A novel method of evaluating the non-invasive tear film break-up time and progression of corneal opacification in dogs using imaging video.

This study aimed to determine the correlation of the parameters that indicate the status of the ocular surface with the prognosis of corneal opacification. Fifty dogs (96 eyes) were examined using a grid-line illuminator (non-invasive tear film break-up time (NIBUT)). Thirty dogs (54 eyes) were included in the final analysis based on the criteria. The NIBUT and tear film break-up time (TFBUT) results of the eyes included in the study were divided into three groups: Group 1 (< 5 s), Group 2 (5 to <10 s), and Group 3 (≥ 10 s). The Schirmer's tear Test 1 (STT-1) results of the included patients were also divided into three groups: Group 1 (< 5 mm/min), Group 2 (5 to <10 mm/min), and Group 3 (≥ 10 mm/min). The corneal opacity grades are divided into four scores, ranging from 0 to 3. The corneal opacity grade score (COS) of 0 indicates a completely clear cornea or only a trace of opacity. COS of 1, 2, 3 indicate the presence of a prominent corneal opacity that does not interfere with the visualization of the fine iris details, the opacity obscures the visibility of the iris and lens details and severe obstruction of the intraocular structure visibility, respectively. The mean difference in COS during the follow-ups for each group of NIBUT were 0.61 ± 0.92 (n = 28), 0.10 ± 0.32 (n = 10), 0.19 ± 0.40 (n = 16). The NIBUT groups were significantly correlated with COS (p-value = 0.073) at a 10% level of significance. Post-hoc test at a 10% level of significance revealed significant correlations between Groups 1 and 2 (p-value = 0.041) and between Groups 1 and 3 (p-value 0.104). Although the TFBUT and STT-1 groups did not show any significant correlation with COS. Eyes with NIBUT of <5 s were found to have a significantly higher chance of increased COS compared with eyes with NIBUT of >5 s in the grid-line illumination plate NIBUT test. Among NIBUT, STT-1, and TFBUT, NIBUT was the only test that showed significant associations with the changes in COS.

CREB5 promotes the proliferation and self-renewal ability of glioma stem cells.

Glioblastoma multiforme (GBM) is the most fatal form of brain cancer in humans, with a dismal prognosis and a median overall survival rate of less than 15 months upon diagnosis. Glioma stem cells (GSCs), have recently been identified as key contributors in both tumor initiation and therapeutic resistance in GBM. Both public dataset analysis and direct differentiation experiments on GSCs have demonstrated that CREB5 is more highly expressed in undifferentiated GSCs than in differentiated GSCs. Additionally, gene silencing by short hairpin RNA (shRNA) of CREB5 has prevented the proliferation and self-renewal ability of GSCs in vitro and decreased their tumor forming ability in vivo. Meanwhile, RNA-sequencing, luciferase reporter assay, and ChIP assay have all demonstrated the closely association between CREB5 and OLIG2. These findings suggest that targeting CREB5 could be an effective approach to overcoming GSCs.

Identification of Muscle Strength-Related Gut Microbes through Human Fecal Microbiome Transplantation.

The gut microbiome is well known for its influence on human physiology and aging. Therefore, we speculate that the gut microbiome may affect muscle strength in the same way as the host's own genes. To demonstrate candidates for gut microbes affecting muscle strength, we remodeled the original gut microbiome of mice into human intestinal microbiome through fecal microbiome transplantation (FMT), using human feces and compared the changes in muscle strength in the same mice before and three months after FMT. After comparing before and after FMT, the mice were divided into three groups based on the observed changes in muscle strength: positive, none, and negative changes in muscle strength. As a result of analyzing the α-diversity, ß-diversity, and co-occurrence network of the intestinal microbial community before and after FMT, it was observed that a more diverse intestinal microbial community was established after FMT in all groups. In particular, the group with increased muscle strength had more gut microbiome species and communities than the other groups. Fold-change comparison showed that Eisenbergiella massiliensis and Anaeroplasma abactoclasticum from the gut microbiome had positive contributions to muscle strength, while Ileibacterium valens and Ethanoligenens harbinense had negative effects. This study identifies candidates for the gut microbiome that contribute positively and those that contribute negatively to muscle strength.

A simplified risk scoring system for predicting high-risk groups in gene expression tests for patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and node-positive breast cancer.

Purpose: The gene expression test (GET) was used to predict the response to chemotherapy and the recurrence risk. Several randomized clinical trials have demonstrated that some patients with node-positive disease can achieve favorable survival outcomes even without adjuvant chemotherapy. This study aimed to predict the results of Oncotype DX (Genomic Health) and MammaPrint (Agendia) using traditional clinicopathological factors. Methods: We reviewed the records of 311 patients who underwent GET for hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative primary invasive breast cancer with node-positive disease between 2015 and 2022 at Severance Hospital and Gangneung Asan Medical Center. Univariate and multivariate logistic regression analyses assessed the relationships between clinicopathological variables and risk stratification using the GET results. Results: A simple scoring system was created by assigning integer values to each variable. A score of 3 was assigned for histological grade 3, a score of 2 for pathologic T2 or above, and a score of 1 for a lower progesterone receptor (1-20 or Alled score 3-6), HER2 2-positive, and high Ki-67 (>20). In the validation cohort, overall accuracy was 0.798 (95% confidence interval, 0.744-0.844). Conclusion: The high GET risk results can be predicted using traditional clinicopathological factors: tumor size, progesterone receptor, histological grade, HER2, and Ki-67. These results will be useful for treatment decision-making among clinically high-risk patients with HR-positive/HER2-negative and node-positive disease, helping to identify patients to whom the GET assay may not apply.

Lymphovascular invasion is an independent prognostic factor in breast cancer irrespective of axillary node metastasis and molecular subtypes.

Purpose: Lymphovascular invasion (LVI) is a well-known poor prognostic factor for early breast cancer. However, the effect of LVI on breast cancer subtype and node status remains unknown. In this study, we aimed to evaluate the clinical significance of LVI on the recurrence and long-term survival of patients with early breast cancer by comparing groups according to the subtype and node status. Methods: We retrospectively reviewed the medical records of 4554 patients with breast cancer who underwent breast cancer surgery between January 2010 and December 2017. The primary endpoints were disease-free survival (DFS) and overall survival (OS). Univariate and multivariate analyses were performed to identify prognostic factors related to the DFS and OS according to the nodal status and breast cancer subtype. Results: During a follow-up period of 94 months, the median OS and DFS were 92 and 90 months, respectively. The LVI expression rate was 8.4%. LVI had a negative impact on the DFS and OS, regardless of the lymph node status. LVI was associated with higher recurrence and lower survival in the luminal A, human epidermal growth factor receptor 2-positive, and triple-negative breast cancer subtypes. The Cox proportional hazards model showed that LVI was a significant prognostic factor for both DFS and OS. No correlation has been observed between LVI and the Oncotype Dx results in terms of prognostic value in early breast cancer. Conclusion: LVI is an independent poor prognostic factor in patients with early breast cancer, regardless of the node status and molecular subtype. Therefore, the LVI status should be considered when making treatment decisions for patients with early stage breast cancer; however, further prospective studies are warranted.

Applying Sequential Pattern Mining to Investigate the Temporal Relationships between Commonly Occurring Internal Medicine Diseases and Intervals for the Risk of Concurrent Disease in Canine Patients.

Sequential pattern mining (SPM) is a data mining technique used for identifying common association rules in multiple sequential datasets and patterns in ordered events. In this study, we aimed to identify the relationships between commonly occurring internal medicine diseases in canine patients. We obtained medical records of dogs referred to the Konkuk University Veterinary Medicine Teaching Hospital. The data used for SPM included comorbidities and intervals between the diagnoses of internal medicine diseases. Additionally, we estimated the 3-year risk of developing an additional disease after the initial diagnosis of a commonly occurring veterinary internal medicine disease using logistic regression. We identified 547 canine patients diagnosed with ≥ 1 internal medicine disease. The SPM-based analysis assessed comorbidities and intervals for each of the five most common internal medical diseases, including hyperadrenocorticism, myxomatous mitral valve disease, canine atopic dermatitis, chronic kidney disease, and chronic pancreatitis. The highest values of the association rule were 3.01%, 6.02%, 3.9%, 4.1%, and 4.84%, and the shortest intervals were 1.64, 13.14, 5.37, 17.02, and 1.7 days, respectively. This study proposes that SPM is an effective technique for identifying common associations and temporal relationships between internal medicine diseases, and can be used to assess the probability of additional admission due to the development of the subsequent disease that may be diagnosed in canine patients. The results of this study will help veterinarians suggest appropriate preventive measures or other medical treatments for canine patients with medical conditions that have not yet been diagnosed, but are likely to develop in the short term.

Changes in Automated Mammographic Breast Density Can Predict Pathological Response After Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: Mammographic density is an independent risk factor for breast cancer that can change after neoadjuvant chemotherapy (NCT). This study aimed to evaluate percent changes in volumetric breast density (ΔVbd%) before and after NCT measured automatically and determine its value as a predictive marker of pathological response to NCT. MATERIALS AND METHODS: A total of 357 patients with breast cancer treated between January 2014 and December 2016 were included. An automated volumetric breast density (Vbd) measurement method was used to calculate Vbd on mammography before and after NCT. Patients were divided into three groups according to ΔVbd%, calculated as follows: Vbd (post-NCT - pre-NCT)/pre-NCT Vbd × 100 (%). The stable, decreased, and increased groups were defined as -20% ≤ ΔVbd% ≤ 20%, ΔVbd% < -20%, and ΔVbd% > 20%, respectively. Pathological complete response (pCR) was considered to be achieved after NCT if there was no evidence of invasive carcinoma in the breast or metastatic tumors in the axillary and regional lymph nodes on surgical pathology. The association between ΔVbd% grouping and pCR was analyzed using univariable and multivariable logistic regression analyses. RESULTS: The interval between the pre-NCT and post-NCT mammograms ranged from 79 to 250 days (median, 170 days). In the multivariable analysis, ΔVbd% grouping (odds ratio for pCR of 0.420 [95% confidence interval, 0.195-0.905; P = 0.027] for the decreased group compared with the stable group), N stage at diagnosis, histologic grade, and breast cancer subtype were significantly associated with pCR. This tendency was more evident in the luminal B-like and triple-negative subtypes. CONCLUSION: ΔVbd% was associated with pCR in breast cancer after NCT, with the decreased group showing a lower rate of pCR than the stable group. Automated measurement of ΔVbd% may help predict the NCT response and prognosis in breast cancer.

Long-term evaluation of the effects of vitreous degeneration on cataracts and retinal detachment in dogs.

OBJECTIVE: We aimed to track and evaluate the association between vitreous degeneration and the development of cataracts or retinal detachments in dogs over a long period. ANIMAL STUDIED: Data on vitreous degeneration, cataracts, and retinal detachment in 102 eyes were collected from 68 dogs who underwent ocular ultrasonography at least twice between March 2017 and November 2021 at the Veterinary Medical Teaching Hospital, Konkuk University. The mean follow-up time was 515 ± 256 (mean ± standard deviation; range: 81-1196) days. PROCEDURE: Development of cataracts and retinal detachment, according to the severity of vitreous degeneration grade (VDG), was evaluated during long-term follow-up. RESULTS: In the cataract study (87 eyes, 61 dogs), the number of cataracts developed according to VDG (grade: 0-3) were as follows: VDG 0: 1 in 10 (10%) eyes, VDG 1: 15 in 35 (43%) eyes, VDG 2: 15 in 30 (50%) eyes, and VDG 3: 10 in 12 (83%) eyes. It was significantly different among grades (p = .026). In the retinal detachment study (95 eyes, 64 dogs), the number of retinal detachments developed according to each VDG were as follows: VDG 0: 0 in 11 (0%) eyes, VDG 1: 1 in 36 (3%) eyes, VDG 2: 5 in 35 (14%) eyes, and VDG 3: 4 in 13 (30%) eyes. It was also significantly different among grades (p = .019). CONCLUSIONS: During long-term follow-up, dogs with severe vitreous degeneration had an increased risk of cataract and retinal detachment development than those without or with mild vitreous degeneration.

Downregulation of ADAMTS3 Suppresses Stemness and Tumorigenicity in Glioma Stem Cell.

AIMS: Glioblastoma multiforme (GBM) is the most aggressive type of human brain tumor, with a poor prognosis and a median overall survival of fewer than 15 months. Glioma stem cells (GSCs) have recently been identified as a key player in tumor initiation and therapeutic resistance in GBM. ADAMTS family of metalloproteinases is known to cleave a wide range of extracellular matrix substrates and has been linked to tissue remodeling events in tumor development. Here, we investigate that ADAMTS3 regulates GSC proliferation and self-renewal activities, and tumorigenesis in orthotopic xenograft models. METHODS: ADAMTS3 mRNA expression levels in normal human astrocyte (NHA), glioma, and GSCs cell lines were compared. After knockdown of ADAMTS3, alamarBlue assay, in vitro limiting dilution, and orthotopic xenograft assays were performed. To investigate the tumor-associated roles of ADAMTS3, several statistical assays were conducted using publicly available datasets. RESULTS: ADAMTS3 level was remarkably higher in GSCs than in NHA, glioma cell lines, and their matched differentiated tumor cells. Interestingly, knockdown of ADAMTS3 disrupted GSC's proliferation, self-renewal activity, and tumor formation in vivo. Furthermore, ADAMTS3 could be used as an independent predictor of malignancy progression in GBM. CONCLUSION: We identified ADAMTS3 as a potential therapeutic target for GBM.

Performance Comparison Between Fourier-Transform Infrared Spectroscopy-based IR Biotyper and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry for Strain Diversity.

Background: Development of an accessible method to routinely evaluate the clonality of strains is needed in microbiology laboratories. We compared the discriminatory power of the Fourier-transform infrared (FTIR) spectroscopy-based IR Biotyper (Bruker Daltonics GmbH, Bremen, Germany) to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), using whole-genome sequencing (WGS) as the reference method. Methods: Eighty-three extended-spectrum ß-lactamase-producing Escherichia coli isolates were tested using WGS, MALDI-TOF MS, and IR Biotyper. Simpson's diversity index (SDI), a statistical analysis for testing the homogeneity of a dendrogram, and the adjusted Rand index (aRI) were used to compare the discriminatory ability between typing tests. Results: The SDI (95% confidence interval) was 0.969 (0.952-0.985) for WGS, 0.865 (0.807-0.924) for MALDI-TOF MS, and 0.974 (0.965-0.983) for IR Biotyper. Compared with WGS, IR Biotyper showed compatible diversity, whereas MALDI-TOF MS did not. The concordance and aRI improved from 66.3% to 84.3% and from 0.173 to 0.538, respectively, for IR Biotyper versus MALDI-TOF MS with WGS as the reference method. IR Biotyper showed substantially improved performance in strain typing compared with MALDI-TOF MS. Conclusions: IR Biotyper is useful for diversity analysis with improved discriminatory power over MALDI-TOF MS in comparison with WGS as a reference method. IR Biotyper is an accessible method to evaluate the clonality of strains and could be applied in epidemiological analysis during an outbreak of a health care facility, as well as for research on the transmission of resistant bacteria in community settings.

Developing a diagnosis model for dry eye disease in dogs using object detection.

The purpose of this study was to develop an object detection method for the diagnosis of dry eye disease (DED) in dogs. To this end, a methodology was designed to evaluate ocular surface video images using the YOLOv5 model, which is an object detection algorithm that has been widely used because of its simple network structure and fast detection speed. Because the cornea is a transparent organ, an illuminator plate with grid squares was used to provide grid lines, which were analyzed as the reflected straight lines of the light source representing the precorneal tear film (PTF) stability. The original video consisted of the number of 12 normal images(normal, [Formula: see text] = 17) and the number of 15 abnormal images(abnormal, [Formula: see text] = 17), converted to JPEG images for labeling, learning, and model validation. The labeled image data were divided into a training image data set (normal, [Formula: see text] = 15,276; abnormal, [Formula: see text] = 26,196) to a validation image data set (normal, [Formula: see text] = 6546; abnormal, [Formula: see text] = 11,228). As a result of the experiment, the mean average precision ([Formula: see text]) achieved 0.995. This study proposes a method to effectively determine ocular surface status in dogs by using YOLOv5 and concludes that an object detection model can be used in the veterinary field.

7ß-22 Dihydroxyhopane, Isolated from the Sub-Antarctic Lichen, Inhibits the Viability and Stemness in Glioma Stem Like Cells.

Background: Glioma stem cells (GSCs) have been reported to contribute to tumor initiation and relapse, therapy resistance, and intra-tumoral heterogeneity of glioblastoma multiforme. Therefore, inhibiting GSCs presents a critical therapeutic tactic to suppress the aggressiveness of tumors. Methods: In this study, we examined the effects of 7ß-22 dihydroxyhopane (AP 18), isolated from the sub-Antarctic lichen, Pseudocyphellaria freycinetii. The cytotoxic effect of AP 18 and its effects on cell proliferation were assessed by alamarBlue assay and 5-ethynyl-2'-deoxyuridine (EdU) assay. Real-time confluence analysis was performed with a Celloger automatic live cell imaging system. Western Blotting and 3-D optical diffraction tomography (ODT) imaging were performed to determine whether apoptosis was triggered by AP 18. A Limiting dilution assay and qRT-PCR were performed to investigate the impact of AP 18 on GSC stemness. Results: AP 18 significantly reduced GSCs viability and proliferation, inducing programmed cell death identified by Annexin V/PI staining and had effects on morphologic features determined by 3-D ODT. Interestingly, treatment with AP 18 suppressed stemness features. Conclusion: Taken together, our results suggest that AP 18 might be a potential therapeutic agent to target GSCs.

Benign multicystic mesothelioma of appendiceal origin treated by hyperthermic intraperitoneal chemotherapy: A case report.

INTRODUCTION AND IMPORTANCE: Peritoneal benign cystic mesothelioma is a rare benign tumor that originates from a mesothelial proliferative lesion of the peritoneum. However, proper surgical management remains unclear due to its low incidence. We report a clinical case of peritoneal benign cystic mesothelioma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). CASE PRESENTATION: A 60-year-old female who underwent laparoscopic appendectomy in 2015 presented with abdominal pain in right lower quadrant area. Computed tomography of the abdomen and pelvis revealed a ruptured appendiceal mucocele or mucinous neoplasm, and several seeding-like small nodules in the greater omentum and right peritoneum. Cytoreductive surgery followed by HIPEC was performed; right hemicolectomy and lymph node dissection, omentectomy, and right abdominal partial peritonectomy. HIPEC with mitomycin was conducted for 90 min and an anastomosis between the ileum and colon was made after HIPEC. The pathologic results revealed the colonic mass was a multi-loculated cyst lined by mesothelial cells containing amorphous eosinophilic fibrinoid material, which are common features of benign cystic mesothelioma. CLINICAL DISCUSSION: Peritoneal benign cystic mesothelioma is known as a borderline disease of mesothelial tumors. Because its etiology is unknown, treatment strategies are not determined. CONCLUSION: Cytoreductive surgery followed by HIPEC can be considered to treat peritoneal benign cystic mesothelioma and prevent its malignant transformation.

Sprouty 1 is associated with stemness and cancer progression in glioblastoma.

Glioblastoma multiforme (GBM) is the most severe type of human brain tumor, with a poor prognosis and a low survival rate. GBM is composed of a variety of cell types, including glioma stem-like cells (GSCs), which attribute to its therapeutic resistance (Boyd et al., 2020). Sprouty1 (SPRY1) was first identified as a receptor tyrosine kinases (RTK) signaling mediator in a mammalian cell (Christofori, 2003), however, its role in GBM is unknown. Therefore, the goal of this study was to investigate the role of SPRY1 in the stemness and aggressiveness of GSCs. The mRNA expression levels of SPRY1 were confirmed using quantitative reverse transcription PCR (RT-qPCR) in normal human astrocytes (NHA), glioma cells, and glioma stem cells. SPRY1 expression was inhibited in glioma stem cells using small interference RNA (siRNAs) to examine its role in cell proliferation and tumorsphere formation. Bioinformatics analyses were also employed to investigate the association of SPRY1 expression with patient survival, tumor grade, and subtypes publicly available datasets. We demonstrated that SPRY1 is highly expressed in glioma stem cells than in NHA, glioma cells, and differentiated glioma stem cells. siRNA-mediated downregulation of SPRY1 expression decreased the stemness and self-renewal ability in GSC11. Bioinformatics results showed that high SPRY1 expression correlates with poor overall survival in glioma patients. Our findings suggest that SPRY1 contributes to the stemness and aggressiveness of GBM.

Evaluation of Atopic Dermatitis and Cutaneous Infectious Disorders Using Sequential Pattern Mining: A Nationwide Population-Based Cohort Study.

According to previous studies, the increased risk of cutaneous infectious disorders in patients with atopic dermatitis (AD) is related to impaired epidermal function, abnormal systemic immune function, and lower antimicrobial peptides. In this study, we analyzed the association between AD and cutaneous infectious disorders in the real world using sequential pattern mining (SPM). We analyzed National Health Insurance data from 2010-2013 using SPM to identify comorbid cutaneous infectious diseases and the onset durations of comorbidities. Patients with AD were at greater risk for molluscum contagiosum (adjusted odds ratio (aOR), 5.273), impetigo (aOR, 2.852), chickenpox (aOR, 2.251), otitis media (aOR, 1.748), eczema herpeticum (aOR, 1.292), and viral warts (aOR, 1.105). In SPM analysis, comorbidity of 1.06% shown in molluscum contagiosum was the highest value, and the duration of 77.42 days documented for molluscum contagiosum was the shortest onset duration among all the association rules. This study suggests that AD is associated with an increased risk of cutaneous infectious disorders. In particular, care should be taken regarding its high relevance with impetigo, molluscum contagiosum, and otitis media, which may help in preventing AD from worsening through appropriately preventing and managing the condition.

Impact of Mitomycin-C-Induced Neutropenia after Hyperthermic Intraperitoneal Chemotherapy with Cytoreductive Surgery in Colorectal Cancer Patients with Peritoneal Carcinomatosis.

BACKGROUND: Mitomycin-C (MMC) is the most commonly used chemotherapeutic agent for hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS). However, MMC has a side effect of myelosuppression. This study aimed to evaluate the clinical manifestations and impact of MMC-induced neutropenia after CRS and HIPEC in colorectal cancer patients. METHODS: A total of 124 colorectal cancer patients who underwent CRS with HIPEC between March 2015 and January 2019 were evaluated. Patients with malignancies of non-colorectal origin, hospital stay longer than 60 days, peritoneal cancer index > 30, and complete cytoreduction score > 2 were excluded. MMC 35 mg/m2 was administered for 90 min at 41-43 °C. The patients were divided into three groups: no neutropenia, mild neutropenia (grade 1-2), and severe neutropenia (grade 3-4). RESULTS: In total, mild and severe neutropenia occurred in 30 (24.2%) and 48 (38.7%) patients, respectively. Age and body surface area were significantly different among the neutropenia groups. Severe neutropenia developed significantly earlier than mild neutropenia (6.9 days vs. 10.4 days, p < 0.001) and also lasted significantly longer (4.6 days vs. 2.5 days, p = 0.005). The rate of major postoperative complications was significantly higher in the severe neutropenia group than in the no and mild neutropenia groups (8.3% vs. 6.7% vs. 6.5%, p = 0.015) CONCLUSIONS: Severe neutropenia starts earlier and lasts longer than mild neutropenia after CRS and HIPEC using an MMC triple method. The higher rate of major postoperative complications in patients with severe neutropenia highlights the importance of postoperative management during the neutropenia period.

Study of lipid proton difference evaluation via 9.4T MRI analysis of fatty liver induced by exposure to methionine and choline-deficient (MCD) diet and high-fat diet (HFD) in an animal model.

The selection of an animal model is based on the pathological mechanism appropriate for experimental investigation because the therapeutic effect was low depending on the pathological occurrence mechanism. The purpose of this study is to elucidate the changes in lipid proton concentration in two animal models of nonalcoholic fatty liver disease (NAFLD): methionine and choline-deficient (MCD) diet and high-fat diet (HFD). We calculated the T2 relaxation time of 7 lipid protons (LP) in the 9.4 T MRS phantom experiment. The concentrations of LPs were adjusted for T2 and T2* of MCD, HFD, and CCl4 fatty liver animal models. Multivariate analysis and Pearson correlation were performed to analyze LP concentration, and the difference was investigated via Kendall correlation and independent t-test using LP composition ratio. The T2 relaxation time of each LP was accurately determined using phantom experiments. The in vivo magnetic resonance spectroscopy (MRS) data were obtained by quantifying the t2/t2* corrected LP concentration in the liver of the animal model. In case of MCD and HFD, there was an average difference in all LPs except 0.9 ppm LP, and the MCD and CCl4 groups showed differences in the average of all LPs. However, there was no difference between LP of HFD and CCl4 groups. A higher level of unsaturated fatty acids was found in the MCD fatty liver model than in HFD induced fatty liver.

Elevated RGMA Expression Predicts Poor Prognosis in Patients with Glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most aggressive type of human brain tumor with a poor prognosis and a low survival rate. Secreted proteins from tumors are recently considered as important modulators to promote tumorigenesis by communicating with microenvironments. Repulsive guidance molecule A (RGMA) was initially characterized as an axon guidance molecule after secretion in the brain during embryogenesis but has not been studied in GBM. In this study, we investigated secreted gene expression patterns and the correlation between RGMA expression and prognosis in GBM using in silico analysis. METHODS: RGMA mRNA levels in normal human astrocyte (NHA), human glioma cells, and GBM patient-derived glioma stem cells (GSCs) were assessed by qRT-PCR. Patient survival analysis was performed with the Kaplan-Meier curve and univariate and multivariate analyses using publicly available datasets. The predictive roles of RGMA in progressive malignancy were evaluated using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). RESULTS: RGMA mRNA expression was elevated in glioma cells and GSCs compared with NHA and correlated with unfavorable prognosis in glioma patients. Thus, RGMA could serve as an independent predictive factor for GBM. Furthermore, the increased levels of RGMA expression and its putative receptor, neogenin (NEO1), were associated with poor patient survival rates in GBM. CONCLUSION: We identified RGMA as an independent prognostic biomarker for progressive malignancy in glioblastoma and address the possibilities to develop novel therapeutic strategies against glioblastoma.

Efficacy of biodegradable collagen matrix (Ologen® CM) in augmenting the success rate of Ahmed glaucoma valve implantation in canine glaucoma.

OBJECTIVE: To prospectively assess the efficacy of a biodegradable collagen matrix (ologen) in dogs with uncontrolled glaucoma receiving an Ahmed glaucoma valve (AGV) implant. ANIMAL STUDIED: Five client-owned dogs with glaucoma (five eyes). PROCEDURES: Five eyes treated for uncontrolled glaucoma underwent AGV implantation with ologen. Ologen was placed on the AGV plate and tube with a scleral flap. Complete ophthalmological examinations were performed preoperatively and at 1 and 3 days, 1 and 2 weeks, and 1, 2, 3, and 6 months postoperatively. Surgical outcomes were assessed based on the intraocular pressure (IOP), vision, frequency of anti-glaucoma eye drops, and bleb morphology; complications, if any, were recorded. The number of dogs with an IOP <20 mmHg with or without topical medications were tabulated and compared to those with an IOP ≥20 mmHg or those requiring surgery to maintain the IOP at <20 mmHg. RESULTS: The IOP significantly decreased from 47.00 ± 5.09 mmHg preoperatively to 17.00 ± 0.71 mmHg 6 months postoperatively (p = .008). IOP was controlled (<20 mmHg) in 5/5 dogs at 6 months postoperatively. Brief periods of elevated IOP (IOP ≥ 20 mmHg, IOP spike) occurred in one eye (case 5) at 1 month (35 mmHg) and 2 months (33 mmHg) postoperatively. The anti-glaucoma eye drop frequency decreased from 3.2 ± 0.44 preoperatively to 1.6 ± 0.90 at 6 months postoperatively (p = .007). CONCLUSIONS: To our knowledge, this is the first study to assess the potential safety of AGV implantation with ologen for canine glaucoma. This method effectively controlled the IOP, without any adverse effects.