Nicotine aggravates liver fibrosis via α7 nicotinic acetylcholine receptor expressed on activated hepatic stellate cells in mice.

BACKGROUND: Smoking is a risk factor for liver cirrhosis; however, the underlying mechanisms remain largely unexplored. The α7 nicotinic acetylcholine receptor (α7nAChR) has recently been detected in nonimmune cells possessing immunoregulatory functions. We aimed to verify whether nicotine promotes liver fibrosis via α7nAChR. METHODS: We used osmotic pumps to administer nicotine and carbon tetrachloride to induce liver fibrosis in wild-type and α7nAChR-deficient mice. The severity of fibrosis was evaluated using Masson trichrome staining, hydroxyproline assays, and real-time PCR for profibrotic genes. Furthermore, we evaluated the cell proliferative capacity and COL1A1 mRNA expression in human HSCs line LX-2 and primary rat HSCs treated with nicotine and an α7nAChR antagonist, methyllycaconitine citrate. RESULTS: Nicotine exacerbated carbon tetrachloride-induced liver fibrosis in mice (+42.4% in hydroxyproline assay). This effect of nicotine was abolished in α7nAChR-deficient mice, indicating nicotine promotes liver fibrosis via α7nAChR. To confirm the direct involvement of α7nAChRs in liver fibrosis, we investigated the effects of genetic suppression of α7nAChR expression on carbon tetrachloride-induced liver fibrosis without nicotine treatment. Profibrotic gene expression at 1.5 weeks was significantly suppressed in α7nAChR-deficient mice (-83.8% in Acta2, -80.6% in Col1a1, -66.8% in Tgfb1), and collagen content was decreased at 4 weeks (-22.3% in hydroxyproline assay). The in vitro analysis showed α7nAChR expression in activated but not in quiescent HSCs. Treatment of LX-2 cells with nicotine increased COL1A1 expression (+116%) and cell proliferation (+10.9%). These effects were attenuated by methyllycaconitine citrate, indicating the profibrotic effects of nicotine via α7nAChR. CONCLUSIONS: Nicotine aggravates liver fibrosis induced by other factors by activating α7nAChR on HSCs, thereby increasing their collagen-producing capacity. We suggest the profibrotic effect of nicotine is mediated through α7nAChRs.

Rim Enhancement on Contrast-Enhanced CT as a Predictor of Prognosis in Patients with Pancreatic Ductal Adenocarcinoma.

This study investigated the utility of imaging features, such as rim enhancement on contrast-enhanced CT (CECT), in predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). This retrospective study included 158 patients (84 men; mean age, 68 years) with pathologically confirmed PDAC. The following imaging features were evaluated on CECT by two radiologists: tumor size, tumor attenuation, and the presence of rim enhancement. Cox proportional hazards analysis was performed to identify the imaging and clinicopathological features for predicting disease-free survival (DFS) and overall survival (OS). Pathological features were compared with the presence of rim enhancement. Among the 158 patients, 106 (67%) underwent curative surgery (surgery group) and 52 (33%) received conservative treatment (non-surgery group). Rim enhancement was observed more frequently in the non-surgery group than in the surgery group (44% vs. 20%; p < 0.001). Rim enhancement showed significant associations with shorter DFS and OS in the surgery group (hazard ratios (HRs), 3.03 and 2.99; p < 0.001 and p = 0.003, respectively), whereas tumor size showed significant associations with shorter OS (HR per 1 mm increase, 1.08; p < 0.001). PDACs with rim enhancement showed significant associations with higher histological tumor grades (p < 0.001). PDAC with rim enhancement on CECT could predict poorer prognosis and more aggressive tumor grades.

Evaluation and Prediction of Post-Hepatectomy Liver Failure Using Imaging Techniques: Value of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging.

Despite improvements in operative techniques and perioperative care, post-hepatectomy liver failure (PHLF) remains the most serious cause of morbidity and mortality after surgery, and several risk factors have been identified to predict PHLF. Although volumetric assessment using imaging contributes to surgical simulation by estimating the function of future liver remnants in predicting PHLF, liver function is assumed to be homogeneous throughout the liver. The combination of volumetric and functional analyses may be more useful for an accurate evaluation of liver function and prediction of PHLF than only volumetric analysis. Gadoxetic acid is a hepatocyte-specific magnetic resonance (MR) contrast agent that is taken up by hepatocytes via the OATP1 transporter after intravenous administration. Gadoxetic acid-enhanced MR imaging (MRI) offers information regarding both global and regional functions, leading to a more precise evaluation even in cases with heterogeneous liver function. Various indices, including signal intensity-based methods and MR relaxometry, have been proposed for the estimation of liver function and prediction of PHLF using gadoxetic acid-enhanced MRI. Recent developments in MR techniques, including high-resolution hepatobiliary phase images using deep learning image reconstruction and whole-liver T1 map acquisition, have enabled a more detailed and accurate estimation of liver function in gadoxetic acid-enhanced MRI.

Chemosensory input from mouthparts in response to sexually dimorphic cuticular wax mediates male sexual discrimination in Galerucella grisescens (Coleoptera: Chrysomelidae).

The surface of the insect body is covered with a hydrophobic layer called cuticular wax (CW). In addition to functioning as an anti-desiccation agent, CW is critical for chemical communication. It has been reported that in Chrysomelidae, males discriminate between sexes based on the sex-specific CW. However, little is known regarding the underlying sensory basis. Herein, we demonstrate that chemosensory input from mouthparts mediates sexual discrimination in male Galerucella grisescens (Chrysomelidae). Observations of mating behaviour, bioassays for CW, and chemical analyses revealed that G. grisescens possess qualitatively sexually dimorphic CW, and such compositional differences allow males to distinguish between sexes. Using electron microscopy, blocking male chemosensory organs, and electrophysiological experiments, we showed that male mouthparts bear chemosensory sensilla tuned to female CW components, and sensory input from them induces male aedeagal insertion, a common male behavioural response to females. Thus, detecting CW via mouthparts is essential for males to distinguish between sexes, consistent with the fact that males inspect conspecific individuals by licking their body surfaces. To our best knowledge, this is the first report describing the detailed functional roles of mouthparts in sexual discrimination in Coleoptera. We believe that this study will promote further studies on insect chemical communication.

Global analyses and potential effects of extracellular vesicles on the establishment of conceptus implantation during the peri-implantation period.

Intrauterine extracellular vesicles (EVs) are involved in establishing proper conceptus-endometrial communication, which is essential for conceptus implantation and subsequent successful placentation. Despite several studies on intrauterine EVs, the composition and quantitative changes in conceptus and endometrial EVs, as well as the effects of intrauterine EVs on endometrial epithelial cells (EECs) during the peri-implantation period, have not been well characterized. To elucidate global changes in proteins in EVs extracted from uterine flushings (UFs) during the pre-implantation (P17), just-implantation (P20), and post-implantation (P22) periods, the datasets of the proteome iTRAQ analysis were compared among P17, P20, and P22 EVs. These analyses revealed that the composition and function of proteins in the EVs changed dramatically during peri-implantation in cattle. Notably, intrauterine P17 EVs affected the high expression of "Developmental Biology" and "morphogenesis of an endothelium" compared with those in P20 and P22 EVs. Furthermore, P20 EVs had the functions of the high expression of "mitochondrial calcium ion homeostasis" and "Viral mRNA Translation" compared with those in P17 EVs. Transcripts extracted from EECs treated with P17, P20, or P22 EVs were subjected to RNA-seq analysis. These analyses identified 60 transcripts in EECs commonly induced by intrauterine EVs recovered from P17, P20, and P22, a large number of which were associated with "type I interferon signaling pathway". Collectively, these findings reveal the presence and multiple functions of EVs that are potentially implicated in facilitating conceptus implantation into the uterine epithelium during the peri-implantation period.

Transcriptome analysis of mesenchymal stromal cells of the large and small intestinal smooth muscle layers reveals a unique gastrontestinal stromal signature.

Mesenchymal stromal cells in the muscle layer of the large intestine are essential for the regulation of intestinal motility. They form electrogenic syncytia with the smooth muscle and interstitial cells of Cajal (ICCs) to regulate smooth muscle contraction. Mesenchymal stromal cells are present in the muscle layer throughout the gastrointestinal tract. However, their area-specific characteristics remain ambiguous. In this study, we compared mesenchymal stromal cells from the large and small intestinal muscle layers. Histological analysis using immunostaining showed that the cells in the large and small intestines were morphologically distinct. We established a method to isolate mesenchymal stromal cells from wild-type mice with platelet-derived growth factor receptor-alpha (PDGFRα) as a marker on the cell surface and performed RNAseq. Transcriptome analysis revealed that PDGFRα+ cells in the large intestine exhibited increased expression levels of collagen-related genes, whereas PDGFRα+ cells in the small intestine exhibited increased expression levels of channel/transporter genes, including Kcn genes. These results suggest that mesenchymal stromal cells differ morphologically and functionally depending on gastrointestinal tract. Further investigations of the cellular properties of mesenchymal stromal cells in the gastrointestinal tract will aid in optimizing methods for the prevention and treatment of gastrointestinal diseases.

Toceranib phosphate (Palladia) reverses type 1 diabetes by preserving islet function in mice.

In recent years, strategies targeting ß-cell protection via autoimmune regulation have been suggested as novel and potent immunotherapeutic interventions against type 1 diabetes mellitus (T1D). Here, we investigated the potential of toceranib (TOC), a receptor-type tyrosine kinase (RTK) inhibitor used in veterinary practice, to ameliorate T1D. TOC reversed streptozotocin-induced T1D and improved the abnormalities in muscle and bone metabolism characteristic of T1D. Histopathological examination revealed that TOC significantly suppressed ß-cell depletion and improved glycemic control with restoration of serum insulin levels. However, the effect of TOC on blood glucose levels and insulin secretion capacity is attenuated in chronic T1D, a more ß-cell depleted state. These findings suggest that TOC improves glycemic control by ameliorating the streptozotocin-induced decrease in insulin secretory capacity. Finally, we examined the role of platelet-derived growth factor receptor (PDGFR) inhibition, a target of TOC, and found that inhibition of PDGFR reverses established T1D in mice. Our results show that TOC reverses T1D by preserving islet function via inhibition of RTK. The previously unrecognized pharmacological properties of TOC have been revealed, and these properties could lead to its application in the treatment of T1D in the veterinary field.

Interstitial cells of Cajal in gastrointestinal inflammatory diseases.

The gastrointestinal (GI) tract is a vital organ that digests food, absorbs nutrients, and excretes waste. Normal GI motility is the basis for these functions. The interstitial cells of Cajal (ICC) in the GI muscularis layer promote GI motility together with the enteric nervous system and smooth muscle cells. Since GI motility results from complex coordination of these heterogeneous cells, failure of any one of them can lead to GI dysmotility. Knowledge about ICC in physiological conditions has accumulated in recent decades, while the pathophysiology of ICC in GI inflammatory diseases, such as inflammatory bowel disease, is not well understood. In this review, we summarize the previous studies about the pathophysiological changes of ICC in inflammatory diseases and discuss the inflammatory mediators that induce ICC dysfunction.

Evaluation and Prediction of Treatment Response for Hepatocellular Carcinoma.

The incidence of hepatocellular carcinoma (HCC) is still on the rise in North America and Europe and is the second leading cause of cancer-related mortality. The treatment of HCC varies, with surgery and locoregional therapy (LRT) such as radiofrequency ablation and transcatheter arterial chemoembolization, and radiation therapy being the primary treatment. Currently, systemic therapy with molecular-targeted agents and immune checkpoint inhibitors (ICIs) is becoming a major treatment option for the unresectable HCC. As the HCC after LRT or systemic therapy often remains unchanged in size and shows loss of contrast effect in contrast-enhanced CT or MRI, the response evaluation criteria in solid tumors (RECIST) and World Health Organization criteria, which are usually used to evaluate the treatment response of solid tumors, are not appropriate for HCC. The modified RECIST (mRECIST) and the European Association for the Study of the Liver (EASL) criteria were developed for HCC, with a focus on viable lesions. The latest 2018 edition of the Liver Imaging Reporting and Data System (LI-RADS) also includes a section on the evaluation of treatment response. The cancer microenvironment influences the therapeutic efficacy of ICIs. Several studies have examined the utility of gadoxetic acid-enhanced MRI for predicting the pathological and molecular genetic patterns of HCC. In the future, it may be possible to stratify prognosis and predict treatment response prior to systemic therapy by using pre-treatment imaging findings.

Added value of contrast enhancement boost images in routine multiphasic contrast-enhanced CT for the diagnosis of small (<20 mm) hypervascular hepatocellular carcinoma.

PURPOSE: To investigate the added value of contrast enhancement boost (CE-boost) images in multiphasic contrast-enhanced CT (CE-CT) for diagnosing small (<20 mm) hypervascular hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 69 patients (age, 74 ± 8 years; 52 men) with 70 hypervascular HCCs (<20 mm) who underwent multiphasic CE-CT (pre-contrast, late arterial phase [LAP], portal venous phase [PVP], and equilibrium phase). Two types of CE-boost images were generated by subtracting PVP from LAP (LA-PV) images and LAP from PVP (PV-LA) images to enhance the contrast effect of hepatic arterial and portal venous perfusion more selectively. Tumor-to-liver contrast-to-noise ratios (CNRs) in CE-boost images were compared with those in CE-CT images using the Wilcoxon signed-rank test. Two independent readers reviewed the imaging datasets: CE-CT alone and CE-CT with CE-boost images. The diagnostic performance of each dataset was compared using jackknife alternative free-response receiver operating characteristics (JAFROC-1). RESULTS: The tumor-to-liver CNRs in the LA-PV (6.4 ± 3.0) and PV-LA (-3.3 ± 2.1) images were greater than those in the LAP (3.2 ± 1.7) and PVP images (-1.1 ± 1.4) (p <.001 for both). The reader-averaged figures of merit were 0.751 for CE-CT alone and 0.807 for CE-CT with CE-boost images (p <.001). Sensitivities increased by adding CE-boost images for both readers (p <.001 and = 0.03), while positive predictive values were equivalent (p >.99). CONCLUSION: Adding CE-boost images to multiphasic CE-CT can improve the diagnostic accuracy and sensitivity for small hypervascular HCC by increasing the tumor-to-liver CNR.

Clinical Application of Quantitative MR Imaging in Nonalcoholic Fatty Liver Disease.

Viral hepatitis was previously the most common cause of chronic liver disease. However, in recent years, nonalcoholic fatty liver disease (NAFLD) cases have been increasing, especially in developed countries. NAFLD is histologically characterized by fat, fibrosis, and inflammation in the liver, eventually leading to cirrhosis and hepatocellular carcinoma. Although biopsy is the gold standard for the assessment of the liver parenchyma, quantitative evaluation methods, such as ultrasound, CT, and MRI, have been reported to have good diagnostic performances. The quantification of liver fat, fibrosis, and inflammation is expected to be clinically useful in terms of the prognosis, early intervention, and treatment response for the management of NAFLD. The aim of this review was to discuss the basics and prospects of MRI-based tissue quantifications of the liver, mainly focusing on proton density fat fraction for the quantification of fat deposition, MR elastography for the quantification of fibrosis, and multifrequency MR elastography for the evaluation of inflammation.

Noninvasive monitoring of muscle atrophy and bone metabolic disorders using dual-energy X-ray absorptiometry in diabetic mice.

Tracking metabolic changes in skeletal muscle and bone using animal models of diabetes mellitus (DM) provides important insights for the management of DM complications. In this study, we aimed to establish a method for monitoring changes in body composition characteristics, such as fat mass, skeletal muscle mass (lean mass), bone mineral density, and bone mineral content, during DM progression using a dual-energy X-ray absorptiometry (DXA) system in a mouse model of streptozotocin (STZ)-induced type 1 DM. In the DM model, STZ administration resulted in increased blood glucose levels, increased water and food intake, and decreased body weight. Serum insulin levels were significantly decreased on day 30 of STZ administration. The DXA analysis revealed significant and persistent decreases in fat mass, lower limb skeletal muscle mass, and bone mineral content in DM mice. We measured tibialis anterior (TA) muscle weight and performed a quantitative analysis of tibial microstructure by micro-computed tomography imaging in DM mice. The TA muscle weight of DM mice was significantly lower than that of control mice. In addition, the trabecular bone volume fraction, trabecular thickness, trabecular number, and cortical thickness were significantly decreased in DM mice. Pearson's product-moment correlation coefficient analysis showed a high correlation between the DXA-measured and actual body composition. In conclusion, longitudinal measurement of body composition changes using a DXA system may be useful for monitoring abnormalities in muscle and bone metabolism in animal models of metabolic diseases such as DM mice.

Deep learning image reconstruction to improve accuracy of iodine quantification and image quality in dual-energy CT of the abdomen: a phantom and clinical study.

OBJECTIVES: To investigate the effect of deep learning image reconstruction (DLIR) on the accuracy of iodine quantification and image quality of dual-energy CT (DECT) compared to that of other reconstruction algorithms in a phantom experiment and an abdominal clinical study. METHODS: An elliptical phantom with five different iodine concentrations (1-12 mgI/mL) was imaged five times with fast-kilovoltage-switching DECT for three target volume CT dose indexes. All images were reconstructed using filtered back-projection, iterative reconstruction (two levels), and DLIR algorithms. Measured and nominal iodine concentrations were compared among the algorithms. Contrast-enhanced CT of the abdomen with the same scanner was acquired in clinical patients. In arterial and portal venous phase images, iodine concentration, image noise, and coefficients of variation for four locations were retrospectively compared among the algorithms. One-way repeated-measures analyses of variance were used to evaluate differences in the iodine concentrations, standard deviations, coefficients of variation, and percentages of error among the algorithms. RESULTS: In the phantom study, the measured iodine concentrations were equivalent among the algorithms: within ± 8% of the nominal values, with root-mean-square deviations of 0.08-0.36 mgI/mL, regardless of radiation dose. In the clinical study (50 patients; 35 men; mean age, 68 ± 11 years), iodine concentrations were equivalent among the algorithms for each location (all p > .99). Image noise and coefficients of variation were lower with DLIR than with the other algorithms (all p < .01). CONCLUSIONS: The DLIR algorithm reduced image noise and variability of iodine concentration values compared with other reconstruction algorithms in the fast-kilovoltage-switching dual-energy CT. KEY POINTS: • In the phantom study, standard deviations and coefficients of variation in iodine quantification were lower on images with the deep learning image reconstruction algorithm than on those with other algorithms. • In the clinical study, iodine concentrations of measurement location in the upper abdomen were consistent across four reconstruction algorithms, while image noise and variability of iodine concentrations were lower on images with the deep learning image reconstruction algorithm.

Hangekobokuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus through its anti-inflammatory action.

BACKGROUND/AIMS: Gastroprokinetic agents are used for patients with postoperative ileus (POI), and the Japanese traditional herbal medicine daikenchuto (DKT) is one such agent used in the clinical setting. POI is caused by inflammation. DKT and rikkunshito have anti-inflammatory abilities in addition to their gastroprokinetic effects. The efficacy of Kampo formulations, including hangekobokuto (HKT), in patients with POI has been reported recently. Several authors have described the efficacy of honokiol, the primary component of Magnoliae Cortex, in HKT in mouse models of POI. We therefore analyzed the effect of HKT on POI model mice to determine the similarities in the mechanism of action between HKT and DKT. METHODS: HKT was administered orally to each mouse before and after intestinal manipulation was performed on the distal ileum. The gastrointestinal transit in vivo, leukocyte infiltration, and levels of inflammatory mediators, such as cytokines and chemokines, were analyzed. RESULTS: HKT significantly inhibited the infiltration of neutrophils and macrophages and led to the recovery of delayed intestinal transit. In addition, it significantly decreased inducible nitric oxide synthase (iNOS) as well as honokiol levels, suggesting anti-inflammatory activity. However, it did not inhibit the increase in levels of interleukin (IL)-1beta and IL-6, which are related to iNOS induction. In contrast, HKT increased levels of nerve growth factor (NGF) and suppressed those of nuclear factor-κB (NFκB), which are related to iNOS induction, suggesting the possibility of a neuronal anti-inflammatory mechanism. CONCLUSIONS: HKT exerted a POI-relieving effect similar to DKT in a murine POI model, and findings suggest that it may exert its anti-inflammatory activity through NGF.

Three-dimensional conditional generative adversarial network-based virtual thin-slice technique for the morphological evaluation of the spine.

Virtual thin-slice (VTS) technique is a generative adversarial network-based algorithm that can generate virtual 1-mm-thick CT images from images of 3-10-mm thickness. We evaluated the performance of VTS technique for assessment of the spine. VTS was applied to 4-mm-thick CT images of 73 patients, and the visibility of intervertebral spaces was evaluated on the 4-mm-thick and VTS images. The heights of vertebrae measured on sagittal images reconstructed from the 4-mm-thick images and VTS images were compared with those measured on images reconstructed from 1-mm-thick images. Diagnostic performance for the detection of compression fractures was also compared. The intervertebral spaces were significantly more visible on the VTS images than on the 4-mm-thick images (P < 0.001). The absolute value of the measured difference in mean vertebral height between the VTS and 1-mm-thick images was smaller than that between the 4-mm-thick and 1-mm-thick images (P < 0.01-0.54). The diagnostic performance of the VTS images for detecting compression fracture was significantly lower than that of the 4-mm-thick images for one reader (P = 0.02). VTS technique enabled the identification of each vertebral body, and enabled accurate measurement of vertebral height. However, this technique is not suitable for diagnosing compression fractures.

Lethal effect of blue light on Asian tiger mosquito, Aedes albopictus (Diptera: Culicidae).

In our previous studies, we found that blue light has a lethal effect on various insect species and demonstrated that the most effective wavelength to control the hygiene pest, the mosquito, Culex pipiens form molestus (Diptera: Culicidae), is ~ 420 nm through all developmental stages. The genera Aedes and Culex include many globally crucial hygiene pest species that transmit serious diseases to humans and animals. However, effective lethal wavelengths have been shown to differ among insect species. In this study, we investigated the lethal effects of blue light on the Asian tiger mosquito, Aedes albopictus, using light-emitting diodes. Blue-light irradiation had a lethal effect on the larvae, pupae, and adults of Ae. albopictus. In particular, the 417-nm blue-light wavelength had a strong lethal effect on the larvae, showing 100% mortality before pupation at the photon flux density of 10 × 1018 photons·m-2·s-1. In contrast, no blue-light wavelength had a lethal effect on the eggs. Moreover, the 417-nm wavelength had the strongest effect on the pupae among the tested blue-light wavelengths. Our findings indicate that ~ 420 nm is the most promising blue-light wavelength to control populations of Ae. albopictus and C. pipiens f. molestus.

Purinergic P2X7 receptor antagonist ameliorates intestinal inflammation in postoperative ileus.

Postoperative ileus (POI) is a postsurgical gastrointestinal motility dysfunction caused by mechanical stress to the intestine during abdominal surgery. POI leads to nausea and vomiting reduced patient quality of life, as well as high medical costs and extended hospitalization. Intestinal inflammation caused by macrophages and neutrophils is thought to be important in the mechanism of POI. Surgery-associated tissue injury and inflammation induce the release of adenosine triphosphate (ATP) from injured cells. Released ATP binds the purinergic P2X7 receptor (P2X7R) expressed on inflammatory cells, inducing the secretion of inflammatory mediators. P2X7R antagonists are thought to be important mediators of the first step in the inflammation process, and studies in chemically induced colitis models confirmed that P2X7R antagonists exhibit anti-inflammatory effects. Therefore, we hypothesized that P2X7R plays an important role in POI. POI models were generated from C57BL/6J mice. Mice were treated with P2X7R antagonist A438079 (34 mg/kg) 30 min before and 2 hr after intestinal manipulation (IM). Inflammatory cell infiltration and gastrointestinal transit were measured. A438079 ameliorated macrophage and neutrophil infiltration in the POI model. Impaired intestinal transit improved following A438079 treatment. P2X7R was expressed on both infiltrating and resident macrophages in the inflamed ileal muscle layer. The P2X7R antagonist A438079 exhibits anti-inflammatory effects via P2X7R expressed on macrophages and therefore could be a target in the treatment of POI.

Characterization of Serum Metabolome and Proteome Profiles Identifies SNX5 Specific for Pregnancy Failure in Holstein Heifers.

Pregnancy loss predominantly occurs during the first 3-4 weeks due to fertilization failure or early embryonic losses in cattle. Insufficient biochemical communication between conceptus (embryo plus extraembryonic membranes) and endometrium has been suspected as the primary cause for early embryonic losses. If molecules regulating this communication were identified, molecular mechanisms associated with early pregnancy losses could be better understood. To identify candidate molecules as detection markers of non-pregnant or females undergoing embryonic loss, peripheral blood from embryo-transferred heifers on day 7 (day 0 = day of estrus) were collected on days 17 (pre-attachment), 20 (during attachment), and 22 (post-attachment), which were subjected to metabolome and global proteome iTRAQ analyses. The metabolome analysis partly divided serum components into pregnant or not. In the iTRAQ analysis, heatmap analysis with top 25 proteins was separated into pregnant or not on day 20 or 22. Furthermore, receiver operating characteristic curve (ROC) analysis identified five candidate proteins detecting non-pregnant heifers, of which SNX5 in day 22 serum had the highest area under the curve (AUC): 0.983. We also detected SNX5 in day 22 serum from non-pregnant heifers using western blotting. These results suggest that high SNX5 in day 22 serum could predict early pregnancy loss in heifers.

Abbreviated Gadoxetic Acid-Enhanced MRI for the Detection of Liver Metastases in Patients With Potentially Resectable Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Gadoxetic acid-enhanced magnetic resonance imaging (MRI) is useful in detecting liver metastases from pancreatic ductal adenocarcinoma (PDAC). However, the long examination time limits its utility in the initial workup of patients with PDAC. PURPOSE: To evaluate the incremental value of an abbreviated gadoxetic acid-enhanced MRI for the detection of liver metastases in patients with PDAC. STUDY TYPE: Retrospective. POPULATION: Patients (N = 130) with potentially resectable PDAC (women, 58 [44.6%]). FIELD STRENGTH/SEQUENCE: 1.5 T and 3 T; gradient dual-echo T1-weighted (in-phase and opposed-phase), fat-suppressed fast spin-echo T2-weighted, single-shot echo-planar diffusion-weighted, and three-dimensional fat-suppressed T1-weighted gradient-echo dynamic contrast-enhanced and hepatobiliary phase sequences, as well as contrast-enhanced computed tomography (CECT). ASSESSMENT: Three radiologists independently reviewed three different image sets to detect liver metastases: set 1, CECT alone; set 2, CECT and abbreviated MRI comprising fat-suppressed T2-weighted, diffusion-weighted, and hepatobiliary phase images; and set 3, CECT and standard gadoxetic acid-enhanced MRI. STATISTICAL TESTS: Figure of merit (FOM) was compared using the jackknife alternative free-response receiver operating characteristics, and other per-lesion and per-patient diagnostic parameters for each image set were compared using McNemar's and Fisher's test. P < 0.05 was considered statistically significant. RESULTS: A total of 43 liver metastases were identified in 13 patients. Reader-averaged FOM to detect liver metastases were significantly higher for sets 2 (0.884) and 3 (0.886) than for set 1 (0.609), while they were comparable between sets 2 and 3 (P = 0.96). The mean per-patient sensitivities, negative predictive values, and accuracies were significantly higher for sets 2 and 3 than for set 1, while those between sets 2 and 3 were not significantly different (not applicable, P > 0.99, and P > 0.99, respectively). DATA CONCLUSION: Gadoxetic acid-enhanced MRI combined with CECT had higher diagnostic performance than CECT alone for the detection of liver metastases in patients with PDAC. The incremental values were comparable for the abbreviated MRI and standard MRI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Diagnosis of Hepatocellular Carcinoma Using Gd-EOB-DTPA MR Imaging.

Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA; Gadoxetic acid; Gadoxetate disodium) is a hepatocyte-specific MR contrast agent. It acts as an extracellular contrast agent in the early phase after intravenous injection, and then is taken up by hepatocytes later. Using this contrast agent, we can evaluate the hemodynamics of the liver and liver tumors, and can therefore improve the detection and characterization of hepatocellular carcinoma (HCC). Gd-EOB-DTPA helps in the more accurate detection of hypervascular HCC than by other agents. In addition, Gd-EOB-DTPA can detect hypovascular HCC, which is an early stage of the multi-stage carcinogenesis, with a low signal in the hepatobiliary phase. In addition to tumor detection and characterization, Gd-EOB-DTPA contrast-enhanced MR imaging can be applied for liver function evaluation and prognoses evaluation. Thus, Gd-EOB-DTPA plays an important role in the diagnosis of HCC. However, we have to employ optimal imaging techniques to improve the diagnostic ability. In this review, we aimed to discuss the characteristics of the contrast media, optimal imaging techniques, diagnosis, and applications.