A functional regulatory variant of MYH3 influences muscle fiber-type composition and intramuscular fat content in pigs.

Muscle development and lipid accumulation in muscle critically affect meat quality of livestock. However, the genetic factors underlying myofiber-type specification and intramuscular fat (IMF) accumulation remain to be elucidated. Using two independent intercrosses between Western commercial breeds and Korean native pigs (KNPs) and a joint linkage-linkage disequilibrium analysis, we identified a 488.1-kb region on porcine chromosome 12 that affects both reddish meat color (a*) and IMF. In this critical region, only the MYH3 gene, encoding myosin heavy chain 3, was found to be preferentially overexpressed in the skeletal muscle of KNPs. Subsequently, MYH3-transgenic mice demonstrated that this gene controls both myofiber-type specification and adipogenesis in skeletal muscle. We discovered a structural variant in the promotor/regulatory region of MYH3 for which Q allele carriers exhibited significantly higher values of a* and IMF than q allele carriers. Furthermore, chromatin immunoprecipitation and cotransfection assays showed that the structural variant in the 5'-flanking region of MYH3 abrogated the binding of the myogenic regulatory factors (MYF5, MYOD, MYOG, and MRF4). The allele distribution of MYH3 among pig populations worldwide indicated that the MYH3 Q allele is of Asian origin and likely predates domestication. In conclusion, we identified a functional regulatory sequence variant in porcine MYH3 that provides novel insights into the genetic basis of the regulation of myofiber type ratios and associated changes in IMF in pigs. The MYH3 variant can play an important role in improving pork quality in current breeding programs.

Transcriptome profiling of in vitro-matured oocytes from a korean native cow (hanwoo) after cysteamine supplementation.

This study elucidated the molecular markers that decrease oocyte quality during in vitro culture, restricting optimal developmental potential. Here, we evaluated the transcriptomic differences between cysteamine-treated and non-treated bovine cumulus oocyte complexes (COCs) after 22 h of co-culture in the maturation media using RNA sequencing. In total, 39,014 transcripts were sequenced between cysteamine-treated and non-treated mature COCs. We evaluated the relative expression of 21,472 genes, with 59 genes showing differential expression between the two COC groups. The cysteamine-treated group had 36 up-regulated gene transcripts and 23 down-regulated gene transcripts. Moreover, gene ontology (GO) enrichment analysis revealed that multiple biological processes were significantly enriched after cysteamine supplementation. Differentially expressed genes appeared to maintain normal oocyte physiology, regulation of apoptosis, differentiation, ossification or bone formation, cardiac and muscle physiology, hormonal secretion, and membrane construction for further embryonic development. In conclusion, cysteamine affects the mRNA level of COCs during oocyte maturation by upregulating potential molecular markers and downregulating genes that affect further embryonic development.

Deep Learning-based Automatic Detection Algorithm for Reducing Overlooked Lung Cancers on Chest Radiographs.

Background It is uncertain whether a deep learning-based automatic detection algorithm (DLAD) for identifying malignant nodules on chest radiographs will help diagnose lung cancers. Purpose To evaluate the efficacy of using a DLAD in observer performance for the detection of lung cancers on chest radiographs. Materials and Methods Among patients diagnosed with lung cancers between January 2010 and December 2014, 117 patients (median age, 69 years; interquartile range [IQR], 64-74 years; 57 women) were retrospectively identified in whom lung cancers were visible on previous chest radiographs. For the healthy control group, 234 patients (median age, 58 years; IQR, 48-68 years; 123 women) with normal chest radiographs were randomly selected. Nine observers reviewed each chest radiograph, with and without a DLAD. They detected potential lung cancers and determined whether they would recommend chest CT for follow-up. Observer performance was compared with use of the area under the alternative free-response receiver operating characteristic curve (AUC), sensitivity, and rates of chest CT recommendation. Results In total, 105 of the 117 patients had lung cancers that were overlooked on their original radiographs. The average AUC for all observers significantly rose from 0.67 (95% confidence interval [CI]: 0.62, 0.72) without a DLAD to 0.76 (95% CI: 0.71, 0.81) with a DLAD (P < .001). With a DLAD, observers detected more overlooked lung cancers (average sensitivity, 53% [56 of 105 patients] with a DLAD vs 40% [42 of 105 patients] without a DLAD) (P < .001) and recommended chest CT for more patients (62% [66 of 105 patients] with a DLAD vs 47% [49 of 105 patients] without a DLAD) (P < .001). In the healthy control group, no difference existed in the rate of chest CT recommendation (10% [23 of 234 patients] without a DLAD and 8% [20 of 234 patients] with a DLAD) (P = .13). Conclusion Using a deep learning-based automatic detection algorithm may help observers reduce the number of overlooked lung cancers on chest radiographs, without a proportional increase in the number of follow-up chest CT examinations. © RSNA, 2020 Online supplemental material is available for this article.

Genomic selection through single-step genomic best linear unbiased prediction improves the accuracy of evaluation in Hanwoo cattle.

OBJECTIVE: Genomic selection (GS) is becoming popular in animals' genetic development. We, therefore, investigated the single-step genomic best linear unbiased prediction (ssGBLUP) as tool for GS, and compared its efficacy with the traditional pedigree BLUP (pedBLUP) method. METHODS: A total of 9,952 males born between 1997 and 2018 under Hanwoo proven-bull selection program was studied. We analyzed body weight at 12 months and carcass weight (kg), backfat thickness, eye muscle area, and marbling score traits. About 7,387 bulls were genotyped using Illumina 50K BeadChip Arrays. Multiple-trait animal model analyses were performed using BLUPF90 software programs. Breeding value accuracy was calculated using two. METHODS: i) Pearson's correlation of genomic estimated breeding value (GEBV) with EBV of all animals (rM1) and ii) correlation using inverse of coefficient matrix from the mixed-model equations (rM2). Then, we compared these accuracies by overall population, info-type (PHEN, phenotyped-only; GEN, genotyped-only; and PH+GEN, phenotyped and genotyped), and bull-types (YBULL, young male calves; CBULL, young candidate bulls; and PBULL, proven bulls). RESULTS: The rM1 estimates in the study were between 0.90 and 0.96 among five traits. The rM1 estimates varied slightly by population and info-type, but noticeably by bull-type for traits. Generally average rM2 estimates were much smaller than rM1 (pedBLUP, 0.40 to0.44; ssGBLUP, 0.41 to 0.45) at population level. However, rM2 from both BLUP models varied noticeably across info-types and bull-types. The ssGBLUP estimates of rM2 in PHEN, GEN, and PH+ GEN ranged between 0.51 and 0.63, 0.66 and 0.70, and 0.68 and 0.73, respectively. In YBULL, CBULL, and PBULL, the rM2 estimates ranged between 0.54 and 0.57, 0.55 and 0.62, and 0.70 and 0.74, respectively. The pedBLUP based rM2 estimates were also relatively lower than ssGBLUP estimates. At the population level, we found an increase in accuracy by 2.0% to 4.5% among traits. Traits in PHEN were least influenced by ssGBLUP (0% to 2.0%), whereas the highest positive changes were in GEN (8.1% to 10.7%). PH+GEN also showed 6.5% to 8.5% increase in accuracy by ssGBLUP. However, the highest improvements were found in bull-types (YBULL, 21% to 35.7%; CBULL, 3.3% to 9.3%; PBULL, 2.8% to 6.1%). CONCLUSION: A noticeable improvement by ssGBLUP was observed in this study. Findings of differential responses to ssGBLUP by various bulls could assist in better selection decision making as well. We, therefore, suggest that ssGBLUP could be used for GS in Hanwoo provenbull evaluation program.

Contrast-enhanced US with Perfluorobutane for Hepatocellular Carcinoma Surveillance: A Multicenter Diagnostic Trial (SCAN).

Background US has served as a standard surveillance tool for hepatocellular carcinoma (HCC); however, the detection rate and false referral rate with this modality are suboptimal. Purpose To evaluate the added value of perfluorobutane-enhanced US when combined with conventional B-mode US as an HCC surveillance tool in participants with liver cirrhosis. Materials and Methods This prospective multi-institution diagnostic trial (https://ClinicalTrials.gov, NCT02188901) used an intraindividual comparison design in a single arm of study participants and was conducted at five referral hospitals. Eligible participants who had liver cirrhosis related to viral hepatitis and were undergoing US for HCC surveillance were enrolled from October 2014 to August 2016. Immediately after completion of B-mode US but before performance of perfluorobutane-enhanced US, operating radiologists entered the results of B-mode US. After completion of subsequent perfluorobutane-enhanced US (Kupffer phase with or without vascular-phase US), the radiologists recorded the results. The presence of HCC was confirmed either with pathologic analysis or radiologically by using dynamic contrast material-enhanced CT or gadoxetic acid-enhanced MRI. The primary end points were the detection rate of early-stage HCC (Barcelona Clinic Liver Cancer staging system stage 0 or A) and false referral rate. The primary end points were compared in a per-participant manner by using the McNemar test. Results A total of 524 participants (mean age, 54 years ± 9 [standard deviation]) were included. Of these, 493 (94.1%) had liver cirrhosis related to the hepatitis B virus. Ten HCCs were confirmed in eight participants. The detection rate of early-stage HCC was not significantly improved by adding perfluorobutane-enhanced US to conventional B-mode US (difference, 0.4% [95% confidence interval: -0.3%, 1.1%]; P = .16). The false referral rate was significantly reduced (difference, -3.2% [95% confidence interval: -5.0%, -1.4%]; P < .001). Conclusion The addition of perfluorobutane-enhanced US to conventional B-mode US reduced the false referral rate without a significant improvement in the detection rate of early-stage hepatocellular carcinoma for surveillance in a population in which the hepatitis B virus predominated. © RSNA, 2019 Online supplemental material is available for this article.

CT in Differentiating Complicated From Uncomplicated Appendicitis: Presence of Any of 10 CT Features Versus Radiologists' Gestalt Assessment.

OBJECTIVE. The purpose of this study is to propose a sensitive CT criterion (the presence of any of 10 CT features) for complicated appendicitis that could be used in the nonoperative management of appendicitis and to compare the diagnostic performance of this sensitive CT criterion with that of gestalt assessment. MATERIALS AND METHODS. This retrospective study, which was conducted in a tertiary teaching hospital, included 100 patients with suspected appendicitis on CT. Complicated appendicitis, defined as gangrenous or perforated appendicitis, was pathologically or surgically confirmed in 32 patients. Six radiologists independently determined the presence of 10 previously reported CT features of complicated appendicitis (contrast enhancement defect of the appendiceal wall, abscess, extraluminal air, intraluminal air, extraluminal appendicolith, intraluminal appendicolith, moderate-to-severe periappendiceal fat stranding, periappendiceal fluid, ileus, and ascites) and rated the likelihood score for complicated appendicitis using gestalt assessment. The sensitivity and specificity of CT for complicated appendicitis were measured by the presence of any of 10 CT features (the any-of-10-features criterion) and by the radiologists' gestalt assessment. Pooled sensitivity and specificity were compared using a generalized linear mixed model. RESULTS. The pooled sensitivity of the presence of any of 10 CT features was higher than that of gestalt assessment (92% vs 64%; difference, 28% [95% CI, 10-46%]; p < 0.001), although the pooled specificity was lower (43% vs 76%; difference, -33% [95% CI, -48% to -17%]; p < 0.001). CONCLUSION. The pooled sensitivity of the presence of any of 10 CT features was higher than that of gestalt assessment, at the cost of lower specificity. For prudent selection of patients who should receive nonoperative treatment of appendicitis, the any-of-10-features criterion may be used to decrease treatment failure associated with a false-negative diagnosis of complication.

Systematic Review and Meta-Analysis of CT Features for Differentiating Complicated and Uncomplicated Appendicitis.

Purpose To perform a systematic review and meta-analysis to identify computed tomographic (CT) features for differentiating complicated appendicitis in patients suspected of having appendicitis and to summarize their diagnostic accuracy. Materials and Methods Studies on diagnostic accuracy of CT features for differentiating complicated appendicitis (perforated or gangrenous appendicitis) in patients suspected of having appendicitis were searched in Ovid-MEDLINE, EMBASE, and the Cochrane Library. Overlapping descriptors used in different studies to denote the same image finding were subsumed under a single CT feature. Pooled diagnostic accuracy of the CT features was calculated by using a bivariate random effects model. CT features with pooled diagnostic odds ratios with 95% confidence intervals not including 1 were considered as informative. Results Twenty-three studies were included, and 184 overlapping descriptors for various CT findings were subsumed under 14 features. Of these, 10 features were informative for complicated appendicitis. There was a general tendency for these features to show relatively high specificity but low sensitivity. Extraluminal appendicolith, abscess, appendiceal wall enhancement defect, extraluminal air, ileus, periappendiceal fluid collection, ascites, intraluminal air, and intraluminal appendicolith showed pooled specificity greater than 70% (range, 74%-100%), but sensitivity was limited (range, 14%-59%). Periappendiceal fat stranding was the only feature that showed high sensitivity (94%; 95% confidence interval: 86%, 98%) but low specificity (40%; 95% confidence interval, 23%, 60%). Conclusion Ten informative CT features for differentiating complicated appendicitis were identified in this study, nine of which showed high specificity, but low sensitivity. © RSNA, 2017 Online supplemental material is available for this article.

Can We Perform CT of the Appendix with Less Than 1 mSv? A De-escalating Dose-simulation Study.

OBJECTIVES: To systematically explore the lowest reasonably achievable radiation dose for appendiceal CT using an iterative reconstruction (IR) in young adults. METHODS: We prospectively included 30 patients who underwent 2.0-mSv CT for suspected appendicitis. From the helical projection data, 1.5-, 1.0- and 0.5-mSv CTs were generated using a low-dose simulation tool and the knowledge-based IR. We performed step-wise non-inferiority tests sequentially comparing 2.0-mSv CT with each of 1.5-, 1.0- and 0.5-mSv CT, with a predetermined non-inferiority margin of 0.06. The primary end point was the pooled area under the receiver-operating-characteristic curve (AUC) for three abdominal and three non-abdominal radiologists. RESULTS: For the abdominal radiologists, the non-inferiorities of 1.5-, 1.0- and 0.5-mSv CT to 2.0-mSv CT were sequentially accepted [pooled AUC difference: 2.0 vs. 0.5 mSv, 0.017 (95% CI: -0.016, 0.050)]. For the non-abdominal radiologists, the non-inferiorities of 1.5- and 1.0-mSv CT were accepted; however, the non-inferiority of 0.5-mSv CT could not be proved [pooled AUC difference: 2.0 vs. 1.0 mSv, -0.017 (-0.070, 0.035) and 2.0 vs. 0.5 mSv, 0.045 (-0.071, 0.161)]. CONCLUSION: The 1.0-mSv appendiceal CT was non-inferior to 2.0-mSv CT in terms of diagnostic performance for both abdominal and non-abdominal radiologists; 0.5-mSv appendiceal CT was non-inferior only for abdominal radiologists. KEY POINTS: • For both abdominal and non-abdominal radiologists, 1.0-mSv appendiceal CT could be feasible. • The 0.5-mSv CT was non-inferior to 2.0-mSv CT only for expert abdominal radiologists. • Reader experience is an important factor affecting diagnostic impairment by low-dose CT.

Low-dose (2-mSv) computed tomography for suspected appendicitis: Applicability in an emergency department.

OBJECTIVES: To document the level of interobserver agreement and compare the diagnostic performances of emergency physicians and radiologists at interpreting low radiation CT images of acute appendicitis in adolescents and young adults. METHODS: One hundred and seven adolescents and young adult patients (aged 15 to 44years) that underwent 2-mSv low-dose CT for suspected acute appendicitis between June and December in 2013 were enrolled in this retrospective study. Three emergency physicians and three radiologists with different experiences of low-dose CT independently reviewed CT images. These six physicians rated the likelihood of acute appendicitis using a 5-point Likert scale. We calculated interobserver agreement and compared the diagnostic performances between emergency physicians and radiologists. And diagnostic confidence was also assessed using the likelihood of acute appendicitis. RESULTS: Acute appendicitis was pathologically confirmed in 42 patients (39%); the remaining 65 patients were considered not to have appendicitis. Fleiss' Kappa for reliability of agreement between emergency physicians and radiologists for the diagnosis of acute appendicitis was 0.720 (95% confidence intervals (CI), 0.685-0.726). Pooled areas under the receiver operating characteristics curve (AUC) for a diagnosis of appendicitis were 0.904 and 0.944 for emergency physicians and radiologists, respectively, and these AUC values were not significantly different (95% confidence interval, -0.087, 0.007; p=0.0855). CONCLUSION: The emergency physicians and radiologists showed good interobserver agreement and comparable diagnostic performances for appendicitis in adolescents and adults using low-dose CT images. Low-dose CT could be a useful tool for the diagnosis of appendicitis by emergency physicians.

Genetic diversity and divergence among Korean cattle breeds assessed using a BovineHD single-nucleotide polymorphism chip.

OBJECTIVE: In Korea, there are three main cattle breeds, which are distinguished by coat color: Brown Hanwoo (BH), Brindle Hanwoo (BRH), and Jeju Black (JB). In this study, we sought to compare the genetic diversity and divergence among there Korean cattle breeds using a BovineHD chip genotyping array. METHODS: Sample data were collected from 168 cattle in three populations of BH (48 cattle), BRH (96 cattle), and JB (24 cattle). The single-nucleotide polymorphism (SNP) genotyping was performed using the Illumina BovineHD SNP 777K Bead chip. RESULTS: Heterozygosity, used as a measure of within-breed genetic diversity, was higher in BH (0.293) and BRH (0.296) than in JB (0.266). Linkage disequilibrium decay was more rapid in BH and BRH than in JB, reaching an average r² value of 0.2 before 26 kb in BH and BRH, whereas the corresponding value was reached before 32 kb in JB. Intra-population, inter-population, and Fst analyses were used to identify candidate signatures of positive selection in the genome of a domestic Korean cattle population and 48, 11, and 11 loci were detected in the genomic region of the BRH breed, respectively. A Neighbor-Joining phylogenetic tree showed two main groups: a group comprising BH and BRH on one side and a group containing JB on the other. The runs of homozygosity analysis between Korean breeds indicated that the BRH and JB breeds have high inbreeding within breeds compared with BH. An analysis of differentiation based on a high-density SNP chip showed differences between Korean cattle breeds and the closeness of breeds corresponding to the geographic regions where they are evolving. CONCLUSION: Our results indicate that although the Korean cattle breeds have common features, they also show reliable breed diversity.

Genome-wide QTL analysis of meat quality-related traits in a large F2 intercross between Landrace and Korean native pigs.

BACKGROUND: We conducted a genome-wide linkage analysis to identify quantitative trait loci (QTL) that influence meat quality-related traits in a large F2 intercross between Landrace and Korean native pigs. Thirteen meat quality-related traits of the m. longissimus lumborum et thoracis were measured in more than 830 F2 progeny. All these animals were genotyped with 173 microsatellite markers located throughout the pig genome, and the GridQTL program based on the least squares regression model was used to perform the QTL analysis. RESULTS: We identified 23 genome-wide significant QTL in eight chromosome regions (SSC1, 2, 6, 7, 9, 12, 13, and 16) (SSC for Sus Scrofa) and detected 51 suggestive QTL in the 17 chromosome regions. QTL that affect 10 meat quality traits were detected on SSC12 and were highly significant at the genome-wide level. In particular, the QTL with the largest effect affected crude fat percentage and explained 22.5% of the phenotypic variance (F-ratio = 278.0 under the additive model, nominal P = 5.5 × 10(-55)). Interestingly, the QTL on SSC12 that influenced meat quality traits showed an obvious trend for co-localization. CONCLUSIONS: Our results confirm several previously reported QTL. In addition, we identified novel QTL for meat quality traits, which together with the associated positional candidate genes improve the knowledge on the genetic structure that underlies genetic variation for meat quality traits in pigs.

Effects of regular exercise on obesity and type 2 diabete mellitus in Korean children: improvements glycemic control and serum adipokines level.

[Purpose] The aim of the study was to clarify the effects of regular exercise on lipid profiles and serum adipokines in Korean children. [Subjects and Methods] Subjects were divided into controls (n=10), children who were obese (n=10), and children with type 2 diabetes mellitus (n=10). Maximal oxygen uptake (VO2max), body composition, lipid profiles, glucagon, insulin and adipokines (leptin, resistin, visfatin and retinol binding protein 4) were measured before to and after a 12-week exercise program. [Results] Body weight, body mass index, and percentage body fat were significantly higher in the obese and diabetes groups compared with the control group. Total cholesterol, triglycerides, low-density lipoprotein cholesterol and glycemic control levels were significantly decreased after the exercise program in the obese and diabetes groups, while high-density lipoprotein cholesterol levels were significantly increased. Adipokines were higher in the obese and diabetes groups compared with the control group prior to the exercise program, and were significantly lower following completion. [Conclusion] These results suggest that regular exercise has positive effects on obesity and type 2 diabetes mellitus in Korean children by improving glycemic control and reducing body weight, thereby lowering cardiovascular risk factors and adipokine levels.

Effect of the low- versus high-intensity exercise training on endoplasmic reticulum stress and GLP-1 in adolescents with type 2 diabetes mellitus.

[Purpose] The primary objective of this study was to investigate the effect of low-intensity exercise training compare with high-intensity exercise training on endoplasmic reticulum stress and glucagon-like peptide-1 in adolescents with type 2 diabetes mellitus. [Subjects and Methods] The low-intensity exercise training group performed aerobic exercise training at an intensity of ≤ 45% of the heart rate reserve. The high-intensity interval exercise training group performed interval exercise training at an intensity of ≥ 80% of the heart rate reserve. The exercise-related energy consumption was determined for both groups on a per-week basis (1,200 kcal/week). [Results] Both groups showed improvement in the glucose-regulated protein 78 and dipeptidyl peptidase-4, but the size of the between-group effect was not statistically significant. The high-intensity interval exercise training group showed a significant reduction in percentage body fat. The C-peptide level increased after the 12-weeks programs and was significantly different, between the groups. Fasting glucose, insulin resistance in the fasting state according to homeostasis model assessment, and leptin decreased after the 12-weeks exercise program and were significantly different between the groups, and glucagon-like peptide-1 increased after the 12-week exercise programs and was significantly different between the groups. [Conclusion] In conclusion high-intensity interval exercise training, as defined in this study, may lead to improvements in body composition, glycemic control, endoplasmic reticulum stress, and the glucagon-like peptide-1 in adolescents with type 2 diabetes mellitus.

Cyr61 expression is associated with prognosis in patients with colorectal cancer.

BACKGROUND: Cysteine-rich 61 (Cyr61), a member of the CCN protein family, possesses diverse functionality in cellular processes such as adhesion, migration, proliferation, and survival. Cyr61 can also function as an oncogene or a tumour suppressor, depending on the origin of the cancer. Only a few studies have reported Cyr61 expression in colorectal cancer. In this study, we assessed the Cyr61 expression in 251 colorectal cancers with clinical follow up. METHODS: We examined Cyr61 expression in 6 colorectal cancer cell lines (HT29, Colo205, Lovo, HCT116, SW480, SW620) and 20 sets of paired normal and colorectal cancer tissues by western blot. To validate the association of Cyr61 expression with clinicopathological parameters, we assessed Cyr61 expression using tissue microarray analysis of primary colorectal cancer by immunohistochemical analysis. RESULTS: We verified that all of the cancer cell lines expressed Cyr61; 2 cell lines (HT29 and Colo205) demonstrated Cyr61 expression to a slight extent, while 4 cell lines (Lovo, HCT116, SW480, SW620) demonstrated greater Cyr61 expression than HT29 and Colo205 cell lines. Among the 20 cases of paired normal and tumour tissues, greater Cyr61 expression was observed in 16 (80%) tumour tissues than in normal tissues. Furthermore, 157 out of 251 cases (62.5%) of colorectal cancer examined in this study displayed strong Cyr61 expression. Cyr61 expression was found to be associated with pN (p = 0.018). Moreover, Cyr61 expression was associated with statistically significant cancer-specific mortality (p = 0.029). The duration of survival was significantly lesser in patients with Cyr61 high expression than in patients with Cyr61 low expression (p = 0.001). These results suggest that Cyr61 expression plays several important roles in carcinogenesis and may also be a good prognostic marker for colorectal cancer. CONCLUSIONS: Our data confirmed that Cyr61 was expressed in colorectal cancers and the expression was correlated with worse prognosis of colorectal cancers.

Cilostazol decreases cerebral arterial pulsatility in patients with mild white matter hyperintensities: subgroup analysis from the Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of Transcranial Doppler (ECLIPse) study.

BACKGROUND: The Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of the Transcranial Doppler (ECLIPse) study showed a significant decrease in the transcranial Doppler (TCD) pulsatility index (PI) with cilostazol treatment at 90 days after acute lacunar infarction. The aim of the present study was to perform a subgroup analysis of the ECLIPse study in order to explore the effect of cilostazol in acute lacunar infarction based on cerebral white matter hyperintensities (WMH) volume. METHODS: The ECLIPse study was a multicenter, randomized, double-blind, placebo-controlled trial that evaluated the difference between the efficacy of cilostazol and a placebo to reduce the PI in patients with acute lacunar infarction using serial TCD examinations. The primary outcome was changes in the PIs of the middle cerebral artery (MCA) and basilar artery at 14 and 90 days from the baseline TCD study. For this subgroup analysis, using semi-automated computerized software, the WMH volume was measured for those subjects for whom fluid-attenuated inversion recovery (FLAIR) images were available. RESULTS: Of the 203 patients in eight hospitals in the ECLIPse study, 130 participants from six hospitals were included in this subgroup analysis. Cilostazol was given to 63 patients (48.5%) and placebo to 67 patients (51.5%). All baseline characteristics were well balanced across the two groups, and there were no significant differences in these characteristics except in the changes of PI from the baseline to the 90-day point. There was a significant decrease of TCD PIs at 90-day study from baseline in the cilostazol group (p = 0.02). The mean WMH volume was 11.57 cm(3) (0.13-68.45, median 4.86) and the mean MCA PI was 0.95 (0.62-1.50). The changes in PIs from the baseline to 14 days and to 90 days were 0.09 (-0.21 to 0.33) and 0.10 (-0.22 to 0.36). While there were no significant correlations between WMH volume and the changes in PIs, a trend of inverse correlation was observed between the WMH volume and the changes in PIs from the baseline to the 90-day point. For the subgroup analysis, the WMH volume was dichotomized based on its median value (4.90 cm(3)). Cilostazol decreased the TCD PIs significantly at the 90-day point in patients with WMH volumes ≤ 4.9 cm(3) (p = 0.002). Significant treatment effects were observed in the cilostazol group. CONCLUSIONS: This study showed that cilostazol decreased cerebral arterial pulsatility in patients with WMH. Our findings indicate the unique effect of cilostazol in small vessel disease (SVD), especially in patients with mild WMH changes. Further clinical trials focusing on WMH volume and clinical outcomes are required to assess the unique efficacy of cilostazol in SVD.

The Effects of 12 Weeks Regular Aerobic Exercise on Brain-derived Neurotrophic Factor and Inflammatory Factors in Juvenile Obesity and Type 2 Diabetes Mellitus.

[Purpose] The purpose of this study was to investigate the effects of 12 weeks regular aerobic exercise on brain-derived neurotrophic factor (BDNF) and inflammatory factors in juvenile obesity and type 2 diabetes mellitus (T2DM). Obesity and T2DM, typically common among adults, have recently become more prevalent in the Korean juvenile population, affecting not only their lipid profiles and oxidant stress levels, but also their BDNF and inflammatory factor levels. [Subjects] This study enrolled 26 juveniles (boys = 15, girls = 9) who were assigned to a control group (CG, n = 11), obesity group (OG, n = 8), or T2DM group (TG, n = 7). [Methods] The outcome of a 40-60-minute aerobic exercise session that took place three times per week for 12 weeks at a maximum oxygen intake (VO2max) of 50~60% was investigated. [Results] The exercise resulted in a significant reduction in the resting serum BDNF and TrkB levels (baseline) among juveniles in the OG and TG as compared to those in the CG. Additionally, the 12 weeks of regular aerobic exercise led to significant reductions in body weight, body fat percentage, and body mass index in the OG and a significant increase of VO2max in the OG and TG. However, no significant differences in serum NGF or inflammatory factors were found among the three groups. There was a significant increase in resting serum BDNF levels following the 12 weeks regular exercise only in the OG. [Conclusion] While 12 weeks of regular aerobic exercise had a positive effect on body composition, and increased BDNF levels of juveniles in the OG, it did not affect the inflammatory factor levels and had no effect on the TG.

Development of a Risk Score to Predict Short-term Smoking Relapse Following an Inpatient Smoking Cessation Intervention.

This study aimed to investigate the factors affecting smoking relapse and to develop predictive models among Korean national 5-day smoking cessation program participants. The subjects were 518 smokers and follow-up was continued for 6 months after discharge. A predictive logistic model and risk score were developed from the multivariate logistic models and compared using the area under the receiver operating characteristic curve (area under the curve [AUC]). The smoking relapse rate within 6 months after program participation was 38.4%. The AUCs of the logistic regression model and risk score model were similar (odds ratio [OR] = 0.69; 0.69, respectively) in the development data set, and those of the risk score model were similar between the development and validation data sets (OR = 0.68). The risk score used by the six risk factors could predict smoking relapse among participants who attended a 5-day inpatient smoking cessation program.

Factors related to the initial stroke severity of posterior circulation ischemic stroke.

BACKGROUND: Posterior circulation (PC) stroke, which was previously less well known than anterior circulation (AC) stroke, has become more identified due to the development of imaging equipment. Recently, the initial stroke severity assessed by the NIH Stroke Scale (NIHSS) was reported as a useful measure for predicting the outcome of PC as well as AC stroke. The aim of our study was to investigate the factors related to the stroke severity of PC ischemic stroke as assessed by the baseline NIHSS and the predictors of progressive neurological deficit and 3-month outcome. METHODS: All patients with first-time PC stroke (onset ≤ 7 days), admitted for a 5-year period and given a complete evaluation including brain MRI and angiographic studies, were enrolled. Patients were divided into two groups by the baseline NIHSS: moderate-to-severe stroke (MTSS, NIHSS > 5) and mild stroke (MS, NIHSS ≤ 5). Baseline characteristics, symptoms and progression, etiological subtypes, lesion characteristics from imaging, and patient 3-month outcome assessed by the modified Rankin Scale (mRS) were compared between the two groups. RESULTS: Among 604 enrolled patients with PC ischemic stroke, 143 belonged to the MTSS group and 461 to the MS group. In logistic regression analysis, MTSS was independently associated with white blood cell count (odds ratio, OR = 1.00, p = 0.001), high sensitivity C-reactive protein level (OR = 1.23, p = 0.004), dysarthria (OR = 2.59, p = 0.013), weakness (OR = 6.43, p < 0.001), dysphagia (OR = 5.77, p < 0.001) and decreased consciousness (OR = 10.54, p < 0.001). The independent predictors associated with progressive neurological deficit were MTSS (OR = 3.82, p = 0.001), the distal territory classified by lesion location (OR = 0.09, p = 0.004) and dysphagia (OR = 2.38, p = 0.010). The independent predictors associated with a 3-month mRS of 3-6 were MTSS (OR = 7.69, p < 0.001), diplopia (OR = 0.26, p = 0.023), visual field defect (OR = 4.87, p = 0.014), dysphagia (OR = 3.15, p < 0.001) and progressive neurological deficit (OR = 4.27, p < 0.001). CONCLUSIONS: The initial severity categorization of PC ischemic stroke by the NIHSS has provided several distinctions and could help with the prediction of neurological deficit progression and 3-month clinical outcome.

No long-term feeding toxicities on the health status in rats fed with cloned Korean native beef cattle (Hanwoo) meat.

This study was designed to undertake a risk assessment to identify the health status of rats fed with somatic cell nuclear transfer (SCNT)-cloned Korean native beef cattle (Hanwoo) meat for 26 weeks. The rats were randomly divided into 5 groups, each consisting of 12 male (142.6 ± 5.23 g) and 12 female (113.7 ± 6.31 g) rats each. The animals were fed commercial pellets (control), pellets containing 5% (N-5) and 10% (N-10) of normal cattle meat, and diets containing 5% (C-5) and 10% (C-10) of cloned cattle meat. The mortality; clinical signs; body weight; food consumption; urinary, hematology, blood biochemistry, and histopathological analyses; and absolute and relative organ weights were analyzed and compared. During the 26-week test period, health status-related factors of the rats fed on cloned Hanwoo meat were found to have no test substance-related toxicities. The only difference was the increased uterus weight in female C-10 rats as compared to their counterparts counterparts (p < .05). On the basis of these health status results, it can be postulated that no food consumption risks might arise from the long-term feeding of cloned cattle meat in rats.