Improved Mobility-Stretchability Properties of Diketopyrrolopyrrole-Based Conjugated Polymers with Diastereomeric Conjugation Break Spacers.

Stretchable conjugated polymers with conjugation break spacers (CBSs) synthesized via random terpolymerization have gained considerable attention because of their efficacy in modulating mobility and stretchability. This study incorporates a series of dianhydrohexitol diastereomers of isosorbide (ISB) and isomannide (IMN) units into the diketopyrrolopyrrole-based backbone as CBSs. It is found that the distorted CBS (IMN) improves the mobility-stretchability properties of the polymer with a highly coplanar backbone, whereas the extended CBS (ISB) enhances those of the polymer with a noncoplanar backbone. Additionally, the different configurations of ISB and IMN sufficiently affect the solid-state packing, aggregation capabilities, crystallographic parameters, and mobility-stretchability properties of the polymer. The IMN-based polymers exhibit the highest mobility of 1.69 cm2 V-1 s-1 and crystallinity retentions of (85.7, 78.6)% under 20% and 60% strains, outperforming their ISB-based or unmodified counterparts. The improvement is correlated with a robust aggregation capability. Furthermore, the CBS content affects aggregation behavior, notably affecting mobility. This result indicates that incorporating CBSs into the polymer can enhance backbone flexibility via movement and rotation of the CBS without affecting the crystalline regions.

The Feasibility of a Model-Based Iterative Reconstruction Technique Tuned for the Myocardium on Myocardial Computed Tomography Late Enhancement.

OBJECTIVES: This study evaluated the feasibility of a model-based iterative reconstruction technique (MBIR) tuned for the myocardium on myocardial computed tomography late enhancement (CT-LE). METHODS: Twenty-eight patients who underwent myocardial CT-LE and late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) within 1 year were retrospectively enrolled. Myocardial CT-LE was performed using a 320-row CT with low tube voltage (80 kVp). Myocardial CT-LE images were scanned 7 min after CT angiography (CTA) without additional contrast medium. All myocardial CT-LE images were reconstructed with hybrid iterative reconstruction (HIR), conventional MBIR (MBIR_cardiac), and new MBIR tuned for the myocardium (MBIR_myo). Qualitative (5-grade scale) scores and quantitative parameters (signal-to-noise ratio [SNR] and contrast-to-noise ratio [CNR]) were assessed as image quality. The sensitivity, specificity, and accuracy of myocardial CT-LE were evaluated at the segment level using an American Heart Association (AHA) 16-segment model, with LGE-MRI as a reference standard. These results were compared among the different CT image reconstructions. RESULTS: In 28 patients with 448 segments, 160 segments were diagnosed with positive by LGE-MRI. In the qualitative assessment of myocardial CT-LE, the mean image quality scores were 2.9 ± 1.2 for HIR, 3.0 ± 1.1 for MBIR_cardiac, and 4.0 ± 1.0 for MBIR_myo. MBIR_myo showed a significantly higher score than HIR (P < 0.001) and MBIR_cardiac (P = 0.018). In the quantitative image quality assessment of myocardial CT-LE, the median image SNR was 10.3 (9.1-11.1) for HIR, 10.8 (9.8-12.1) for MBIR_cardiac, and 16.8 (15.7-18.4) for MBIR_myo. The median image CNR was 3.7 (3.0-4.6) for HIR, 3.8 (3.2-5.1) for MBIR_cardiac, and 6.4 (5.0-7.7) for MBIR_myo. MBIR_myo significantly improved the SNR and CNR of CT-LE compared to HIR and MBIR_cardiac (P < 0.001). The sensitivity, specificity, and accuracy for the detection of myocardial CT-LE were 70%, 92%, and 84% for HIR; 71%, 92%, and 85% for MBIR_cardiac; and 84%, 92%, and 89% for MBIR_myo, respectively. MBIR_myo showed significantly higher image quality, sensitivity, and accuracy than the others (P < 0.05). CONCLUSIONS: MBIR tuned for myocardium improved image quality and diagnostic performance for myocardial CT-LE assessment.

Comparisons of Hepatobiliary Phase Imaging Using Combinations of Parallel Imaging and Variable Degrees of Compressed Sensing With Use of Parallel Imaging Alone.

OBJECTIVE: This study aimed to compare the image quality in the hepatobiliary phase images of gadoxetic acid-enhanced liver magnetic resonance imaging using parallel imaging (PI) and compressed sensing (CS) reconstruction, using variable CS factors with the standard method using the PI technique. METHODS: In this study, 64 patients who underwent gadoxetic acid-enhanced liver magnetic resonance imaging at 3.0 T were enrolled. Hepatobiliary phase images were acquired 6 times using liver acquisition with volume acceleration (LAVA) and CS reconstruction with 5 CS factors 1.4, 1.6, 1.8, 2.0, and 2.5 (LAVA-CS 1.4, 1.6, 1.8, 2.0, and 2.5) and standard LAVA (LAVA-noCS). For objective analysis, the signal intensity ratios (SIRs) of the liver-to-spleen (SIR liver/spleen ), liver-to-portal vein (SIR liver/portal vein ), and liver-to-fat (SIR liver/fat ) were estimated. For subjective analysis, 2 radiologists independently evaluated the quality of all the images. RESULTS: The objective analysis demonstrated no significant difference in all evaluation parameters of all the images. Subjective analysis revealed that the scores of all evaluation items were higher for LAVA-noCS images than for LAVA-CS images, and only LAVA-CS 1.4 did not significantly differ from LAVA-noCS in all evaluation items ( P = 1.00 in 2 readers). CONCLUSIONS: A CS factor of 1.4 in the hepatobiliary phase image with combined PI and CS can reduce the scan time without degrading the image quality compared with the standard method.

Enhanced Masses on Contrast-Enhanced Breast: Differentiation Using a Combination of Dynamic Contrast-Enhanced MRI and Quantitative Evaluation with Synthetic MRI.

BACKGROUND: The addition of synthetic MRI might improve the diagnostic performance of dynamic contrast-enhanced MRI (DCE-MRI) in patients with breast cancer. PURPOSE: To evaluate the diagnostic value of a combination of DCE-MRI and quantitative evaluation using synthetic MRI for differentiation between benign and malignant breast masses. STUDY TYPE: Retrospective, observational. POPULATION: In all, 121 patients with 131 breast masses who underwent DCE-MRI with additional synthetic MRI were enrolled. FIELD STRENGTH/SEQUENCE: 3.0 Tesla, T1 -weighted DCE-MRI and synthetic MRI acquired by a multiple-dynamic, multiple-echo sequence. ASSESSMENT: All lesions were differentiated as benign or malignant using the following three diagnostic methods: DCE-MRI type based on the Breast Imaging-Reporting and Data System; synthetic MRI type using quantitative evaluation values calculated by synthetic MRI; and a combination of the DCE-MRI + Synthetic MRI types. The diagnostic performance of the three methods were compared. STATISTICAL TESTS: Univariate (Mann-Whitney U-test) and multivariate (binomial logistic regression) analyses were performed, followed by receiver-operating characteristic curve (AUC) analysis. RESULTS: Univariate and multivariate analyses showed that the mean T1 relaxation time in a breast mass obtained by synthetic MRI prior to injection of contrast agent (pre-T1 ) was the only significant quantitative value acquired by synthetic MRI that could independently differentiate between malignant and benign breast masses. The AUC for all enrolled breast masses assessed by DCE-MRI + Synthetic MRI type (0.83) was significantly greater than that for the DCE-MRI type (0.70, P < 0.05) or synthetic MRI type (0.73, P < 0.05). The AUC for category 4 masses assessed by the DCE-MRI + Synthetic MRI type was significantly greater than that for those assessed by the DCE-MRI type (0.74 vs. 0.50, P < 0.05). DATA CONCLUSION: A combination of synthetic MRI and DCE-MRI improves the accuracy of diagnosis of benign and malignant breast masses, especially category 4 masses. Level of Evidence 4 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53:381-391.

Macrophage Toll-like Receptor 9 Contributes to Chemotherapy-Induced Neuropathic Pain in Male Mice.

Chemotherapy-induced peripheral neuropathy (CIPN) remains a pressing clinical problem; however, our understanding of sexual dimorphism in CIPN remains unclear. Emerging studies indicate a sex-dimorphic role of Toll-like receptor 4 (TLR4) in driving neuropathic pain. In this study, we examined the role of TLR9 in CIPN induced by paclitaxel in WT and Tlr9 mutant mice of both sexes. Baseline pain sensitivity was not affected in either Tlr9 mutant male or female mice. Intraplantar and intrathecal injection of the TLR9 agonist ODN 1826 induced mechanical allodynia in both sexes of WT and Tlr4 KO mice but failed to do so in Tlr9 mutant mice. Moreover, Trpv1 KO or C-fiber blockade by resiniferatoxin failed to affect intraplantar ODN 1826-induced mechanical allodynia. Interestingly, the development of paclitaxel-evoked mechanical allodynia was attenuated by TLR9 antagonism or Tlr9 mutation only in male mice. Paclitaxel-induced CIPN caused macrophage infiltration to DRGs in both sexes, and this infiltration was not affected by Tlr9 mutation. Paclitaxel treatment also upregulated TNF and CXCL1 in macrophage cultures and DRG tissues in both sexes, but these changes were compromised by Tlr9 mutation in male animals. Intraplantar adoptive transfer of paclitaxel-activated macrophages evoked mechanical allodynia in both sexes, which was compromised by Tlr9 mutation or by treatment with TLR9 inhibitor only in male animals. Finally, TLR9 antagonism reduced paclitaxel-induced mechanical allodynia in female nude mice (T-cell and B-cell deficient). Together, these findings reveal sex-dimorphic macrophage TLR9 signaling in chemotherapy-induced neuropathic pain.SIGNIFICANCE STATEMENT Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect in cancer patients undergoing clinical chemotherapy treatment regimens. The role of sex dimorphism with regards to the mechanisms of CIPN and analgesia against CIPN remains unclear. Previous studies have found that the infiltration of immune cells, such as macrophages into DRGs and their subsequent activation promote CIPN. Interestingly, the contribution of microglia to CIPN appears to be limited. Here, we show that macrophage TLR9 signaling promotes CIPN in male mice only. This study suggests that pathways in macrophages may be sex-dimorphic in CIPN. Our findings provide new insights into the role of macrophage signaling mechanisms underlying sex dimorphism in CIPN, which may inspire the development of more precise and effective therapies.

Is Optogenetic Activation of Vglut1-Positive Aß Low-Threshold Mechanoreceptors Sufficient to Induce Tactile Allodynia in Mice after Nerve Injury?

Mechanical allodynia is a cardinal feature of pathological pain. Recent work has demonstrated the necessity of Aß-low-threshold mechanoreceptors (Aß-LTMRs) for mechanical allodynia-like behaviors in mice, but it remains unclear whether these neurons are sufficient to produce pain under pathological conditions. We generated a transgenic mouse in which channelrhodopsin-2 (ChR2) is conditionally expressed in vesicular glutamate transporter 1 (Vglut1) sensory neurons (Vglut1-ChR2), which is a heterogeneous population of large-sized sensory neurons with features consistent with Aß-LTMRs. In naive male Vglut1-ChR2 mice, transdermal hindpaw photostimulation evoked withdrawal behaviors in an intensity- and frequency-dependent manner, which were abolished by local anesthetic and selective A-fiber blockade. Surprisingly, male Vglut1-ChR2 mice did not show significant differences in light-evoked behaviors or real-time aversion after nerve injury despite marked hypersensitivity to punctate mechanical stimuli. We conclude that optogenetic activation of cutaneous Vglut1-ChR2 neurons alone is not sufficient to produce pain-like behaviors in neuropathic mice.SIGNIFICANCE STATEMENT Mechanical allodynia, in which innocuous touch is perceived as pain, is a common feature of pathological pain. To test the contribution of low-threshold mechanoreceptors (LTMRs) to nerve-injury-induced mechanical allodynia, we generated and characterized a new transgenic mouse (Vglut1-ChR2) to optogenetically activate cutaneous vesicular glutamate transporter 1 (Vglut1)-positive LTMRs. Using this mouse, we found that light-evoked behaviors were unchanged by nerve injury, which suggests that activation of Vglut1-positive LTMRs alone is not sufficient to produce pain. The Vglut1-ChR2 mouse will be broadly useful for the study of touch, pain, and itch.

Post-surgical chronic pain and quality of life in children operated for congenital heart disease.

BACKGROUND: Advances in medical technology have resulted in an increased life expectancy in pediatric patients with congenital heart diseases. Assessment of health-related quality of life is crucial to improving their healthcare status. We aimed to assess post-surgical pain prevalence and its impact on health-related quality of life in pediatric patients who underwent cardiac surgery during childhood. METHODS: This cross-sectional study recruited patients aged 4 years or older who underwent cardiac surgery for congenital heart disease at least 1 year prior, during the age of 0-10 years, and were admitted for post-surgical follow-up at our institute. The prevalence, intensity, and location of pain and health-related quality of life were assessed in an interview. Perioperative information was collected from the patients' medical records. Health-related quality of life was assessed using the Pediatric quality of life inventory 4.0 (PedsQL). RESULTS: Pain was reported by 24 (17%) of the 141 participants. One-third of them reported moderate to severe pain that required medical intervention. After adjustment for several confounding factors, multivariable linear regression analysis demonstrated that the presence of pain and the number of surgeries were associated with lower total PedsQL scores. CONCLUSIONS: Pain was present in 17% of the patients who underwent cardiac surgery during childhood. Presence of pain had a negative impact on long-term health-related quality of life after pediatric cardiac surgery.

Roles of inflammation, neurogenic inflammation, and neuroinflammation in pain.

Inflammation is the body's response to injury and infection, involving a complex biological response of the somatosensory, immune, autonomic, and vascular systems. Inflammatory mediators such as prostaglandin, proinflammatory cytokines, and chemokines induce pain via direct activation of nociceptors, the primary sensory neurons that detect noxious stimuli. Neurogenic inflammation is triggered by nerve activation and results in neuropeptide release and rapid plasma extravasation and edema, contributing to pain conditions such as headache. Neuroinflammation is a localized inflammation in the peripheral nervous system (PNS) and central nervous system (CNS). A characteristic feature of neuroinflammation is the activation of glial cells in dorsal root ganglia, spinal cord, and brain which leads to the production of proinflammatory cytokines and chemokines in the PNS and CNS that drives peripheral sensitization and central sensitization. Here, we discuss the distinct roles of inflammation, neurogenic inflammation, and neuroinflammation in the regulation of different types of pain conditions, with a special focus on neuroinflammation in postoperative pain and opioid-induced hyperalgesia.

Synergistic activation of ERK1/2 between A-fiber neurons and glial cells in the DRG contributes to pain hypersensitivity after tissue injury.

Background Intense nociceptive signaling arising from ongoing injury activates primary afferent nociceptive systems to generate peripheral sensitization. ERK1/2 phosphorylation in dorsal root ganglion can be used to visualize intracellular signal activity immediately after noxious stimulation. The aim of this study was to investigate spatiotemporal characteristics of ERK1/2 phosphorylation against tissue injury in the primary afferent neurons. Methods Plantar incisions were made in the hind paws of Sprague-Dawley rats (n =150). Levobupivacaine was injected into the plantar aspect of the paws and ankles, Mitogen-activated protein kinase kinase (MEK) inhibitor was injected into the paw, and carbenoxolone, dual inhibitor of the gap junction and pannexin channel, was intraperitoneally injected. Pain hypersensitivity was investigated by a behavioral study, while phosphorylated ERK1/2 was detected in dorsal root ganglion and hind paw using immunohistochemistry and Western blot. Results Phosphorylated ERK1/2 was induced in dorsal root ganglion (26.8 ± 2.9% at baseline, 65.6 ± 3.6% at 2 min, and 26.3 ± 3.4% at 2 h) after the incision. NF-200 positive A-fiber neurons and satellite glial cells were positive for phosphorylated ERK1/2. Injury-induced pain hypersensitivity was abolished by MEK inhibitor. Levobupivacaine treatment inhibited phosphorylated ERK1/2 induction, carbenoxolone treatment inhibited glial phosphorylated ERK1/2 at 2 min after the injury, and carbenoxolone inhibited pain hypersensitivity and neuronal phosphorylated ERK1/2 at 1 h after the injury. Conclusion ERK1/2 phosphorylation in A-fiber neurons and satellite glial cells immediately after injury contributes to the generation of pain hypersensitivity. Signal communication between neurons and satellite glial cells expands the duration of neuronal ERK1/2 phosphorylation and pain hypersensitivity at 1 h after tissue injury.

Dual-Energy Computed Tomography in Patients With Small Hepatocellular Carcinoma: Utility of Noise-Reduced Monoenergetic Images for the Evaluation of Washout and Image Quality in the Equilibrium Phase.

PURPOSE: This study aimed to evaluate the utility of virtual monoenergetic images for detecting washout of small (≤2 cm) hepatocellular carcinoma (HCC) in the equilibrium phase. METHODS: We performed 120-kVp-equivalent linear-blended (M120) and monoenergetic reconstructions from 40 to 90 keV by standard (40, 50, 60, 70, 80, 90) and novel noise-reduced (nMERA: 40+, 50+, 60+, 70+, 80+, 90+) monoenergetic reconstruction algorithms. Image quality and tumor visibility of delayed washout of HCCs in the equilibrium phase were compared between standard monoenergetic reconstruction algorithm and nMERA by objective and subjective analyses. RESULTS: Contrast-to-noise ratio of the tumor at 40+ was the highest, whereas the score of tumor visibility peaked at 50+. The score of overall image quality at 40+ was significantly lower than those on all other image series, and the image quality among other image series were not significantly different. CONCLUSIONS: Virtual monoenergetic image reconstructed with nMERA 50+ was most appropriate to detect washout of small HCCs.

Acquired Exchange Protein Directly Activated by Cyclic Adenosine Monophosphate Activity Induced by p38 Mitogen-activated Protein Kinase in Primary Afferent Neurons Contributes to Sustaining Postincisional Nociception.

BACKGROUND: The molecular mechanisms responsible for sustained pain after tissue injury are largely unknown. The aim of this study was to clarify the role of exchange protein directly activated by cyclic adenosine monophosphate (EPAC) in sustained postincisional nociception, using tissue injury-induced nociceptor priming, and involvement of p38 mitogen-activated protein kinase (p38MAPK) in EPAC-mediated nociceptor priming. METHODS: Plantar incisions were made in the hind paws of Sprague-Dawley rats (n = 144). Nociceptor priming was confirmed by behavior testing followed by prostaglandin E2 injection 14 to 21 days after the incision. ESI-09, a selective EPAC inhibitor, was administered to assess its effects on nociceptor priming. Expression of two isoforms of EPAC (EPAC1/EPAC2) in dorsal root ganglions from naive rats and those 14 days after the incision was detected by immunohistochemistry and Western blotting. Separately, FR167653, a selective p38MAPK inhibitor, was administered to assess its effect on EPAC1/EPAC2 expression and the development of nociceptor priming. RESULTS: Prostaglandin E2 injection 14 to 21 days after the plantar incision induced persistent mechanical hyperalgesia for 7 days. EPAC1/EPAC2 expression in dorsal root ganglion neurons was trivial in naive rats (7.7 ± 4.8% for EPAC1; 6.3 ± 4.1% for EPAC2) but markedly increased 14 days after the incision (21.0 ± 9.4% and 20.1 ± 3.8%, respectively). ESI-09 treatment inhibited prostaglandin E2-induced persistent mechanical hypersensitivity but had no effect on incision-induced acute nociceptive hypersensitivity. Treatment with FR167653 before the incision inhibited the development of nociceptor priming and incision-induced EPAC1/EPAC2 expression (8.5 ± 5.4% and 7.6 ± 3.3%, respectively). CONCLUSIONS: Transient inflammatory stimulation causes long-lasting nociceptive hypersensitivity via nociceptor priming during the subacute period after incision. Acquired EPAC activity by p38MAPK in the dorsal root ganglion neurons is a key for this event.

Duplicate origin and extremely long P1 segment of the posterior cerebral artery diagnosed by MR angiography.

We present what we believe is the first report of a patient with an anomalous artery arising from the distal basilar artery and fusing with the mid-portion of an extremely long P1 segment of the left posterior cerebral artery that was diagnosed on magnetic resonance (MR) angiography. Careful review of MR angiographic images is important to detect rare arterial variations, and partial maximum-intensity-projection images aid their identification on MR angiography.

[Risk Factors for the Postsurgical Hoarseness Contribution of the Intubation Device].

BACKGROUND: Postsurgical hoarseness is one of the major postoperative complications. METHODS: Risk factors associated with the postsur- gical hoarseness were investigated from medical records of 579 adult patients undergoing general anes- thesia with tracheal intubation. Postsurgical hoarseness was judged if a patient developed hoarseness at PODO or PODI by postanesthesia round. Multivariate logistic regression was performed to identify the parameters associated with postsurgical hoarseness. RESULTS: Postsurgical hoarseness developed in 16.1% of patients. None of the patients suffered hoarseness continuing more than 4 days. Multivariate logistic regression revealed increased BMI (odds ratio (OR) 1.06 [95% confidence interval (CI):1.00-1.131], depth of tracheal tube (OR 0.71 [95% CI : 0.57-0.86]), intu- bation performed by doctors in training (OR 4.07 [95% CI : 2.42-7.10]) and intubation with Airway Scope® (OR 2.03 [95% CI : 1.10-3.66]). CONCLUSIONS: Increased BMI, depth of tracheal tube, intubation performed by doctors in training and intu- bation with Airway Scope® are risk factors of postsur- gical hoarseness.

Gadolinium-based Contrast Agent Accumulates in the Brain Even in Subjects without Severe Renal Dysfunction: Evaluation of Autopsy Brain Specimens with Inductively Coupled Plasma Mass Spectroscopy.

PURPOSE: To use inductively coupled plasma mass spectroscopy (ICP-MS) to evaluate gadolinium accumulation in brain tissues, including the dentate nucleus (DN) and globus pallidus (GP), in subjects who received a gadolinium-based contrast agent (GBCA). MATERIALS AND METHODS: Institutional review board approval was obtained for this study. Written informed consent for postmortem investigation was obtained either from the subject prior to his or her death or afterward from the subject's relatives. Brain tissues obtained at autopsy in five subjects who received a linear GBCA (GBCA group) and five subjects with no history of GBCA administration (non-GBCA group) were examined with ICP-MS. Formalin-fixed DN tissue, the inner segment of the GP, cerebellar white matter, the frontal lobe cortex, and frontal lobe white matter were obtained, and their gadolinium concentrations were measured. None of the subjects had received a diagnosis of severely compromised renal function (estimated glomerular filtration rate <45 mL/min/1.73 m(2)) or acute renal failure. Fisher permutation test was used to compare gadolinium concentrations between the two groups and among brain regions. RESULTS: Gadolinium was detected in all specimens in the GBCA agent group (mean, 0.25 µg per gram of brain tissue ± 0.44 [standard deviation]), with significantly higher concentrations in each region (P = .004 vs the non-GBCA group for all regions). In the GBCA group, the DN and GP showed significantly higher gadolinium concentrations (mean, 0.44 µg/g ± 0.63) than other regions (0.12 µg/g ± 0.16) (P = .029). CONCLUSION: Even in subjects without severe renal dysfunction, GBCA administration causes gadolinium accumulation in the brain, especially in the DN and GP.

Effects of exenatide on postprandial vascular endothelial dysfunction in type 2 diabetes mellitus.

BACKGROUND: Basic studies have shown that glucagon-like peptide-1 (GLP-1) analogs exert a direct protective effect on the vascular endothelium in addition to their indirect effects on postprandial glucose and lipid metabolism. GLP-1 analogs are also reported to inhibit postprandial vascular endothelial dysfunction. This study examined whether the GLP-1 analog exenatide inhibits postprandial vascular endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM). METHODS: Seventeen patients with T2DM underwent a meal tolerance test to examine changes in postprandial vascular endothelial function and in glucose and lipid metabolism, both without exenatide (baseline) and after a single subcutaneous injection of 10 µg exenatide. Vascular endothelial function was determined using reactive hyperemia index (RHI) measured by peripheral arterial tonometry before and 120 min after the meal loading test. The primary endpoint was the difference in changes in postprandial vascular endothelial function between the baseline and exenatide tests. RESULTS: The natural logarithmically-scaled RHI (L_RHI) was significantly lower after the baseline meal test but not in the exenatide test. The use of exenatide resulted in a significant decrease in triglycerides (TG) area under the curve and coefficient of variation (CV). The change in L_RHI correlated with changes in CV of triglycerides and HDL-cholesterol. Multivariate analysis identified changes in triglyceride CV as the only determinant of changes in L_RHI, contributing to 41% of the observed change. CONCLUSIONS: Exenatide inhibited postprandial vascular endothelial dysfunction after the meal loading test, suggesting that exenatide has a multiphasic anti-atherogenic action involving not only glucose but also lipid metabolism. TRIAL REGISTRATION: ClinicalTrials.gov: UMIN000015699.

Preoperative anesthesia clinic in Japan: a nationwide survey of the current practice of preoperative anesthesia assessment.

PURPOSE: In order to investigate the current practice of preoperative anesthesia assessment in Japan, we conducted a nationwide survey of the preoperative anesthesia clinic (PAC). METHODS: A written questionnaire was sent to anesthesia teaching hospitals certified by the Japanese Society of Anesthesiologists. RESULTS: Completed questionnaires were received from 789 hospitals (response rate 62.5 %). PACs were conducted in 52.0 % of these hospitals and were more frequently implemented in large hospitals. Services covered by the PAC included medical history taking, physical examination, review of laboratory data, and obtaining informed consent. Majority of the anesthesiologists at hospitals that did not have a PAC responded that although they acknowledged that a PAC is necessary, they were unable to set one up. The main obstacle preventing establishment of the PAC was shortage of human resources. CONCLUSIONS: Half the anesthesia teaching hospitals in Japan use a PAC for preoperative assessment. At such hospitals, all the procedures required before anesthesia are performed in the clinic. Lack of human resources is the major obstacle preventing establishment of PACs in all hospitals.

[A Case of Emergency Cesarean Section and Craniotomy in a 26 Week Pregnant Woman].

Intracranial hemorrhage is a rare complication during the pregnancy but carries a poor prognosis. We experienced a case of emergency cesarean section and craniotomy for removal of hematoma due to arteriovenous malformation (AVM) rupture. A 33-year-old woman at 26 weeks of pregnancy suffered a sudden onset of headache and disturbance of consciousness. She was diagnosed with left cerebral hemorrhage due to AVM rupture. Emergency cesarean section was followed by the surgical removal of the hematoma under general anesthesia. Postoperative courses of both mother and baby were satisfactory. The severity of illness of the mother strongly influences her fetus and vise versa. When performing cesarean section before craniotomy, anesthesia should be managed to prevent recurrence of intracranial hemorrhage during the cesarean section and atonic bleeding during the craniotomy. Anesthetist should have adequate knowledge and communicate adequately with obstetrician and pediatrician to achieve better prognosis for the intracranial hemorrhage during pregnancy.

Coronary computed tomography angiography for clinical practice.

Coronary artery disease (CAD) is a common condition caused by the accumulation of atherosclerotic plaques. It can be classified into stable CAD or acute coronary syndrome. Coronary computed tomography angiography (CCTA) has a high negative predictive value and is used as the first examination for diagnosing stable CAD, particularly in patients at intermediate-to-high risk. CCTA is also adopted for diagnosing acute coronary syndrome, particularly in patients at low-to-intermediate risk. Myocardial ischemia does not always co-exist with coronary artery stenosis, and the positive predictive value of CCTA for myocardial ischemia is limited. However, CCTA has overcome this limitation with recent technological advancements such as CT perfusion and CT-fractional flow reserve. In addition, CCTA can be used to assess coronary artery plaques. Thus, the indications for CCTA have expanded, leading to an increased demand for radiologists. The CAD reporting and data system (CAD-RADS) 2.0 was recently proposed for standardizing CCTA reporting. This RADS evaluates and categorizes patients based on coronary artery stenosis and the overall amount of coronary artery plaque and links this to patient management. In this review, we aimed to review the major trials and guidelines for CCTA to understand its clinical role. Furthermore, we aimed to introduce the CAD-RADS 2.0 including the assessment of coronary artery stenosis, plaque, and other key findings, and highlight the steps for CCTA reporting. Finally, we aimed to present recent research trends including the perivascular fat attenuation index, artificial intelligence, and the advancements in CT technology.

Tissue injury and related mediators of pain exacerbation.

Tissue injury and inflammation result in release of various mediators that promote ongoing pain or pain hypersensitivity against mechanical, thermal and chemical stimuli. Pro-nociceptive mediators activate primary afferent neurons directly or indirectly to enhance nociceptive signal transmission to the central nervous system. Excitation of primary afferents by peripherally originating mediators, so-called "peripheral sensitization", is a hallmark of tissue injury-related pain. Many kinds of pro-nociceptive mediators, including ATP, glutamate, kinins, cytokines and tropic factors, synthesized at the damaged tissue, contribute to the development of peripheral sensitization. In the present review we will discuss the molecular mechanisms of peripheral sensitization following tissue injury.

Simultaneous intracranial and extracranial vertebral artery dissections: a case report.

Vertebral artery dissection can occur in intracranial or extracranial vertebral arteries. However, the simultaneous dissection of both intracranial and extracranial vertebral arteries is extremely rare. We describe a 45-year-old man with simultaneous intracranial and extracranial vertebral artery dissections in separate sites. The patient visited a neurosurgical clinic because of headache; he was diagnosed with right vertebral artery dissection and referred to our hospital. Magnetic resonance imaging showed an intramural hematoma and mild dilation of the external lumen in the right vertebral artery distal to the posterior inferior cerebellar artery. Magnetic resonance angiography revealed poor delineation of the entire right vertebral artery, including the proximal portion from the posterior inferior cerebellar artery. Computed tomography angiography revealed right extracranial vertebral artery dissection. Careful imaging assessment is thus important for identifying simultaneous intracranial and extracranial vertebral artery dissections.