and Relevance: Here, we report atypical clinicopathological features observed in the case of CEL. These findings have potential biological, diagnostic, and prognostic relevance, emphasizing the need for further studies to elucidate their clinical significance and to expand the understanding of this disease.

An adult castrated male dog was presented with persistent hematochezia. Digital rectal examination and endoscopy found multiple colorectal masses. Complete blood count and serum biochemical results were within the reference interval. Fine needle aspirate of the masses indicated a diagnosis of inflamed polyps with a primary differential of malignancy. Histopathologic examination using endoscopy-guided incisional biopsy of the masses revealed an inflamed neoplasm with ossification. A colectomy was performed to remove the tumor. Subsequent histopathologic examination of the surgically resected masses resulted in a diagnosis of colorectal carcinoma in situ (CiS) with immune infiltrates, which were subject to immunohistochemical and flow cytometric immunophenotyping. The immunohistochemistry confirmed intraepithelial CD3 + T cells within CiS. The flow cytometric analysis indicated tumor-infiltrating CD4 + T, CD8 + T, and CD11b + myeloid subsets. The flow cytometric analysis of circulating and tumor-infiltrating leukocytes demonstrated a preferential expansion of CD25 + FOXP3 + regulatory T cells within CiS. To the author’s knowledge, this is the first report to show clinical evidence emphasizing the immunogenicity and immune-suppressive environment of canine colorectal CiS. Our case will be valuable in providing a rationale for basic research that dissects the immune environment for canine colorectal cancers for the future development of cancer immunotherapy.

A 6-year-old spayed female French Bulldog presented with a left-sided chest wall tumor. Physical examination revealed that the tumor was firmly adhered to the chest wall. A preoperative punch biopsy of the tumor revealed a grade 2 soft tissue sarcoma (STS). On computed tomography, the tumor’s dimensions were assessed as 6.5 × 5.7 × 3.5 cm, and it exhibited invasiveness near the tissue surrounding the ninth rib. The tumor size was large in comparison to the dog’s chest wall area. Hence, if the traditional wide-margin resection surgery were to be performed, primary wound closure seemed impractical and could potentially result in respiratory function complications. Therefore, considering the extent of tumor invasion and grade, deep margins were established to include the removal of the eighth to tenth ribs, and a 1-cm lateral margin was designated to enable primary wound closure. To reconstruct the chest wall, polypropylene mesh was attached to the adjacent ribs and the remaining muscles were sutured and covered over the mesh. The dog exhibited a rapid recovery beginning the day after the operation. Postoperative biopsy confirmed that the tumor was a grade 2 STS, and the surgical margins were evaluated as incomplete. The owner chose to pursue follow-up observation instead of chemotherapy. In this study, the surgical approach was chosen based on the importance of functional recovery after surgery. Recent research indicates that the tumor grade is more critical for postoperative prognosis than the extent of surgical margins when removing an STS.

An adult male dog was presented for hemorrhagic pericardial effusion. Echocardiography and computed tomography revealed nodule-like lesions on the pericardium. Cytology of pericardial effusion and excisional pericardial lesions indicated neoplastic effusion. Histopathology indicated an inflamed neoplasm with a primary differential diagnosis of hemangiosarcoma and malignant mesothelioma (MM). Immunohistochemistry showed that atypical cells were positive for cytokeratin and vimentin, but negative for CD31, strongly favoring pericardial MM. Postoperative NT-proBNP level remained increased, which led to the administration of epirubicin to minimize potential cardiotoxicity. During the 4 cycles of epirubicin treatment, a total cumulative dose of 108 mg/m ² was administrated and no effusion recurrence was observed. After a month post-completion of chemotherapy, however, pleural effusion was detected with cardiac masses. The owner requested no further diagnostic investigations and chemotherapy. Due to deteriorating conditions, the dog died 132 days after the first presentation. Our case is the first notable attempt to treat canine malignant mesothelioma with epirubicin, providing the clinicopathologic, diagnostic routine, and clinical course of the affected dog.

Traumatic reticuloperitonitis (TRP) often referred to as hardware disease is a common disease of cattle, which is considered the most frequent cause of anterior abdominal pain in cattle. The incidence of TRP has decreased significantly, but the diagnosis and treatment of TRP are still clinically significant because of its economic impact. An eight-year-old female Mongolian cow weighing 400 kg, was presented to the Korean (College of Veterinary Medicine, Jeju National University)–Mongolian (School of Veterinary Medicine, Mongolian University of Life Science) volunteer team (KMVT) with the primary complaints of depression and anorexia during their outreach activity for veterinary volunteer service in the field of the suburban farm of Mongolia. TRP was diagnosed based on the clinical symptoms, auscultation, and back grip test results. An emergency rumenotomy was performed with the consent of the owner. The patient was anesthetized using distal paravertebral anesthesia and the inverted L block method while a makeshift restraint frame was constructed on-site. The rumenotomy was performed to explore the rumen and reticulum. Foreign bodies were identified and removed. The surgery was performed successfully. The patient’s recovery after the surgery was normal, and the appetite was restored. This paper describes a case of TRP in a Mongolian cow, including the diagnosis, surgical preparation, and surgery successfully performed in the field of suburban farm of Mongolia in detail.

Background: In this study, the relationship between depression and stress-coping strategies among public enterprise workers whose workplaces were relocated to a newly-built innovation city was investigated. Methods: This study included a total of 922 public enterprise workers living in Naju Innovation City. Along with their sociodemographic data, each subject was assessed concerning depression, occupational stress, and stress-coping strategies using the Center for Epidemiologic Studies Depression Scale(CES-D), Korean Occupational Stress Scale (KOSS), and stress-coping scale (SCS), respectively. Logistic regression was performed to investigate the impact of the relevant factors on depressive symptoms. Results: The overall prevalence of depressive symptoms was 14%. Some sociodemographic variables, the total scores of the KOSS, and four subscales of the SCS revealed significant differences between the depressed and normal groups. Multivariate regression analysis revealed that the KOSS (odds ratio [OR], 1.17; p<0.001) and SCS, such as problem-solving-focused (OR, 0.75; p<0.001), emotion-focused (OR, 1.15; p<0.05), and wishful-thinking-focused (OR, 1.10; p<0.05), were significantly associated with depression. Conclusion The results indicated that depressive symptoms were highly prevalent among workers whose workplaces were relocated. In addition, these symptoms were found to be related with occupational stress and stress-coping strategies. Our findings also suggest that promoting healthy stress-coping strategies and reducing occupational stress may help in preventing the occurrence of depression and managing depressed workers.

It was recently reported that the C(max) and AUC of rosuvastatin increases when it is coadministered with telmisartan and cyclosporine. Rosuvastatin is known to be a substrate of OATP1B1, OATP1B3, NTCP, and BCRP transporters. The aim of this study was to explore the mechanism of the interactions between rosuvastatin and two perpetrators, telmisartan and cyclosporine. Published (cyclosporine) or newly developed (telmisartan) PBPK models were used to this end. The rosuvastatin model in Simcyp (version 15)'s drug library was modified to reflect racial differences in rosuvastatin exposure. In the telmisartan–rosuvastatin case, simulated rosuvastatin C(maxI)/C(max) and AUC(I)/AUC (with/without telmisartan) ratios were 1.92 and 1.14, respectively, and the T(max) changed from 3.35 h to 1.40 h with coadministration of telmisartan, which were consistent with the aforementioned report (C(maxI)/C(max): 2.01, AUCI/AUC:1.18, T(max): 5 h → 0.75 h). In the next case of cyclosporine–rosuvastatin, the simulated rosuvastatin C(maxI)/C(max) and AUC(I)/AUC (with/without cyclosporine) ratios were 3.29 and 1.30, respectively. The decrease in the CL(int,BCRP,intestine) of rosuvastatin by telmisartan and cyclosporine in the PBPK model was pivotal to reproducing this finding in Simcyp. Our PBPK model demonstrated that the major causes of increase in rosuvastatin exposure are mediated by intestinal BCRP (rosuvastatin–telmisartan interaction) or by both of BCRP and OATP1B1/3 (rosuvastatin–cyclosporine interaction).
Area Under Curve ; Cyclosporine ; Drug Interactions* ; Rosuvastatin Calcium*

BACKGROUND: With increasing use of medical radiologic procedures, wearing proper protector should be emphasized to reduce occupational radiation exposures. This research describes the rates of lead apron wearing for radiation protection and assessed occupational factors related to wearing rates for various types of healthcare professionals. METHODS: We conducted a self-administered questionnaire survey through a website, on-site visits, fax, and mail. Of the 13,489 participants, 8858 workers who could not completely separate themselves from radiological procedure areas. Their general characteristics (sex and age), work history (job title, duration of employment, and hospital type), and practices (frequency of radiation procedures, ability to completely separate from radiation, and frequency of wearing protective lead aprons) were examined. RESULTS: The mean rate of lead apron wearing during radiologic procedures was 48.0 %. The rate was different according to sex (male: 52.9 %, female: 39.6 %), hospital type (general hospital: 63.0 %, hospital: 51.3 %, clinic: 35.6 %, dental hospital/clinic: 13.3 %, public health center: 22.8 %), and job title (radiologic technologist: 50.3 %, doctor: 70.3 %, dentist/dental hygienist: 15.0 %, nurse/nursing assistant: 64.5 %) (p < 0.001). By logistic regression analysis stratified by job title, use of lead aprons by radiologic technologists and nurses/nursing assistants was associated with hospital type and exposure frequency score. For doctors, apron wearing was associated with employment duration. For dentists/dental hygienists, apron wearing was associated with the exposure frequency score. CONCLUSIONS: To improve working environments for healthcare professionals exposed to radiation, it is necessary to consider related factors, such as job title, duration of employment, and hospital type, when utilizing a planning and management system to prevent radiation-related health problems.
Delivery of Health Care* ; Employment ; Female ; Humans ; Logistic Models ; Postal Service ; Public Health ; Radiation Protection

SKL10406, triple monoamine reuptake inhibitor, is a novel antidepressant candidate. A PET study was performed to investigate the occupancies of serotonin and dopamine transporters (SERT and DAT) in human brain, and the relationship between SKL10406 concentration and SERT occupancy was assessed using pharmacokinetic-pharmacodynamic (PK-PD) modeling methods. Fifteen healthy volunteers were given SKL10406 100 mg/day for 6 days or 150 mg/day for 6 days after 100 mg/day for 4 days. Each subject underwent full PK sampling for SKL10406 and PET scans at predose, 4 h and 16 h after dosing at a steady state to investigate the occupancies of SERT and DAT using 11C-DASB and 11C-PE2I, respectively. Naive pooled method (NPM) and nonlinear mixed-effect methods (ME) including a direct ME (DME) and an effect compartmental ME (EME) were used (NONMEM Ver. 7.2). Six and five subjects completed the studies for SERT and DAT, respectively. The final estimates of Emax (53.4%) and EC50 (11.8 ng/mL) from DME were relatively lower than those from NPM (Emax, 74.1%; EC50, 36.8 ng/mL) and EME (Emax, 68.6%; EC50, 40.2 ng/mL). DAT occupancy results were not modeled because of lower occupancies. The results showed that the dosage regimens may be applied in patient studies. However, difference between estimation methods alerts that ME may not be a recommendable analysis tool for sparsely sampled PET scan data.
Brain ; Dopamine ; Healthy Volunteers ; Humans ; Positron-Emission Tomography ; Serotonin ; Serotonin Plasma Membrane Transport Proteins*

The structural complexity of crossover studies for bioequivalence test confuses analysts and leaves them a hard choice among various programs. Our study reviews PROC GLM and PROC MIXED in SAS and compares widely used SAS codes for crossover studies. PROC MIXED based on REML is more recommended since it provides best linear unbiased estimator of the random between-subject effects and its variance. Our study also considers the covariance structure within subject over period which most PK/PD studies and crossover studies ignore. The QT interval data after the administration of moxifloxacin for a fixed time point are analyzed for the comparison of representative SAS codes for crossover studies.
Cross-Over Studies* ; Therapeutic Equivalency