Epidemiological Assessment of Risk Factors Associated with Bovine Ephemeral Fever Virus Exposure among Sheep and Goats in South Korea

Background: Bovine ephemeral fever virus (BEFV) is an arthropod-borne virus classified as a type species of the genus Ephemerovirus, family Rhabdoviridae. BEFV is the causative agent of bovine ephemeral fever (BEF), a non-contagious disease of acute febrile clinical signs in cattle and water buffalo. Some species might act as reservoir hosts, and antibodies to BEFV have also been found in asymptomatic sheep, goats, pigs, and many wild animals. This study aimed to conduct a retrospective cross-sectional serological screening in South Korea to address BEFV seroprevalence and identify risk factors for becoming seropositive for the virus in sheep and goats. Materials, Methods & Results: The apparent prevalence rates were considered to be the animal-level prevalence, defined as the proportion of serum neutralization test (SNT)-positive animals out of the total number of animals tested in the study area, and flock prevalence was defined as the proportion of SNT-positive flocks out of the total number of tested flocks in the area. A flock was classified as positive if at least one animal was SNT-positive. At the national level in 2011, 28 of 177 flocks (15.8%; 95% CI, 11.2−21.9%) and 71 of 498 heads (14.3%, 95% CI: 11.5-17.6%) that were analyzed showed serum neutralizing antibodies against BEFV. Our results revealed that age class, vector control, and geographic location affected seroprevalence to differing extents. In the univariate analysis, older age was a significant risk factor (OR, 2.327; 95% CI, 1.147-4.721; P = 0.017 in adults). The management risk factor attributes showed that preventive measures, such as routine application of insecticides in farms, decreased the odds of seropositivity for BEFV (OR, 0.514; 95% CI, 0.267-0.991; P = 0.044). Vector control was a significant protective factor, while animal species, flock size, and flock structure were not significantly associated. Differences in seroprevalence between variations in the presence of ruminant farms, lakes, or rice paddies within a 1-km radius or type of land use were not statistically significant (P > 0.05). We observed a significant difference in the individual likelihood of being positive in the southern provinces with respect to that in the northern provinces (OR, 2.166; 95% CI, 1.228-3.824; P = 0.007). Differences in seroprevalence between variations in the eastern and western regions were not statistically significant (P > 0.05). The retrospective study results showed that the virus was widely distributed in sheep and goats in South Korea, with seropositive rates ranging from 7.8% to 19.7% between 2003 and 2008.Discussion: This is the first report of circulating antibodies against BEFV in sheep and goats in South Korea. The serological prevalence of BEFV infection in sheep and goats was significantly different between different age cohorts, vector control, and geographical locations: it was higher in the older group and the southern and western regions of South Korea. Determination of seropositivity rates often leads to an understanding of virus circulation dynamics and is useful in the formulation of disease control measures. Our results demonstrated that vector control was a significant protective factor; therefore, the summer control of vectors could be better implemented in provinces with elevated seropositivity rates. The results of this seroprevalence study may serve as a basis for future epidemiological studies on BEFV infection in South Korea

Seasonal Abundance of Biting Midges, Culicoides spp. (Diptera: Ceratopogonidae), Collected at Cowsheds in the Southern Part of the Republic of Korea

Black light traps were used to measure the seasonal and geographical distribution of Culicoides spp. (biting midges or no-see-ums) at 9 cowsheds in the southern half of the Republic of Korea (ROK) from June through October 2010. A total of 25,242 Culicoides females (24,852; 98.5%) and males (390; 1.5%) comprising of 9 species were collected. The most commonly collected species was Culicoides punctatus (73.0%) followed by C. arakawae (25.7%), while the remaining 7 species accounted for <1.0% of all Culicoides spp. collected. The mean number of Culicoides spp. collected per trap night (Trap Index [TI]) was highest for C. punctatus (409.3), followed by C. arakawae (144.2), C. tainanus (4.1), C. oxystoma (1.2), C. circumscriptus (0.7), C. homotomus (0.6), C. erairai (0.4), C. kibunensis (0.3), and C. nipponensis (0.04). Peak TIs were observed for C. punctatus (1,188.7) and C. arakawae (539.0) during July and August, respectively. C. punctatus and C. arakawae have been implicated in the transmission of arboviruses and other pathogens of veterinary importance that adversely impact on animal and bird husbandry

Surveillance for West Nile Virus in Dead Wild Birds, South Korea, 2005–2008

To investigate the possibility of West Nile virus (WNV) introduction into South Korea, the National Veterinary Research and Quarantine Service has conducted nationwide surveillance of WNV activity in dead wild birds since 2005. Surveillance conducted during 2005–2008 found no evidence of WNV activity

Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition

Background Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are currently used to treat patients with diabetes. Previous studies have demonstrated that treatment with SGLT-2 inhibitors is accompanied by altered metabolic phenotypes. However, it has not been investigated whether the hypothalamic circuit participates in the development of the compensatory metabolic phenotypes triggered by the treatment with SGLT-2 inhibitors. Methods Mice were fed a standard diet or high-fat diet and treated with dapagliflozin, an SGLT-2 inhibitor. Food intake and energy expenditure were observed using indirect calorimetry system. The activity of hypothalamic neurons in response to dapagliflozin treatment was evaluated by immunohistochemistry with c-Fos antibody. Quantitative real-time polymerase chain reaction was performed to determine gene expression patterns in the hypothalamus of dapagliflozin-treated mice. Results Dapagliflozin-treated mice displayed enhanced food intake and reduced energy expenditure. Altered neuronal activities were observed in multiple hypothalamic nuclei in association with appetite regulation. Additionally, we found elevated immunosignals of agouti-related peptide neurons in the paraventricular nucleus of the hypothalamus. Conclusion This study suggests the functional involvement of the hypothalamus in the development of the compensatory metabolic phenotypes induced by SGLT-2 inhibitor treatment

Endothelial Dysfunction and Microvascular Complications in Type 1 Diabetes Mellitus

We examined whether alterations in vascular endothelial function and early structural changes in atherosclerosis are associated with microvascular complications in patients with type 1 diabetes mellitus (DM). Flow-mediated dilation (FMD) of the brachial artery and carotid intima-media thickness (IMT) measurement were performed in 70 young adults (aged 19 to 35 yr), 48 with type 1 DM, and 22 normal controls. Patients with diabetes had a lower peak FMD response (7.8±3.9 vs. 11.1±1.9%, p<0.001) and increased IMT (0.51±0.10 vs. 0.42±0.07 mm, p<0.001) compared with controls. Twenty (41.7%) of the patients had microvascular complications including neuropathy, nephropathy, or retinopathy. In these complicated diabetic patients, we found a lower FMD response (6.1±2.5 vs. 9.9±3.5%, p=0.001) compared with diabetics without microvascular complications. The presence of microvascular complications was also associated with older age and longer duration of the disease. However, no differences were observed in IMT, body size, blood pressure, HbA1c, C-reactive protein, low-density lipoprotein or high-density lipoprotein cholesterol levels between complicated and non-complicated patients. Endothelial dysfunction and early structural atherosclerotic changes are common manifestations in type 1 DM, and endothelial dysfunction is thought to be an early event in the atherosclerotic process and important in the pathogenesis of microvascular complications

Coregulator Control of Androgen Receptor Action by a Novel Nuclear Receptor-Binding Motif

The androgen receptor (AR) is a ligand-activated transcription factor that is essential for prostate cancer development. It is activated by androgens through its ligand-binding domain (LBD), which consists predominantly of 11 α-helices. Upon ligand binding, the last helix is reorganized to an agonist conformation termed activator function-2 (AF-2) for coactivator binding. Several coactivators bind to the AF-2 pocket through conserved LXXLL or FXXLF sequences to enhance the activity of the receptor. Recently, a small compound-binding surface adjacent to AF-2 has been identified as an allosteric modulator of the AF-2 activity and is termed binding function-3 (BF-3). However, the role of BF-3 in vivo is currently unknown, and little is understood about what proteins can bind to it. Here we demonstrate that a duplicated GARRPR motif at the N terminus of the cochaperone Bag-1L functions through the BF-3 pocket. These findings are supported by the fact that a selective BF-3 inhibitor or mutations within the BF-3 pocket abolish the interaction between the GARRPR motif(s) and the BF-3. Conversely, amino acid exchanges in the two GARRPR motifs of Bag-1L can impair the interaction between Bag-1L and AR without altering the ability of Bag-1L to bind to chromatin. Furthermore, the mutant Bag-1L increases androgen-dependent activation of a subset of AR targets in a genome-wide transcriptome analysis, demonstrating a repressive function of the GARRPR/BF-3 interaction. We have therefore identified GARRPR as a novel BF-3 regulatory sequence important for fine-tuning the activity of the AR

LAP2 Is Widely Overexpressed in Diverse Digestive Tract Cancers and Regulates Motility of Cancer Cells

BACKGROUND: Lamina-associated polypeptides 2 (LAP2) is a nuclear protein that connects the nuclear lamina with chromatin. Although its critical roles in genetic disorders and hematopoietic malignancies have been described, its expression and roles in digestive tract cancers have been poorly characterized. METHODS: To examine the expression of LAP2 in patient tissues, we performed immunohistochemistry and real-time PCR. To examine motility of cancer cells, we employed Boyden chamber, wound healing and Matrigel invasion assays. To reveal its roles in metastasis in vivo, we used a liver metastasis xenograft model. To investigate the underlying mechanism, a cDNA microarray was conducted. RESULTS: Immunohistochemistry in patient tissues showed widespread expression of LAP2 in diverse digestive tract cancers including stomach, pancreas, liver, and bile duct cancers. Real-time PCR confirmed that LAP2β is over-expressed in gastric cancer tissues. Knockdown of LAP2β did not affect proliferation of most digestive tract cancer cells except pancreatic cancer cells. However, knockdown of LAP2β decreased motility of all tested cancer cells. Moreover, overexpression of LAP2β increased motility of gastric and pancreatic cancer cells. In the liver metastasis xenograft model, LAP2β increased metastatic efficacy of gastric cancer cells and mortality in tested mice. cDNA microarrays showed the possibility that myristoylated alanine-rich C kinase substrate (MARCKS) and interleukin6 (IL6) may mediate LAP2β-regulated motility of cancer cells. CONCLUSIONS: From the above results, we conclude that LAP2 is widely overexpressed in diverse digestive tract cancers and LAP2β regulates motility of cancer cells and suggest that LAP2β may have utility for diagnostics and therapeutics in digestive tract cancers

Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients

This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004–2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22–0.63) for those without cirrhosis and 0.54 (0.31–0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p < 0.001). The treatment of chronic hepatitis C patients before they developed cirrhosis showed a higher efficacy than did the treatment of those who had already developed cirrhosis. Patients with SVR may still have a risk of HCC and need to be regularly monitored