Risk of anesthesia-related complications in brachycephalic dogs.

OBJECTIVE To determine whether brachycephalic dogs were at greater risk of anesthesia-related complications than nonbrachycephalic dogs and identify other risk factors for such complications. DESIGN Retrospective cohort study. ANIMALS 223 client-owned brachycephalic dogs undergoing general anesthesia for routine surgery or diagnostic imaging during 2012 and 223 nonbrachycephalic client-owned dogs matched by surgical procedure and other characteristics. PROCEDURES Data were obtained from the medical records regarding dog signalment, clinical signs, anesthetic variables, surgery characteristics, and complications noted during or following anesthesia (prior to discharge from the hospital). Risk of complications was compared between brachycephalic and nonbrachycephalic dogs, controlling for other factors. RESULTS Perianesthetic (intra-anesthetic and postanesthetic) complications were recorded for 49.1% (n = 219) of all 446 dogs (49.8% [111/223] of brachycephalic and 48.4% [108/223] of nonbrachycephalic dogs), and postanesthetic complications were recorded for 8.7% (39/446; 13.9% [31/223] of brachycephalic and 3.6% [8/223] of nonbrachycephalic dogs). Factors associated with a higher perianesthetic complication rate included brachycephalic status and longer (vs shorter) duration of anesthesia; the risk of perianesthetic complications decreased with increasing body weight and with orthopedic or radiologic procedures (vs soft tissue procedures). Factors associated with a higher postanesthetic complication rate included brachycephalic status, increasing American Society of Anesthesiologists status, use of ketamine plus a benzodiazepine (vs propofol with or without lidocaine) for anesthetic induction, and invasive (vs noninvasive) procedures. CONCLUSIONS AND CLINICAL RELEVANCE Controlling for other factors, brachycephalic dogs undergoing routine surgery or imaging were at higher risk of peri- and postanesthetic complications than nonbrachycephalic dogs. Careful monitoring is recommended for brachycephalic dogs in the perianesthetic period.

Pulmonary artery dissection in eight dogs with patent ductus arteriosus.

OBJECTIVES: To describe a series of dogs with pulmonary artery dissection and patent ductus arteriosus (PDA). ANIMALS: Eight dogs. METHODS: Retrospective case series. RESULTS: Pulmonary artery dissection was diagnosed in 8 dogs, 3 were Weimaraners. Four dogs presented in left-sided congestive heart failure, 4 presented for murmur evaluation and without clinical signs, and 1 presented in right-sided congestive heart failure. In 7 dogs the dissection was first documented concurrent with a diagnosis of uncorrected PDA. In the other dog, with pulmonary valve stenosis and PDA, the dissection was observed on autopsy examination 17 months after balloon pulmonary valvuloplasty and ductal closure. Median age at presentation for the 7 dogs with antemortem diagnosis of pulmonary artery dissection was 3.5 years (range, 1.5-4 years). Three dogs had the PDA surgically ligated, 2 dogs did not undergo PDA closure, 1 dog failed transcatheter occlusion of the PDA with subsequent surgical ligation, 1 dog underwent successful transcatheter device occlusion of the PDA, and 1 dog had the PDA closed by transcatheter coil delivery 17 months prior to the diagnosis of pulmonary artery dissection. The 2 dogs that did not have the PDA closed died 1 and 3 years after diagnosis due to heart failure. CONCLUSIONS: Pulmonary artery dissection is a potential complication of PDA in dogs, the Weimaraner breed may be at increased risk, presentation is often in mature dogs, and closure of the PDA can be performed and appears to improve outcome.

Dual MMP7-proximity-activated and folate receptor-targeted nanoparticles for siRNA delivery.

A dual-targeted siRNA nanocarrier has been synthesized and validated that is selectively activated in environments where there is colocalization of two breast cancer hallmarks, elevated matrix metalloproteinase (MMP) activity and folate receptor overexpression. This siRNA nanocarrier is self-assembled from two polymers containing the same pH-responsive, endosomolytic core-forming block but varying hydrophilic, corona-forming blocks. The corona block of one polymer consists of a 2 kDa PEG attached to a terminal folic acid (FA); the second polymer contains a larger (Y-shaped, 20 kDa) PEG attached to the core block by a proximity-activated targeting (PAT), MMP7-cleavable peptide. In mixed micelle smart polymer nanoparticles (SPNs) formed from the FA- and PAT-based polymers, the proteolytically removable PEG on the PAT polymers shields nonspecific SPN interactions with cells or proteins. When the PAT element is cleaved within an MMP-rich environment, the PEG shielding is removed, exposing the underlying FA and making it accessible for folate receptor-mediated SPN uptake. Characterization of mixed micelles prepared from these two polymers revealed that uptake and siRNA knockdown bioactivity of a 50% FA/50% PAT formulation was dependent on both proteolytic activation and FA receptor engagement. MMP activation and delivery of this formulation to breast cancer cells expressing the FA receptor achieved greater than 50% protein-level knockdown of a model gene with undetectable cytotoxicity. This modular nanoparticle design represents a new paradigm in cell-selective siRNA delivery and allows for stoichiometric tuning of dual-targeting components to achieve superior targeting specificity.

Kinematic and behavioral evidence for a distinction between trotting and ambling gaits in the cockroach Blaberus discoidalis.

Earlier observations had suggested that cockroaches might show multiple patterns of leg coordination, or gaits, but these were not followed by detailed behavioral or kinematic measurements that would allow a definite conclusion. We measured the walking speeds of cockroaches exploring a large arena and found that the body movements tended to cluster at one of two preferred speeds, either very slow (<10 cm s(-1)) or fairly fast (∼30 cm s(-1)). To highlight the neural control of walking leg movements, we experimentally reduced the mechanical coupling among the various legs by tethering the animals and allowing them to walk in place on a lightly oiled glass plate. Under these conditions, the rate of stepping was bimodal, clustering at fast and slow speeds. We next used high-speed videos to extract three-dimensional limb and joint kinematics for each segment of all six legs. The angular excursions and three-dimensional motions of the leg joints over the course of a stride were variable, but had different distributions in each gait. The change in gait occurs at a Froude number of ∼0.4, a speed scale at which a wide variety of animals show a transition between walking and trotting. We conclude that cockroaches do have multiple gaits, with corresponding implications for the collection and interpretation of data on the neural control of locomotion.

Computer-assisted 3D kinematic analysis of all leg joints in walking insects.

High-speed video can provide fine-scaled analysis of animal behavior. However, extracting behavioral data from video sequences is a time-consuming, tedious, subjective task. These issues are exacerbated where accurate behavioral descriptions require analysis of multiple points in three dimensions. We describe a new computer program written to assist a user in simultaneously extracting three-dimensional kinematics of multiple points on each of an insect's six legs. Digital video of a walking cockroach was collected in grayscale at 500 fps from two synchronized, calibrated cameras. We improved the legs' visibility by painting white dots on the joints, similar to techniques used for digitizing human motion. Compared to manual digitization of 26 points on the legs over a single, 8-second bout of walking (or 106,496 individual 3D points), our software achieved approximately 90% of the accuracy with 10% of the labor. Our experimental design reduced the complexity of the tracking problem by tethering the insect and allowing it to walk in place on a lightly oiled glass surface, but in principle, the algorithms implemented are extensible to free walking. Our software is free and open-source, written in the free language Python and including a graphical user interface for configuration and control. We encourage collaborative enhancements to make this tool both better and widely utilized.