Assessment of MMP-9 and clinical characteristics in dogs with tracheal collapse based on cough severity and fluoroscopic findings: a cross-sectional study.

BACKGROUND: Tracheal collapse (TC), a common disease in dogs, is characterized by cough; however, little is known about the serum biomarkers that can objectively evaluate the severity of cough in canine TC. Furthermore, studies elucidating the relationship of fluoroscopic characteristics with the severity of cough are lacking. Therefore, this study aimed to evaluate the relationship between cough severity and clinical characteristics, fluoroscopic images, and new serum biomarkers in canine TC. RESULTS: Fifty-one client-owned dogs diagnosed with TC based on fluoroscopic and clinical signs were enrolled in this study and divided into three groups according to the severity of cough (grade of cough: 0, 1, and 2). Signalments, comorbidities, and fluoroscopic characteristics were compared among the groups retrospectively. The serum matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), surfactant protein-A (SP-A), and syndecan-1 (SDC-1) levels were measured in all groups. No significant differences in age, breed, sex, or clinical history were observed among the groups. Concomitant pharyngeal collapse increased significantly with the severity of cough (p = .031). Based on the fluoroscopic characteristics, the TC grade of the carinal region increased significantly and consistently with the grade of cough (p = .03). The serum MMP-9 level was significantly higher in the grade 2 group than that in the grade 0 group (p = .014). The serum IL-6 level was significantly lower in the grade 1 group than that in the grade 0 group (p = .020). The serum SP-A and SDC-1 levels did not differ significantly among the groups. CONCLUSIONS: The severity of cough with the progression of TC can be predicted with the fluoroscopic TC grade at the carinal region. MMP-9 may be used as an objective serum biomarker that represents cough severity to understand the pathogenesis.

Pamidronate-induced irreversible symptomatic hypocalcemia in a dog with hypercalcemia after glucocorticoid withdrawal: a case report.

BACKGROUND: Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an unusual case of severe, irreversible hypocalcemia after a single injection of pamidronate for the treatment of hypercalcemia due to glucocorticoid withdrawal in a dog. CASE PRESENTATION: An 11-year-old castrated male Maltese dog presented with anorexia, vomiting, and diarrhea (day 0). The patient had calcinosis cutis throughout the body, calcification of intraabdominal organs, mild azotemia, and severe hypercalcemia. The severe calcification was attributed to long-term glucocorticoid administration, which was discontinued 1 month before presentation. Fluid therapy, diuretics, calcitonin, and a single intravenous injection of pamidronate were used for the treatment of hypercalcemia. On day 14, normocalcemia was achieved, but renal failure occurred. On day 20, severe and irreversible hypocalcemia occurred, and on day 42, the patient was euthanized at the owner's request because of worsened hypocalcemia and renal failure. CONCLUSIONS: Although hypocalcemia is an extremely rare adverse event of bisphosphonate treatment, bisphosphonates like pamidronate can result in potentially life-threatening conditions according to the patient's underlying conditions. Therefore, the patient's condition should be closely monitored and any underlying conditions should be carefully evaluated before initiating the treatment for hypercalcemia using pamidronate.

Anti-cancer effects of DHP107 on canine mammary gland cancer examined through in-vitro and in-vivo mouse xenograft models.

BACKGROUND: Canine mammary gland cancer (CMGC) is a common neoplasm in intact bitches. However, the benefit of adjuvant chemotherapy is unclear. The aim of this study was to investigate the anti-proliferative effects of paclitaxel on CMGC in in-vitro and in-vivo settings. RESULTS: Paclitaxel dose-dependently inhibited viability and induced G2/M phase cell cycle arrest and apoptosis in both primary and metastatic CMGC cell lines (CIPp and CIPm). In animal experiments, the average tumour volume decreased significantly in proportion to the administered oral paclitaxel dose. By examining tumour tissue using a TUNEL assay and immunohistochemical staining with anti-CD31 as a marker of endothelial differentiation, respectively, it was confirmed that oral paclitaxel induced apoptosis and exerted an anti-angiogenetic effect in tumour tissues. Further, downregulation of cyclin D1 in tumour tissues suggested that oral paclitaxel induced cell cycle arrest in tumour tissues in-vivo. CONCLUSIONS: Our results suggest that paclitaxel may have anti-cancer effects on CMGC through cell cycle arrest, induction of apoptosis, and anti-angiogenesis. This study could provide a novel approach to treat CMGC.

Integrating Biomarkers From Virtual Reality and Magnetic Resonance Imaging for the Early Detection of Mild Cognitive Impairment Using a Multimodal Learning Approach: Validation Study.

BACKGROUND: Early detection of mild cognitive impairment (MCI), a transitional stage between normal aging and Alzheimer disease, is crucial for preventing the progression of dementia. Virtual reality (VR) biomarkers have proven to be effective in capturing behaviors associated with subtle deficits in instrumental activities of daily living, such as challenges in using a food-ordering kiosk, for early detection of MCI. On the other hand, magnetic resonance imaging (MRI) biomarkers have demonstrated their efficacy in quantifying observable structural brain changes that can aid in early MCI detection. Nevertheless, the relationship between VR-derived and MRI biomarkers remains an open question. In this context, we explored the integration of VR-derived and MRI biomarkers to enhance early MCI detection through a multimodal learning approach. OBJECTIVE: We aimed to evaluate and compare the efficacy of VR-derived and MRI biomarkers in the classification of MCI while also examining the strengths and weaknesses of each approach. Furthermore, we focused on improving early MCI detection by leveraging multimodal learning to integrate VR-derived and MRI biomarkers. METHODS: The study encompassed a total of 54 participants, comprising 22 (41%) healthy controls and 32 (59%) patients with MCI. Participants completed a virtual kiosk test to collect 4 VR-derived biomarkers (hand movement speed, scanpath length, time to completion, and the number of errors), and T1-weighted MRI scans were performed to collect 22 MRI biomarkers from both hemispheres. Analyses of covariance were used to compare these biomarkers between healthy controls and patients with MCI, with age considered as a covariate. Subsequently, the biomarkers that exhibited significant differences between the 2 groups were used to train and validate a multimodal learning model aimed at early screening for patients with MCI among healthy controls. RESULTS: The support vector machine (SVM) using only VR-derived biomarkers achieved a sensitivity of 87.5% and specificity of 90%, whereas the MRI biomarkers showed a sensitivity of 90.9% and specificity of 71.4%. Moreover, a correlation analysis revealed a significant association between MRI-observed brain atrophy and impaired performance in instrumental activities of daily living in the VR environment. Notably, the integration of both VR-derived and MRI biomarkers into a multimodal SVM model yielded superior results compared to unimodal SVM models, achieving higher accuracy (94.4%), sensitivity (100%), specificity (90.9%), precision (87.5%), and F1-score (93.3%). CONCLUSIONS: The results indicate that VR-derived biomarkers, characterized by their high specificity, can be valuable as a robust, early screening tool for MCI in a broader older adult population. On the other hand, MRI biomarkers, known for their high sensitivity, excel at confirming the presence of MCI. Moreover, the multimodal learning approach introduced in our study provides valuable insights into the improvement of early MCI detection by integrating a diverse set of biomarkers.

Exploring the Relationship between Behavioral and Neurological Impairments Due to Mild Cognitive Impairment: Correlation Study between Virtual Kiosk Test and EEG-SSVEP.

Amnestic mild cognitive impairment (aMCI) is a transitional stage between normal aging and Alzheimer's disease, making early screening imperative for potential intervention and prevention of progression to Alzheimer's disease (AD). Therefore, there is a demand for research to identify effective and easy-to-use tools for aMCI screening. While behavioral tests in virtual reality environments have successfully captured behavioral features related to instrumental activities of daily living for aMCI screening, further investigations are necessary to establish connections between cognitive decline and neurological changes. Utilizing electroencephalography with steady-state visual evoked potentials, this study delved into the correlation between behavioral features recorded during virtual reality tests and neurological features obtained by measuring neural activity in the dorsal stream. As a result, this multimodal approach achieved an impressive screening accuracy of 98.38%.

Subcutaneous emphysema and pneumomediastinum following orbital blowout pathological fracture in a cat with nasal lymphoma: a case report.

BACKGROUND: Subcutaneous emphysema and pneumomediastinum are rare complications associated with orbital blowout pathological fracture. CASE PRESENTATION: A 7-year old, castrated male Abbysinian cat presented with anorexia, lethargy, nausea, eyelid swelling, nasal discharge, and sneezing. Based on the clinical and diagnostic work-up, the cat was diagnosed with T cell high-grade nasal lymphoma associated with orbital pathological fracture due to the tumour invasion. After chemotherapy, the cat showed massive subcutaneous emphysema from frontal region to abdomen and pneumomediastinum due to orbital blowout pathological fracture. As the nasal mass decreased in volume; the air had moved from the maxillary sinus to the subcutaneous region and the mediastinum through fascial planes in the head and neck region. CONCLUSIONS: This is a first case report of a massive subcutaneous emphysema and pneumomediastinum due to an orbital blowout pathological fracture following chemotherapy in feline nasal lymphoma in veterinary medicine.

Retrospective evaluation of prognosis and survival with various immunosuppressants in 82 dogs diagnosed with meningoencephalitis of unknown etiology (2010-2021).

BACKGROUND: Meningoencephalomyelitis of unknown etiology (MUE) is a comprehensive term for non-infectious inflammatory brain diseases of the central nervous system (CNS) caused by abnormal autoimmune responses. This study aims to compare the differences in survival and clinical response of MUE according to the adjuvant immunosuppressant use. Medical records of 82 dogs diagnosed with MUE were reviewed retrospectively. RESULTS: The overall survival time was 769 days (range 14-2687 days). The median survival time for each adjunctive was: leflunomide 1035 days (range 126-2163 days), mycophenolate mofetil 865 days (range 39-2191 days), cyclosporin 441 days (range 11-2176 days), cytosine arabinoside 754 days (range 6-1898 days) and a combination of mycophenolate mofetil and cytosine arabinoside 132 days (range 23-1227 days). There was no significant difference in the incidence rate of adverse events according to the immunosuppressants, but moderate to severe anemia was confirmed in 3 patients (18.7%) in the leflunomide group. CONCLUSIONS: The survival time and response rate of MUE dogs differed depending on which adjunctive immunosuppressants were used. Leflunomide showed a long survival time and a relatively good response rate in dogs with MUE. However, a large-scale further study with standardized doses of immunosuppressants and supportive treatment and constant monitoring interval is needed.

Digital Marker for Early Screening of Mild Cognitive Impairment Through Hand and Eye Movement Analysis in Virtual Reality Using Machine Learning: First Validation Study.

BACKGROUND: With the global rise in Alzheimer disease (AD), early screening for mild cognitive impairment (MCI), which is a preclinical stage of AD, is of paramount importance. Although biomarkers such as cerebrospinal fluid amyloid level and magnetic resonance imaging have been studied, they have limitations, such as high cost and invasiveness. Digital markers to assess cognitive impairment by analyzing behavioral data collected from digital devices in daily life can be a new alternative. In this context, we developed a "virtual kiosk test" for early screening of MCI by analyzing behavioral data collected when using a kiosk in a virtual environment. OBJECTIVE: We aimed to investigate key behavioral features collected from a virtual kiosk test that could distinguish patients with MCI from healthy controls with high statistical significance. Also, we focused on developing a machine learning model capable of early screening of MCI based on these behavioral features. METHODS: A total of 51 participants comprising 20 healthy controls and 31 patients with MCI were recruited by 2 neurologists from a university hospital. The participants performed a virtual kiosk test-developed by our group-where we recorded various behavioral data such as hand and eye movements. Based on these time series data, we computed the following 4 behavioral features: hand movement speed, proportion of fixation duration, time to completion, and the number of errors. To compare these behavioral features between healthy controls and patients with MCI, independent-samples 2-tailed t tests were used. Additionally, we used these behavioral features to train and validate a machine learning model for early screening of patients with MCI from healthy controls. RESULTS: In the virtual kiosk test, all 4 behavioral features showed statistically significant differences between patients with MCI and healthy controls. Compared with healthy controls, patients with MCI had slower hand movement speed (t49=3.45; P=.004), lower proportion of fixation duration (t49=2.69; P=.04), longer time to completion (t49=-3.44; P=.004), and a greater number of errors (t49=-3.77; P=.001). All 4 features were then used to train a support vector machine to distinguish between healthy controls and patients with MCI. Our machine learning model achieved 93.3% accuracy, 100% sensitivity, 83.3% specificity, 90% precision, and 94.7% F1-score. CONCLUSIONS: Our research preliminarily suggests that analyzing hand and eye movements in the virtual kiosk test holds potential as a digital marker for early screening of MCI. In contrast to conventional biomarkers, this digital marker in virtual reality is advantageous as it can collect ecologically valid data at an affordable cost and in a short period (5-15 minutes), making it a suitable means for early screening of MCI. We call for further studies to confirm the reliability and validity of this approach.

Clinical infection of Brucella canis in a companion dog with discospondylitis in the Republic of Korea.

A 2-year-old, spayed female, Bichon Frise dog was presented with reluctance to exercise, back pain, and frequent sitting down. Multiple osteolysis, periosteal proliferation, and sclerosis of the vertebral endplates of T11-13 were observed in the radiography, computed tomography, and magnetic resonance imaging. The bacterial culture of the urine specimen, the polymerase chain reaction (PCR) of the blood, and the antibody tests were positive for Brucella canis. Accordingly, discospondylitis caused by B. canis was diagnosed and doxycycline was administered. The clinical signs resolved and the culture and PCR results were negative afterwards. Doxycycline was discontinued after 6 months. The clinical signs recurred 2 weeks later, and the combination treatment of doxycycline and enrofloxacin was initiated. Though no clinical signs were observed after 9 months and the bacterial cultures and PCR were negative, the antibody titre remained at 1 : 200 or more. The dog will continue taking antibiotics until the antibody titre drops. To the best of our knowledge, this is the first case report of a clinical infection of B. canis associated with canine discospondylitis in the Republic of Korea. Although the clinical signs of brucellosis might improve with antibiotic treatment, the disease cannot be cured due to Brucella's various strategies to evade host immune systems. Specifically, it can proliferate and replicate within the host cells, resulting in an environment that makes treatment less effective. Furthermore, owing to its zoonotic potential, owners and veterinarians should consider lifelong management or euthanasia.

Corrigendum to 'Technostress causes cognitive overload in high-stress people: Eye tracking analysis in a virtual kiosk test'; Information Processing & Management 59 (2022) 103093 /6.

[This corrects the article DOI: 10.1016/j.ipm.2022.103093.].

Assessment of salivary alpha-amylase and cortisol as a pain related stress biomarker in dogs pre-and post-operation.

BACKGROUND: The use of salivary biomarkers has garnered attention because the composition of saliva reflects the body's physiological state. Saliva contains a wide range of components, including peptides, nucleic acids, electrolytes, enzymes, and hormones. It has been reported that salivary alpha-amylase and cortisol are biomarkers of stress related biomarker in diseased dogs; however, evaluation of salivary alpha-amylase and cortisol pre- and post- operation has not been studied yet. The aim of this study was to evaluate salivary alpha-amylase and cortisol levels in dogs before and after they underwent surgery and investigate the association between the salivary alpha-amylase and cortisol activity and pain intensity. For this purpose, a total of 35 dogs with disease-related pain undergoing orthopedic and soft tissue surgeries were recruited. Alpha-amylase and cortisol levels in the dogs' saliva and serum were measured for each using a commercially available canine-specific enzyme-linked immunosorbent assay kit, and physical examinations (measurement of heart rate and blood pressure) were performed. In addition, the dogs' pre- and post-operative pain scores determined using the short form of the Glasgow Composite Measure Pain Scale (CMPS-SF) were evaluated. RESULTS: After surgery, there was a significant decrease in the dogs' pain scores (0.4-fold for the CMPS-SF, p < 0.001) and serum cortisol levels (0.73-fold, p < 0.01). Based on their pre-operative CMPS-SF scores, the dogs were included in either a high-pain-score group or a low-pain-score group. After the dogs in the high-pain-score group underwent surgical intervention, there was a significant decrease in their CMPS-SF scores and levels of salivary alpha-amylase, serum alpha-amylase, and serum cortisol. Additionally, there was a positive correlation between salivary alpha-amylase levels and CMPS-SF scores in both the high- and low-pain-score groups. CONCLUSIONS: The measurement of salivary alpha amylase can be considered an important non-invasive tool for the evaluation of pain-related stress in dogs.

Evaluation of endothelial cell-specific molecule-1 as a biomarker of glycocalyx damage in canine myxomatous mitral valve disease.

BACKGROUND: Endothelial cell-specific molecule-1 (ESM-1) has emerged as a potential biomarker for cardiovascular disease in humans. Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs, and we hypothesized that MMVD causes chronic inflammation that increases susceptibility to endothelial glycocalyx (eGCX) damage. In this study, we measured the concentration of ESM-1 in a group of dogs with MMVD and evaluated factors affecting eGCX damage. RESULTS: Sixty-four dogs (control, n = 6; MMVD, n = 58) were enrolled in this study. There was no significant difference in serum ESM-1 concentrations among the MMVD stages. The serum ESM-1 concentration was significantly higher in the death group than in the alive group in MMVD dogs. (p = 0.006). In five dogs with MMVD, serum ESM-1 concentrations tended to decrease when the cardiac drug (pimobendan, furosemide, and digoxin) dose was increased. CONCLUSIONS: In cases where MMVD progressed to decompensated heart failure with clinical symptoms and resulted in death, the concentration of serum ESM-1 increased significantly. Therefore, ESM-1 could be utilized as a new potential negative prognostic factor in patients with MMVD.

Technostress causes cognitive overload in high-stress people: Eye tracking analysis in a virtual kiosk test.

In the midst of the COVID-19 pandemic, the use of non-face-to-face information and communication technology (ICT) such as kiosks has increased. While kiosks are useful overall, those who do not adapt well to these technologies experience technostress. The two most serious technostressors are inclusion and overload issues, which indicate a sense of inferiority due to a perceived inability to use ICT well and a sense of being overwhelmed by too much information, respectively. This study investigated the different effects of hybrid technostress-induced by both inclusion and overload issues-on the cognitive load among low-stress and high-stress people when using kiosks to complete daily life tasks. We developed a 'virtual kiosk test' to evaluate participants' cognitive load with eye tracking features and performance features when ordering burgers, sides, and drinks using the kiosk. Twelve low-stress participants and 13 high-stress participants performed the virtual kiosk test. As a result, regarding eye tracking features, high-stress participants generated a larger number of blinks, a longer scanpath length, a more distracted heatmap, and a more complex gaze plot than low-stress participants. Regarding performance features, high-stress participants took significantly longer to order and made more errors than low-stress participants. A support-vector machine (SVM) using both eye tracking features (i.e., number of blinks, scanpath length) and a performance feature (i.e., time to completion) best differentiated between low-stress and high-stress participants (89% accuracy, 100% sensitivity, 83.3% specificity, 75% precision, 85.7% F1 score). Overall, under technostress, high-stress participants experienced cognitive overload and consequently decreased performance; whereas, low-stress participants felt moderate arousal and improved performance. These varying effects of technostress can be interpreted through the Yerkes-Dodson law. Based on our findings, we proposed an adaptive interface, multimodal interaction, and virtual reality training as three implications for technostress relief in non-face-to-face ICT.

Prevalence, co-infection and seasonality of fecal enteropathogens from diarrheic cats in the Republic of Korea (2016-2019): a retrospective study.

BACKGROUND: Diarrhea is one of the most common clinical symptoms in cats and can be caused by infectious pathogens and investigation of the prevalence, co-infection and seasonality of enteropathogens are not well-established in diarrheic cats. RESULTS: Fecal samples of 1620 diarrheic cats were collected and enteropathogens were detected using real-time PCR. We retrospectively investigated the clinical features, total/seasonal prevalence, and infection patterns of enteropathogens. The positive infection rate was 82.59%. Bacterial, viral, and protozoal infections accounted for 49.3, 37.57, and 13.13% of cases, respectively. Feline enteric coronavirus (FECV) was the most common pathogen (29.37%), followed by Clostridium (C.) perfringens, Campylobacter (C.) coli, feline parvovirus, and Tritrichomonas foetus. The seasonality of enteropathogens was observed with peaks as follows: bacterial infections peaked in October, viral infections peaked in November, and protozoal infections peaked in August. Viral and protozoal infections showed differences in prevalence according to patient age. In the infection patterns, the ratios of single infections, mixed infections, and co-infections were 35.72, 9.87, and 54.41%, respectively. FECV was predominant in single infections. The most common patterns of multiple infections were C. perfringens and C. coli in mixed infections and C. perfringens and FECV in co-infections. CONCLUSIONS: Infection patterns differed according to the enteropathogen species, seasonality, and age distribution in cats. The results of this study might be helpful to understand in clinical characteristics of feline infectious diarrhea. In addition, continued monitoring of feline enteropathogens is required.

Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs.

BACKGROUND: Furosemide, a diuretic that acts on the loop of Henle, is commonly used to treat congestive heart failure in veterinary medicine. Some owners have difficulty in administering oral tablet medication to animal patients, which leads to noncompliance, especially during long-term administration. Oral disintegrating film (ODF) has the advantages of easy administration via a non-invasive route, rapid dissolution, and low suffocating risk. The objective of this study was to research the pharmacokinetic (PK) profiles and diuretic effect of furosemide after intravenous (IV), orally uncoated tablet (OUT), and newly developed ODF administration in healthy beagle dogs. In this study, a furosemide-loaded ODF (FS-ODF) formulation was developed and five beagle dogs were administered a single dose (2 mg/kg) of furosemide via each route using a cross-over design. RESULTS: The most suitable film-forming agent was sodium alginate; thus, this was used to develop an ODF for easy drug administration. No significant differences were detected in the PK profiles between OUT and FS-ODF. In the blood profiles, the concentration of total protein was significantly increased compared to the baseline (0 h), whereas no significant difference was detected in the concentration of creatinine and hematocrit compared to the baseline. FS-ODF resulted in a similar hourly urinary output to OUT during the initial 2 h after administration. The urine specific gravity was significantly decreased compared to the baseline in each group. The peak times of urine electrolyte (sodium and chloride) excretion per hour were 1 h (IV), 2 h (OUT), and 2 h (FS-ODF). CONCLUSIONS: These results suggest that the PK/PD of furosemide after administration of newly developed FS-ODF are similar to those of OUT in healthy dogs. Therefore, the ODF formulation has the benefits of ease and convenience, which would be helpful to owners of companion animals, such as small dogs (< 10 kg), for the management of congestive heart failure.

Comparative single-dose pharmacokinetics of sildenafil after oral and rectal administration in healthy beagle dogs.

BACKGROUND: Sildenafil citrate, a highly selective phosphodiesterase type 5 inhibitor, is used to treat pulmonary hypertension (PH) in veterinary medicine. The objective of this study was to investigate pharmacokinetic profiles by oral administration of orally disintegrating film (ODF) and film coated tablet (FCT) formulations and rectal administration of ODF formulation in healthy dogs. Twelve healthy beagle dogs were administered four separate doses of sildenafil: FCT formulation 2 mg/kg orally, ODF formulation 2 mg/kg orally, ODF formulation 2 mg/kg rectally, and ODF formulation 10 mg/kg rectally. For 24 hours following administration, blood samples were collected and the plasma concentrations of sildenafil were assayed by liquid chromatography-tandem mass spectrometry. RESULTS: There were no significant differences in all the pharmacokinetic parameters between FCT and ODF formulations when administrated orally. Cmax at the time of rectal administration was lower when the same dose was given as that orally administered. No serious systemic adverse events (AEs) were observed. CONCLUSIONS: These findings suggest that sildenafil ODF formulation can be used as an alternative to FCT formulation in the treatment of canine PH patients; additionally, rectal administration of sildenafil ODF may be a beneficial treatment option for canine patients who are unable to receive medication orally.

Comparison of Fecal Microbiota between German Holstein Dairy Cows with and without Left-Sided Displacement of the Abomasum.

One of the most common diseases in high-performance German Holstein dairy cows is left-sided displacement of the abomasum (LDA). Hypomotility of the abomasum is detrimental during the pathogenesis of LDA. It is known that improper interactions between the gut microbiota and the enteric nervous system contribute to dysfunctions of gastrointestinal motility. Therefore, we hypothesized that the gut microbial composition will be different between German Holstein dairy cows with and without LDA. We used 16S rRNA gene analysis to evaluate whether there are any differences in bacterial composition between German Holstein dairy cows with and without LDA. Even though our data are limited to being used to correlate compositional changes with corresponding functional aspects in the pathogenesis of LDA, results from this study show that the fecal microbial compositions of German Holstein dairy cows with LDA shifted and were less diverse than those in normal cows. In particular,Spirochaeteswere absent in cows with LDA.

CTLA4 overexpressing adipose tissue-derived mesenchymal stem cell therapy in a dog with steroid-refractory pemphigus foliaceus.

BACKGROUND: Canine pemphigus foliaceus is an autoimmune antibody-mediated skin disease characterized by acantholysis. The objective of this case report is to present the successful management of steroid refractory pemphigus foliaceus with cytotoxic T-lymphocyte antigen 4 (CTLA4)-overexpressing adipose tissue mesenchymal stem cells (ATMSCs). CASE PRESENTATION: A 10-year-old, 12.3-kg, castrated male Shih Tzu presented with severe pruritus and anorexia. The diagnosis of pemphigus foliaceus was made based on its history, physical examination, and histopathology results of a skin biopsy. Treatment with prednisolone and combination therapy of other immunosuppressive drugs had failed; therefore, immunosuppressive gene, CTLA4 overexpressing ATMSCs (CTLA4-ATMSCs) and/or naive ATMSCs administration was performed with the consent of the owner. ATMSCs were administered 21 times over a period of 20 months with intervals of 2 to 8 week. Prednisolone was gradually tapered concurrently and no relapse of the clinical signs was observed. After the termination of CTLA4-ATMSCs and/or naive ATMSCs treatment, the skin lesions had improved and could be managed with a low dose of prednisolone for 12 months. CONCLUSION: CTLA4-ATMSCs or naive ATMSCs transplantation may be beneficial as adjunctive therapy to initiate and maintain the remission of skin lesions caused by pemphigus foliaceus in veterinary medicine.

Molecular Detection of Giardia intestinalis from Stray Dogs in Animal Shelters of Gyeongsangbuk-do (Province) and Daejeon, Korea.

Giardia is a major public health concern and considered as reemerging in industrialized countries. The present study investigated the prevalence of giardiosis in 202 sheltered dogs using PCR. The infection rate was 33.2% (67/202); Gyeongsangbuk-do and Daejeon showed 25.7% (39/152, P<0.0001) and 56% (28/50), respectively. The prevalence of infected female dogs (46.7%, P<0.001) was higher than in male dogs (21.8%). A higher prevalence (43.5%, P<0.0001) was observed in mixed breed dogs than purebred (14.1%). Although most of the fecal samples collected were from dogs of ≥1 year of age which showed only 27.4% positive rate, 61.8% (P<0.001) of the total samples collected from young animals (<1 year of age) were positive for G. intestinalis. A significantly higher prevalence in symptomatic dogs (60.8%, P<0.0001) was observed than in asymptomatic dogs (23.8%). Furthermore, the analysis of nucleotide sequences of the samples revealed that G. intestinalis Assemblages A and C were found in the feces of dogs from Gyeongsangbuk-do and Daejeon. Since G. intestinalis Assemblage A has been known to infect humans, our results suggest that dogs can act as an important reservoir of giardiosis in Korea. Hence, hygienic management should be given to prevent possible transmission to humans.

Stimulatory effect of HGF-overexpressing adipose tissue-derived mesenchymal stem cells on thymus regeneration in a rat thymus involution model.

The thymus is the central lymphoid organ providing a unique and essential microenvironment for T-cell precursor development into mature functionally competent T-lymphocytes. Thus, it is important to develop the strategies for enhancing thymic regeneration from involution induced by a variety of clinical treatments and conditions. Hepatocyte growth factor (HGF) promotes proliferation in a variety of cell types. We have used stem cell-based HGF gene therapy to enhance regeneration from acute thymic involution. HGF-overexpressing human adipose tissue-derived mesenchymal stem cells (HGF-hATMSCs) were generated by liposomal transfection with the pMEX expression vector, constructed by inserting the HGF gene. Significantly increased HGF expression in these cells was confirmed by reverse transcription-polymerase chain reaction and an enzyme-linked immunosorbent assay. HGF produced by HGF-hATMSCs enhanced the proliferation of a mouse thymic epithelial cell line and the expression of interleukin-7 in vitro. We also examined the effect of HGF-hATMSCs on thymic regeneration in rats with acute thymic involution. Significant increases in thymus size and weight, as well as the number of thymocytes (especially, early thymocyte progenitors), were seen in the HGF-hATMSCs-treated rats compared to saline-treated control animals. A stimulatory effect of HGF-hATMSCs on thymic regeneration has therefore been shown, highlighting the clinical value of HGF-hATMSCs for treating thymic involution.