Cellular acquisition of copper in eukaryotes is primarily accomplished through the Ctr family of copper transport proteins. In both humans and yeast, methionine-rich “Mets” motifs in the amino-terminal extracellular domain of Ctr1 are thought to be responsible for recruitment of copper at the cell surface. Unlike yeast, mammalian Ctr1 also contains extracellular histidine-rich motifs, although a role for these regions in copper uptake has not been explored in detail. Herein, synthetic model peptides containing the first 14 residues of the extracellular domain of human Ctr1 (MDHSHHMGMSYMDS) have been prepared and evaluated for their apparent binding affinity to both Cu(I) and Cu(II). These studies reveal a high affinity Cu(II) binding site (logK = 11.0 ± 0.3 at pH 7.4) at the amino-terminus of the peptide as well as a high affinity Cu(I) site (logK = 10.2 ± 0.2 at pH 7.4) that utilizes adjacent HH residues along with an additional His or Met ligand. These model studies suggest that the histidine domains may play a direct role in copper acquisition from serum copper-binding proteins and in facilitating the reduction of Cu(II) to the active Ctr1 substrate, Cu(I). We tested this hypothesis by expressing a Ctr1 mutant lacking only extracellular histidine residues in Ctr1-knockout mouse embryonic fibroblasts. Results from live cell studies support the hypothesis that extracellular amino-terminal His residues directly participate in the copper transport function of Ctr1.

Objective To evaluate the effect of combining a continuous epitendinous suture with three‐loop pulley (3LP) and locking‐loop (LL) core patterns for flexor tendon repair. Study design Ex vivo biomechanical study. Sample population Seventy‐two cadaveric superficial digital flexor musculotendon (SDFT) units. Methods Tendons were divided into four groups (n = 18/group). After sharp transection, SDFT were repaired with 3LP, LL, 3LP + epitendinous (E), or LL + E suture patterns. After preloading, repaired constructs were tested to failure. Video data acquisition allowed evaluation of failure mode and quantitation of gap formation. Yield, peak, and failure force were measured from force‐displacement data. Significance was set at P < .05. Results Mode of failure did not differ between repairs with or without an epitendinous suture (P = .255). Gap formation was best prevented with 3LP compared with LL when used alone (P = .001). Mean yield force for 3LP, LL, 3LP + E, and LL + E were 91.4 N ± 25.4, 61.3 N ± 18.4, 195.2 N ± 66.0, 165.3 N ± 46.8, respectively. Tenorrhaphies combined with an epitendinous suture achieved higher yield (P < .0001), peak (P < .0001), and failure forces (P < .0001), without gapping between tendon ends. Conclusion Addition of an epitendinous suture eliminated gapping between tendon ends until failure and increased resistance to loads tolerated at the repair site. Clinical significance The addition of an epitendinous suture may increase the strength of tendon repairs and resistance to gap formation over core suture use alone. The influence of epitendinous suture placement on tendinous healing and blood supply warrants in‐vivo testing.

Objective: To determine the influence of normograde (NG) versus retrograde (RG) catheterization of the cystic duct and common bile duct (CBD) in dogs with gallbladder mucoceles (GBM) treated with open cholecystectomy.Study design: Retrospective study. Animals: Dogs (n = 117) with GBM.Methods: Medical records were reviewed for signalment, history, clinical laboratory and diagnostic imaging findings, details of surgery including catheterization method, complications, and outcome. Long-term follow-up data were obtained by telephone or electronic communication. Relationships between catheterization method and clinical variables and outcome were evaluated.Results: Dogs catheterized RG were more likely to experience any postoperative complication (p = .0004) including persistence of gastrointestinal signs (p = .0003). Survival to discharge and long-term survival did not differ by group (p = .23 and p = .49). Total bilirubin (TB) decreased by 70.3% after NG catheterization compared to 39.1% after RG catheterization (p = .03) and increased in 14.9% dogs catheterized NG and 38.0% dogs catheterized RG (p = .004). The presence of a diplomate surgeon at surgery resulted in decreased incidences of any perioperative or postoperative complication (p = .003 and p = .05). Conclusion: Retrograde catheterization was associated with more postoperative concerns than NG catheterization, but similar survival times. Surgery should be performed by diplomates experienced in biliary surgery to minimize complications.Clinical significance: Although both NG and RG techniques to catheterize the cystic duct and CBD are options for treatment of GBM with low mortality,

OBJECTIVE To compare complications and outcome following unilateral, staged bilateral, and single-stage bilateral ventral bulla osteotomy (VBO) in cats. ANIMALS 282 client-owned cats treated by VBO at 25 veterinary referral and academic hospitals from 2005 through 2016. PROCEDURES Medical records of cats were reviewed to collect information on signalment, clinical signs, diagnostic test results, surgical and postoperative management details, complications (anesthetic, surgical, and postoperative), and outcome. Associations were evaluated among selected variables. RESULTS Unilateral, staged bilateral, and single-stage bilateral VBO was performed in 211, 7, and 64 cats, respectively, representing 289 separate procedures. Eighteen (9%), 2 (29%), and 30 (47%) of these cats, respectively, had postoperative respiratory complications. Cats treated with single-stage bilateral VBO were significantly more likely to have severe respiratory complications and surgery-related death than cats treated with other VBO procedures. Overall, 68.2% (n = 197) of the 289 procedures were associated with Horner syndrome (19.4% permanently), 30.1% (87) with head tilt (22.1% permanently), 13.5% (39) with facial nerve paralysis (8.0% permanently), and 6.2% (18) with local disease recurrence. Cats with (vs without) Horner syndrome, head tilt, and facial nerve paralysis before VBO had 2.6, 3.3, and 5.6 times the odds, respectively, of having these conditions permanently. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that staged bilateral VBO should be recommended over single-stage bilateral VBO for cats with bilateral middle ear disease. Cats with Horner syndrome, head tilt, and facial nerve paralysis before surgery were more likely to have these conditions permanently following surgery than were cats without these conditions.

To identify which classification systems have been used for tumor margin reporting and to determine whether factors (publication year, tumor type, and specialty of the contributing authors) influenced trends in margin reporting within literature describing canine soft tissue sarcoma (STS) and cutaneous mast cell tumors (MCT). Study design: Systematic literature review. Methods: Eligible articles were identified through electronic database searches performed for STS and MCT. Data abstracted from relevant studies included publication year, author list, specialty of contributing authors, criteria used to report the planned surgical margins, and the status of histologic margins. Categorization of papers was based on the classification systems used to report surgical and histologic tumor margins. Results: Fifty-three articles were included, 11 on STS, 37 on MCT, and five that included both tumor types. Criteria for classifying the planned surgical margins were described in only 50.9% of studies. Articles that listed a veterinary surgeon as a contributing author (P = .01) and STS articles compared to MCT papers (P = .01) were more likely to report surgical margins. Most (56.6%) studies reported the status of histologic margins dichotomously as "complete" or "incomplete." Although a previously published consensus statement recommended that quantitative criteria be used to report histologic margins, only 7.5% of articles used quantitative methods.