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The vasa vasorum is a delicate network of small arterioles that supplies nutrients to the adventitia and outer media of large arteries. In humans, dysfunction of the vasa vasorum contributes to the pathogenesis of aortic dissection and atherosclerosis. Twenty-four cats from 1 to 18 years of age were prospectively evaluated. Cases were divided into 3 cohorts—with systemic hypertension, without systemic hypertension, and uncertain. Histologic sections of the aorta and main pulmonary artery, as well as sections of kidney and lung, were blindly examined by 2 pathologists. The severity of vasa vasorum arteriopathy was compared to the presence of renal arteriosclerosis, aortic medial degeneration, subintimal fibroplasia of the main pulmonary artery, and blood pressure. We found that vasa vasorum arteriopathy correlated strongly with hypertensive status, degree of renal arteriosclerosis, and lesions in the great vessels. The positive predictive value of a severe vasa vasorum score for systemic hypertension was 84.6%. Lesions of vasa vasorum arteriopathy were predictive of renal arteriosclerosis with 100% sensitivity and 64.7% specificity. The positive predictive value of a severe vasa vasorum score for the presence of aortic lesions was 69.2% vs 91.6% for lesions in the main pulmonary artery. The vasa vasorum appears to be an important responder to systemic hypertension in cats, and arteriopathy of this vascular bed has significant implications for the integrity of the great vessels. [ABSTRACT FROM AUTHOR]

Metastasis is the primary cause of death in breast cancer patients, yet there are challenges to modeling this process in vivo. The goal of this study was to analyze the effects of injection site on tumor growth and metastasis and gene expression of breast cancer cells in vivo using the MMTV-PymT breast cancer model (Met-1 cells). Met-1 cells were injected into 5 sites (subcutaneous, mammary fat pad, tail vein, intracardiac, and intratibial), and tumors and metastases were monitored using bioluminescent imaging and confirmed with gross necropsy and histopathology. Met-1 tumors were analyzed based on morphology and changes in gene expression in each tissue microenvironment. There were 6 permissible sites of Met-1 tumor growth (mammary gland, subcutis, lung, adrenal gland, ovary, bone). Met-1 cells grew faster in the subcutis compared to mammary fat pad tumors (highest Ki-67 index). Morphologic differences were evident in each tumor microenvironment. Finally, 7 genes were differentially expressed in the Met-1 tumors in the 6 sites of growth or metastasis. This investigation demonstrates that breast cancer progression and metastasis are regulated by not only the tumor cells but also the experimental model and unique molecular signals from the tumor microenvironment. [ABSTRACT FROM PUBLISHER]

Amnion-derived acellular bioscaffold (ADABP) products demonstrate interesting anti-inflammatory and healing properties which could be beneficial for intrauterine use. The objective of this study was to evaluate the safety of intrauterine injection of ADABP on systemic and uterine health. The study design randomly assigned subjects to one of two groups, control mares (n = 3) which received 3 mL injection of sterile saline in the base of each uterine horn, and treatment mares (n = 9) which received 3 mL of ADABP in the base of one uterine horn and 3 mL injection of sterile saline in the base of the other uterine horn. The leukogram had no significant effect of group and no group by day interaction. The serum biochemistry panel had no effect of group on any of the parameters examined. There were no significant differences in uterine culture or uterine biopsy results. The data suggests intrauterine injection of ADABP has no negative systemic or uterine effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Bronchiectasis is irreversible bronchial dilation that can be congenital or acquired secondary to chronic airway obstruction. Feline bronchiectasis is rare and, to our knowledge, has not been reported previously in a non-domestic felid. An ~10-y-old female jungle cat ( Felis chaus ) was presented for evaluation of an abdominal mass and suspected pulmonary metastasis. The animal died during exploratory laparotomy and was submitted for postmortem examination. Gross examination revealed consolidation of the left caudal lung lobe and hila of the cranial lung lobes. Elsewhere in the lungs were several pale-yellow pleural foci of endogenous lipid pneumonia. On cut section, there was severe distension of bronchi with abundant white mucoid fluid. The remaining lung lobes were multifocally expanded by marginal emphysema. Histologically, ectatic bronchi, bronchioles, and fewer alveoli contained degenerate neutrophils, fibrin, and mucin (suppurative bronchopneumonia) with rare gram-negative bacteria. Aerobic culture yielded low growth of Proteus mirabilis and Escherichia coli . There was chronic bronchitis, marked by moderate bronchial gland hyperplasia, lymphoplasmacytic inflammation, and lymphoid hyperplasia. The palpated abdominal mass was a uterine endometrial polyp, which was considered an incidental, but novel, finding. Chronic bronchitis and bronchopneumonia should be considered as a cause of bronchiectasis and a differential diagnosis for respiratory disease in non-domestic felids., Competing Interests: Declaration of conflicting interestsThe authors declared no conflicts of interest regarding the research, authorship, and/or publication of this article.

Endoscopic-assisted transcervical inseminations (TCIs) have become increasingly popular. The aim of this retrospective clinical study was to evaluate data from the TCIs performed at our facility. We evaluated data from January 2018 through December 2021. This included 137 cases with fresh, 67 cases chilled, and 63 cases using frozen-thawed semen. All bitches underwent breeding management to determine the ideal breeding period. All semen samples were evaluated for total number of sperm, total motility, and progressive motility. Pregnancy was determined by B-mode ultrasonography about 4 weeks after the breeding. Litter size was determined by radiographs performed around the last week of gestation. The pregnancy rate was 83.21% for fresh, 67.16% for chilled, and 66.67% for frozen-thawed semen. There was a significant difference in litter size between fresh semen (6.82 puppies per litter) and both chilled (5.21 puppies per litter) and frozen-thawed (4.59 puppies per litter) semen (P < .05). There was no significant difference in litter size between chilled and frozen-thawed semen. There was no difference in pregnancy rates between clinicians performing the inseminations. Pregnancy rate was not different when sedation was used for the insemination (66.67%) compared to when sedation was not used (74.84%; P > .05). Performing 2 TCIs during the fertile period, regardless of the semen type, resulted in an increase of 6.6% in pregnancy rate (P > .05) and an increase of 0.7 puppies per litter, on average (P > .05). These results can be used to help guide recommendations for breeding clients on the best options to increase both pregnancy rate and litter size for their breeding., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In Brief: The bovine high fecundity allele, Trio, results in the occurrence of multiple ovulations and is characterized by antral follicles that develop slower and acquire ovulatory capacity at smaller sizes. This study provides novel information on the effect of the Trio allele on early folliculogenesis., Abstract: The bovine high fecundity allele, Trio, causes overexpression in granulosa cells (GCs) of SMAD6, an inhibitor of BMP15-activated SMAD signalling. Furthermore, the Trio allele results in antral follicles that develop slower, acquire ovulatory capacity at smaller sizes, and have three-fold greater ovulation rate compared to half-sib non-carriers. The present study was designed to determine preantral follicle numbers and size in Trio carrier and non-carrier cattle testing the hypothesis that inhibition of SMAD signalling would alter preantral follicle activation and/or growth. Ovarian tissues from Trio carrier (n = 12) and non-carrier (n = 12) heifers were obtained by laparotomy after follicle wave synchronization. Follicle numbers and dimensions were determined for each stage of development (primordial, transitional, primary, and secondary) from paraffin-embedded sections. There were no differences in the number of primordial, transitional, or secondary follicles or in antral follicle count, circulating AMH, or ovarian volume between carriers and non-carriers. Trio carriers had ~2.5-fold greater (P < 0.01) number of primary follicles than non-carriers, and transitional and primary follicles were larger (~1.2-fold; P < 0.1) in Trio carriers. Oocyte volume of primordial and transitional follicles was not different between genotypes; however, oocytes were larger (P < 0.05) in primary (~1.3-fold) and secondary (~1.8-fold) follicles for Trio carriers. Granulosa cell numbers were not different (P > 0.3) between carriers and non-carriers, irrespective of the stage of development. These results suggest that, after primordial follicle activation, follicles in Trio carrier cattle have slower progression through the primary stage, hence the larger oocyte and greater number of primary follicles.

The sperm plasma membrane is a multifunctional organelle essential to fertilization. However, assisted reproduction techniques often negatively affect this structure, resulting in reduced fertility. These reductions have been attributed to plasma membrane damage in a wide array of species, including fish. Considerable research has been conducted on the fish sperm membrane, but few have examined the effect of cryopreservation and other assisted reproduction techniques (ARTs) on not only membrane composition, but also specific characteristics (e.g., fluidity) and organization (e.g., lipid rafts). Herein, we determined the effects of three ARTs (testicular harvest, strip spawning, and cryopreservation) on the sperm plasma membrane, using Sauger (Sander canadensis) sperm as a model. To this end, a combination of fluorescent dyes (e.g., merocyanine 540, filipin III, cholera toxin subunit β), liquid chromatography - mass spectroscopy (LC-MS) analysis of membrane lipids, and membrane ultracentrifugation coupled with plate assays and immunofluorescence were used to describe and compare sperm fluidity, membrane composition, as well as lipid raft composition and distribution among sperm types. Stripped sperm became more fluid following motility activation (40% increase in highly fluid cells characterized by a 2 × increase in fluorescence) and contained lipid rafts restricted to the midpiece. Testicular harvest yielded sperm with characteristics similar to stripped sperm. By contrast, cryopreservation impacted every aspect of membrane physiology. Two cell populations, one highly fluid and the other rigid, resulted from the freeze-thaw process. Cryopreservation reduced lipid raft cholesterol content by 44% and flotilin-2 (a lipid raft marker) was partially displaced owing to a decrease in buoyancy. Unlike stripped and testicular sperm, LC-MS analysis revealed increases in oxidative damage markers, membrane destabilization, and apoptotic signaling in cryopreserved sperm. Ultrastructural analysis also revealed widespread physical damage to the membrane following freeze-thaw. Sperm motility, however, was unrelated to any measure of membrane physiology used in this study. Our results demonstrate that ARTs have the potential to substantially affect the sperm plasma membrane, but not always detrimentally. These results provide multiple potential biomarkers of sperm quality as well as insight into sources of sub-fertility resulting from use of ARTs., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Next-generation in vitro culture model systems are needed to study the reproductive pathologies that affect domestic animals. These 3D culture models more closely mimic normal physiological function to allow a greater understanding of reproductive pathology and to trial therapeutics without the welfare concerns and the increased time and cost associated with live animal research. Recent advances with in vitro cell culture systems utilizing human and laboratory animal tissues have been reported, but implementation of these technologies in veterinary species has been slower. Organoids are a physiologically representative 3D cell culture system that can be maintained long-term. By combining organoid culture with cryopreservation, a long-term, experimental model can be available for year-round application, thus bypassing seasonality and reproductive tract availability restrictions. Here we report the generation and cryopreservation of feline oviductal organoids for the first time. Optimal culture medium for the generation of feline oviductal organoids was established, and organoids were successfully cryopreserved using three different freezing media with organoids from each treatment demonstrating comparable viability, growth rate, and protein expression after thawing and culture. Feline oviductal organoids may facilitate an in vivo-like environment that, in conjunction with co-culture for in vitro maturation and in vitro fertilization, may positively influence in vitro gamete and embryo development, embryo quality, and pregnancy rates after embryo transfer in domestic and nondomestic felids. Furthermore, readily available cryopreserved feline oviductal organoids will facilitate this co-culture, which is of particular importance to endangered felid breeding programs where tissue and gamete samples are often opportunistically obtained with little or no notice., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Currently, intraoperative tumour margin imaging is not routinely utilized in veterinary medicine. Optical coherence tomography (OCT) allows for real-time assessment of tissue morphology of 1-2 mm depth. The aims of this study were (1) to compare the histologic and OCT features of excised canine skin and subcutaneous specimens, and (2) to determine the diagnostic accuracy of OCT for surgical margin evaluation. The authors hypothesized that OCT imaging would correlate well with histopathology and that OCT would be sensitive for detection of incomplete margins. Eighty dogs were prospectively enrolled. Tumours were excised, and the surgical margins were imaged using a spectral domain OCT system. The tumour type and completeness of excision were determined by histopathology. Nine blinded observers received training in OCT image interpretation and were then given a set of OCT images and videos. The observers assigned each image/video a grade from 1 (no tumour) to 4 (tumour) and the results were compared to histopathology. The overall median sensitivity and specificity of OCT imaging for detection of incomplete margins were 86.7% and 84.6%, respectively. A potential limitation is that observers had varied experience with OCT image interpretation, ranging from no prior experience to participating in a previous OCT project. OCT is sensitive for detection of incomplete margins and could be a promising real-time surgical margin imaging modality. Further study is needed to evaluate intraoperative applications of OCT and its impact on tumour recurrence and long-term outcome., (© 2022 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

In collaboration with the American College of Veterinary Pathologists.

An adult alpaca (Vicugna pacos) with a history of colic and anorexia was euthanized because of failure to respond to treatment. Macroscopically, pale-tan, multifocal to coalescing, firm nodules and plaques markedly expanded the omentum, mesentery and the parietal and visceral peritoneum of multiple abdominal organs, especially the right oviduct and associated mesosalpinx. Abundant dark-red watery digesta were present in the duodenum and jejunum. Histological evaluation of the right oviduct, abdominal visceral nodules and plaques and mesenteric lymph nodes revealed transmural expansion and replacement by an epithelial malignant neoplasm, comprised of tubules and acini of ciliated columnar cells supported by abundant fibrous connective tissue. Both ovaries were histologically normal. On the basis of the ciliated morphology of the neoplastic cells, the focus on the proximal reproductive tract and the unremarkable ovaries, a reproductive tubal adenocarcinoma with carcinomatosis was diagnosed, with both the endometrium and oviduct considered as the tissues of origin. The prominent ciliated morphology of the neoplastic cells and the classification of human fallopian tube (oviduct) neoplasia lead us to propose oviductal adenocarcinoma with widespread carcinomatosis as the definitive diagnosis. The lamina propria of the small intestine was infiltrated segmentally by lymphocytes, plasma cells and neutrophils, and Clostridium perfringens with beta2 toxin production was identified by polymerase chain reaction in the small intestinal contents. To our knowledge, this is the first report of these two distinct diseases in an alpaca., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine the diagnostic accuracy of optical coherence tomography (OCT) to assess surgical margins of canine soft tissue sarcoma (STS) and determine the influence of observer specialty and training., Study Design: Blinded clinical prospective study., Animals: Twenty-five dogs undergoing surgical excision of STS., Methods: In vivo and ex vivo surgical margins were imaged with OCT after tumor resection. Representative images and videos were used to generate a training presentation and data sets. These were completed by 16 observers of four specialties (surgery, radiology, pathology, and OCT researchers). Images and videos from data sets were classified as cancerous or noncancerous., Results: The overall sensitivity and specificity were 88.2% and 92.8%, respectively, for in vivo tissues and 82.5% and 93.3%, respectively, for ex vivo specimens. The overall accurate classification for all specimens was 91.4% in vivo and 89.5% ex vivo. There was no difference in accuracy of interpretation of OCT imaging by observers of different specialties or experience levels., Conclusion: Use of OCT to accurately assess surgical margins after STS excision was associated with a high sensitivity and specificity among various specialties. Personnel of all specialties and experience levels could effectively be trained to interpret OCT imaging., Clinical Significance: Optical coherence tomography can be used by personnel of different specialty experience levels and from various specialties to accurately identify canine STS in vivo and ex vivo after a short training session. These encouraging results provide evidence to justify further research to assess the ability of OCT to provide real-time assessments of surgical margins and its applicability to other neoplasms., (© 2020 American College of Veterinary Surgeons.)

The endometrium, the inner uterine lining, is composed of cell layers that come in direct contact with an embryo during early pregnancy and later with the fetal placenta. The endometrium is responsible for signals associated with normal reproductive cyclicity as well as maintenance of pregnancy. In the mare, functionally competent in vitro models of the endometrium have not been successful. Furthermore, the ability to study various reproductive processes in vitro may allow critical evaluation of signaling pathways involved in the reproductive diseases of animals that cannot be handled frequently, such as various wildlife species. Here we report the establishment of organoids, 3D structures, derived from fresh and frozen-thawed equine endometrium (Equus ferus caballus and E. f. przewalskii). Although organoids from domestic mares responded to exogenous hormonal stimuli, organoids from Przewalski's horse failed to respond to exogenous hormones. The present study represents a 'first' for any large animal model or endangered species. These physiologically functional organoids may facilitate improved understanding of normal reproductive mechanisms, uterine pathologies, and signaling mechanisms between the conceptus and endometrium and may lead to the development of novel bioassays for drug discovery.

The inner layer of the uterus, the endometrium, is responsible and necessary for many reproductive functions. Normal reproductive cyclicity, maternal recognition of pregnancy, maternal interaction with the embryo, and interaction of the reproductive tract with pathogens are dependent on the endometrium. Although most studies have been conducted in vivo using live animals, recent advances in in vitro approaches could facilitate future research in a laboratory setting with minimal effect on animals. Many reproductive studies have been performed in vivo and in vitro in equids, but new in vitro methods to study the endometrium of mares remain unexplored. In this review, there is a description of the normal anatomy and physiology of the mare endometrium in vivo, in vitro endometrial cell culture techniques that have been previously described for the mare, and opportunities for future reproductive research using in vitro methods., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The WW domain-containing oxidoreductase (WWOX) tumor suppressor gene is frequently lost in a variety of solid and hematopoietic malignancies in humans. Dysregulation of WWOX has been implicated as playing a key role in tumor cell survival, DNA damage repair, and genomic stability. The purpose of this study was to characterize WWOX expression in spontaneous canine mast cell tumors (MCTs) and malignant cell lines and investigate the potential contribution of WWOX loss on malignant mast cell behavior., Methods/results: WWOX expression is decreased in primary canine MCTs and malignant mast cell lines compared to normal canine bone marrow-cultured mast cells. In transformed canine mastocytoma cell lines, overexpression of WWOX or WWOX knockdown had no effect on mast cell viability. Inhibition of WWOX enhanced clonogenic survival following treatment with ionizing radiation in the C2 mast cell line. Lastly, immunohistochemistry for WWOX was performed using a canine MCT tissue microarray, demonstrating that WWOX staining intensity and percent of cells staining for WWOX is decreased in high-grade MCTs compared to low-grade MCTs., Conclusions: These data suggest that WWOX expression is attenuated or lost in primary canine MCTs and malignant mast cell lines. Given the observed increase in clonogenic survival in WWOX-deficient C2 mast cells treated with ionizing radiation, further investigation of WWOX and its role in mediating the DNA damage response in malignant mast cells is warranted.

Objectives: A notable, although relatively uncommon, finding during feline ovariohysterectomy is the presence of parovarian nodules, located proximal to the ovary, near or within the ovarian vascular bundle. They are usually 2-3 mm in diameter, white-to-tan in color and glandular in appearance. The objective of this study was to either decisively reinforce the existing findings reported in the literature, which suggest that these parovarian nodules are incidental adrenocortical nodules that are clinically and surgically insignificant, or capture any samples that were not ectopic adrenal tissue in order to characterize them histologically., Methods: Ninety-one formalin-preserved tissue sections containing parovarian nodules were collected during routine feline elective ovariohysterectomy and evaluated histologically., Results: Definitive histologic information was obtained from 73/91 (80.2%) submitted samples. Fifty-two of 73 (71.2%) samples were determined to contain accessory adrenal gland cortex. Twenty of 73 (27.4%) samples were determined to contain residual mesonephric structures. While accessory adrenocortical nodules were found bilaterally in cats of all ages, mesonephric structures were predominantly right-sided, and only found in one cat over the age of 1 year. Ectopic or accessory ovarian tissue was not found in any of the samples., Conclusions and Relevance: This study adds to the existing body of data which suggest these nodules are incidental structures that do not need to be removed during surgical sterilization. However, further in vivo studies with larger sample sizes and years of follow-up would be required to more definitively prove this theory.

Many Escherichia coli (E. coli) strains produce biofilm that confers antimicrobial resistance. However, studies of biofilm production by E. coli from canine pyometra are lacking. Objectives were to elucidate the role of biofilm production by E. coli in pyometra by: (1) assessing the ability of E. coli to produce biofilm in vitro, and (2) confirming biofilm in situ. Endometrial biopsies were obtained from bitches with pyometra and preserved for microscopic analysis (n = 25). An endometrial swab was submitted for aerobic culture. Samples with confirmed E. coli were evaluated further for biofilm production in vitro and in vivo. Seventy percent of cases (16/23) resulted in pure growth of 1 or 2 E. coli strains, totaling 20 isolates. Fifteen isolates (15/20, 75%) had higher optical densities then negative controls (P < .05). On histopathology, all tissues exhibited endometrial inflammation and mucus was located within endometrial glands and occasionally overlying epithelium on 14 slides (14/16, 88%). Bacteria was noted in 50% of slides (8/16). During FISH acellular debris within the uterine lumen consistent with biofilm was noted on 94% of samples (15/16) and E coli was positively identified on all samples (15/15). Areas suggestive of the presence of biofilm were observed on all samples on scanning electron microscopy; but, bacteria consistent with E. coli were only visualized in 9 samples (9/16, 56%). In conclusion, we demonstrated that relevant strains of E. coli produce biofilm in vitro and in vivo, which may be considered in the development of new pyometra treatments aimed at disrupting these E. coli biofilm., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Availability of viable frozen-thawed endometrial tissues could facilitate detailed studies into physiologic and disease processes influencing the endometrium. This study was designed to investigate the cryosurvival of equine endometrial tissue. Previous studies in the human and horse have focused on cryopreservation of dissociated endometrial cells. To our knowledge, there are no studies on cryopreservation of endometrial explants. Our objectives were to 1) determine the influence of differing concentrations of the permeating cryoprotectant dimethyl sulfoxide (Me 2 SO) on viability, structural integrity, and gene expression of cryopreserved equine endometrial tissues prior to and following a 5-day explant culture in vitro and 2) examine the influence of low (1000 mg/L dextrose) vs high (4500 mg/L dextrose) glucose medium during in vitro culture. Both 10% and 20% (v/v) concentrations of Me 2 SO maintained viability following cryopreservation and in vitro culture. In addition, gene expression remained unaltered following cryopreservation with either 10% or 20% Me 2 SO. However, tissue structural integrity was slightly reduced compared to the fresh control. Furthermore, there was no difference in structural integrity, cell viability, or gene expression between low and high glucose medium during in vitro culture. Although E-cadherin and Ki67 gene expression was not different among fresh, 10% Me 2 SO, and 20% Me 2 SO treatments prior to or following tissue culture, estrogen receptor-α and progesterone receptor gene expression were reduced in all groups after explant culture. This is the first report of successful cryopreservation of equine endometrial explants., (Copyright © 2019. Published by Elsevier Inc.)

The emergence of additive manufacturing has afforded the ability to fabricate intricate, high resolution, and patient-specific polymeric implants. However, the availability of biocompatible resins with tunable resorption profiles remains a significant hurdle to clinical translation. In this study, 3D scaffolds are fabricated via stereolithographic cDLP printing of poly(propylene fumarate) (PPF) and assessed for bone regeneration in a rat critical-sized cranial defect model. Scaffolds are printed with two different molecular mass resin formulations (1000 and 1900 Da) with narrow molecular mass distributions and implanted to determine if these polymer characteristics influence scaffold resorption and bone regeneration in vivo. X-ray microcomputed tomography (µ-CT) data reveal that at 4 weeks the lower molecular mass polymer degrades faster than the higher molecular mass PPF and thus more new bone is able to infiltrate the defect. However, at 12 weeks, the regenerated bone volume of the 1900 Da formulation is nearly equivalent to the lower molecular mass 1000 Da formulation. Significantly, lamellar bone bridges the defect at 12 weeks with both PPF formulations and there is no indication of an acute inflammatory response., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: To determine whether nylon fibers improve the performance of platinum embolization coils in porcine arteries., Materials and Methods: Platinum 0.035" embolization coils, both with and without nylon fibers, were used to embolize a total of 24 hindlimb arteries in 6 swine: 12 with fibered coils and 12 with non-fibered coils. Apart from fibers, the coils were identical. Immediate and late results were studied, including number of coils needed to achieve vessel occlusion and durability of occlusion at 1 and 3 months. Arteriographic as well as histopathologic analysis were performed., Results: A mean of 3.2 (range, 2-4) non-fibered coils was required to achieve occlusion, whereas a mean of 1.3 (range, 1-2) fibered coils achieved occlusion in similarly sized arteries (2.3-3.2-mm diameter, P < .001). The mean percent cross-sectional area occupied by thrombus was greater in arteries with fibered coils than with non-fibered coils at 1 month (63% ± 6% and 48% ± 15%, respectively, P = .03) but not at 3 months (61% ± 6% and 49% ± 15%, respectively, P = .06). Some recanalization was observed at follow-up and did not differ between groups at 1 month (P = .07) or 3 months (P = .22)., Conclusions: Nylon fibers allow significantly fewer embolization coils to achieve acute occlusion of arteries compared to bare metal coils. Both fibered and non-fibered coils showed recanalization at follow-up., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

The use of degradable materials is required to address current performance and functionality shortcomings from biologically-derived tissues and non-resorbable synthetic materials used for hernia mesh repair applications. Herein a series of degradable l-valine-co-l-phenylalanine poly(ester urea) (PEU) copolymers were investigated for soft-tissue repair. Poly[(1-VAL-8) 0.7 -co-(1-PHE-6) 0.3 ] showed the highest uniaxial mechanical properties (332.5 ± 3.5 MPa). Additionally, l-valine-co-l-phenylalanine poly(ester urea)s were blade coated on small intestine submucosa extracellular matrix (SIS-ECM) and found to enhance the burst test mechanical properties of SIS-ECM in composite films (force at break between 102.6 ± 6.5-151.4 ± 11.3 N). Free standing films of l-valine-co-l-phenylalanine PEUs were found to have superior extension at break when compared to SIS-ECM (averages between 1.2 and 1.9 cm and 1.2 cm respectively). Fibroblast (L-929) spreading, proliferation, and improved attachment over control were observed without toxicity in vitro, while a reduced inflammatory response at both 7 and 14 days post-implant was observed for poly[(1-VAL-8)⁠ 0.7 -co-(1-PHE-6)⁠ 0.3 ] when compared to polypropylene in an in vivo rat hernia model. These results support the use of PEU copolymers as free-standing films or as composite materials in soft-tissue applications for hernia-repair., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Platelet-rich plasma (PRP) is a clinically relevant source of growth factors used commonly by surgeons. The clinical efficacy of PRP use as reported in the literature is widely variable which is likely attributed to poorly defined retention time of PRP at the repair site. To overcome this limitation, branched poly(ester urea) (PEU) nanofibers were used to adsorb and retain PRP at the implant site in an acute rotator-cuff tear model in rats. The adsorption of PRP to the branched-PEU 8% material was characterized using quartz crystal microbalance (QCM) and immuno-protein assay. After adsorption of PRP to the nanofiber sheet, the platelets actively released proteins. The adhesion of platelets to the nanofiber material was confirmed by immunofluorescence using a p-selectin antibody. In vivo testing using a rat rotator-cuff repair model compared five groups; no repair (control), suture repair only, repair with disc implant (Disc), repair with PRP-soaked disc (Disc PRP), and a PRP injection (PRP). Mechanical testing at 84 d for the four surgical repair groups resulted in a higher stiffness (11.8 ± 3.8 N/mm, 13.5 ± 3.8 N/mm, 16.8 ± 5.8 N/mm, 12.2 ± 2.6 N/mm, respectively) for the Disc PRP group. Histological staining using trichrome, hematoxylin, and eosin Y (H&E), and safranin O confirmed more collagen organization in the Disc PRP group at 21 and 84 d. Limited inflammation and recovery toward preoperative mechanical properties indicate PEU nanofiber discs as translationally relevant.

Two unrelated bovine beef calves, aged 2 mo and 3 mo, were presented to The Ohio State University Veterinary Medical Center because of scrotal swelling and abdominal distension. On postmortem examination, there was abundant peritoneal fluid and numerous small friable masses covering all peritoneal surfaces and extending into the scrotum via the tunica vaginalis, with no identifiable primary neoplasm. Based on light microscopy, differential diagnoses included malignant mesothelioma and anaplastic carcinoma. Immunohistochemically, the neoplasms labeled positive for cytokeratin, and negative for vimentin and calretinin. Neoplastic cells contained periodic acid-Schiff-positive, diastase-resistant cytoplasmic granules, and lacked Alcian blue-positive, hyaluronidase-negative cytoplasmic vacuoles. Ultrastructurally, the cells had features of carcinoma, including secretory granules, and lacked typical features of mesothelioma, such as long slender microvilli. Our final diagnosis was carcinoma in both calves, despite the equivocal gross and light microscopic findings. We propose that a presumptive diagnosis of peritoneal mesothelioma in bovine calves should be avoided without corroboration by a combination of histology, histochemistry, immunohistochemistry, and, if possible, electron microscopy.

New polymers are needed to address the shortcomings of commercially available materials for soft tissue repair. Herein, we investigated a series of l-valine-based poly(ester urea)s (PEUs) that vary in monomer composition and the extent of branching as candidate materials for soft tissue repair. The preimplantation Young's moduli (105 ± 30 to 269 ± 12 MPa) for all the PEUs are comparable to those of polypropylene (165 ± 5 MPa) materials currently employed in hernia-mesh repair. The 2% branched poly(1-VAL-8) maintained the highest Young's modulus following 3 months of in vivo implantation (78 ± 34 MPa) when compared to other PEU analogues (20 ± 6-45 ± 5 MPa). Neither the linear or branched PEUs elicited a significant inflammatory response in vivo as noted by less fibrous capsule formation after 3 months of implantation (80 ± 38 to 103 ± 33 μm) relative to polypropylene controls (126 ± 34 μm). Mechanical degradation in vivo over three months, coupled with limited inflammatory response, suggests that l-valine-based PEUs are translationally relevant materials for soft tissue applications.

Objective: Expression of the 70-kDa heat-shock protein (HSP70) has been demonstrated in normal canine corneal epithelium, and inducible expression has been suggested to facilitate wound resolution through organized migration, proliferation, and adhesion of the corneal epithelial cells. Diminished expression of HSP70 may therefore contribute to prolonged healing in the pathologic cornea of other companion animal species, including the horse., Animal Studied: Normal and pathologic equine cornea was evaluated to determine whether the expression of HSP70 is correlated with appropriate corneal epithelial wound healing., Procedures: Paraffin-embedded tissue from normal equine cornea and therapeutic keratectomies of sterile keratopathies was subject to routine immunohistochemistry for HSP70., Results: Normal equine corneas exhibited the baseline expression of HSP70 in the nuclei of all epithelial cells as well as the cytoplasm of the basal epithelium. Expression of HSP70 in suspected immune-mediated keratitis was localized to the cytoplasm of basal epithelial cells and nuclei of all epithelial cells, similar to the normal equine cornea. Expression in indolent ulcers was diminished; weak, diffuse staining was noted in the cytoplasm of all epithelial cells., Conclusions: These findings suggest the expression of HSP70 is induced in the normal equine cornea during re-epithelialization and may be altered in sterile keratopathies., (© 2016 American College of Veterinary Ophthalmologists.)

Background: Development of a non-hormonal long-acting reversible contraceptive for men could have a significant impact on reducing unintended pregnancies. Vasalgel™ is a high molecular weight polymer consisting of styrene-alt-maleic acid (SMA) dissolved in dimethyl sulfoxide being developed as a reversible male contraceptive device. It forms a hydrogel when implanted into the vasa deferentia, which prevents the passage of sperm. Previous studies in the rabbit have proven its efficacy, durability and rapid onset. This study evaluates the capacity to restore sperm concentrations in ejaculates after a reversal procedure., Methods: Sodium bicarbonate was injected into the vasa deferentia after fourteen months of azoospermia following the injection of two device variations (Vasalgel 100 and Vasalgel 80). Semen samples were then collected for six months and sperm characteristics were compared to baseline levels. Samples of vasa deferentia were obtained for histological examination., Results: Spermatozoa were present in all subject ejaculates after the reversal procedure. Sperm concentration and sperm motility were similar to baseline levels after reversal, while sperm forward progression was significantly lower and normal acrosomes were not observed. Forward progression percentages increased linearly during six months of semen collection, however, normal acrosomes were not observed at the conclusion of the study. Histologically, several vasa deferentia were clear of the device and contained an intact epithelial lining. A smaller proportion of tissues contained residual test material. A secondary intraluminal inflammatory response was seen occasionally in the tissues containing residual material. There was no difference between the two device variations for studied parameters., Conclusions: Vasalgel's prevention of sperm transport for 14 months was reversed through an intravasal injection of sodium bicarbonate. Post-reversal sperm concentrations and motility returned to baseline levels during the six-month follow up. Residual material in the vas lumen or compromised epididymal and vas deferens function may be resulting in reduced forward progression and loss of acrosomes during transit through the vas. Reduced forward progression and the lack of normal acrosomes strongly suggest impaired sperm function.

Background: Vasectomy is currently the only long-acting contraceptive option available for men, despite increasing demand and potentially significant positive impacts on human health of additional male contraceptive options. Vasalgel ™ is a high molecular weight hydrogel polymer being developed as a non-hormonal long-acting reversible male contraceptive. Vasalgel consists of styrene-alt-maleic acid dissolved in dimethyl sulfoxide, which is distinct from styrene-alt-maleic anhydride materials previously studied., Methods: The goal of the study was to determine the contraceptive efficacy of two test articles with different levels of styrene maleic acid (100 %, and 80 % acid/20 % anhydride). The test articles were injected bilaterally in the vasa deferentia of mature male rabbits. Post-implantation analyses of semen parameters were completed over a 12 month period and compared to baseline measures of sperm concentration, motility and forward progression., Results: Both test articles were effective in blocking the passage of spermatozoa through the vasa deferentia in the 12 subjects completing the study. A significant decrease in sperm concentration occurred following implantation of the test material, with no measurable sperm concentration except for a few samples in one animal that were markedly oligospermic. Vasalgel produced a rapid onset of azoospermia, with no sperm in semen samples collected as early as 29-36 days post-implantation, and was durable over a 12 month period., Conclusion: This study indicated that Vasalgel is an effective non-hormonal long-acting male contraceptive in a rabbit model.

Routine detection of porcine epidemic diarrhea virus (PEDV) is currently limited to RT-PCR but this test cannot distinguish between viable and inactivated virus. We evaluated the capability of disinfectants to both inactivate PEDV and sufficiently damage viral RNA beyond RT-PCR detection. Five classes of disinfectants (phenol, quaternary ammonium compound, sodium hypochlorite, oxidizing agent, and quaternary ammonium/glutaraldehyde combination) were evaluated in vitro at varying concentrations, both in the presence and absence of swine feces, and at three different temperatures. No infectious PEDV was recovered after treatment with evaluated disinfectants. Additionally, all tested disinfectants except for 0.17% sodium hypochlorite dramatically reduced qRT-PCR values. However, no disinfectants eliminated RT-PCR detection of PEDV across all replicates; although, 0.52%, 1.03% and 2.06% solutions of sodium hypochlorite and 0.5% oxidizing agent did intermittently produce RT-PCR negatives. To simulate field conditions in a second aim, PEDV was applied to pitted aluminum coupons, which were then treated with either 2.06% sodium hypochlorite or 0.5% oxidizing agent. Post-treatment surface swabs of the coupons tested RT-PCR positive but were not infectious to cultured cells or naïve pigs. Ultimately, viable PEDV was not detected following application of each of the tested disinfectants, however in most cases RT-PCR detection of viral RNA remained. RT-PCR detection of PEDV is likely even after disinfection with many commercially available disinfectants., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Signal transducer and activator of transcription 3 (STAT3) plays a critical role in tumor development by regulating signaling pathways involved in cell proliferation, survival, metastasis and angiogenesis. STAT3 is activated in many cancers, including head and neck squamous cell carcinoma (HNSCC) in people. Feline oral squamous cell carcinoma (OSCC) is similar to advanced or recurrent HNSCC as it is poorly responsive to traditional therapies and carries a poor long-term prognosis. The purpose of this study was to characterize expression and activation of STAT3 in feline OSCC cell lines and tumor samples and to investigate the biologic activity of a novel, allosteric STAT3 inhibitor, LLL12, in feline OSCC cell lines., Results: We evaluated 3 feline OSCC cell lines and one of these (SCCF2) exhibited high levels of constitutive STAT3 phosphorylation and high sensitivity to LLL12 treatment. Exposure of SCCF2 cells to LLL12 resulted in decreased expression of pSTAT3 and total STAT3, apoptosis as assessed by caspase 3/7 activation, inhibition of colony formation and reduced expression of the STAT3 transcriptional target survivin. In contrast, the STAT3 transcriptional targets VEGF and MCL-1 increased after LLL12 treatment. This was, in part, likely due to LLL12 mediated upregulation of HIF-1α, which is known to drive VEGF and MCL-1 expression. The OSCC cell lines with low basal STAT3 phosphorylation did not exhibit these effects, suggesting that STAT3 inhibition was responsible for the observed results. Lastly, immunohistochemistry for pSTAT3 was performed using a feline OSCC tissue microarray, demonstrating expression in 48 % of samples tested., Conclusions: These data demonstrate that LLL12 has biologic activity against a feline OSCC cell line expressing pSTAT3 and that STAT3 represents a target for therapeutic intervention in this disease. However, given the up-regulation of several STAT3 transcriptional targets following treatment, further investigation of STAT3 and its related signaling pathways in OSCC is warranted.