Predictions of PD-L1 Expression Based on CT Imaging Features in Lung Squamous Cell Carcinoma.

Purpose: To develop models to predict programmed death ligand 1 (PD-L1) expression in pulmonary squamous cell carcinoma (SCC) using CT. Materials and Methods: A total of 97 patients diagnosed with SCC who underwent PD-L1 expression assay were included in this study. We performed a CT analysis of the tumors using pretreatment CT images. Multiple logistic regression models were constructed to predict PD-L1 positivity in the total patient group and in the 40 advanced-stage (≥ stage IIIB) patients. The area under the receiver operating characteristic curve (AUC) was calculated for each model. Results: For the total patient group, the AUC of the 'total significant features model' (tumor stage, tumor size, pleural nodularity, and lung metastasis) was 0.652, and that of the 'selected feature model' (pleural nodularity) was 0.556. For advanced-stage patients, the AUC of the 'selected feature model' (tumor size, pleural nodularity, pulmonary oligometastases, and absence of interstitial lung disease) was 0.897. Among these factors, pleural nodularity and pulmonary oligometastases had the highest odds ratios (8.78 and 16.35, respectively). Conclusion: Our model could predict PD-L1 expression in patients with lung SCC, and pleural nodularity and pulmonary oligometastases were notable predictive CT features of PD-L1.

Spikebot: A Multigait Tensegrity Robot with Linearly Extending Struts.

Numerous recent research efforts have leveraged networks of rigid struts and flexible cables, called tensegrity structures, to create highly resilient and packable mobile robots. However, the locomotion of existing tensegrity robots is limited in terms of both speed and number of distinct locomotion modes, restricting the environments that a robot is capable of exploring. In this study, we present a tensegrity robot inspired by the volumetric expansion of Tetraodontidae. The robot, referred to herein as Spikebot, employs pneumatically actuated rigid struts to expand its global structure and produce diverse gaits. Spikebot is composed of linear actuators that dually serve as rigid struts linked by elastic cables for stability. The linearly actuating struts can selectively protrude to initiate thrust- and instability-driven locomotion primitives. Such motion primitives allow Spikebot to reliably locomote, achieving rolling, lifting, and jumping. To highlight Spikebot's potential for robotic exploration, we demonstrate how it achieves multi-dimensional locomotion over varied terrestrial conditions.

Deep learning-based diagnosis of Alzheimer's disease using brain magnetic resonance images: an empirical study.

The limited accessibility of medical specialists for Alzheimer's disease (AD) can make obtaining an accurate diagnosis in a timely manner challenging and may influence prognosis. We investigated whether VUNO Med-DeepBrain AD (DBAD) using a deep learning algorithm can be employed as a decision support service for the diagnosis of AD. This study included 98 elderly participants aged 60 years or older who visited the Seoul Asan Medical Center and the Korea Veterans Health Service. We administered a standard diagnostic assessment for diagnosing AD. DBAD and three panels of medical experts (ME) diagnosed participants with normal cognition (NC) or AD using T1-weighted magnetic resonance imaging. The accuracy (87.1% for DBAD and 84.3% for ME), sensitivity (93.3% for DBAD and 80.0% for ME), and specificity (85.5% for DBAD and 85.5% for ME) of both DBAD and ME for diagnosing AD were comparable; however, DBAD showed a higher trend in every analysis than ME diagnosis. DBAD may support the clinical decisions of physicians who are not specialized in AD; this may enhance the accessibility of AD diagnosis and treatment.

MRI features of symptomatic amputation neuromas.

OBJECTIVES: To demonstrate the magnetic resonance imaging (MRI) features of amputation neuromas in lower extremity amputees and investigate independent predictive MRI features for symptomatic neuromas. METHODS: This retrospective study included 45 amputation neuromas in 44 lower extremity amputees. Two radiologists assessed the imaging features, including shape, size, type (end-bulb or spindle), signal intensity (SI), heterogeneity, margins, enlarged fascicles, dark outer rim, tail sign, target sign, enhancement, perilesional fibrosis, and muscle denervation. The neuromas were categorized into symptomatic (n = 24) or asymptomatic (n = 21). Symptomatic neuromas were determined based on neuropathic pain characteristics, the presence of Tinel's sign or tenderness, and response to local anesthetic injection. Univariate and multivariate analyses were performed to identify independent predictive MRI features. RESULTS: Of 45 neuromas, 80% (36/45) were end-bulb neuromas and 20% (9/45) were spindle-type neuromas. Eighty percent of the neuromas (36/45) were heterogeneous on T2-weighted images (WIs). Enlarged fascicles were present in 42% (19/45) and dark outer rims in 27% (12/45) of the neuromas. Among the 23 neuromas with enhanced images, 78% (18/23) showed enhancement. Heterogeneity on T2-WIs and enhancement ratios were significantly different between the asymptomatic and symptomatic neuroma groups (p < 0.05). The multivariate analyses indicated that heterogeneity on T2-WIs was an independent factor associated with symptomatic neuromas (p < 0.001). CONCLUSIONS: Heterogeneity on T2-WIs could be a predictive indicator for symptomatic neuromas in lower extremity amputees. KEY POINTS: • Amputation neuromas are classified as either end-bulb or spindle-type. They can show enlarged fascicles, dark outer rims, and enhancement. • Heterogeneity on T2-weighted images could be a predictive indicator for symptomatic neuromas. • Predicting the symptomatic neuroma on MRI would help in effective management of stump pain.

Deep learning-based image reconstruction for brain CT: improved image quality compared with adaptive statistical iterative reconstruction-Veo (ASIR-V).

PURPOSE: To compare the image quality of brain computed tomography (CT) images reconstructed with deep learning-based image reconstruction (DLIR) and adaptive statistical iterative reconstruction-Veo (ASIR-V). METHODS: Sixty-two patients underwent routine noncontrast brain CT scans and datasets were reconstructed with 30% ASIR-V and DLIR with three selectable reconstruction strength levels (low, medium, high). Objective parameters including CT attenuation, noise, noise reduction rate, artifact index of the posterior cranial fossa, and contrast-to-noise ratio (CNR) were measured at the levels of the centrum semiovale and basal ganglia. Subjective parameters including gray matter-white matter differentiation, sharpness, and overall diagnostic quality were also assessed and compared with the interobserver agreement. RESULTS: There was a gradual reduction in the image noise and artifact index of the posterior cranial fossa as the strength levels of DLIR increased (all P < 0.001) compared with that of ASIR-V. CNR in both the centrum semiovale and basal ganglia levels also improved from the low to high strength levels of DLIR compared with that of ASIR-V (all P < 0.001). DLIR images with medium and high strength levels demonstrated the best subjective image quality scores among the reconstruction datasets. There was moderate to good interobserver agreement for the subjective image quality assessments with ASIR-V and DLIR. CONCLUSION: On routine brain CT scans, optimized protocols with DLIR allowed significant reduction of noise and artifacts with improved subjective image quality compared with ASIR-V.

Validation of Deep-Learning Image Reconstruction for Low-Dose Chest Computed Tomography Scan: Emphasis on Image Quality and Noise.

OBJECTIVE: Iterative reconstruction degrades image quality. Thus, further advances in image reconstruction are necessary to overcome some limitations of this technique in low-dose computed tomography (LDCT) scan of the chest. Deep-learning image reconstruction (DLIR) is a new method used to reduce dose while maintaining image quality. The purposes of this study was to evaluate image quality and noise of LDCT scan images reconstructed with DLIR and compare with those of images reconstructed with the adaptive statistical iterative reconstruction-Veo at a level of 30% (ASiR-V 30%). MATERIALS AND METHODS: This retrospective study included 58 patients who underwent LDCT scan for lung cancer screening. Datasets were reconstructed with ASiR-V 30% and DLIR at medium and high levels (DLIR-M and DLIR-H, respectively). The objective image signal and noise, which represented mean attenuation value and standard deviation in Hounsfield units for the lungs, mediastinum, liver, and background air, and subjective image contrast, image noise, and conspicuity of structures were evaluated. The differences between CT scan images subjected to ASiR-V 30%, DLIR-M, and DLIR-H were evaluated. RESULTS: Based on the objective analysis, the image signals did not significantly differ among ASiR-V 30%, DLIR-M, and DLIR-H (p = 0.949, 0.737, 0.366, and 0.358 in the lungs, mediastinum, liver, and background air, respectively). However, the noise was significantly lower in DLIR-M and DLIR-H than in ASiR-V 30% (all p < 0.001). DLIR had higher signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) than ASiR-V 30% (p = 0.027, < 0.001, and < 0.001 in the SNR of the lungs, mediastinum, and liver, respectively; all p < 0.001 in the CNR). According to the subjective analysis, DLIR had higher image contrast and lower image noise than ASiR-V 30% (all p < 0.001). DLIR was superior to ASiR-V 30% in identifying the pulmonary arteries and veins, trachea and bronchi, lymph nodes, and pleura and pericardium (all p < 0.001). CONCLUSION: DLIR significantly reduced the image noise in chest LDCT scan images compared with ASiR-V 30% while maintaining superior image quality.

Early-onset mild cognitive impairment in Parkinson's disease: Altered corticopetal cholinergic network.

Degeneration of the substantia innominata (SI) is significantly correlated with cognitive performance in Parkinson's disease (PD). We examined functional and structural patterns of SI degeneration in drug-naïve PD patients according to the duration of parkinsonism before mild cognitive impairment (MCI) diagnosis. Twenty PD patients with a shorter duration (PD-MCI-SD, <1 year), 18 patients with a longer duration (PD-MCI-LD, ≥1 year), and 29 patients with intact cognition (PD-IC) were included. Seed-based resting-state functional connectivity (rsFC) analysis using bilateral SI seed and region-of-interest-based volumetric analysis were performed. Compared to PD-IC, the collapsed PD-MCI group showed altered rsFC in the right frontal and bilateral parietal areas. PD-MCI-SD showed rsFC alteration in broader frontal and parietal areas compared to the other groups. Decreased rsFC in the right frontal area was also significantly correlated with shorter disease duration. No significant SI volume change was found between the groups. Altered rsFC between the SI and the frontal and parietal areas might be relevant to cognitive dysfunction in PD. Decreased rsFC between the SI and frontal area might be associated with early-onset MCI, suggesting that cholinergic deficits in the frontal brain areas might play an important role in the acceleration of cognitive decline in PD.

Genetic characterization of porcine epidemic diarrhea virus in Korea from 1998 to 2013.

The number of porcine epidemic diarrhea (PED) cases has increased over the past 20 years in Korea, with a major outbreak in 2013. A total of 27 Korean strains from 1998 to 2013 were analyzed (excluding the noncoding regions) and divided into two groups for comparison of the spike (S), ORF3, envelope (E), membrane (M), and nucleocapsid (N) genes with those of reference strains, vaccine strains, and previously identified strains based on phylogenetic analysis. Analysis of the selection patterns of PEDV isolated in Korea indicated positive selection of nine nonsynonymous sites in the S and N proteins and negative selection at 97 sites for all of the proteins. Interestingly, eight nonsynonymous mutations in S showed no significant pattern change over the 15-year period, and one of eight mutation sites was found only in IC05TK, GN05DJ, and KNU0802 in the epidemic years 2005 and 2008. These eight mutations were also present during the epidemic years in China. Furthermore, of the signs of positive selection in the S protein, the conservative substitutions were more frequent than radical substitutions in PEDVs, suggesting that the evolution of Korean strains has been slow. Serological cross-reactivity was detected between three field PEDVs and two vaccine strains, with different serum neutralization titers. In conclusion, although Korean PEDVs have been evolving slowly, their diverse antigenicity and genetics imply that multilateral efforts to prevent future PED outbreaks are required.

Functional hierarchy of herpes simplex virus type-1 membrane proteins in corneal infection and virus transmission to ganglionic neurons.

PURPOSE: To determine the relative importance of viral glycoproteins gK, gM, gE and the membrane protein UL11 in infection of mouse corneas and ganglionic neurons. METHODS: Mouse eyes were scarified and infected with herpes simplex virus (HSV)-1(F), gE-null, gM-null, gK-null, or UL11-null viruses. Clinical signs of ocular disease were monitored daily. Virus shedding was determined at 24, 48 and 72 h post infection. Viral DNA within trigeminal ganglia (TG) was quantified by quantitative PCR at 30 d post infection. RESULTS: The gE-null virus replicated as efficiently as the parental virus and formed viral plaques approximately half-the-size in comparison with the HSV-1(F) wild-type virus. The UL11-null and gM-null viruses replicated approximately one log less efficiently than the wild-type virus, and formed plaques that were on average one-third the size and one-half the size of the wild-type virus, respectively. The gK-null virus replicated more than 3-logs less efficiently than the wild-type virus and formed very small plaques (5-10 cells). Mice infected with the wild-type virus exhibited mild clinical ocular symptoms, while mice infected with the mutant viruses did not show any significant ocular changes. The wild-type virus produced the highest virus shedding post infection followed by the gM-null, gE-null and UL11-null viruses, while no gK-null virus was detected at any time point. All TG collected from mice infected with the wild-type virus and 6-of-10 of TG retrieved from mice infected with the UL11-null virus contained high numbers of viral genomes. The gE-null and gM-null-infected ganglia contained moderate-to-low number of viral genomes in 4-of-10 and 2-of-10 mice, respectively. No viral genomes were detected in ganglionic tissues obtained from gK-null eye infections. CONCLUSIONS: The results show that gK plays the most important role among gM, gE and UL11 in corneal and ganglionic infection in the mouse eye model.

Diagnostic role of conventional ultrasonography and shearwave elastography in asymptomatic patients with diffuse thyroid disease: initial experience with 57 patients.

PURPOSE: Thyroid ultrasonography (US) is a useful diagnostic tool in the evaluation of diffuse thyroid disease (DTD), whereas shearwave elastography is a dynamic technique that can provide information about tissue hardness by using acoustic shearwaves remotely induced by a focused ultrasonic beam. This study aims at investigating the role of conventional US and shearwave elastography in the diagnosis of asymptomatic patients with DTD. MATERIALS AND METHODS: Fifty-seven patients who underwent both conventional US and shearwave elastography were included in this study. Interobserver variability of the three radiologists in assessment of underlying thyroid echogenicity on conventional US was analyzed. Diagnostic performances for diagnosing DTD on conventional US and shearwave elastography were calculated and compared. RESULTS: Fair agreement was observed in the identification of DTD with conventional US (kappa value= 0.27). The area under the receiver operating characteristic curve (Az) were 0.52-0.585 on conventional US by three radiologists. The Az values when using the mean and maximum elasticity values as a diagnostic criteria for DTD were 0.619 and 0.59 on shearwave elastography. Patients with DTD showed higher mean [24.1±10 kilo-Pascals (kPa)] and maximum (36.4±13.3 kPa) elasticity values on shearwave elastography when compared to the normal group (23.4±10.8 kPa and 33.7±12.4 kPa, respectively), although without statistical significance (p=0.802 and p=0.452, respectively). CONCLUSION: Conventional US did not show reliable interobserver agreement in the diagnosis of DTD. Although not statistically significant, shearwave elastography may provide additional information in the diagnosis of DTD. Therefore, larger prospective studies are needed to define the values of shearwave elastography for diagnosing DTD.

Herpes simplex virus 1 glycoprotein M and the membrane-associated protein UL11 are required for virus-induced cell fusion and efficient virus entry.

Herpes simplex virus 1 (HSV-1) facilitates virus entry into cells and cell-to-cell spread by mediating fusion of the viral envelope with cellular membranes and fusion of adjacent cellular membranes. Although virus strains isolated from herpetic lesions cause limited cell fusion in cell culture, clinical herpetic lesions typically contain large syncytia, underscoring the importance of cell-to-cell fusion in virus spread in infected tissues. Certain mutations in glycoprotein B (gB), gK, UL20, and other viral genes drastically enhance virus-induced cell fusion in vitro and in vivo. Recent work has suggested that gB is the sole fusogenic glycoprotein, regulated by interactions with the viral glycoproteins gD, gH/gL, and gK, membrane protein UL20, and cellular receptors. Recombinant viruses were constructed to abolish either gM or UL11 expression in the presence of strong syncytial mutations in either gB or gK. Virus-induced cell fusion caused by deletion of the carboxyl-terminal 28 amino acids of gB or the dominant syncytial mutation in gK (Ala to Val at amino acid 40) was drastically reduced in the absence of gM. Similarly, syncytial mutations in either gB or gK did not cause cell fusion in the absence of UL11. Neither the gM nor UL11 gene deletion substantially affected gB, gC, gD, gE, and gH glycoprotein synthesis and expression on infected cell surfaces. Two-way immunoprecipitation experiments revealed that the membrane protein UL20, which is found as a protein complex with gK, interacted with gM while gM did not interact with other viral glycoproteins. Viruses produced in the absence of gM or UL11 entered into cells more slowly than their parental wild-type virus strain. Collectively, these results indicate that gM and UL11 are required for efficient membrane fusion events during virus entry and virus spread.

Histologic characteristics of hepatocellular carcinomas showing atypical enhancement patterns on 4-phase MDCT examination.

OBJECTIVE: To retrospectively define which histologic characteristics of small-sized hepatocellular carcinomas (HCCs) are related to atypical dynamic enhancement on multi-detector computed tomography (MDCT) imaging. MATERIALS AND METHODS: Seventy-three patients with 83 HCCs (3 cm or less in diameter) were included in this study. All patients underwent 4-phase MDCT imaging and subsequent surgery within eight weeks. Two independent radiologists blinded to the histologic findings retrospectively classified the HCCs as either typical (showing increased enhancement on arterial phase images followed by washout in late phase images) or atypical lesions demonstrating any other enhancement pattern. From the original pathologic reports, various histologic characteristics including gross morphology, nuclear histologic grades, presence of capsule formation, and capsule infiltration when a capsule was present, were compared among the two groups. RESULTS: An atypical enhancement pattern was seen in 30 (36.2%) of the 83 HCCs. The mean size of atypical HCCs (1.71 ± 0.764) was significantly smaller than that of typical HCCs (2.31 ± 0.598, p < 0.001). Atypical HCCs were frequently found to be vaguely nodular in gross morphology (n = 13, 43.3%) and to have grade I nuclear grades (n = 17, 56.7%). Capsule formation was significantly more common in typical HCCs (p < 0.001). Capsular infiltration was also more common in typical HCCs (p = 0.001). CONCLUSION: HCCs showing atypical dynamic enhancement on MDCT imaging are usually smaller than typical HCCs, vaguely nodular type in gross morphology in most cases, and well-differentiated in nuclear grades, and they lack of capsule formation or capsular infiltration.

Functional hierarchy of herpes simplex virus 1 viral glycoproteins in cytoplasmic virion envelopment and egress.

Herpes simplex virus 1 (HSV-1) viral glycoproteins gD (carboxyl terminus), gE, gK, and gM, the membrane protein UL20, and membrane-associated protein UL11 play important roles in cytoplasmic virion envelopment and egress from infected cells. We showed previously that a recombinant virus carrying a deletion of the carboxyl-terminal 29 amino acids of gD (gDΔct) and the entire gE gene (ΔgE) did not exhibit substantial defects in cytoplasmic virion envelopment and egress (H. C. Lee et al., J. Virol. 83:6115-6124, 2009). The recombinant virus ΔgM2, engineered not to express gM, produced a 3- to 4-fold decrease in viral titers and a 50% reduction in average plaque sizes in comparison to the HSV-1(F) parental virus. The recombinant virus containing all three mutations, gDΔct-ΔgM2-ΔgE, replicated approximately 1 log unit less efficiently than the HSV-1(F) parental virus and produced viral plaques which were on average one-third the size of those of HSV-1(F). The recombinant virus ΔUL11-ΔgM2, engineered not to express either UL11 or gM, replicated more than 1 log unit less efficiently and produced significantly smaller plaques than UL11-null or gM-null viruses alone, in agreement with the results of Leege et al. (T. Leege et al., J. Virol. 83:896-907, 2009). Analyses of particle-to-PFU ratios, relative plaque size, and kinetics of virus growth and ultrastructural visualization of glycoprotein-deficient mutant and wild-type virions indicate that gDΔct, gE, and gM function in a cooperative but not redundant manner in infectious virion morphogenesis. Overall, comparisons of single, double, and triple mutant viruses generated in the same HSV-1(F) genetic background indicated that lack of either UL20 or gK expression caused the most severe defects in cytoplasmic envelopment, egress, and infectious virus production, followed by the double deletion of UL11 and gM.

Escherichia coli expressing single-chain Fv on the cell surface as a potential prophylactic of porcine epidemic diarrhea virus.

Porcine epidemic diarrhea virus (PEDV) is a causative agent of severe diarrhea which leads to death in piglets. Because of the high mortality which is up to 100% in suckling piglets, PED is an important porcine disease in Korea. In this study, we developed a prophylactic candidate using single-chain Fvs to prevent the PEDV infection. ScFvs of mouse monoclonal antibody which was verified to neutralize PEDV was expressed in Escherichia coli expression system. After the confirmation of PEDV neutralizing activity of purified recombinant scFvs by VN test, scFvs were expressed on the surface of E. coli cells. The signal sequence and autotransporter beta domain of protease IgA (IgAP) of Neisseria gonorrhoeae were introduced to endow scFvs with the direction to the cell surface and the support as a transmembrane domain. 5x10(6)CFU of E. coli expressing scFvs against PEDV showed promising result of 94% foci reduction compared to wild type E. coli. This result demonstrated that E. coli expressing scFvs on the cell surface retained functional potency of parent antibody and therefore blocked PEDV infection into target cells in vitro. This in vitro assay result proposes the perspective of recombinant E. coli cells expressing scFvs as a novel prophylactic against PEDV infection.

Multiplex real-time RT-PCR for the simultaneous detection and quantification of transmissible gastroenteritis virus and porcine epidemic diarrhea virus.

Transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) are major etiological agents of diarrhea and death in piglets. Multiplex real-time reverse transcriptase (RT)-PCR was developed for simultaneous differential quantification of each virus in a single reaction tube, using Cy5- and FAM-labeled TaqMan-probes based on sequences from the TGEV and PEDV nucleocapsid genes. The copy numbers for transcripts of TGEV and PEDV were quantified using this assay over a range from 9x10(7) to 9x10(1) copies and 7x10(7) to 7x10(1) copies, respectively. The variability of the intra-assay and inter-assay were evaluated using standard solutions of each transcript, with coefficients of variation (CV) less than 3.43 and 3.33%, respectively. Piglets were experimentally infected with virulent TGEV and PEDV, and the amounts of virus from the onset of diarrhea were measured. Samples obtained from farms experiencing PED or TGE were quantified between 10(2) and 10(5) RNA copies. In conclusion, this assay provides an effective etiological diagnostic tool for detecting and quantifying viral loads. The assay may also prove useful for detecting infections, ultimately leading to better disease control on farms.

Delayed wound healing in Mac-1-deficient mice is associated with normal monocyte recruitment.

The Mac-1 integrin is an important mediator of migration and inflammatory activation of neutrophils and monocytes. However, the role of Mac-1 in modulating macrophage emigration and activation and its subsequent impact on cutaneous wound healing have not been fully elucidated. To examine the significance of Mac-1 to murine wound healing, we measured epithelialization and granulation tissue formation in partial-thickness ear wounds and full-thickness head wounds, respectively, in Mac-1-deficient mice. Wounds were histologically analyzed at postwounding days 3, 5, and 7. The gap measured between the leading edges of inward-migrating granulation tissue was significantly increased in knockout mice compared with control animals at day 5 (3.8+/-0.3 vs. 2.6+/-0.5 mm; p<0.001) and day 7 (2.2+/-0.4 vs. 0.96+/-0.73 mm; p=0.005). Epithelial gap measurements were also increased in knockout mice vs. wild-type controls at days 3 (0.62+/-0.02 vs. 0.54+/-0.07 mm; p<0.05) and 5 (0.58+/-0.06 vs. 0.39+/-0.08 mm; p<0.001). Immunohistochemistry showed equal numbers of macrophages in knockout and control wounds. These findings show that Mac-1 is required for normal wound healing but that the attenuation in the deposition of granulation tissue and wound epithelialization in Mac-1 knockout mice is not associated with decreased monocyte migration into the wound.

Identification of bovine viral diarrhea virus type 2 in Korean native goat (Capra hircus).

In the genus Pestivirus, four genetically distinct viral species are currently recognized: bovine viral diarrhea viruses type 1 and 2 (BVDV-1, BVDV-2), classical swine fever virus (CSFV) and border disease virus (BDV). BVDV-1 and BDV infections have been described in goat species. Since 1998, border disease (BD) like symptoms in goats have been reported repeatedly in two southern-most provinces of Korea, which until then had been regarded as being free from BD. As a result of retrospective investigations of BD-like syndrome in goat reported between 1998 and 2004, a pestivirus was identified from intestinal content of an affected kid submitted in 1999. Both sequences of 5'-non-coding region and complete N(pro) gene from the isolate were analyzed to identify the genotype. Interestingly, the results revealed that the isolate belonged to BVDV-2 that is rarely reported even in cattle. The isolate showed close relationship to North American and European strains rather than the geographically closer Japanese strains. To authors' knowledge, this is the first identification of BVDV-2 in goat species.

Age effect on HSP70: decreased resistance to ischemic and oxidative stress in HDF.

BACKGROUND: Heat pre-conditioning results in induction of heat shock proteins including HSP70 that gives a cytoprotective effect against further stress. However, HSP70 induction is attenuated in aged cells. The lower HSP70-levels may contribute to the impaired stress response seen in the aged, and to the higher rates of chronic wounds in aged, which arise from repeated ischemia-reperfusion injury. The aim of this study was to investigate a possible connection by comparing the viability of heat pre-conditioned aged versus young human dermal fibroblasts (HDF) after exposure to stress. MATERIALS AND METHODS: Young (15-28) and aged (61-77) HDF were heat pre-conditioned (42 degrees C, 1 h) and after recovery (1, 2, or 20 h) treated with carbonyl-cyanide-m-chlorophenylhydrazone (hypoxic stress) or with hydrogen peroxide (oxidative stress) for 1 h. HSP70 levels were determined by Western blot. Cell damage was assessed by quantifying lactic dehydrogenase (LDH) in conditioned media. Aged HDF were transfected with HSP70-plasmid, consecutively heat pre-conditioned and exposed to oxidative stress. RESULTS: HSP70 increased in heat pre-conditioned young HDF by 96, 189, and 237% after 1, 2, and 20-h recovery, respectively, and in aged HDF by 27, 61, and 26%. LDH-release was only decreased in young HDF 20-h after heat-treatment compared with non-heat treated cells (P < 0.001). HSP70-transfection of aged HDF with plasmid reduced LDH-release by 29%. CONCLUSIONS: Heat pre-conditioning fails to protect aged HDF to oxidative or hypoxic stress due in part to impaired HSP70 induction compared to young.

Molecular epidemiology of rabies virus isolates from South Korea.

A molecular epidemiological study was performed on 13 Korean virus isolates, which were collected from wild and domestic animals diagnosed as rabid between 1998 and 2004. Seven samples were from domestic animals such as dogs and cattle infected by rabid raccoon dogs (Nyctereutes procyonoides koreensis), and the rest of the six samples were from raccoon dogs in the wild. The study was carried out based on the comparison of nucleotide and amino acid sequences of nucleoprotein (N) and glycoprotein (G) coding regions and nucleotide sequence of the G-L intergenic (Psi) non-coding region of the isolates. The similarities of nucleotide and amino acid sequence were at least 97.8 and 98.5%, respectively, between all Korean isolates. Phylogenetic analyses of the isolate showed that they formed a monophyletic group closely related to the Arctic strains but distant from other Asian strains, including Chinese strains. The fact that the raccoon dog is the main epidemic carrier of rabies in Korea and the results of these studies supported the conclusion of previous studies (Kuzmin et al.) that the raccoon dogs take part in the circulation of rabies virus within their natural territories in the Far East. The Korean isolates can be divided into two subgroups. All the topology of the most likelihood tree of Korean isolates using nucleotide and amino acid sequences of N, G and G-L region reflected not the species but the year of isolation and geographical location of the virus isolates. This study presents the detailed description of the molecular epidemiology of rabies virus in Korea.

Inhibition of prolyl 4-hydroxylase reduces scar hypertrophy in a rabbit model of cutaneous scarring.

Hypertrophic scars result from excessive collagen deposition at sights of healing dermal wounds and can be functionally and cosmetically problematic. Pharmacological regulation of collagen synthesis and deposition is a direct approach to the control of scar tissue formation. We tested the ability of the phenanthrolinone derivative FG-1648 (in 0.5% Carbopol 971 PNF gel, pH 6.5), a prolyl 4-hydroxylase inhibitor, to reduce hypertrophic scar formation in a rabbit ear hypertrophic scar model. New Zealand White rabbits were divided into two treatment groups (n = 12 wounds per group with an equal number of controls): low-dose group: 0.5% FG-1648; high-dose group: 1% FG-1648. Left ears were used for treatment and right ear for control. Four 7-mm dermal ulcer wounds were made on each ear. The inhibitor was topically applied to the wound at the time of wounding and once daily up to postoperative day 7. Wounds were harvested at postoperative day 28 and scar hypertrophy quantified by measurement of the scar elevation index. All wounds showed complete healing. Treatment of wounds with 1% prolyl 4-hydroxylase inhibitor decreased the scar elevation index by 26% compared to control wounds (p < 0.01). Wounds treated with 0.5% FG-1648 inhibitor showed no difference in scar elevation compared to control wounds. These results suggest that inhibition of prolyl 4-hydroxylase may be a suitable agent for topical treatment for the prevention of hypertrophic scar tissue.