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Peritoneal fibrosis, a common complication observed in long-term peritoneal dialysis patients, can gradually lead to ultrafiltration failure and the development of encapsulating peritoneal sclerosis. Although mechanisms of peritoneal fibrosis have been proposed, effective therapeutic options are unsatisfactory. Recently, several tyrosine kinase inhibitors have proven to be anti-fibrosis in rodent models. To assess the potential therapeutic effects of tyrosine kinase inhibitors on peritoneal fibrosis in the larger animal model, a novel porcine model of peritoneal fibrosis induced by 40 mM methylglyoxal in 2.5 % dialysate was established, and two different doses (20 mg/kg and 30 mg/kg) of sorafenib were given orally to evaluate their therapeutic efficacy in this study. Our results showed that sorafenib effectively reduced adhesions between peritoneal organs and significantly diminished the thickening of both the parietal and visceral peritoneum. Angiogenesis, vascular endothelial growth factor A production, myofibroblast infiltration, and decreased endothelial glycocalyx resulting from dialysate and methylglyoxal stimulations were also alleviated with sorafenib. However, therapeutic efficacy in ameliorating loss of mesothelial cells, restoring decreased ultrafiltration volume, and improving elevated small solutes transport rates was limited. In conclusion, this study demonstrated that sorafenib could potentially be used for peritoneal fibrosis treatment, but applying sorafenib alone might not be sufficient to fully rescue methylglyoxal-induced peritoneal defects. [Display omitted] • A novel porcine model of peritoneal fibrosis for anti-fibrotic drug screening. • Sorafenib effectively alleviated myofibroblast infiltration and angiogenesis. • Sorafenib finitely restored ultrafiltration capacity and solute transport in pigs. • Sorafenib exhibits limited therapeutic effects on MGO-induced peritoneal fibrosis. [ABSTRACT FROM AUTHOR]

Background: Canine keratoconjunctivitis sicca (KCS) is predominantly an immune-mediated disease. Current therapy of canine KCS is mainly by immunosuppressant, but the effectiveness was limited in some patients. In the past few years, some studies showed the results of the use of mesenchymal stem cells in treating canine KCS via periocular injections. However, the periocular injection procedure requires sedation or general anesthesia, and may lead to iatrogenic or incidental injury during the injection process. The aim of this study was to investigate the efficacy of topical allogenic canine adipose-derived mesenchymal stem cells (cAD-MSCs) in clinical patients of canine KCS. Results: The cAD-MSCs used in this study were characterized for their capability of tri-lineage differentiation and immunomodulatory properties. In addition, preparation methods for eye drops of cAD-MSCs was developed and its optimal preservation was tested. The canine KCS patients were recruited for clinical trial and divided into two groups based on their history of previous treatment. All patients received topical cAD-MSCs treatment once per week for 6 consecutive weeks and complete ophthalmic examinations were performed 1 week before treatment (week 0) and at 3rd, 6th, 9th weeks, respectively. The results showed that the quantity and quality of tears have improved significantly following topical cAD-MSCs treatment based on Schirmers tear test-1 and tear break-up time. More than half of all patients were found improved in the tear quantity. In particular, 56.5% of the patients that were unresponsive to prior immunosuppressant therapy had an effective increase in tear volume. The severity of clinical signs was also ameliorated according to the numeric rating scale score from both patient owners and the clinician. Conclusion: To sum up, topical cAD-MSCs may be beneficial especially in KCS patients with poor owner compliance for frequent daily use of eye drops or those who are unresponsive to immunosuppressant therapy. [ABSTRACT FROM AUTHOR]

Patients with kidney failure rely on life-saving peritoneal dialysis to facilitate waste exchange and maintain homeostasis of physical conditions. However, peritoneal dialysis often results in peritoneal fibrosis and organ adhesion that subsequently compromise the efficiency of peritoneal dialysis and normal functions of visceral organs. Despite rodent models provide clues on the pathogenesis of peritoneal fibrosis, no current large animal model which shares high degree of physiological and anatomical similarities to human is available, limiting their applications on the evaluation of pre-clinical therapeutic efficacy. Here we established for the first time, hypochlorite-induced porcine model of peritoneal fibrosis in 5-week-old piglets. We showed that administration 15–30 mM hypochlorite, a dose- and time-dependent severity of peritoneal fibrosis characterized by mesothelium fragmentation, αSMA+ myofibroblasts accumulation, organ surface thickening and type I collagen deposition were observed. We also demonstrated in vitro using human mesothelial cells that hypochlorite-induced fibrosis was likely due to necrosis, but not programmed apoptosis; besides, overexpression of IL1β, CX3CL1 and TGFβ on the peritoneal mesothelium in current model was detected, similar to observations from peritoneal dialysis-induced peritoneal fibrosis in human patients and earlier reported mouse model. Moreover, our novel antemortem evaluation using laparoscopy provided instant feedback on the progression of organ fibrosis/adhesion which allows immediate adjustments on treatment protocols and strategies in alive individuals that can not and never be performed in other animal models. [ABSTRACT FROM AUTHOR]

Background: Skin marker-based three-dimensional kinematic gait analysis were commonly used to assess the functional performance and movement biomechanics of the pelvic limb in dogs. Unfortunately, soft tissue artefact would compromise the accuracy of the reproduced pelvic limb kinematics. Multibody kinematics optimization framework was often employed to compensate the soft tissue artefact for a more accurate description of human joint kinematics, but its performance on the determination of canine pelvic limb skeletal kinematics has never been evaluated. This study aimed to evaluate a multibody kinematics optimization framework used for the determination of canine pelvic limb kinematics during gait by comparing its results to those obtained using computed tomography model-based fluoroscopy analysis. Results: Eight clinically normal dogs were enrolled in the study. Fluoroscopy videos of the stifle joint and skin marker trajectories were acquired when the dogs walked on a treadmill. The pelvic limb kinematics were reconstructed through marker-based multibody kinematics optimization and single-body optimization. The reference kinematics data were derived via a model-based fluoroscopy analysis. The use of multibody kinematics optimization yielded a significantly more accurate estimation of flexion/extension of the hip and stifle joints than the use of single-body optimization. The accuracy of the joint model parameters and the weightings to individual markers both influenced the soft tissue artefact compensation capability. Conclusions: Multibody kinematics optimization designated for soft tissue artefact compensation was established and evaluated for its performance on canine gait analysis, which provided a further step in more accurately describing sagittal plane kinematics of the hip and stifle joints. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation has been implicated in sarcomagenesis. Among various factors, activation of nuclear factor-kappa B (NF-κB) signaling pathway has been documented being able to target genes associated with tumor progression and up-regulate the expression of tumor-promoting cytokines and survival genes in several human solid tumors. Feline injection sites sarcomas (FISS) are malignant entities derived from the mesenchymal origin. The disease has been considered to be associated with vaccine adjuvant, aluminum, which serves as a stimulus continuously inducing overzealous inflammatory and immunologic reactions. To understand the contribution of NF-κB in FISS, detection of activated NF-κB in paraffin-embedded specimens, in vitro establishment of primary cells derived from FISS, and evaluation of the effects of the NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on primary tumor cells were conducted. Results: In this study, nuclear expression of NF-κB p65 was detected in 83.3% of FISS cases and not correlated with tumor grading, sex, and age. Primary cells derived from FISS in three cats exhibiting same immunohistochemical characteristics as their original tumor were successfully established. The NF-κB inhibitor, DHMEQ, was able to prevent nuclear translocation of NF-κB p65, inhibit cell proliferation, migration, and colonization in dosage-dependent manners, and induce cell apoptosis in these primary FISS cells. Conclusions: High expression rate of nuclear NF-κB p65 in FISS cases and dose-dependent inhibitory effects on the growth of FISS primary cells treated with NF-κB inhibitor suggested that NF-κB might be a potential molecular therapeutic target for FISS. [ABSTRACT FROM AUTHOR]

Knowledge regarding the ligament footprints in the canine stifle is essential for biomechanical modeling of the joint and patient-specific surgical planning for anatomical ligament reconstruction. The present study aimed to establish and evaluate deformable shape templates (DSTs) of the femur and tibia with footprints of the cruciate and collateral ligaments embedded for the noninvasive estimation of ligament footprint positions. To this end, a data set of computed tomography (CT)-derived surface models of the femur and tibia were established and used to build statistical shape models (SSMs). The contours of the stifle ligaments were obtained from CT scans of 27 hindlimb specimens with radio-opaque markings on the ligament footprints. The DST, constructed by embedding averaged footprint contours into the SSM, was used to estimate subject-specific ligament footprints in a leave-one-out cross-validation framework. The DST predictions were compared with those derived from radio-opaque-marked footprints. The results showed that the averaged Euclidean distances between the estimated and reference footprint centroids were less than 1.2 mm for the cruciate ligaments and 2.0 mm for the collateral ligaments. The DST appeared to provide a feasible alternative approach for noninvasively estimating the footprints of the stifle ligaments in vivo. [ABSTRACT FROM AUTHOR]

Background: Cranial cruciate ligament (CCL) disease is one of the most common causes of lameness in dogs. The extracapsular stabilization (ECS) utilizing bone anchors and monofilament nylon leader was an alternative treatment for CCL-deficient (CCLD) dogs. However, the biomechanical response of the canine stifle to such a surgical repair strategy in conjunction with the use of recently reported quasi-isometric anchoring points remains unclear. The objectives of the study were to evaluate the mobility and stability of CCL-intact, CCLD, and CCLD stifles repaired with ECS at two different pairs of quasi-isometric points (quasi-IPs). Methods: Twelve stifle specimens from 7 dogs underwent mobility and stability tests under 4 different conditions, namely, CCL-intact, CCLD, and ECS-repaired at 2 different pairs of quasi-IPs (referred to as ECS-IP1 and ECS-IP2). The mobility tests evaluated 6 degrees-of-freedom stifle kinematics during flexion and extension. The stability tests involved cranial drawer and tibial internal rotation (IR) tests at various stifle opening angles and quantifying the cranial tibial translation (CTT) and tibial IR angles under constantly applied loadings. Results: The ECS repaired at quasi-IPs was shown to restore cranial instability of the stifles with averaged CTT magnitudes < 1.4 mm. During the tibial IR test, the ECS treatments resulted in significantly less tibial IR compared to those in intact CCL stifles. The mobility tests showed similar results. Conclusion: The 2 chosen pairs of quasi-IPs were shown to effectively correct the excessive CTT caused by CCLD stifles, whereas the excessive tibial external rotation in comparison to those of intact stifles should be considered for its subsequent influence on joint alignment and the contact pressure applied to the stifle joint. [ABSTRACT FROM AUTHOR]

Background: Total hip replacement (THR) is considered to be the most effective treatment option for advanced osteoarthritis of the hip in large breed dogs. However, a proportion of post-THR patients suffer prosthesis dislocation for various reasons, which may be addressed by a constrained acetabular prosthesis design. The study proposed a new THR with constrained acetabular component that aimed to decrease the incidence of postoperative dislocation while maintaining the necessary range of motion (ROM); and, through computer-simulated implantations, evaluated the ROM of the THR with and without malpositioning of the acetabular component.Methods: A new THR with a constrained acetabular component that had an inward eccentric lining and a 60° cut-out on the dorsal side was designed, and its computer-aided design models were implanted into the pelvic and femoral models reconstructed from the computed tomography data of six healthy Labrador Retriever dogs. The allowable and functional ROM of the implanted THR were determined via computer simulations. The contact patterns between the bone or the prosthetic components at extreme positions of the THR were analyzed. Influence of malpositioning of the acetabular component on the ROM was assessed.Results: The means (SD) of the functional ranges for flexion, extension, adduction, abduction, internal rotation and external rotation were 51.8° (6.6°), 163.3° (7.3°), 33.5° (5.7°), 74.0° (3.7°), 41.5° (8.3°) and 65.2° (9.9°), respectively. Malpositioning of the acetabular component by 20° in one direction was found to reduce ROM in other directions (reducing lateral opening: flexion: 12°, adduction: 20°, internal/external rotations: < 20°; increasing lateral opening: extension and abduction: < 16°; reducing retroversion: extension: < 20°, abduction: 15°, external rotation: < 20°; increasing retroversion: flexion: < 20°, abduction, adduction and internal rotation: 20°).Conclusions: From the computer-aided surgical simulations, the new THR was found to have sufficient functional ranges for flexion, extension, abduction, adduction and external rotation for Labrador Retrievers. Analysis of the malpositioning of the acetabular component suggests that accurate placement of the acetabular component is critical for achieving desirable ROM for daily activities. [ABSTRACT FROM AUTHOR]

Simple Summary: Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit to the host. Probiotics have also been introduced in companion animals in recent years, and the main priority of probiotic use has focused on the health of individual animals. This study aimed to compare the fecal microbiota of cats with chronic diarrhea with that of healthy cats from the same household and evaluate the effectiveness of oral administration of Bacillus licheniformis-fermented products (BLFP) in relieving clinical signs and altering the intestinal microbiota in diarrheal cats. Overall, this study provides basic information on the types and ratios of fecal microbiota in healthy cats and cats with chronic diarrhea. Our results also demonstrated that oral administration of BLFP could significantly impact the relief of clinical gastrointestinal symptoms and the gastrointestinal microbiomes in cats with diarrhea. Bacillus licheniformis-fermented products (BLFP) are probiotics with antibacterial, antiviral, and anti-inflammatory properties that can improve growth performance. This study aimed to compare the fecal microbiota of diarrheal cats with chronic diarrhea (n = 8) with that of healthy cats (n = 4) from the same household using next-generation sequencing, and evaluate the effectiveness of oral administration of BLFP in relieving clinical signs and altering the intestinal microbiota in diarrheal cats. Six out of eight diarrheal cats showed clinical improvement after BLFP administration for 7 days, and the stool condition of the other two was normal. A higher Firmicutes/Bacteroidetes ratio was noted in the feces of diarrheal cats without clinical improvement as compared with those in the healthy cats and in the diarrheal cats with clinical improvement after receiving BLFP. The phylum Bacteroidetes and class Bacteroidia decreased significantly in diarrheal cats regardless of BLFP administration. Blautia spp., Ruminococcus torques, and Ruminococcus gnavus, which belong to the Clostridium cluster XIVa and have been reported as beneficial to intestinal health, increased significantly in feces after treatment. Furthermore, Clostridium perfringens also significantly decreased in diarrheal cats after BLFP administration. Overall, BLFP could be a potential probiotic to relieve gastrointestinal symptoms and improve fecal microbiota in cats with chronic diarrhea. [ABSTRACT FROM AUTHOR]

Background: The term big kidney‐little kidney syndrome in cats has been used for many years, but the definitions are not consistent and relevant research is limited. Objective: To determine the factors that differ between normal and BKLK cats, as well as to develop models for predicting the 30‐day survival of cats with ureteral obstruction (UO). Animals Sixteen healthy cats and 64 cats with BKLK. Methods: Retrospective study. To define BKLK by reference to data from clinically healthy cats. The demographic and clinicopathological data among groups were statistically analyzed. Results: Big kidney‐little kidney syndrome cats had higher blood urea nitrogen (BUN) (median [interquartile range] 69 [28‐162] vs 21 [19–24] mg/dL, P <.001), creatinine (5.6 [1.9‐13.3] vs 1.3 [1.05‐1.40] mg/dL, P <.001), and white blood cells (10 800 [7700‐17 500] vs 6500 [4875‐9350] /μL, P <.001) and lower hematocrit (32.8 [27.1‐38.4] vs 39.1 [38.1‐40.4]%, P <.001), urine specific gravity (1.011 [1.009‐1.016] vs 1.049 [1.044‐1.057], P <.001) and pH (5.88 [5.49‐6.44] vs 6.68 [6.00‐7.18], P =.001) compared to the control cats. A lower body temperature (BT; 38.1 [37.9‐38.2] vs 38.7 [38.3‐39.2]°C, P =.009), higher BUN (189 [150‐252] vs 91 [36‐170] mg/dL, P =.04), and creatinine (15.4 [13.3‐17.4] vs 9.0 [3.1‐14.2] mg/dL, P =.03) were found among the UO cats that were not 30‐day survivors. A combination of BUN, phosphorus, and BT can predict 30‐day survival among UO cats with an area under receiver operating characteristic curve of 0.863. (P =.01). Conclusion: An increase in the length difference between kidneys can indicate UO, but cannot predict outcome for BKLK cats. [ABSTRACT FROM AUTHOR]

Breathing is one of the vital signs used to assess the physical health of a subject. Non-contact-based measurements of both breathing rate and changes in breathing rate help monitor health condition of subjects more flexibly. In this paper, we present an improved real-time camera-based adaptive breathing monitoring system, which includes real time (1) adaptive breathing motion detection, (2) adaptive region of interest detection to eliminate environmental noise, (3) breathing and body movement classification, (4) respiration rate estimation, (5) monitor change in respiration rate to examine overall health of an individual, and (6) online adaptation to lighting. The proposed system does not pose any positional and postural constraint. For evaluation, 30 videos of 15 animals are tested with drugs to simulate various medical conditions and breathing patterns, and the results from the proposed system are compared with the outputs of an existing FDA-approved invasive medical system for patient monitoring. The results show that the proposed method performs significantly correlated RR results to the reference medical device with the correlation coefficient equal to 0.92 and p-value less than 0.001, and more importantly the proposed video-based method is demonstrated to produce alarms 10 to 20 s earlier than the benchmark medical device. [ABSTRACT FROM AUTHOR]

Bacillus licheniformis (B. licheniformis) is commonly used as probiotic and its secondary metabolites are attractive anti-microbial candidate. In the present study, we aimed to evaluate the antiviral activity of crude extracts from B. licheniformis against porcine epidemic diarrhea virus (PEDV), a highly contagious enveloped porcine virus that has caused great economic loss in pigs. In vivo, PEDV-infected piglets supplemented with air-dried solid state fermentative cultivate containing B. licheniformis-fermented products (BLFP) showed milder clinical symptoms and decreased viral shedding. Importantly, no significant systemic pathological lesions and no reduction in average daily gain were noted in pigs supplemented with the BLFP, which suggests that it is safe for use in pigs. In vitro experiments revealed that while B. licheniformis crude extracts exhibited no toxicity in Vero cells, co-cultivation of B. licheniformis crude extracts with PEDV significantly reduced viral infection and replication. Summarized current results suggest that the B. licheniformis-fermented products could be a novel candidate food additive for reducing the impact of PED on the swine industry. [ABSTRACT FROM AUTHOR]

Background: The microenvironment within solid malignant tumors, including feline mammary gland carcinomas (FMGCs), is commonly hypoxic, possibly due to the lack of functional blood vessels in rapidly proliferating neoplastic tissue. Malignant cells can undergo genetic and adaptive changes that prevent them from dying due to oxygen deprivation through expressions of hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Therefore, HIF-1α and VEGF are ideal biomarkers for cancer therapy and prognostic evaluation. The aims of this study were to evaluate the expression of HIF-1α and VEGF in feline mammary carcinomas and analyze their correlations with clinical and pathological factors, such as clinical stage, histologic grading, regional metastasis, and overall survival rate. Results: Paraffin-embedded tissue samples collected from 72 cats with FMGCs were retrospectively studied. Histologic pattern and histologic grading (Elston and Ellis grading system) of these FMGCs were determined. Our data indicated that grade II tubulopapillary carcinomas (43/72, 59.7%) prevailed in this study, and most FMCGs showed apparent necrosis, squamous metaplasia, and intratumoral stromal response. According to the results of immunohistochemical (IHC) stainings performed in tissue microarrays (TMAs), HIF-1α and VEGF overexpressions were respectively noted in 69.4% (50/72) and 77.8% (56/72) of FMGC cases. Chi-square test showed no correlation of HIF-1α overexpression with clinical and pathological factors. VEGF overexpression was significantly correlated with histologic pattern (p = 0.021), stromal response (p = 0.048), squamous metaplasia (p = 0.001), and lymphovascular invasion (p = 0.007). However, neither HIF-1α nor VEGF overexpression was correlated with histologic grading and metastasis. Of 38 cats with 1-year follow-up, IHC stainings of HIF-1α and VEGF were performed on whole tissue sections. The results showed that overexpression of HIF-1α was significantly correlated with the overall survival rate (p < 0.05) (log-rank test), whereas there was no significant correlation between VEGF overexpression and overall survival rate. Conclusions: This study suggests that the overexpression of HIF-1α may indicate poor prognosis/overall survival rate in cats with FMGCs. Developing compounds that inhibit HIF-1α may be a potential approach to FMGC treatment. [ABSTRACT FROM AUTHOR]

Background: Three-dimensional joint kinematics during canine locomotion are commonly measured using skin marker-based stereophotogrammetry technologies. However, marker-related errors caused by the displacement of the skin surface relative to the underlying bones (i.e., soft tissue artifacts, STA) may affect the accuracy of the measurements and obscure clinically relevant information. Few studies have assessed STA in canine limbs during kinematic analysis. The magnitudes and patterns of the STA and their influence on kinematic analysis remain unclear. Therefore, the current study aims to quantify the in vivo STA of skin markers on the canine thigh and crus during passive joint motion. The stifle joints of ten dogs were passively extended while the skin markers were measured using a motion capture system, and skeletal kinematics were determined using a CT-to-fluoroscopic image registration method. Results: The skin markers exhibited considerable STA relative to the underlying bones, with a peak amplitude of 27.4 mm for thigh markers and 28.7 mm for crus markers; however, the amplitudes and displacement directions at different attachment sites were inconsistent. The markers on the cranial thigh and lateral crus closer to the stifle joint had greater STA amplitudes in comparison to those of other markers. Most markers had STA with linear and quadratic patterns against the stifle flexion angles. These STA resulted in underestimated flexion angles but overestimated adduction and internal rotation when the stifle was flexed to greater than 90°. Conclusions: Marker displacements relative to the underlying bones were prominent in the cranial aspect of the thigh and the proximal-lateral aspect of the crus. The calculated stifle kinematic variables were also affected by the STA. These findings can provide a reference for marker selection in canine motion analysis for similar motion tasks and clarify the relationship between STA patterns and stifle kinematics; the results may therefore contribute to the development of STA models and compensation techniques for canine motion analysis. [ABSTRACT FROM AUTHOR]