were identified in 3.5% of osseous specimens and 1.8% of scapulae, with significantly higher prevalence in male and African-American specimens.

Vital and enchanted: Jane Bennett and new materialism for nursing philosophy and practice.

Nursing theories are typically anthropocentric and emphasize caring for a person as a unitary whole. They maintain the dualisms of human-nonhuman, natural-social and material-ideal. Recent developments in nonhuman ontology question the utility of that approach. One important philosopher in this new materialism is political theorist Jane Bennett. In this paper, I explore Bennett's vital materialism and enchantment as two concepts arising from the nonhuman turn that should inform nursing philosophy. Vital materialism considers the lively power of matter to affect the world and be affected in relations. Enchantment refers to a sense of wonder and captivation with matter. While summarizing her important contributions, I also describe common criticisms and responses. I consider the human as an assemblage of matter as well as the agency or "thing power" of matter external to humans. This has implications for nursing thought and practice, and it can inform a more capacious research methodology. I also discuss how compassion fatigue or burnout and other professional issues may be seen as a form of disenchantment with the material world. I argue that embracing these and other elements of Bennett's new materialist philosophy can help nurses and other health professionals enrich their theories and practice to advance their disciplines and improve care for persons and populations.

Multiensemble Markov models of molecular thermodynamics and kinetics.

We introduce the general transition-based reweighting analysis method (TRAM), a statistically optimal approach to integrate both unbiased and biased molecular dynamics simulations, such as umbrella sampling or replica exchange. TRAM estimates a multiensemble Markov model (MEMM) with full thermodynamic and kinetic information at all ensembles. The approach combines the benefits of Markov state models-clustering of high-dimensional spaces and modeling of complex many-state systems-with those of the multistate Bennett acceptance ratio of exploiting biased or high-temperature ensembles to accelerate rare-event sampling. TRAM does not depend on any rate model in addition to the widely used Markov state model approximation, but uses only fundamental relations such as detailed balance and binless reweighting of configurations between ensembles. Previous methods, including the multistate Bennett acceptance ratio, discrete TRAM, and Markov state models are special cases and can be derived from the TRAM equations. TRAM is demonstrated by efficiently computing MEMMs in cases where other estimators break down, including the full thermodynamics and rare-event kinetics from high-dimensional simulation data of an all-atom protein-ligand binding model.

Bennett lesions in overhead athletes and associated shoulder abnormalities on MRI.

OBJECTIVE: To determine if a Bennett lesion and its size are associated with additional MRI shoulder abnormalities in an overhead athlete. MATERIALS AND METHODS: An IRB-approved retrospective review of our database from 1 January 2012 to 1 April 2018 identified 35 overhead athletes with a Bennett lesion on MRI. A control group consisting of 35 overhead athletes without a Bennett lesion were matched for age, level of play (professional vs non-professional), and type of study (arthrogram vs non-arthrogram). Each study was assessed independently by two MSK fellowship trained radiologists. The sizes of the Bennett lesions were measured. Each MRI was assessed for the presence of a labral tear, posterior glenoid cartilage abnormality, humeral head notching or cysts, and fraying or tear of the supraspinatus or infraspinatus tendons. Statistical analyses were performed using Student's t test, Fisher's exact test, and Chi-squared test. RESULTS: There was an increased incidence of posterior glenoid cartilage abnormalities in athletes with Bennett lesions vs those without (23% vs 3%, p value = 0.01). There was no difference in any other MRI abnormalities, including labral tears and findings of internal impingement between these two groups (p value range = 0.09-0.46). There was no association between the size of a Bennett lesion and the presence of glenoid cartilage lesions, labral tears, internal impingement, age, professional status, or need for surgery (p value range = 0.08-0.96). CONCLUSION: Symptomatic overhead athletes with Bennett lesions have an increased frequency of posterior glenoid cartilage abnormalities, but not labral tears or findings of internal impingement compared to those without Bennett lesions.

Bennett Fractures: A Biomechanical Model and Relevant Ligamentous Anatomy.

PURPOSE: This study examined a palmar beak fracture model to determine which thumb carpometacarpal (CMC) joint ligament is the primary ligament relevant to the pattern of injury. METHODS: Six fresh-frozen cadaveric wrists were used. The radius, ulna, and first metacarpal were secured and tested with a materials testing system, holding the wrist in 20° extension, 20° ulnar deviation, and 30° palmar abduction of the first metacarpal. Testing consisted of preconditioning cycles followed by compressive loading at 100 mm/s. We confirmed fractures with fluoroscopy and dissected the specimens to examine the CMC joint ligaments. The metacarpal was stressed through a range of motion to determine which maneuvers reduced or displaced the fractures. RESULTS: Our model successfully created palmar beak fractures in all cadaveric specimens. All fractures were displaced and intra-articular. The anterior oblique ligament (AOL) was thin and partially attached to the palmar beak fracture fragment. The ulnar collateral ligament was attached in its entirety to the fracture fragment and represented a thicker, more robust ligament compared with the AOL. Radial abduction and pronation of the metacarpal reduced fracture displacement. Extension of the CMC joint or tensioning the AOL did not decrease fracture displacement. CONCLUSIONS: This model successfully created a reproducible and clinically relevant palmar beak fracture in a biomechanical setting. The primary ligament attached to the palmar beak fracture fragment was the ulnar collateral ligament, and not the AOL as previously described. These findings suggest that the AOL may not be a substantial contributor to palmar beak fracture morphology. CLINICAL RELEVANCE: A refined description of the ligamentous anatomy of the palmar break fracture enhances opportunities for improved reduction and treatment of this common hand injury.

Common Upper Extremity Fracture Eponyms: A Look Into What They Really Mean.

Eponyms, whereas commonly used in hand surgery, are perhaps misused as often as they are used correctly. Many commonly used eponyms, such as Colles fracture, Barton fracture, Smith fracture, and Bennett fracture, were actually described decades before the development of radiographs. The goal of this article is to revisit the original descriptions of commonly used eponymous terms for distal radius and first metacarpal base fractures to provide clarity and enhance understanding of what these eponyms actually mean.

The Good, the Bad, and the Ugly: "HiPen", a New Dataset for Validating (S)QM/MM Free Energy Simulations.

Indirect (S)QM/MM free energy simulations (FES) are vital to efficiently incorporating sufficient sampling and accurate (QM) energetic evaluations when estimating free energies of practical/experimental interest. Connecting between levels of theory, i.e., calculating Δ A l o w → h i g h , remains to be the most challenging step within an indirect FES protocol. To improve calculations of Δ A l o w → h i g h , we must: (1) compare the performance of all FES methods currently available; and (2) compile and maintain datasets of Δ A l o w → h i g h calculated for a wide-variety of molecules so that future practitioners may replicate or improve upon the current state-of-the-art. Towards these two aims, we introduce a new dataset, "HiPen", which tabulates Δ A g a s M M → 3 o b (the free energy associated with switching from an M M to an S C C - D F T B molecular description using the 3ob parameter set in gas phase), calculated for 22 drug-like small molecules. We compare the calculation of this value using free energy perturbation, Bennett's acceptance ratio, Jarzynski's equation, and Crooks' equation. We also predict the reliability of each calculated Δ A g a s M M → 3 o b by evaluating several convergence criteria including sample size hysteresis, overlap statistics, and bias metric ( Π ). Within the total dataset, three distinct categories of molecules emerge: the "good" molecules, for which we can obtain converged Δ A g a s M M → 3 o b using Jarzynski's equation; "bad" molecules which require Crooks' equation to obtain a converged Δ A g a s M M → 3 o b ; and "ugly" molecules for which we cannot obtain reliably converged Δ A g a s M M → 3 o b with either Jarzynski's or Crooks' equations. We discuss, in depth, results from several example molecules in each of these categories and describe how dihedral discrepancies between levels of theory cause convergence failures even for these gas phase free energy simulations.

First foods: Diet quality among infants aged 6-23 months in 42 countries.

Diet quality is closely linked to child growth and development, especially among infants aged 6-23 months who need to complement breastmilk with the gradual introduction of nutrient-rich solid foods. This paper links Demographic and Health Survey data on infant feeding to household and environmental factors for 76,641 children in 42 low- and middle-income countries surveyed in 2006-2013, providing novel stylized facts about diets in early childhood. Multivariate regressions examine the associations of household socioeconomic characteristics and community level indicators of climate and infrastructure with dietary diversity scores (DDS). Results show strong support for an infant-feeding version of Bennett's Law, as wealthier households introduce more diverse foods at earlier ages, with additional positive effects of parental education, local infrastructure and more temperate agro-climatic conditions. Associations with consumption of specific nutrient-dense foods are less consistent. Our findings imply that while income growth is indeed an important driver of diversification, there are strong grounds to also invest heavily in women's education and food environments to improve diet quality, while addressing the impacts of climate change on livelihoods and food systems. These results reveal systematic patterns in how first foods vary across developing countries, pointing to new opportunities for research towards nutrition-smart policies to improve children's diets.

Standard and limit values for the symmetry of articulation parameters in the temporomandibular joint area - evaluations of the associated project of the SHIP study.

The articulation parameters, especially the horizontal condylar inclination angle (HCI), the Bennett angle (BA), and the immediate side shift (ISS) were determined in 259 subjects (100 males; 159 females) of the associated project with reference to the population-representative baseline study (Study of Health in Pomerania, SHIP 0). The evaluations were based on a clinical functional status and electronic motion recording with the ultrasonic measuring system Jaw Motion Analyser (JMA, Zebris, Isny, Germany). The reference plane, to which all measured values were represented and the HCI calculated, was the hinge axis infraorbital plane (HA-IOP). The HCI was determined after an excursive movement with a length of 4 mm to the HA-IOP in the sagittal view and the BA after a mediotrusive excursion movement of 6 mm in the horizontal view to the midsagittal plane. For the standard and limit values, the average value in addition to the standard deviation and the 10th and 90th percentile value (10th percentile value, 90th percentile value) were determined: HCI right 52.1 ± 10.14 degrees (39.4 degrees, 64.0 degrees), HCI left 53.1 ± 9.67 degrees (42.3 degrees, 67.0 degrees), BA right 15.2 ± 7.53 degrees (6.7 degrees, 25.0 degrees), BA left 14.2 ± 7.84 degrees (5.4 degrees, 24.1 degrees). The HCI was approximately 2 to 3 degrees larger in females (males: right 50.5 ± 9.47 degrees, left 51.9 ± 8.99 degrees; females: right 53.1 ± 10.42 degrees, left 53.8 ± 10.03 degrees). Likewise, the BA in the age group ≥ 40 years (males: right 14.4 ± 6.62 degrees, left 13.1 ± 7.14 degrees; females: right 17.0 ± 9.02 degrees, left 16.9 ± 8.72 degrees). The latter proved to be statistically significant in the t test for independent samples, assuming variance equivalence on the right, with P = 0.009, and with rejection of the variant equivalence on the left, with P = 0.002. The right and left HCI and BA joint values showed highly significant linear dependence at P < 0.001, but rather low, however, for the HCI with r2 = 0.175 for the HCI and r2 = 0.228 for the BA. In 46% of cases, the right and left HCI values differed up to 5 degrees only; a further 20.9% were in an interval difference of between 5 and 10 degrees. The following results were shown for the differences in the BA: 56.4% of the cases were between 0 and 5 degrees, and 26.2% were in the interval ranges of 5 to 10 degrees. ISS occurred in 18.1% of cases on the right side of the joint, and in 27.8% of cases on the left side. On both sides of the joint it was significantly more frequent in the age group ≥ 40 years with assumed variance equality than in the age group < 40 years (P = 0.002 right, P = 0.003 left). The groups relating to the Helkimo index (HI) did not differ significantly in all function-specific parameters. If it is assumed that there is no significant influence on the occlusion if the HCI values differ by 7 to 8 degrees from the average value, only approximately one third of all cases (35.1%) were characterized by a purely average value setting in the articulator. In 41.7% of cases, one joint value was situated outside the average value range; in 23.2% of the cases both values were outside the average value range. Without a measurement of the condylar path inclination, however, it is impossible to decide to what extent the HCI deviates from the average value, and which joint side is larger or smaller than the other and to what extent. These results suggest that in extensive and complex cases, the articulator should be adjusted according to individual, function-specific joint values.

EVALUATION OF NONINVASIVE OSCILLOMETRIC BLOOD PRESSURE MONITORING IN ANESTHETIZED BENNETT'S WALLABIES (MACROPUS RUFOGRISEUS).

The objective of this study was to determine the accuracy of a noninvasive oscillometric method in relation to invasively measured blood pressure in anesthetized Bennett's wallabies (Macropus rufogriseus) and also to compare the accuracy of two commonly used oscillometric blood pressure monitors (manufactured by Cardell and Datascope). Eleven animals were anesthetized, and each animal was instrumented with an arterial catheter in the right medial metatarsal artery connected to a pressure transducer to obtain invasive measurements of systolic (SAP), diastolic (DAP), and mean (MAP) arterial blood pressure as well as a pressure waveform. A cuff connected to an oscillometric device was placed on the base of the tail for noninvasive measurements. Paired data from noninvasive and invasive blood pressure measurements (SAP, DAP, and MAP) were obtained every 5 min for 60 min. Bland-Altman plots were used to compare invasive and noninvasive measurements and calculate bias and 95% limits of agreement for SAP, DAP, and MAP. For both monitors, the bias of SAP, DAP, and MAP was significant, although the bias of the Cardell was consistently lower than that of the Datascope for all parameters. Limits of agreement were wide for all parameters. In conclusion, when using an oscillometric blood pressure monitor on anesthetized Bennett's wallabies, trends in blood pressure may be monitored, although all displayed readings may not represent the true blood pressure measurement. Indirect measurements of blood pressure made with the oscillometric device cannot substitute for direct measurements.

Prediction of CB[8] host-guest binding free energies in SAMPL6 using the double-decoupling method.

This study reports the results of binding free energy calculations for CB[8] host-guest systems in the SAMPL6 blind challenge (receipt ID 3z83m). Force-field parameters were developed specific for each of host and guest molecules to improve configurational sampling. We used quantum mechanical (QM) implicit solvent calculations and QM force matching to determine non-bonded (partial atomic charges) and bonded terms, respectively. Free energy calculations were carried out using the double-decoupling method (DDM) combined with Hamiltonian replica exchange method (HREM) and Bennett acceptance ratio (BAR) method. The root mean square error (RMSE) of the predicted values using DDM with respect to the experimental results was 4.32 kcal/mol. The coefficient of determination (R2) and Kendall rank coefficient (τ) were 0.49 and 0.52, respectively, highest of all submissions. In addition, these were compared to the results obtained by umbrella sampling (US) and weighted histogram analysis method (WHAM). Overall, DDM achieved a higher prediction accuracy than the US method. Results are discussed in terms of parameterization and free energy simulations.

Comparison of the umbrella sampling and the double decoupling method in binding free energy predictions for SAMPL6 octa-acid host-guest challenges.

We calculate the absolute binding free energies of tetra-methylated octa-acids host-guest systems as a part of the SAMPL6 blind challenge (receipt ID vq30p). We employed two different free energy simulation methods, i.e., the umbrella sampling (US) and double decoupling method (DDM). The US method was used with the weighted histogram analysis method (WHAM) (US-WHAM scheme). In the DDM scheme, Hamiltonian replica-exchange method (HREM) was combined with the Bennett acceptance ratio (BAR) (HREM-BAR scheme). We obtained initial binding poses via molecular docking using GalaxyDock-HG program, which is developed for the SAMPL challenge. The root mean square deviation (RMSD) and the mean absolute deviations (MAD) using US-WHAM scheme were 1.33 and 1.02 kcal/mol, respectively. The MAD was the top among all submissions, however the correlation with respect to experiment was unexceptional. While the RMSD and MAD via HREM-BAR scheme were greater than US-WHAM scheme, (i.e., 2.09 and 1.76 kcal/mol), their correlations were slightly better than US-WHAM. The correlation between the two methods was high. Further discussion on the DDM method can be found in a companion paper by Han et al. (receipt ID 3z83m) in the same issue.

Binding affinities of the farnesoid X receptor in the D3R Grand Challenge 2 estimated by free-energy perturbation and docking.

We have studied the binding of 102 ligands to the farnesoid X receptor within the D3R Grand Challenge 2016 blind-prediction competition. First, we employed docking with five different docking software and scoring functions. The selected docked poses gave an average root-mean-squared deviation of 4.2 Å. Consensus scoring gave decent results with a Kendall's τ of 0.26 ± 0.06 and a Spearman's ρ of 0.41 ± 0.08. For a subset of 33 ligands, we calculated relative binding free energies with free-energy perturbation. Five transformations between the ligands involved a change of the net charge and we implemented and benchmarked a semi-analytic correction (Rocklin et al., J Chem Phys 139:184103, 2013) for artifacts caused by the periodic boundary conditions and Ewald summation. The results gave a mean absolute deviation of 7.5 kJ/mol compared to the experimental estimates and a correlation coefficient of R 2 = 0.1. These results were among the four best in this competition out of 22 submissions. The charge corrections were significant (7-8 kJ/mol) and always improved the results. By employing 23 intermediate states in the free-energy perturbation, there was a proper overlap between all states and the precision was 0.1-0.7 kJ/mol. However, thermodynamic cycles indicate that the sampling was insufficient in some of the perturbations.

TREATMENT OF MYCOTIC RHINOSINUSITIS IN A BENNETT'S WALLABY ( MACROPUS RUFOGRISEUS) USING TOPICAL VORICONAZOLE SUSPENDED IN A REVERSE THERMODYNAMIC PLURONIC GEL.

An approximately 4-yr-old female Bennett's wallaby ( Macropus rufogriseus) was evaluated for chronic left-sided facial swelling and nasal discharge. Computed tomography, endoscopy, biopsy, mycologic culture, and panfungal polymerase chain reaction were consistent with destructive mycotic rhinosinusitis. The patient's infection was treated with a long-term injectable antibiotic, oral antifungal therapy, and multiple intranasal infusions of voriconazole suspended in a reverse thermodynamic pluronic gel. This case represents the first documented case of mycotic rhinosinusitis in a macropod and underlines the importance of advanced cross-sectional imaging in the diagnosis, monitoring, and management of nasal cavity disease in zoo animals.

Absolute binding free energy calculations of CBClip host-guest systems in the SAMPL5 blind challenge.

Herein, we report the absolute binding free energy calculations of CBClip complexes in the SAMPL5 blind challenge. Initial conformations of CBClip complexes were obtained using docking and molecular dynamics simulations. Free energy calculations were performed using thermodynamic integration (TI) with soft-core potentials and Bennett's acceptance ratio (BAR) method based on a serial insertion scheme. We compared the results obtained with TI simulations with soft-core potentials and Hamiltonian replica exchange simulations with the serial insertion method combined with the BAR method. The results show that the difference between the two methods can be mainly attributed to the van der Waals free energies, suggesting that either the simulations used for TI or the simulations used for BAR, or both are not fully converged and the two sets of simulations may have sampled difference phase space regions. The penalty scores of force field parameters of the 10 guest molecules provided by CHARMM Generalized Force Field can be an indicator of the accuracy of binding free energy calculations. Among our submissions, the combination of docking and TI performed best, which yielded the root mean square deviation of 2.94 kcal/mol and an average unsigned error of 3.41 kcal/mol for the ten guest molecules. These values were best overall among all participants. However, our submissions had little correlation with experiments.