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123 I-ioflupane single-photon emission computed tomography (SPECT) is a highly sensitive and established neuroimaging technique for parkinsonian syndromes (PS). However, differentiating PS by visual inspection or analysis of regions of interest is challenging. To date, image analysis has not been able to differentiate dementia with Lewy bodies (DLB) from Parkinson's disease with dementia (PDD). This study aimed to differentiate PS based on the characteristics of striatal dopamine transporter (DAT) binding using voxel-based analysis. We acquired 123 I-ioflupane SPECT data from patients with DLB (n = 30), Parkinson's disease (PD; n = 122), PDD (n = 19), multiple system atrophy with predominant parkinsonism (MSA-P; n = 18), and progressive supranuclear palsy (PSP; n = 45). DAT binding was reduced in the posterior striatum of patients with PD and PDD, whereas it was similar in MSA-P, PSP, and DLB. Hippocampal atrophy, visually evaluated by cerebral magnetic resonance imaging, did not affect striatal DAT binding in DLB. DAT binding in the anterior striatum was inversely correlated with the severity of parkinsonism in PD and PDD but not in DLB. Thus, the appearance of striatal DAT binding might indicate different pathological processes in DLB and PDD., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Asymmetric features of nonfunctioning pituitary adenoma (NFPA) are poorly understood. We investigated the asymmetry in NFPA on magnetic resonance imaging., Methods: We reviewed preoperative magnetic resonance imaging findings of patients initially treated for NFPA. The internal carotid artery (ICA) often seemed to cause an indentation in the external shape of the tumor (i.e., the ICA notch)., Results: Two cases with a normal pituitary gland located at the midline were excluded. The remaining 66 cases were examined. The side where the normal gland was located was defined as the normal pituitary side and the opposite side as the cavernous sinus side. The Knosp grade was significantly higher on the cavernous sinus side (P < 0.001), and the vertical distance of the ICA was significantly greater on the cavernous sinus side (P < 0.001). The ICA notch was found in 87.9% of all cases on the normal pituitary side, but in only 45.5% on the cavernous sinus side (P < 0.001). In cases with a single-side ICA notch (34 of 68), the ICA notch was found in 91.2% of cases and on the cavernous sinus side in 8.8% (P < 0.001)., Conclusions: Magnetic resonance imaging of NFPA frequently shows asymmetry. The tumor does not extend laterally on the normal pituitary side but extends laterally more freely on the cavernous sinus side. The ICA notch is often found on the normal pituitary side where the position of ICA does not move. This may be useful as a preoperative sign to indicate the normal pituitary side., (Copyright © 2022 Elsevier Inc. All rights reserved.)

To elucidate clinically useful imaging characteristics of multiple system atrophy with predominant cerebellar ataxia (MSA-C) at the initial stage showing pure cerebellar ataxia but unfilling consensus criteria (MSA-pc), clinical and neuroradiological analyses on cerebral MRI and single-photon emission computed tomography (SPECT) for measuring regional cerebral blood flow (rCBF) were performed. Seven MSA-pc patients meeting the above condition at an initial evaluation were identified, and all the MSA-pc patients later developed autonomic dysfunction and finally fulfilled the criteria for probable or possible category of MSA-C. For comparison, two patients with spinocerebellar ataxia type 6 and three patients with idiopathic cerebellar ataxia who did not exhibit autonomic dysfunction for more than three years were enrolled in this study (non-MSA-pc). As non-ataxic controls without cerebellar involvement, seven patients with Parkinson's disease were also enrolled. As a result, MRI analysis clarified a smaller pontine area and significant laterality of middle cerebellar peduncle (MCP) width in MSA-pc in comparison to non-MSA-pc and controls. SPECT analysis revealed that pontine rCBF was reduced even at the initial stage of MSA-pc. Moreover, the laterality of cerebellar rCBF values and the laterality of MCP width in MSA-pc patients exhibited a significant positive correlation, indicating anatomical and functional laterality of afferent projections to cerebellum is a characteristic finding for MSA-pc. These neuroimaging characteristics could be clinically useful to consider the possibility of the criteria-unfulfilled MSA and promote an earlier intervention after obtaining a diagnosis of probable MSA-C., (Copyright © 2021. Published by Elsevier B.V.)

Purpose: To assess the associations between simple measurements of left atrial (LA) size and image quality of coronary computed tomography angiography (CCTA)., Materials and Methods: Four hundred and nineteen patients who underwent CCTA were retrospectively examined. Image quality was measured by coronary artery attenuation and contrast-to-noise ratio (CNR) of the proximal coronary artery (mean values of right coronary artery and left main trunk). LA transverse (LA-TRA) and anterior-posterior (LA-AP) diameter were measured on non-contrast CT images of the chest. The relationships of coronary attenuation and CNR with LA diameters were assessed by Pearson's correlation or Spearman's rank correlation coefficient and multivariate linear regression analysis. Receiver operating characteristic curves were used to assess the predictive value of LA diameters for image quality., Results: Both coronary artery attenuation value and CNR were independently correlated with LA-AP diameter (r = -0.38, for artery attenuation; r = -0.16, for CNR, both p < 0.001), and LA-TRA diameter (r = -0.2, p < 0.001, for artery attenuation; r = -0.11, p = 0.02, for CNR), respectively. With a cutoff value of 34 mm, the LA-AP diameter had a sensitivity of 85.2%, a specificity of 68.4% and an area under curve (AUC) of 0.77 for prediction of insufficient image quality (coronary artery attenuation less than 326 Hounsfield units)., Conclusion: Coronary artery attenuation and CNR in CCTA decreased with larger LA size., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Obesity is a major risk factor for developing various respiratory diseases. Patients with anti-aminoacyl tRNA synthetase (ARS) antibodies often have interstitial lung disease (ILD). The present study was conducted to evaluate the association between obesity and outcomes of anti-ARS antibody-related ILD (ARS-ILD)., Methods: We retrospectively investigated 58 patients with ARS-ILD and compared the clinical characteristics, treatment, and prognoses between obese (body mass index [BMI] ≥25 kg/m 2 ) and nonobese (BMI <25 kg/m 2 ) patients. Chest fat was quantified via computed tomography (CT). Thoracic subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured at diagnosis and first relapse of ILD., Results: Sixteen patients were obese. Obese patients had lower percentages of predicted diffusing capacity of the lungs for carbon monoxide and higher high-resolution CT scores and SAT and VAT indexes than did nonobese patients. The ILD relapse rate was higher in obese patients (P < 0.01), especially among those with high SAT indexes (P < 0.01). The SAT and VAT indexes increased significantly from diagnosis until first relapse. Among clinical parameters at first relapse, SAT and VAT indexes were correlated with serum Krebs von den Lungen-6 levels (r = 0.720, P = 0.008) and total ground-glass attenuation scores (r = 0.620, P = 0.024), respectively., Conclusions: Obesity and high SAT indexes are risk factors for ILD relapse in patients positive for anti-ARS antibodies. Evaluating and quantifying patients' chest fat on CT is important for predicting ILD relapse., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Preoperative portal vein embolization (PVE) stimulates liver hypertrophy and improves the safety of major hepatectomy. It is essential to predict the future remnant liver volume (FRLV) and resection limit following PVE. Previously, we reported that evaluating functional FRLV (fFRLV) using EOB-MRI could predict post-hepatectomy liver failure. In this study, we investigated the usefulness of fFRLV in predicting the achieving of adequate resection limit for safe hepatectomy following PVE., Methods: We included 55 patients who underwent PVE and were scheduled for major hepatectomy. We calculated the liver-to-muscle ratio in the remnant liver and fFRLV using EOB-MRI. We investigated the pre-PVE variables in determining the nonachievement of the resection limit., Results: The median observation period between PVE and the first evaluation was 21 days, and the median growth rate of FRLV was 26.4%. In 54.5% of patients, the resection limit of fFRLV (615 mL/m 2 ) was achieved. In logistic regression and receiver-operating characteristic analyses, pre-PVE fFRLV (p < 0.001, area under the curve: 0.852) was the reliable predictor of achieving the resection limit; the cutoff value of pre-PVE fFRLV was 446 mL/m 2 ., Conclusion: Pre-PVE fFRLV can be useful in predicting the achievement of adequate resection limit following PVE., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: 3-[ 18 F]fluoro-α-methyl-L-tyrosine ([ 18 F]FAMT) is a promising amino acid tracer targeting L-type amino acid transporter 1 (LAT1). One concern regarding the diagnosis using [ 18 F]FAMT is the possibility of false-negative findings because of its relatively low accumulation level even in malignant tumors. Moreover, preloading probenecid, an organic anion transporter inhibitor, markedly increased the tumor accumulation level of radioiodine-labeled α-methyltyrosine. In this study, we evaluated the usefulness of preloading probenecid in improving the tumor-imaging capability of [ 18 F]FAMT., Methods: Three biodistribution studies of [ 18 F]FAMT were conducted in normal mice to elucidate the usefulness of probenecid preloading. Later, a biodistribution study and positron emission tomography (PET) imaging of [ 18 F]FAMT were conducted with or without probenecid injection in tumor-bearing mice., Results: Probenecid preloading significantly delayed blood clearance and consequently enhanced the accumulation of [ 18 F]FAMT in the pancreas, a LAT1-positive organ. The effects of probenecid preloading were independent of the administration route. Tumor accumulation level in the biodistribution study and the maximum standardized uptake value in tumors on PET imaging of the probenecid preloading group were significantly higher than those of the control (without probenecid injection) group in tumor-bearing mice., Conclusions: Preloading probenecid significantly delayed blood clearance and consequently enhanced the accumulation of [ 18 F]FAMT in tumors. These results indicate that preloading probenecid could improve the diagnostic accuracy of [ 18 F]FAMT., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Targeted α-radionuclide therapy has attracted attention as a promising therapy for refractory cancers. However, the application is limited to certain types of cancer. Since L-type amino acid transporter 1 (LAT1) is highly expressed in various human cancers, we prepared an LAT1-selective α-radionuclide-labeled amino acid analog, 2-[ 211 At]astato-α-methyl-L-phenylalanine (2-[ 211 At]AAMP), and evaluated its potential as a therapeutic agent., Methods: 2-[ 211 At]AAMP was prepared from the stannyl precursor. Stability of 2-[ 211 At]AAMP was evaluated both in vitro and in vivo. In vitro studies using an LAT1-expressing human ovarian cancer cell line, SKOV3, were performed to evaluate cellular uptake and cytotoxicity of 2-[ 211 At]AAMP. Biodistribution and therapeutic studies in SKOV3-bearing mice were performed after intravenous injection of 2-[ 211 At]AAMP., Results: 2-[ 211 At]AAMP was stable in murine plasma in vitro and excreted intact into urine. Cellular uptake of 2-[ 211 At]AAMP was inhibited by treatment with an LAT1-selective inhibitor. After 24 h incubation, 2-[ 211 At]AAMP suppressed clonogenic growth at 10 kBq/ml, and induced cell death and DNA double-strand breaks at 25 kBq/ml. When injected into mice, 2-[ 211 At]AAMP exhibited peak accumulation in the tumor at 30 min postinjection, and radioactivity levels in the tumor were retained up to 60 min. The majority of the radioactivity was rapidly eliminated from the body into urine in an intact form immediately after injection. 2-[ 211 At]AAMP significantly improved the survival of mice (P < 0.05) without serious side effects., Conclusion: 2-[ 211 At]AAMP showed α-radiation-dependent cellular growth inhibition after it was taken up via LAT1. In addition, 2-[ 211 At]AAMP had a beneficial effect on survival in vivo. These findings suggest that 2-[ 211 At]AAMP would be useful for the treatment of LAT1-positive cancer., Advances in Knowledge and Implications for Patient Care: This is the first report of an LAT1-targeting radiopharmaceutical for α-radionuclide therapy; this agent would be applicable for the treatment of various types of cancer., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Gd-EOB-DTPA-enhanced magnetic resonance imaging (EOB-MRI) can be used for evaluating liver functional reserve. We assessed whether functional remnant liver volumetry (FRLV) using EOB-MRI predicted post-hepatectomy liver failure (PHLF) in resection of more than one segment., Methods: We retrospectively analyzed 155 cases of hepatectomy of more than one segment. For assessment of FRLV, signal intensity (SI) of remnant liver was measured in T1-weighted images. Functional remnant liver score was derived by division of SI of liver by SI of muscle (or spleen), resulting in liver-to-muscle ratio (LMR) and liver-to-spleen ratio (LSR). FRLV were calculated by multiplying LMR (or LSR) and remnant liver volume. We investigated preoperative factors predicting PHLF (≥grade B) in study cohort (all cases except for portal vein embolization [PVE], n = 129) and validation cohort (PVE cases, n = 26)., Results: In study cohort, PHLF occurred in 5 patients (3.9%). In multivariate analysis, FRLV (LMR) was the most reliable predictor of PHLF (P = 0.013). The cutoff value of FRLV (LMR) predicting PHLF was 615 mL/m 2 (AUC: 0.939). In validation cohort (n = 26), the cutoff value of FRLV (LMR) indicated reliable results, sensitivity (100%), specificity (77.3%), and accuracy (80.8%)., Conclusions: FRLV using LMR could precisely predict PHLF of more than one segment, and was useful even in patients who underwent PVE., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The acute angle between inflow cannula and device body of HeartMate II left ventricular assist device (LVAD) (Abbott, Pleasanton, California) is associated with device thrombosis. However, most studies utilized two-dimensional (2D) angle obtained from chest roentgenogram (CXR), which is unlikely accurate. We aimed to create and validate a formula to estimate actual three-dimensional (3D) angle., Methods: We retrospectively reviewed the cohort undergoing HeartMate II LVAD implantation between 2008 and 2016. A formula for calculating 3D angles of the LVAD inflow cannula relative to the device body was mathematically derived, using simple 2D measurements from CXR., Results: The cohort included consecutive 275 patients with HeartMate II (median age: 60 [25% quartile: 51, 75% quartile: 68] years). There was no significant difference between the calculated 3D angles (from formula) and actual 3D angles (from computed tomography) from the subset group with 3D computed tomography (n = 28) (71.7° ± 13.4° vs 71.1° ± 11.5°, P = .858). Among all participants, the calculated 3D angle (from formula) was 74.4° ± 14.2°, which was significantly larger than the 2D projected angle (from CXR) (65.2° ± 11.3°, P < .001). There was no statistical difference in the calculated 3D angles (from formula) between patients with/without device thrombosis, hemorrhagic stroke, ischemic stroke, or mortality (P > .05 for all)., Conclusions: We established a novel formula to mathematically calculate actual 3D angles between inflow cannula and device body of HeartMate II. The formula would help investigators to validate their findings of the relationship between 2D projected angle (from CXR) and device thrombosis., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the correlation between cardiac functional parameters and image quality in coronary computed tomography angiography (CCTA)., Material and Methods: Sixty-six patients who underwent both CCTA and echocardiography were included. The coronary artery attenuation values and contrast-to-noise ratios (CNR) were measured in the proximal right coronary arteries (RCA) and left main (LM) trunk. Then, the averages of the mean values derived from RCA and LM were calculated. The cardiac output (CO), left atrial (LA) volume, and early mitral inflow velocity to mitral annular early diastolic velocity ratio (E/e') were measured by echocardiography. The relationship of cardiac parameters with arterial attenuation and CNR were assessed by Pearson's correlation, Spearman's rank correlation and multivariable linear regression analysis adjusted for age, gender, body surface area and heart rate., Results: The coronary artery attenuation value was negatively correlated with CO (r = -0.30, p = 0.01) and LA volume (r = -0.37, p = 0.002). CNR was negatively correlated with LA volume (r = -0.4, p = 0.001) and E/e' (r = -0.27, p = 0.03). These associations remained significant in the multivariable analysis., Conclusion: CO and diastolic function had an impact on image quality of CCTA. Adjusting CCTA protocol may improve image quality in patients with known diastolic dysfunction or reduced cardiac output., (Copyright © 2018. Published by Elsevier Inc.)

Background: Exercise therapy is one of the recognized treatment methods for knee osteoarthritis (KOA). One such exercise technique, straight leg raising (SLR), is widely known as a home exercise method for strengthening the quadriceps femoris muscle. However, whether this exercise truly strengthens the quadriceps is not known. The objective of the present study was to investigate which lower limb muscle is stimulated and shows increased activity with SLR., Methods: A total of 14 lower limbs in seven healthy adult male volunteers (mean age: 31.3 ± 2.2 years) were investigated. Participants were asked to perform SLR and subsequently underwent FDG-PET/CT examination for evaluation of the muscles of the entire lower limb. The maximum standardized uptake value (SUVmax) of each muscle (iliacus, psoas major, gluteus maximus, gluteus medius, gluteus minimus, vastus medialis, vastus intermedius, vastus lateralis, rectus femoris, biceps femoris, semimembranosus, semitendinosus, adductor, sartorius, gracilis, tibialis anterior, tibialis posterior, soleus, medial head of gastrocnemius, and lateral head of gastrocnemius) was measured in four cross-sections: at the trunk, pelvis, thigh, and lower leg., Results: SUVmax was significantly greater in: iliacus and adductor compared to vastus medialis, vastus lateralis, biceps, semitendinosus, gracilis, tibialis anterior, and gastrocnemius; psoas major compared to all muscles except for gluteus minimus and adductor; gluteus minimus compared to all muscles except for iliacus, psoas major, gluteus medius, and adductor; and gluteus medius compared to semitendinosus and gracilis., Conclusions: After SLR, SUVmax was significantly greater in iliacus, psoas major, gluteus minimus, gluteus medius, and adductor compared to some of the other muscles. Performing SLR increased glucose metabolism of the above muscles in particular, and this may have increased their activity levels., (Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objective: Various diseases can occur in the sellar and suprasellar regions. The potential of [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography (PET) for the preoperative evaluation of sellar and parasellar lesions was investigated., Methods: A total of 49 patients aged 8-82 years with sellar and parasellar macroscopic lesions (≥10 mm) underwent FDG PET. Twenty-two patients had pituitary adenomas, including 14 nonfunctioning and 8 growth hormone-secreting adenomas. Eleven patients had craniopharyngiomas, including 5 adamantinomatous and 6 squamous-papillary types. Eight patients had chordoma, 4 had meningioma, and 4 had a Rathke cleft cyst. The maximum standardized uptake value (SUV max ), and the ratio of the SUV max in the tumor to the mean standardized uptake value in the normal cortex (T/N ratio) or in the normal white matter (T/W ratio) were calculated. The relationships between SUV max , T/N ratio, and T/W ratio, and lesion disease were evaluated., Results: Uptakes of FDG, including SUV max , T/N ratio, and T/W ratio, were lower in chordoma and Rathke cleft cyst compared with pituitary adenoma. SUV max , T/N ratio, and T/W ratio of nonfunctioning adenoma were significantly higher than those of growth hormone-secreting adenoma. SUV max , T/N ratio, and T/W ratio of squamous-papillary type were significantly higher than those of the adamantinomatous type of craniopharyngioma., Conclusions: FDG PET is useful for the preoperative diagnosis of sellar and parasellar macrolesions. High uptake in nonfunctioning pituitary adenoma, and low uptake in chordoma are significant. The difference in FDG uptake dependent on the histologic subtype may be related to the specific genetics of the craniopharyngioma subtype., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The safety and efficacy of the contemporary atrial fibrillation (AF) ablation in patients with a recent or previous history of cardioembolic stroke (CS) or transient ischemic attack (TIA) remain to be established., Methods: A total of 447 patients who underwent first-ever contact force (CF)-guided AF ablation with circumferential pulmonary vein isolation were included. Of these, 17 had CS or TIA within 6 months before ablation (Group 1), 30 more than 6 months before ablation (Group 2), and the other 400 without CS or TIA (Group 3). Procedural complications and recurrence of AF and atrial tachyarrhythmias were compared among the 3 groups., Results: The mean age was 71±7, 66±9, and 61±11 years in Groups 1, 2, and 3, respectively (p<0.05, Group 1 versus Group 3). The oral anticoagulants were warfarin (n=108, 24.1%), dabigatran (n=101, 22.6%), rivaroxaban (n=147, 32.9%), apixaban (n=87, 19.5%), and edoxaban (n=4, 0.9%), and did not differ among the 3 groups. Median follow-up period was 14 [IQR 12-22], 13 [12-14], and 12 [10-16] months, respectively. One episode of cardiac tamponade, 2 episodes of arteriovenous fistula, and some minor complications occurred in Group 3, but no complications occurred in Groups 1 and 2 in the periprocedural period. Although one episode of CS occurred 11 days after the procedure in Group 3, there were no periprocedural CS, TIA, or major bleedings in Groups 1 and 2. AF recurrence-free rate after the procedure was 76.5%, 86.7%, and 79.1% in Groups 1, 2, and 3, respectively, and there was no difference in Kaplan-Meier curves among the 3 groups., Conclusion: The safety and efficacy of CF-guided AF ablation in the era of direct oral anticoagulants in patients with a recent or previous history of CS or TIA are similar to those in patients without it., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: The wearable cardioverter-defibrillator (WCD) has been expected to play a role as an effective bridge therapy to implantable cardioverter-defibrillator (ICD) implantation in patients at high risk of ventricular tachyarrhythmias (VA). Although WCD has been available since April 2014 in Japan, its usefulness remains unclear., Methods and Results: During the early period after hospitalization, patients at high risk of VA after excluding some elderly patients were prescribed WCD. The consecutive 50 patients with WCD use (median age 56 years, 38 for secondary prevention) were studied. We analyzed clinical efficacy and safety of WCD, and examined its potential roles. Of the 50 patients, 38 used WCD only during hospitalization. During WCD use [median 16 (IQR 8-33) days], all patients wore WCD for 98% of a day regardless of in or out-of-hospital use. Sustained VA was detected in 4 patients (8%; for primary prevention in 1) with 7 episodes, and 6 of 7 episodes required shock therapy. Of the 6 shock therapies, 4 were for sustained ventricular tachycardia with the median rate of 236beats/min (IQR 203-250), and the other 2 for ventricular fibrillation. Subsequently, only 27 patients (54%) of all underwent ICD implantation following the WCD use, because of reduced risk of VA after optimal pharmacological therapy or improvement in the left ventricular function., Conclusions: The WCD use for the acute phase care of patients at high risk of VA can be safe and effective, and may be useful for evaluating indication of ICD implantation., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Hypothermia can occur during fasting when thermoregulatory mechanisms, involving fatty acid (FA) utilization, are disturbed. CD36/FA translocase is a membrane protein which facilitates membrane transport of long-chain FA in the FA consuming heart, skeletal muscle (SkM) and adipose tissues. It also accelerates uptake of triglyceride-rich lipoprotein by brown adipose tissue (BAT) in a cold environment. In mice deficient for CD36 (CD36(-/-) mice), FA uptake is markedly reduced with a compensatory increase in glucose uptake in the heart and SkM, resulting in lower levels of blood glucose especially during fasting. However, the role of CD36 in thermogenic activity during fasting remains to be determined. In fasted CD36(-/-) mice, body temperature drastically decreased shortly after cold exposure. The hypothermia was accompanied by a marked reduction in blood glucose and in stores of triacylglycerols in BAT and of glycogen in glycolytic SkM. Biodistribution analysis using the FA analogue (125)I-BMIPP and the glucose analogue (18)F-FDG revealed that uptake of FA and glucose was severely impaired in BAT and glycolytic SkM in cold-exposed CD36(-/-) mice. Further, induction of the genes of thermogenesis in BAT was blunted in fasted CD36(-/-) mice after cold exposure. These findings strongly suggest that CD36(-/-) mice exhibit pronounced hypothermia after fasting due to depletion of energy storage in BAT and glycolytic SkM and to reduced supply of energy substrates to these tissues. Our study underscores the importance of CD36 for nutrient homeostasis to survive potentially life-threatening challenges, such as cold and starvation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A 71-year-old man, a heavy smoker, was admitted for evaluation of "chest oppression" after every dinner. Cardiac CT with a beta-blocker showed coronary stenosis in the left circumflex. Although adenosine triphosphate-stress perfusion single-photon emission CT revealed no ischemia, Holter electrocardiography belatedly indicated an ST elevation associated with his symptoms while smoking. He was diagnosed to have vasospastic angina. Cardiac CT without a beta-blocker showed thin diffuse plaque and negative remolding without any significant stenosis at the same site. Asian patients have a tendency to develop vasospastic angina. Although beta-blockers are recommended for cardiac CT, the routine administration of beta-blockers in cardiac CT may have some risk for such cases., (Copyright © 2014 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Despite the improvement of cardiac CT, right heart visualization remains challenging., Objective: We herein describe a new method, called the time-adjusted gradual replacement injection protocol. The aim of this study was to compare this protocol with the split-bolus injection protocol., Methods: Fifty-two patients who had undergone dual-source cardiac CT were retrospectively recruited. Twenty-six patients were injected by using the split-bolus injection protocol, and 26 patients were injected by using the time-adjusted gradual replacement injection protocol. For this method, we injected contrast medium for 10 seconds at a flow rate of 0.07 × body weight mL/s, then gradually replaced the contrast material with saline until 2 seconds before finishing the scans. The CT attenuation was measured in 4 chambers, the aorta, and the coronary arteries. The visualization of the anatomic structures and the occurrence and severity of streak artifacts were scored for the cardiac structures in the heart. For the analyses, either Welch t-test or Student t-test was performed., Results: In the right heart, the CT values and visualization scores were significantly higher in the time-adjusted replacement injection group than in the split-bolus injection group, whereas the artifact scores were comparable between the 2 groups. The CT values, visualization scores, and artifact scores of the left heart were not significantly different between the 2 groups., Conclusions: In this study, the time-adjusted gradual replacement injection protocol provided excellent attenuation for visualization of the right heart. This method may help to accurately evaluate the right cardiac anatomy and thereby identify any potential diseases., (Copyright © 2014 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Obesity is associated with heart failure and cardiac hypertrophy. Adiponectin has been shown to play a protective role for cardiovascular diseases. The β-catenin signaling pathway is deeply involved in cardiac hypertrophy. However, the effect of adiponectin on β-catenin signaling has not been investigated in cardiac hypertrophy. Present study aimed to clarify the involvement of adiponectin and β-catenin signaling pathway in the mouse model of angiotensin II (AngII)-induced cardiac hypertrophy. In hearts of Wild type (WT) mice, AngII dose-dependently augmented cytosolic β-catenin protein level. WT and adiponectin knockout (Adipo-KO) mice were administered with AngII at 2.4 mg/kg/day for 14 days and were also injected with adenovirus expressing the adiponectin (Ad-Adipo) or the β-galactosidase (Ad-βgal). Cardiac mRNA levels relating to hypertrophy and β-catenin signaling were increased in Adipo-KO mice and these changes were reversed by Ad-Adipo. Phosphorylation of Akt was increased in Adipo-KO mice and such increases were reversed by Ad-Adipo. Furthermore, the phosphorylation of glycogen synthase kinase 3β (GSK3β) at Ser(9) and cytosolic β-catenin level were increased in Adipo-KO mice and they were significantly reduced by Ad-Adipo treatment. Phosphorylation of mammalian target of rapamycin (mTOR) was reduced by Ad-Adipo-mediated adiponectin supplementation in WT and Adipo-KO mice. The current study suggests that adiponectin attenuates AngII-induced cardiac hypertrophic signals partly through Akt/GSK3β/β-catenin and Akt/mTOR pathways., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We present the first clinical report of the successful treatment of an infected thoracic aortic arch aneurysm with the use of endovascular repair as a bridge to second-stage open operation. A 70-year-old patient underwent urgent endovascular repair through the right femoral approach because of a diagnosis of sepsis and impending rupture of an infected thoracic aortic arch aneurysm. After 2 weeks of medical treatment, we successfully performed explantation of the stent graft, wide debridement of the surrounding tissue, and in-situ replacement using a rifampicin-bonded four-branched prosthetic graft with omental flap., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

One of the most difficult aspects of complete segmentectomy of the lung is the identification of the intersegmental plane. Instead of a conventional residual segment inflation method, we have developed a new technique for detecting intersegmental planes using indocyanine green medium. The technique is simple and consists of (1) ligation of the segmental vein to prevent loss of the indocyanine green and (2) injection of indocyanine green through the segmental bronchus. These two steps result in easy identification of intersegmental planes by a change of color not only of the surface but also of the parenchyma of the lung. This technique can be indicated for atypical segmentectomy., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Visceral fat obesity is located upstream of metabolic syndrome and atherosclerotic diseases. Accumulating evidences indicate that several immunocytes including macrophages infiltrate into adipose tissue and induce chronic low-grade inflammation. We recently analyzed the association between visceral fat adiposity and the gene expression profile in peripheral blood cells in human subjects and demonstrated the close relationship of visceral fat adiposity and disturbance of circadian rhythm in peripheral blood cells. In a series of studies, we herein investigated the association of visceral fat adiposity and mRNA levels relating to inflammatory genes in peripheral blood cells., Approach and Results: Microarray analysis was performed in peripheral blood cells from 28 obese subjects. Reverse transcription-polymerase chain reaction (RT-PCR) was conducted by using blood cells from 57 obese subjects. Obesity was defined as body mass index (BMI) greater than 25 kg/m2 according to the Japanese criteria. Gene expression profile analysis was carried out with Agilent whole human genome 4×44K oligo-DNA microarray. Gene ontology (GO) analysis showed that 14 genes were significantly associated with visceral fat adiposity among 239 genes relating to inflammation. Among 14 genes, RT-PCR demonstrated that S100A8, S100A9, and S100A12 positively correlated with visceral fat adiposity in 57 subjects. Stepwise multiple regression analysis showed that S100A8 and S100A12 mRNA levels were closely associated with HOMA-IR and S100A9 mRNA was significantly related to adiponectin and CRP., Conclusions: Peripheral blood mRNA levels of S100 family were closely associated with insulin resistance and inflammation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Distal anastomosis during total arch replacement for thoracic aortic aneurysm is at times difficult, and bleeding from it is a serious problem because of its limited surgical exposure. We have modified a new procedure, the branched graft inversion (BGI) technique. We investigated the effectiveness of our technique by comparing it with the conventional stepwise technique. Between January 2008 and August 2011, 40 patients, divided into two groups of 20 each, underwent elective total arch replacement. One group underwent surgery using BGI; the stepwise technique was performed on the remaining 20 patients. Our modified BGI technique offers easy and secure distal anastomosis under good surgical procedure, resulting in shorter durations of operation, cardiopulmonary bypass, and circulatory arrest (455.1±101.3 min versus 354.7±49.3 min, p<0.001; 248.2±46.6 min versus 199.7±28.2 min, p<0.001; 76.6±27.7 min versus 61.6±10.4 min, p=0.029, respectively). As a result, this technique could be a useful in performing total arch replacement., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Small lung cancers showing a wide area of ground-grass opacity (GGO) on thin-section computed tomography (CT) are considered good candidates for limited surgical resection because of its minimally invasive nature. Conversely, the validity of limited resection for radiologically "solid" tumors is still controversial in small non-small cell lung carcinomas., Methods: Between 2008 and 2010, 680 consecutive patients underwent pulmonary resection for lung cancer. The findings obtained by preoperative CT were reviewed for all 680 patients and categorized as pure GGO, mixed GGO, or purely solid. All patients were evaluated by positron emission tomography (PET) and the maximum standardized uptake value (SUV(max)) was recorded. Several clinicopathologic features were investigated to identify predictors of hilar or mediastinal lymph node metastasis using univariate or multivariate analysis., Results: Two hundred twenty-seven of the patients with clinical stage IA lung cancer showed a solid or mixed GGO appearance on thin-section CT. Among them, nodal involvement was found pathologically in 42 (26%) patients with pure solid tumors, but in only 4 (6%) patients with mixed GGO tumors (p = 0.0002). Among the 131 patients with stage T1a disease, 94 (71.8%) had solid tumors, and nodal involvement was observed in 15 (16.0%). Among the 94 pure solid stage T1a tumors, the carcinoembryonic antigen (CEA) level and SUV(max) were significant predictors of lymph node involvement by tumor based on a multivariate analysis. The frequency of lymph node metastasis was approximately 27% for patients with pure "solid" lung cancer and high SUV(max), even for stage T1a tumor., Conclusions: Lymph node metastasis is frequently observed for pure solid lung cancer, especially for tumors that show a high SUV(max). If limited resection is indicated for solid lung cancer, a thorough intraoperative evaluation of lymph nodes is needed to prevent locoregional failure., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Learning a second language as an adult is particularly effortful when new phonetic representations must be formed. Therefore the processes that allow learning of speech sounds are of great theoretical and practical interest. Here we examined whether perception of single formant transitions, that is, sound components critical in speech perception, can be enhanced through an implicit task-irrelevant learning procedure that has been shown to produce visual perceptual learning. The single-formant sounds were paired at subthreshold levels with the attended targets in an auditory identification task. Results showed that task-irrelevant learning occurred for the unattended stimuli. Surprisingly, the magnitude of this learning effect was similar to that following explicit training on auditory formant transition detection using discriminable stimuli in an adaptive procedure, whereas explicit training on the subthreshold stimuli produced no learning. These results suggest that in adults learning of speech parts can occur at least partially through implicit mechanisms.

It is difficult to distinguish multiple primary lung cancers from pulmonary metastasis. We experienced a case of surgically resected lung tumors that showed multiple ground-glass opacities on thoracic computed tomographic scan. There were eight nonsolid and two part-solid ground-glass opacities in the bilateral lungs. Surgical resection was performed because all tumors had a ground-glass opacity appearance on computed tomographic scan, which is compatible with a finding of primary lung adenocarcinoma. The postoperative pathologic diagnoses were two cases of invasive adenocarcinoma, six cases of bronchioloalveolar carcinoma, and eight cases of atypical adenomatous hyperplasia. The patient remains alive without any evidence of recurrence 40 months after surgery. A ground-glass opacity appearance on computed tomographic scan could be interpreted as supportive evidence for multiple primary lung adenocarcinoma rather than pulmonary metastases.

Purpose: A minimally invasive vascular surgery (MIVS) technique for repair of infrarenal abdominal aortic aneurysm (AAA) with iliac involvement was evaluated, and its outcome was compared with conventional open repair., Methods: Twenty patients with AAA with iliac involvement underwent treatment with bifurcated graft replacement with the MIVS technique. The procedure was performed via minilaparotomy, with the incision length determined according to the extent of the AAA obtained with ultrasound scanning and with the small intestine confined completely within the abdominal cavity. The proximal and distal operating fields were obtained with changing the patient position and arranging for the abdominal incision to be retracted cephalad and caudad. Perioperative courses in these 20 patients (the MIVS group) were analyzed in comparison with 14 patients who underwent conventional open repair, which was performed through the full midline laparotomy with the intestine simply covered with moistened towels (the conventional group)., Results: The MIVS technique for AAA repair was performed with a mean abdominal incision length of 8.4 cm and a range from 6.5 to 11.2 cm. The patients in the MIVS group showed earlier resumption of oral intake and ambulation in comparison with those patients in the conventional group (liquid diet: 1.1 +/- 0.3 days versus 2.9 +/- 1.4 days; P <.01; solid diet: 2.0 +/- 0.2 days versus 3.9 +/- 1.4 days; P <.01; ambulation: 2.1 +/- 0.8 days versus 4.3 +/- 2.3 days; P <.01), with comparable mortality and morbidity rates. Accordingly, the patients in the MIVS group were discharged earlier (20.7 +/- 6.3 days versus 33.9 +/- 12.6 days; P <.01), and total hospitalization charges were significantly decreased (2,232,791 +/- 200,747 Japanese yen versus 2,640,441 +/- 243,889 Japanese yen; P <.01)., Conclusion: The MIVS technique allowed earlier postoperative recovery with comparable morbidity and mortality rates with the conventional technique and, therefore, saved hospital stay length and total hospitalization charges. Thus, the MIVS technique is considered as a new and effective minimally invasive technique for open AAA repair.

The RNase 4 family is unique among RNase enzymes, displaying the highest level of sequence similarity and encompassing the shortest polypeptide chain. It is the only one showing high specificity. The human representative is an intracellular and plasma enzyme, first isolated from colon adenocarcinoma cell line HT-29. The crystal structures of human recombinant RNase 4, unliganded and in complex with d(Up), have been determined, revealing in the unique active site an explanation for the uridine specificity. Arg101, at a position not involved in catalysis in the other RNase enzymes, penetrates the enzyme moiety shaping the recognition pocket, a flip that is mediated by the interaction with the (shorter chain) C-terminal carboxylate group, providing an anchoring point for the O4 atom of the substrate uridine. The bulky Phe42 side-chain forces Asp80 to be in the chi1=-72.49 degrees rotamer, accepting a hydrogen bond from Thr44, further converting the latter into a hydrogen bond acceptor. This favours an interaction with the -NH-donor group of uridine at position 3 over that with the =N-acceptor of cytidine. The two chemical groups that distinguish uracyl from cytosine are used by the enzyme to discriminate between these two bases., (Copyright 1999 Academic Press.)

Primary cardiac angiosarcoma occurs rarely, and surgical resection is often required to relieve symptoms. A 66-year-old man whose presenting symptoms were palpitations and general fatigue is presented. Echocardiography revealed a large tumour occupying most of the right atrium. When superior vena caval (SVC) syndrome developed, surgical resection of the tumour was attempted. The tumour was found to have invaded the inflow of SVC, left atrium, right ventricle and ascending aorta. The bulk of the tumour was resected, requiring reconstruction of the right atrium and caval inflows. Histopathological diagnosis of the tumour was primary angiosarcoma. In the postoperative period, symptoms of SVC syndrome recurred, which were relieved temporarily by balloon angioplasty. After one month, recurrence of symptoms was again managed by catheter dilation. On this occasion a metallic stent was deployed, which prevented further symptoms of SVC syndrome during the eight months before the patient died with generalized metastases.

This report describes the preparation of injectable microspheres containing a neurotensin analogue (NA), which is a hexapeptide with neurotensin activity. NA, a hydrophilic drug, was successfully entrapped into poly(dl-lactic acid) microspheres prepared by a novel oil-in-water solvent evaporation method. The preparation method was investigated with regard to the partition of NA into the oily phase and the rapid phase separation of the polymer. Successful entrapment was achieved with the following conditions: (1) an alkaline water phase, (2) addition of fatty acid salt in the oily phase, and (3) addition of a water-miscible solvent in the oily phase. Under these conditions, NA was completely entrapped into the microspheres at poly(dl-lactic acid):NA molar ratios of greater than 3.

Poly(DL-lactic acid) (PLA) microspheres containing a neurotensin analogue [NA; H(CH3)-Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt.3HCl] were prepared by a novel oil-in-water (o/w) solvent evaporation method, and the release behaviors were evaluated in vitro. About 20% of the loaded NA was released initially, and the subsequent release lasted for a month from microspheres prepared with PLA of molecular weight 2000 (PLA 2000). A smaller initial release from PLA 4000 and PLA 6000 microspheres was found, but a lag time of 2-3 weeks during which the drug was not released was observed with PLA 4000 and PLA 6000 microspheres. The addition of relatively hydrophilic monoglycerides decreased the lag time, and a fairly constant release of NA was achieved. The pharmacokinetic behavior of NA from PLA 2000 microspheres was studied in rats. The release of the drug after a subcutaneous injection exhibited pseudo-zero-order kinetics for 1 month. The initial release of the drug from the microspheres was reflected in a sharp increase of the plasma levels of the de-ester form of NA [H(CH3)-Arg-Lys-Pro-Trp-tert-Leu-Leu-OH], and the subsequent steady-state levels agreed well with the predicted levels obtained from analysis of constant-infusion kinetics.

The present investigation is concerned with an improvement of the bioavailability of cinnarizine by administering its beta-cyclodextrin complex together with another compound which competes with the beta-cyclodextrin molecule in complex formation in aqueous solution (competing agent). The bioavailability of cinnarizine on oral administration of the cinnarizine-beta-cyclodextrin inclusion complex was enhanced by the simultaneous administration of DL-phenylalanine as a competing agent, e.g., the AUC was 1.9 and 2.7 times as large as those of the cinnarizine-beta-cyclodextrin complex alone and cinnarizine alone, respectively. The enhancement of AUC and Cmax completely depended on the dose of DL-phenylalanine. It was found from these results that DL-phenylalanine acted as a competing agent in the GI tract and the minimum effective dose required of DL-phenylalanine might be 1 g for 50 mg of cinnarizine in the cinnarizine-beta-cyclodextrin complex. Evaluating the competing effect of DL-phenylalanine in vitro using an absorption simulator, it was found that the decreased penetration rate of cinnarizine through the artificial lipid barrier with addition of beta-cyclodextrin was restored with the addition of DL-phenylalanine.

The present study was an attempt to develop a new dosage form of cinnarizine, which is slightly soluble in water, using lipid as a vehicle. The solubility of cinnarizine in several organic solvents was determined. It was found that cinnarizine dissolved well in oleic and linoleic acids. The bioavailability of cinnarizine from the oral administration of an oleic acid solution in a hard capsule was investigated and compared with that of a cinnarizine tablet, using beagle dogs. When cinnarizine was administered in a capsule, the bioavailability was greatly enhanced [i.e., the maximum concentration (Cmax) and AUC values were 2.9 and 4.0 times larger than those of a cinnarizine tablet, respectively]. Meanwhile, the tmax value (the time to reach Cmax) was unchanged. The absorption of cinnarizine from an oleic acid solution was considered to depend on the action of bile salts. This was supported by the results of a dissolution test using a bile salts solution as the dissolution test medium.