Case report: Investigation of genetic mutations in a case of schistosomus reflexus in a Holstein dairy cattle fetus in Korea.

Schistosomus reflexus (SR) is one of the most common congenital anomalies found in cases of cattle dystocia; this disorder occurs mostly in cattle. Congenital anomalies such as SR are caused by various genetic and environmental factors, but no specific cause has been elucidated for SR. This study reports a case of SR in a Holstein dairy cattle fetus with congenital anomalies in Korea. Grossly, a distinct spine curvature was observed between the thoracic and lumbar vertebrae, accompanied by a consequential malformation from the sacrum to the occipital bone. Furthermore, the thoracic and abdominal organs were exposed. In computed tomography (CT) images, mild and severe kyphoscoliosis was observed in T1~11 and L1~6, respectively. Additionally, vertebral dysplasia was observed in S1~5 and Cd 1~5. To pinpoint the causal genes and mutations, we leveraged a custom 50K Hanwoo SNP-Chip and the Online Mendelian Inheritance in Animals (OMIA) database. As a result, we identified a nonsense mutation in apoptotic protease activating factor 1 (APAF1) within HH1 that was associated with a decrease in conception rate and an increase in abortion in Holstein dairy cattle. The genotype of the SR case was A/A, and most of the 1,142 normal Holstein dairy cattle tested as a control group had the genotype G/G. In addition, the A/A genotype did not exist in the control group. Based on the pathological, genetic, and radiological findings, the congenital abnormalities observed were diagnosed as SR.

Case study: Pathological and phylogenetic analysis of coccidiosis in two goats with heavy infection of unrecorded Eimeria sp.

Two 3-month-old goats (Capra aegagrus hircus and C. hircus coreanae) died after ataxia. In both goats, white nodules 3 mm in diameter were scattered from the duodenum to the ileum and well-raised white nodules 2-3 mm-diameter in the mucosa of the small intestine. Histopathologically, numerous mucosal polyps with coccidial oocysts were observed in the small intestine and several schizonts, macrogametocytes, microgametocytes, and macrogametes were observed in mucosal polyps in the jejunum. Based on fecal flotation tests, the oocysts morphologically resembled those of Eimeria christenseni and E. sundarbanensis; however, their sizes were different. The 18S rRNA gene and COI were phylogenetically analyzed for the molecular identification and characterization of Eimeria sp. Based on 18S rRNA gene similarity, the isolates formed an independent cluster within the related goat Eimeria clade, and the closest species were E. christenseni C2_42, E. hirci C2_99, and E. arloingi C2_119. Furthermore, these were also distinguished from other related goat Eimeria spp. in the phylogenetic tree based on the COI gene. Considering all histopathological, morphological, and phylogenetic analyses, the current study was diagnosed as fatal coccidiosis due to heavy infection with an unrecorded Eimeria species. Thus, we report in this study with caution regarding coccidiosis caused by an unrecorded Eimeria.

The Relationship Between Breast Density Change During Menopause and the Risk of Breast Cancer in Korean Women.

BACKGROUND: The aim of this study was to investigate the relationship between changes in breast density during menopause and breast cancer risk. METHODS: This study was a retrospective, longitudinal cohort study for women over 30 years of age who had undergone breast mammography serially at baseline and postmenopause during regular health checkups at Samsung Medical Center. None of the participants had been diagnosed with breast cancer at baseline. Mammographic breast density was measured using the American College of Radiology Breast Imaging Reporting and Data System. RESULTS: During 18,615 person-years of follow-up (median follow-up 4.8 years; interquartile range 2.8-7.5 years), 45 participants were diagnosed with breast cancer. The prevalence of dense breasts was higher in those who were younger, underweight, had low parity or using contraceptives. The cumulative incidence of breast cancer increased 4 years after menopause in participants, and the consistently extremely dense group had a significantly higher cumulative incidence (CI) of breast cancer compared with other groups [CI of extremely dense vs. others (incidence rate per 100,000 person-years): 375 vs. 203, P < 0.01]. CONCLUSION: Korean women whose breast density was extremely dense before menopause and who maintained this density after menopause were at two-fold greater risk of breast cancer. PREVENTION RELEVANCE: Extremely dense breast density that is maintained persistently from premenopause to postmenopause increases risk of breast cancer two fold in Korean women. Therefore, women having risk factors should receive mammography frequently and if persistently extremely dense breast had been detected, additional modalities of BC screening could be considered.

Highly Pathogenic Avian Influenza A(H5N6) in Domestic Cats, South Korea.

In December 2016, highly pathogenic avian influenza (HPAI) infection with systemic pathologic lesions was found in cats in South Korea. Genetic analyses indicated that the feline isolates were similar to HPAI H5N6 viruses isolated in chicken farms nearby. This finding highlights the need for monitoring of domestic mammals during HPAI outbreaks.

Experimental infection of mice with noncytopathic bovine viral diarrhea virus 2 increases the number of megakaryocytes in bone marrow.

BACKGROUND: Bovine viral diarrhea virus (BVDV) causes significant economic losses worldwide in the cattle industry through decrease in productive performance and immunosuppression of animals in herds. Recent studies conducted by our group showed that mice can be infected with BVDV-1 by the oral route. The purpose of this study was to assess the clinical signs, hematological changes, histopathological lesions in lymphoid tissues, and the distribution of the viral antigen after oral inoculation with a Korean noncytopathic (ncp) BVDV-2 field isolate in mice. METHODS: Mice were orally administered a low or high dose of BVDV-2; blood and tissue samples were collected on days 2, 5, and 9 postinfection (pi). We monitored clinical signs, hematological changes, histopathological lesions, and tissue distribution of a viral antigen by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) and then compared these parameters with those in ncp BVDV-1 infections. RESULTS: None of the infected mice developed any clinical signs of the illness. Significant thrombocytopenia was found in both low- and high-dose-inoculated mice on day 2 pi. Leukopenia was apparent only in low-dose-inoculated mice on day 2 pi, whereas lymphopenia was not observed in any ncp BVDV-2-infected animal. Viral RNA was found in the spleen in of low- and high-dose-inoculated mice by RT-PCR. According to the results of IHC, the viral antigen was consistently detected in lymphocytes of bone marrow and spleen and less frequently in bronchus-associated lymphoid tissue (BALT), mesenteric lymph nodes, and Peyer's patches. Despite the antigen detection in BALT and mesenteric lymph nodes, histopathological lesions were not observed in these tissues. Lympholysis, infiltration by inflammatory cells, and increased numbers of megakaryocytes were seen in Peyer's patches, spleens, and bone marrow, respectively. In contrast to ncp BVDV-1 infection, lympholysis was found in the spleen of ncp BVDV-2-infected mice. These histopathological lesions were more severe in high-dose-inoculated mice than in low-dose-inoculated mice. CONCLUSIONS: Our results provide insight into the pathogenesis of ncp BVDV-2 infection in mice. Collectively, these results highlight significant differences in pathogenesis between ncp BVDV-1 and ncp BVDV-2 infections in a murine model.

Experimental infection with cytopathic bovine viral diarrhea virus in mice induces megakaryopoiesis in the spleen and bone marrow.

Here, we infected mice with cytopathic bovine viral diarrhea virus 1 (cp BVDV1) by oral inoculation and investigated the effects of infection by histopathological, immunohistochemical (IHC), hematological methods. Twelve mice were infected, and samples were obtained at day 2, 5, and 9 postinfection (pi). Most of the infected mice exhibited clinical signs of illness such as reduced movement, crouching, loose feces, loss of appetite, and reduced water intake. Blood samples from six mice were positive for BVDV based on reverse transcription polymerase chain reaction (RT-PCR). Blood analysis also revealed thrombocytopenia and lymphopenia. Viral antigens were detected in the spleen (12/12), bone marrow (12/12), and/or mesenteric lymph nodes (4/12) of all infected mice by IHC analysis. The spleens showed significant histopathological changes including (i) substantially increased numbers of megakaryocytes, (ii) lymphocyte depletion, and (iii) hemorrhages. The bone marrow also had an increased number of megakaryocytes, although this increase was not as strong as it was in the spleen. Severe lymphoid depletion was observed in the mesenteric lymph nodes. Viral infections were present in the lymphocytes but not detected in megakaryocytes of the spleen, bone marrow, or mesenteric lymph nodes. These results suggest that the increased numbers of megakaryocytes may be a direct result of BVDV infection. BVDV infection in mice following oral inoculation of cp BVDV1 leads to megakaryopoiesis in the spleen and bone marrow to replenish the platelets.

Molecular Magnetic Resonance Imaging of Tumor Response to Therapy.

Personalized cancer medicine requires measurement of therapeutic efficacy as early as possible, which is optimally achieved by three-dimensional imaging given the heterogeneity of cancer. Magnetic resonance imaging (MRI) can obtain images of both anatomy and cellular responses, if acquired with a molecular imaging contrast agent. The poor sensitivity of MRI has limited the development of activatable molecular MR contrast agents. To overcome this limitation of molecular MRI, a novel implementation of our caspase-3-sensitive nanoaggregation MRI (C-SNAM) contrast agent is reported. C-SNAM is triggered to self-assemble into nanoparticles in apoptotic tumor cells, and effectively amplifies molecular level changes through nanoaggregation, enhancing tissue retention and spin-lattice relaxivity. At one-tenth the current clinical dose of contrast agent, and following a single imaging session, C-SNAM MRI accurately measured the response of tumors to either metronomic chemotherapy or radiation therapy, where the degree of signal enhancement is prognostic of long-term therapeutic efficacy. Importantly, C-SNAM is inert to immune activation, permitting radiation therapy monitoring.

Meningoencephalitis caused by Halicephalobus gingivalis in a thoroughbred gelding.

A 6-year-old Thoroughbred gelding was euthanized after a 2-month period of abnormal neurological signs, such as circling left in his pen and hitting his head and body against the wall. After the horse was euthanized on the farm, a half of the brain and whole blood were submitted for diagnostic tests. Histopathological examination of the brain revealed granulomatous and eosinophilic meningoencephalitis with numerous intralesional nematodes, predominantly affecting the cerebrum. Multifocal malacic foci were scattered in the brain parenchyma. The intralesional parasites were identified as Halicephalobus gingivalis by morphological features and PCR testing. To the best of our knowledge, this is the first report of meningoencephalitis caused by H. gingivalis in the horse in Korea.

Phylogenetic analysis and characterization of Korean orf virus from dairy goats: case report.

An outbreak of orf virus infection in dairy goats in Korea was investigated. Suspected samples of the skin and lip of affected goats were sent to the laboratory for more exact diagnosis. Orf virus was detected by electron microscopy and viral DNA was identified by PCR. To reveal the genetic characteristics of the Korean strain (ORF/09/Korea), the sequences of the major envelope protein (B2L) and orf virus interferon resistance (VIR) genes were determined and then compared with published reference sequences. Phylogenetic analysis revealed that the ORF/09/Korea strain was closest to the isolates (Taiping) from Taiwan. This is believed to be the first report on the molecular characterization of orf virus in Korea.