Accuracy of correction of a hexapod frame, patient-specific osteotomy and reduction guides, and hinged circular external fixation in a 3D-printed canine antebrachial deformity model.

Objectives: This study aimed to objectively define whether human hexapod fixation (Maxframe), with or without the use of 3D-printed positioning guides, can correct a canine antebrachial deformity with greater accuracy than the clinically established techniques of 3D patient-specific osteotomy and reduction guides (3D-PSORG) or hinged circular external skeletal fixation (CESF). Methods: CT of a canine antebrachium was manipulated to induce distal radial deformity of the valgus, external torsion, and procurvatum, each of magnitude 20o. Five experiments were performed to correct the deformity via a distal radial and ulna opening osteotomy using: (1) A 3D-PSORG with the application of a locking plate, (2) hinged CESF, (3) Maxframe standard protocol, (4) Maxframe applied with patient-specific positioning guides (PSPGs), and (5) Maxframe with frame adjustment calculated from post-application CT. Following correction, all constructs were optically scanned, and objective measurement of the correction achieved was performed. Results: No construct returned the distal bone segment to its preoperative position in all planes. Translational malalignment in the sagittal plane had the highest magnitude of error for all constructs, with the Maxframe standard protocol showing the greatest error. Maxframe (PSPGs) showed the minimum error of all constructs in the frontal and sagittal planes. Clinical significance: In this 3D-printed model of antebrachial deformity correction, the hexapod frame with the use of PSPGs achieved better accuracy than 3D-PSORG and hinged CESF and may be a technique of future interest and development in the management of canine antebrachial limb deformity.

A neural network potential based on pairwise resolved atomic forces and energies.

Molecular simulations have become a key tool in molecular and materials design. Machine learning (ML)-based potential energy functions offer the prospect of simulating complex molecular systems efficiently at quantum chemical accuracy. In previous work, we have introduced the ML-based PairF-Net approach to neural network potentials, that adopts a pairwise interatomic scheme to predicting forces within a molecular system. Here, we further develop the PairF-Net model to intrinsically incorporate energy conservation and couple the model to a molecular mechanical (MM) environment within the OpenMM package. The updated PairF-Net model yields energy and force predictions and dynamical distributions in good agreement with the rMD17 dataset of ten small organic molecules in the gas-phase. We further show that these in vacuo ML models of small molecules can be applied to force predictions in aqueous solution via hybrid ML/MM simulations. We present a new benchmark dataset for these ten molecules in solution, obtained from QM/MM simulations, which we denote as rMD17-aq (https://zenodo.org/records/10048644); and assess the ability of PairF-Net to reproduce the molecular energy, atomic forces and dynamical distributions of these solution conformations via ML/MM simulations.

A ring of rotaxanes: studies of a large paramagnetic assembly in solution.

Here we report the synthesis and structural characterization of four [7]rotaxanes formed by coordinating hybrid inorganic-organic [2]rotaxanes to a central {Ni12} core. X-ray single crystal diffraction demonstrate that [7]rotaxanes are formed, with a range of conformations in the crystal. Small angle X-ray scattering supported by molecular dynamic simulations demonstrates that the large molecules are stable in solution and also show that the conformers present in solution are not those found in the crystal. Pulsed EPR spectroscopy show that phase memory times for the {Cr7Ni} rings, which have been proposed as qubits, are reduced but not dramatically by the presence of the {Ni12} cage.

Review of minimally invasive surgical procedures for assessment and treatment of medial coronoid process disease.

OBJECTIVE: To summarize the current peer-reviewed publications on minimally invasive surgery (MIS) for medial coronoid process disease (MCPD) in dogs. STUDY DESIGN: Invited review. METHODS: Pubmed, CAB Abstracts and Scopus databases were utilized for literature review (1990-2023). RESULTS: More than 60 papers have been published that involve MIS evaluation or treatment of MCPD. Six prospective trials incorporated quantitative gait analysis evaluating outcome following MCPD debridement, of which three included a control group. Whilst case numbers were limited, all studies employing a control group failed to demonstrate superiority of surgery over nonsurgical management. Of three studies employing gait analysis and no control group, all documented some improvement in function compared to pretreatment lameness. Multiple studies document progression of osteoarthritis in dogs following MCPD debridement although this may not be synonymous with worsened function. Subtotal coronoid osteotomy (SCO) is described as an alternative to MCP fragment removal, although the long-term biomechanical consequences are currently unclear and quantitative data on the efficacy of this treatment in isolation for MCPD is awaited. CONCLUSION: Arthroscopy of the canine elbow joint is a safe means by which to evaluate MCP pathology. Quantitative longitudinal analysis of outcome following minimally invasive surgery for MCPD is required. Correlation with clearly defined subclassification inclusion criteria such as age, incongruity and the precise arthroscopic findings in each case are required to more accurately differentiate any superiority of surgery over nonsurgical management for this disease.

Evaluation of cervical lymph nodes using multispectral optoacoustic tomography: a proof-of-concept study.

OBJECTIVES: Examination of lymph nodes is one of the most common indications for imaging in the head and neck region. The purpose of this study is to evaluate whether multispectral optoacoustic tomography can be used to observe chromophore differences between benign and malignant neck lymph nodes. MATERIALS AND METHODS: Proof-of-concept ex vivo study of resected cervical lymph nodes from 11 patients. The examination of lymph nodes included imaging with hybrid ultrasound and multispectral tomography system followed by spectral unmixing to separate signals from the endogenous chromophores water, lipid, hemoglobin and oxygenated hemoglobin; calculation of semi-quantitative parameters (total hemoglobin and relative oxygenation of hemoglobin). Comparison of the results from the hybrid measurement with the histopathological results. RESULTS: Most patients suffered from squamous cell carcinoma (n = 7), also metastasis from salivary gland adenocarcinoma and papillary thyroid carcinoma, were included. The comparison between benign cervical lymph nodes and metastases showed significant differences for the absorbers water, lipid, hemoglobin and oxygenated hemoglobin and total hemoglobin. CONCLUSIONS: Our ex vivo study suggests that multispectral optoacoustic tomography can be used to detect differences between reactive lymph nodes and metastases. The measurement of endogenous chromophores can be used for this purpose. The examinations are non-invasively and thus potentially improve diagnostic prediction. However, potential influences from the ex vivo setting must be considered.

Adduct Ions as Diagnostic Probes of Metallosupramolecular Complexes Using Ion Mobility Mass Spectrometry.

Following electrospray ionization, it is common for analytes to enter the gas phase accompanied by a charge-carrying ion, and in most cases, this addition is required to enable detection in the mass spectrometer. These small charge carriers may not be influential in solution but can markedly tune the analyte properties in the gas phase. Therefore, measuring their relative influence on the target molecule can assist our understanding of the structure and stability of the analyte. As the formed adducts are usually distinguishable by their mass, differences in the behavior of the analyte resulting from these added species (e.g., structure, stability, and conformational dynamics) can be easily extracted. Here, we use ion mobility mass spectrometry, supported by density functional theory, to investigate how charge carriers (H+, Na+, K+, and Cs+) as well as water influence the disassembly, stability, and conformational landscape of the homometallic ring [Cr8F8(O2CtBu)16] and the heterometallic rotaxanes [NH2RR'][Cr7MF8(O2CtBu)16], where M = MnII, FeII, CoII, NiII, CuII, ZnII, and CdII. The results yield new insights on their disassembly mechanisms and support previously reported trends in cavity size and transition metal properties, demonstrating the potential of adduct ion studies for characterizing metallosupramolecular complexes in general.

Design and topographic evaluation of a canine humeral anatomic plating system (CHAPS) for humeral condylar fracture repair in spaniels.

OBJECTIVE: To design a precontoured plating system for humeral condylar fracture repair in spaniels with humeral intracondylar fissure (HIF) and quantify accuracy of fit of the system on 3D printed bone models. STUDY DESIGN: Experimental on 3D printed models. METHODS: The plating system was based on morphometric data obtained from CT. Plates were applied to models and impression material was measured under the plates at points of interest to define plate bone gap (PBG). Data on locking screw interference on plate application were also obtained. RESULTS: Eleven elbows models were plated. Statistical analysis to assess for any difference in PBG measurements between left and right humuri revealed two loci (3 and 17) under the lateral plate and two loci (3 and 17) under the medial plate. On cumulate portion analysis, 67% of lateral plate loci and 80% of medial plate loci had a PBG of ≤2 mm respectively. An incidence of 2.1% (3/143) screw interference occurred. CONCLUSION: Design of a contoured plating system for application to humeral models from spaniels with HIF and its application with objective measurement of PBG is described. The majority of the loci measured under both lateral and medial plates had a BPG of ≤2 mm and the incidence of locking screw interference on plate application was low. CLINICAL SIGNIFICANCE: This novel system may have application for the stabilization of humeral condylar fractures in spaniels avoiding the need for plate contouring and minimizing the incidence of locking screw interference.

Disassembly Mechanisms and Energetics of Polymetallic Rings and Rotaxanes.

Understanding the fundamental reactivity of polymetallic complexes is challenging due to the complexity of their structures with many possible bond breaking and forming processes. Here, we apply ion mobility mass spectrometry coupled with density functional theory to investigate the disassembly mechanisms and energetics of a family of heterometallic rings and rotaxanes with the general formula [NH2RR'][Cr7MF8(O2CtBu)16] with M = MnII, FeII, CoII, NiII, CuII, ZnII, CdII. Our results show that their stability can be tuned both by altering the d-metal composition in the macrocycle and by the end groups of the secondary ammonium cation [NH2RR']+. Ion mobility probes the conformational landscape of the disassembly process from intact complex to structurally distinct isobaric fragments, providing unique insights to how a given divalent metal tunes the structural dynamics.

Efficacy of Co-Trimoxazole against Experimental Melioidosis Acquired by Different Routes of Infection.

Burkholderia pseudomallei is the causative agent of melioidosis and presents with diverse clinical manifestations. Naturally occurring infection occurs following contamination of cuts or skin abrasions, or ingestion of contaminated water, and occasionally through inhalational of infected soil or water particles. The influence of the route of disease acquisition on the efficacy of medical countermeasures has not been explored in humans or in appropriate animal models. The efficacy of co-trimoxazole against melioidosis acquired by different routes of exposure was assessed in postexposure prophylaxis (PEP) and treatment studies in marmoset models of melioidosis. Following challenge with B. pseudomallei by the inhalational, subcutaneous, or ingestion routes of administration, animals were given co-trimoxazole at 12 hourly intervals for 14 days, starting either 6 h postchallenge or at the onset of fever. Animals were then observed for 28 days. All animals that received antibiotic 6 h postchallenge survived the duration of dosing. All animals that received antibiotics at the onset of fever completed the treatment, but 10%, 57%, and 60% of those with ingestion, subcutaneous, and inhalation challenge relapsed, respectively. Bacteriological and histological differences were observed between placebo-control animals and those that relapsed. Immunological profiles indicate difference between animals given placebo and those that relapsed or survived the duration of the study. A broad T-cell activation was observed in animals that survived. Overall, these data suggest the efficacy of co-trimoxazole, as measured in the incidence of relapse, differs depending on the disease-acquisition route. Therefore, there are implications in treating this disease in regions of endemicity.

Disproportionation of the Uranyl(V) Coordination Complexes in Aqueous Solution through Outer-Sphere Electron Transfer.

Among the linear actinyl(VI/V) cations, the uranyl(V) species are particularly intriguing because they are unstable and exhibit a unique behavior to undergo H+ promoted disproportionation in aqueous solution and form stable uranyl(VI) and U(IV) complexes. This study uses density functional theory (DFT) combined with the conductor-like polarizable continuum model approach to investigate [UO2]2+/+ to [UIVO2] reduction free energies (RFEs) and explores the stability of uranyl(V) complexes in aqueous solution through computing disproportionation free energies (DFEs) for an outer-sphere electron transfer process. In addition to the aqua complex (U1), another three commonly encountered ligands such as chloride (U2), acetate (U3), and carbonate (U4) in aqueous environmental conditions are taken into account. For the U1 complex, the computed 1e- (V/IV) and 2e- (VI/IV) RFEs are in good agreement with experiments. The computed DFEs reveal that the presence of H+ is imperative for the disproportionation to take place. Although the presence of the alkali cations favors the disproportionation to some extent, they cannot fully make the reaction thermodynamically feasible. For the anionic complexes, the high negative charge does not allow for the formation of a cation-cation encounter complex due to Coulombic repulsion. Furthermore, an additional factor is the ligand exchange reaction which is also an energy-demanding step. Therefore, the current study examined the Kern-Orlemann mechanism and our results validate the mechanism based on DFT computed DFEs and propose that for the anionic complexes, an outer-sphere electron transfer is highly probable and our computed protonation free energies further support this claim.

Clients' perception of referral and veterinary specialists in a U.K. small animal referral hospital.

BACKGROUND: A 2011 RCVS report published following review of veterinary referral and specialisation suggested that the general public may have a lack of understanding of what constitutes specialisation. Our questionnaire study evaluated client understanding of the term 'Specialist' and the information obtained prior to referral. METHODS: Questionnaires were completed prior to consultation. Client age, medical knowledge, how referral was initiated, options discussed by the primary care practice for treatment, expectations of the referral appointment, understanding of the term Specialist and what constitutes specialist training were assessed. RESULTS: A total of 241 questionnaires were completed: 6.2% (15/241) of clients were working in the veterinary/medical industry; 52% (104/200) of clients assumed they were seeing a Specialist for consultation but only 49% (51/104) saw a Specialist; 0.4% (1/232) of owners correctly identified a Specialist as a clinician with a diploma, and incorrect definitions included having experience with a procedure or a postgraduate certificate; 13.6% (31/228) of clients identified that an internship and residency constituted Specialist training; and 66.8% (155/232) of clients had not researched the referral process. CONCLUSIONS: From the population sampled, a minority of clients understand the term Specialist and the postgraduate training this entails. Clients may erroneously assume they are receiving Specialist consultation.

Gold(i) bridged dimeric and trimeric heterometallic {Cr7Ni}-based qubit systems and their characterization.

Gold(i) bridged dimeric and trimeric structures of a ground state spin S = 1/2 heterometallic {Cr7Ni} wheel have been prepared and studied by continuous wave (CW) and pulsed wave EPR spectrometry. The {Cr7Ni} relaxation time constants (T1 and Tm) show rates matching well with previous observations. Four pulse Double Electron Resonance (DEER) studies suggest presence of more than one conformations. Small Angle X-ray Scattering (SAXS) in conjunction with Molecular Dynamic (MD) Simulations were performed to look at the possible conformations in solution. In line with DEER results, simulation data further indicated more flexible molecular geometry in solution than the one in solid state.

The potential of microdialysis to estimate rifampicin concentrations in the lung of guinea pigs.

Optimised pre-clinical models are required for TB drug development to better predict the pharmacokinetics of anti-tuberculosis (anti-TB) drugs to shorten the time taken for novel drugs and combinations to be approved for clinical trial. Microdialysis can be used to measure unbound drug concentrations in awake freely moving animals in order to describe the pharmacokinetics of drugs in the organs as a continuous sampling technique. The aim of this work was to develop and optimise the microdialysis methodology in guinea pigs to better understand the pharmacokinetics of rifampicin in the lung. In vitro experiments were performed before progressing into in vivo studies because the recovery (concentration of the drug in the tissue fluid related to that in the collected dialysate) of rifampicin was dependent on a variety of experimental conditions. Mass spectrometry of the dialysate was used to determine the impact of flow rate, perfusion fluid and the molecular weight cut-off and membrane length of probes on the recovery of rifampicin at physiologically relevant concentrations. Following determination of probe efficiency and identification of a correlation between rifampicin concentrations in the lung and skeletal muscle, experiments were conducted to measure rifampicin in the sacrospinalis of guinea pigs using microdialysis. Lung concentrations of rifampicin were estimated from the rifampicin concentrations measured in the sacrospinalis. These studies suggest the potential usefulness of the microdialysis methodology to determine drug concentrations of selected anti-TB drugs to support new TB drug development.

Three-Dimensional-Printed Patient-Specific Osteotomy Guides, Repositioning Guides and Titanium Plates for Acute Correction of Antebrachial Limb Deformities in Dogs.

OBJECTIVE: The aim of this study was to describe the use of patient-specific three-dimensional (3D)-printed osteotomy guides, repositioning guides and custom-printed titanium plates for acute correction of antebrachial limb deformities in four dogs. METHODS: Retrospective review of antebrachial limb deformities in small breed chondrodystrophic dogs that were surgically corrected using a closing wedge ostectomy of the radius at a predetermined site using patient-specific osteotomy guides. Reduction was achieved without the need for intraoperative measurements using patient-specific 3D-printed repositioning guides secured and manipulated using temporary Kirschner wire fixation. The ostectomy of the radius was stabilized with a patient-specific 3D-printed titanium plate. RESULTS: All limbs were corrected to within 3.5 degrees (standard deviation [SD]: 1 degree) and 7.5 degrees (SD: 3 degrees) of the pre-planned deformity correction in the frontal and sagittal planes, respectively. No complications were encountered. Owners completed a canine orthopaedic index survey at a median postoperative follow-up time of 19 months. Surgery eliminated the main presenting complaint of buckling over of the manus in all cases. CLINICAL SIGNIFICANCE: The 3D-printed osteotomy repositioning guides and titanium plates facilitated accurate acute correction of antebrachial deformities in this case series. The methodology described simplifies intraoperative surgical decision-making on limb position with good clinical outcomes seen in a small number of clinical cases.

Isolated Articular Fractures of the Canine Talus: Diagnosis and Signalment in Fourteen Dogs.

OBJECTIVE: The aim of this retrospective multicentre case series was to describe signalment, presenting signs and imaging findings in dogs with isolated articular fractures of the talus. STUDY DESIGN: Medical records (2008-2019) of dogs with isolated articular talar fractures were reviewed. RESULTS: Fourteen dogs met the inclusion criteria; affected breeds were four German Pointer (three shorthair and one wirehaired), three Labrador Retrievers, two Rottweilers, two Springer Spaniels, one cross breed, one Greyhound and one Great Münsterländer. The age range was 1 to 8 years with a median of 4.7 years. Lameness was usually acute in onset and had been present for a range of 4 to 540 days prior to referral.The most common fracture configuration involved the lateral trochlear ridge only (n = 9). Two of the fourteen fractures affected both trochlear ridges. Thirteen dogs were initially assessed radiographically with classic orthogonal views, but a fracture was only visible in five cases. The remainder were confirmed with further radiographic projections (n = 4) or computed tomography (n = 5). In one case, the lameness was located to the tarsus by scintigraphy. CONCLUSION: Isolated articular fracture of the talus is rare and may prove a diagnostic challenge due to the varied presentations and complex anatomy of the bone. Pathology of the talus may be suspected in any case of lameness localized to the tarsus and oblique/skyline radiographic views or advanced imaging should be performed if standard radiographic views are unremarkable.

Outcome following surgical stabilization of distal diaphyseal and supracondylar femoral fractures in dogs.

Signalment, clinical features, fixation techniques, complications, and outcome for dogs presenting with distal diaphyseal and supracondylar femoral fractures were retrospectively reviewed. A total of 45 dogs with unilateral femoral fractures were included. Supracondylar femoral plates were the most popular method of fixation. However, various fixation techniques resulted in favorable outcomes in most dogs with 19/45 cases achieving full function and 22/45 achieving acceptable function. Degree of fracture comminution did not appear to affect complication rate or be a surrogate for worse clinical outcome.

Résultats de stabilisation chirurgicale de fractures fémorales diaphysaires distales et supracondylaires chez le chien. Une étude rétrospective portant sur le signalement, la présentation clinique, les techniques de réduction de fracture, les complications et les résultats de chiens atteints de fractures fémorales supracondyliennes et diaphysaires distales a été réalisée. Quarante-cinq chiens présentant une fracture fémorale unilatérale ont été inclus au total. Les plaques fémorales supracondyliennes représentaient la méthode d'ostéosynthèse la plus courante. Diverses techniques de fixation ont abouti à des résultats favorables dans la majorité des cas, avec 19/45 cas récupérant une fonction complète et 22/45 une fonction considérée acceptable. Le degré de comminution de la fracture n'apparaissait pas comme étant un facteur de risque de complication ou étant associé à des résultats défavorables.(Traduit par Emilie Fauchon et Emilie Hanot).

Conformational Flexibility of Hybrid [3]- and [4]-Rotaxanes.

The synthesis, structures, and properties of [4]- and [3]-rotaxane complexes are reported where [2]-rotaxanes, formed from heterometallic {Cr7Ni} rings, are bound to a fluoride-centered {CrNi2} triangle. The compounds have been characterized by single-crystal X-ray diffraction and have the formulas [CrNi2(F)(O2CtBu)6]{(BH)[Cr7NiF8(O2CtBu)16]}3 (3) and [CrNi2(F)(O2CtBu)6(THF)]{(BH)[Cr7NiF8(O2CtBu)16]}2 (4), where B = py-CH2CH2NHCH2C6H4SCH3. The [4]-rotaxane 3 is an isosceles triangle of three [2]-rotaxanes bound to the central triangle while the [3]-rotaxane 4 contains only two [2]-rotaxanes bound to the central triangle. Studies of the behavior of 3 and 4 in solution by small-angle X-ray scattering and atomistic molecular dynamic simulations show that the structure of 3 is similar to that found in the crystal but that 4 has a different conformation to the crystal. Continuous wave and pulsed electron paramagnetic resonance spectroscopy was used to study the structures present and demonstrate that in frozen solutions (at 5 K) 4 forms more extended molecules than 3 and with a wider range of conformations.

A [13]rotaxane assembled via a palladium molecular capsule.

Molecules that are the size of small proteins are difficult to make. The most frequently examined route is via self-assembly, and one particular approach involves molecular nanocapsules, where ligands are designed that will enforce the formation of specific polyhedra of metals within the core of the structure. Here we show that this approach can be combined with mechanically interlocking molecules to produce nanocapsules that are decorated on their exterior. This could be a general route to very large molecules, and is exemplified here by the synthesis and structural characterization of a [13]rotaxane, containing 150 metal centres. Small angle X-ray scattering combined with atomistic molecular dynamics simulations demonstrate the compound is intact in solution.

Uranyl-Bound Tetra-Dentate Non-Innocent Ligands: Prediction of Structure and Redox Behaviour Using Density Functional Theory.

Computational methods have been applied to understand the reduction potentials of [UO2 -salmnt-L] complexes (L=pyridine, DMSO, DMF and TPPO), and their redox behavior is compared with previous experiments in dichloromethane solution. Since the experimental results were inconclusive regarding the influence of the uranyl-bound tetra-dentate 'salmnt' ligand, here we will show that salmnt acts as a redox-active ligand and exhibits non-innocent behavior to interfere with the otherwise expected one-electron metal (U) reduction. We have employed two approaches to determine the uranyl (VI/V) reduction potentials, using a direct study of one-electron reduction processes and an estimation of the overall reduction using isodesmic reactions. Hybrid density functional theory (DFT) methods were combined with the Conductor-like Polarizable Continuum Model (CPCM) to account for solvation effects. The computationally predicted one-electron reduction potentials for the range of [UO2 -salmnt-L] complexes are in excellent agreement with shoulder peaks (∼1.4 eV) observed in the cyclic voltammetry experiments and clearly correlate with ligand reduction. Highly conjugated pi-bonds stabilize the ligand based delocalized orbital relative to the localized U f-orbitals, and as a consequence, the ligand traps the incoming electron. A second reduction step results in metal U(VI) to U(V) reduction, in good agreement with the experimentally assigned uranyl (VI/V) reduction potentials.