Accuracy of external measurements of 3-dimensional (3D) printed biomodels of the canine radius used in an in-hospital setting.

The objective of this study was to determine if biomodels printed on a fused deposition modeling (FDM) device from computed tomography (CT) data are accurate by comparing external measurements to the native bone, considering that the clinical usefulness of the printed biomodels in an in-hospital setting depends on their verified accuracy and consistency. Using canine cadaveric radii previously stripped of all soft tissues, 7 parameters of the actual bone and the 3-dimensional (3D) printed biomodels were measured and compared to determine how accurately the models represent the cadaveric bone. A total of 28 canine radii were collected, in which the landmarks for measurements were established. Radiographs were then taken to determine the frontal center of rotation of angulation (CORA) and CT scans were carried out. Finally, a 3D virtual reconstruction was done and converted into a stereolithography (STL) format file, from which 2 biomodels were printed per bone. Measurements for biomodels were compared for equivalence to cadaveric measurements. For the 7 measured parameters, the mean difference between biomodel and cadaveric parameters ranged from an increase of +0.66% in cranial-caudal proximal (CrCdP)-CORA to a decrease of -1.32% in distal width of the radius. For all 7 measured parameters, measurements for biomodels were statistically equivalent to their corresponding cadaveric bone (P < 0.001). The 7 measured parameters in the 3D models printed with an FDM device were not significantly different than those in the original bone. In fact, these measurements closely approximated original bone measurements (within 1.5%); therefore, validating their application in future presurgical planning for various orthopedic procedures.

L'objectif de la présente étude était de déterminer si les biomodèles imprimés par un appareil de modélisation par dépôt en fusion (MDF) à partir de données obtenues par tomodensitométrie (TMD) sont précis en comparant les mesures externes à l'os naturel, considérant que l'utilité clinique des biomodèles imprimés dans un milieu hospitalier dépend de leur précision vérifiée et de leur constance. Utilisant des radius canins provenant de cadavres et dont on a retiré tous les tissus mous, sept paramètres de l'os naturel et des biomodèles imprimés en trois dimensions (3D) ont été mesurés et comparés afin de déterminer jusqu'à quel point les modèles représentent l'os cadavérique. Vingt-huit radius canins ont été amassés, et à partir desquels les critères de mesure ont été établis. Des radiographies ont été prises afin de déterminer le centre frontal de rotation d'angulation (CORA) et des TMDs effectuées. Finalement, une reconstruction virtuelle 3D a été faite et convertie en fichier de format de stéréolithographie, à partir desquels deux biomodèles ont été imprimés par os. Les mesures des biomodèles ont été comparées pour équivalence aux mesures des os cadavériques. Pour les sept paramètres mesurés, la différence moyenne entre les paramètres des biomodèles et ceux des os cadavériques variait d'une augmentation de +0,66 % du CORA-crânial-caudal proximal à une diminution de −1,32 % dans la largeur distale du radius. Pour les sept paramètres mesurés, les mesures des biomodèles étaient statistiquement équivalentes (P < 0,001) à leurs mesures correspondantes sur les os cadavériques. Les sept paramètres mesurés sur les modèles 3D imprimés avec un appareil à MDF n'étaient pas différents statistiquement de ceux de l'os original. En fait, ces mesures étaient très près des mesures des os naturels (en dedans de 1,5 %), validant ainsi leur application dans la planification pré-chirurgicale future de différentes procédures orthopédiques.(Traduit par Docteur Serge Messier).

Structure-Activity Relationship Studies of a Series of Semisynthetic Lipopeptides Leading to the Discovery of Surotomycin, a Novel Cyclic Lipopeptide Being Developed for the Treatment of Clostridium difficile-Associated Diarrhea.

Novel cyclic lipopeptides with different acyl tails were synthesized via a semisynthetic approach. Structure-activity relationship studies revealed that lipophilicity, chain length, and the location of key aromatic functionalities of the tail modulated activity. The lead compound surotomycin exhibited significantly improved in vitro activity compared with daptomycin (MIC90 0.5 vs 2 µg/mL) against Clostridium difficile including NAP1 epidemic strains. In hamster efficacy studies, surotomycin protected animals at a dose of 0.5 mg/kg, PO.

Reduced pulmonary surfactant interaction of daptomycin analogs via tryptophan replacement with alternative amino acids.

Daptomycin was shown to interact in vitro with pulmonary surfactant leading to reduction of its antibacterial activity. We report herein the preparation and anti-staphylococcal activity of a series of daptomycin analogs with reduced pulmonary surfactant interaction by replacing tryptophan with various amino acids.

Relationship between radiographic hilar lymphadenopathy and serologic titers for Coccidioides sp. in dogs in an endemic region.

Hilar lymphadenopathy is a common radiographic finding in coccidioides infections. Serologic studies are used most often for the diagnosis of coccidioidomycosis in endemic areas, with IgG titers > 1:8 considered positive for infection and lower IgG titers of < 1:8 considered indicative of exposure and not necessarily related to organism presence. The objective of this study was to determine the relationship of hilar lymphadenopathy to coccidioidomycosis titers for dogs in an endemic area. A positive association between these parameters would allow treatment to be initiated before obtaining titer results. Thoracic radiographs of 131 dogs from an endemic area were reviewed for evidence of hilar lymphadenopathy. These results were compared with serology results. There was a significant association between hilar lymphadenopathy and a positive serology result (P < 0.001). With hilar lymphadenopathy as a predictor of a positive titer result, sensitivity was 28.0%, specificity was 91.5%, the positive predictive value was 43.8%; and the negative predictive value was 84.4%. There was no association between the titer result and gender, age, or weight. The radiographic finding of hilar lymphadenopathy appears to be a useful indicator of coccidioidomycosis infection in an endemic population of dogs supporting the treatment of patients for coccidioidomycosis when hilar lymphadenopathy is present and before obtaining serology results.

Potent and selective inhibitors of bacterial methionyl tRNA synthetase derived from an oxazolone-dipeptide scaffold.

The preparation and structure-activity relationships (SARs) of potent and selective small molecule inhibitors of bacterial methionyl-tRNA synthetase (MetRS) derived from an oxazolone-dipeptide scaffold are described. Examples combine Staphylococcus aureus MetRS (SaMetRS) potency with selectivity over human MetRS. As a result of the SAR expansion compound 14a was identified, as a potent SaMetRS inhibitor (IC(50)=18 nM) having moderate inhibition of MetRS derived from Enterococci faecalis (IC(50)=3.51 microM).

A series of spirocyclic analogues as potent inhibitors of bacterial phenylalanyl-tRNA synthetases.

We have identified a series of spirocyclic furan and pyrrolidine inhibitors of Enterococcus faecalis and Staphylococcus aureus phenylalanyl-tRNA synthetases. The most potent analogue 1b showed IC50=5 nM (E. faecalis PheRS) and IC50=2 nM (S. aureus PheRS) with high selectivity over the human enzyme. The crystal X-ray structure of analogue 1b was determined.

A series of heterocyclic inhibitors of phenylalanyl-tRNA synthetases with antibacterial activity.

A series of novel heterocyclic analogues have been synthesized and evaluated for their ability to inhibit phenylalanyl-t-RNA synthetases and act as antibacterial agents. Several analogues have good antibacterial activity against Staphylococcus aureus.

Synthesis and biological activity of N-Acylated ornithine analogues of daptomycin.

N-Acylated ornithine analogues of daptomycin were synthesized and tested for their antibacterial efficacy.

Array synthesis of novel lipodepsipeptide.

Synthetic array technology was utilized to rapidly synthesize and analyze a diverse set of reductive alkylation analogues of daptomycin. Analysis of the array suggested the use of polar functionality such as sulfonamides or amide or polar spaces such as piperazine would beneficially affect activity.

Discovery of a potent and selective series of pyrazole bacterial methionyl-tRNA synthetase inhibitors.

Starting with a micromolar lead identified from high-throughput screening, a series of pyrazoles were discovered with significantly improved potency on bacterial methionyl-tRNA synthetase and selectivity over human methionyl-tRNA synthetase.

Use of computed tomography renal angiography for screening feline renal transplant donors.

Preoperative knowledge of the renal vascular anatomy is important for selection of the appropriate feline renal donor. Intravenous urograms (IVUs) have been performed routinely to screen potential donors at the Veterinary Hospital of the University of Pennsylvania (VHUP), but the vascular phase views lack sufficient detail of the renal vascular anatomy. Computed tomography angiography (CTA), which requires a helical computed tomography (CT) scanner, has been found to provide superior renal vascular anatomic information of prospective human renal donors. The specific aims of this study were as follows: 1) develop the CTA technique for the feline patient; and 2) obtain preliminary information on feline renal vessel anatomy in potential renal donors. Ten healthy, potential feline renal donors were anesthetized and imaged using a third-generation helical CT scanner. The time delay between i.v. contrast medium injection and image acquisition, and other parameters of slice collimation, slice interval, pitch, exposure settings, and reconstruction algorithms were varied to maximize contrast medium opacification of the renal vascular anatomy. Optimal CTA acquisition parameters were determined to be: 1) 10-sec delay post-i.v. bolus of iodinated contrast medium; 2) two serially acquired (corresponding to arterial and venous phases) helical scans through the renal vasculature; 3) pitch of 2 (4 mm/sec patient translation, 2 mm slice collimation); and 4) 120-kVp, 160-mA, and 1-sec exposure settings. Retrospective reconstructed CTA transverse images obtained at a 2-mm slice width and a 1-mm slice interval in combination with two-dimensional reformatted images and three-dimensional reconstructed images were qualitatively evaluated for vascular anatomy; vascular anatomy was confirmed at surgery. Four cats had single renal arteries and veins bilaterally; four cats had double renal veins. One cat had a small accessory artery supplying the caudal pole of the left kidney. One cat had a left renal artery originating from the aorta at a 90 degrees angle with the cranial mesenteric artery. CTA of the feline renal vascular anatomy is feasible, and reconstruction techniques provide excellent anatomic vascular detail. CTA is now used routinely at VHUP to screen all potential feline renal donors.