Iatrogenic vertebral artery injury during catheter ablation treated using coil embolization.

The internal jugular vein (IJV) is occasionally used for blood access during catheter ablation. Additionally, accidental injury of the vertebral artery during an IJV puncture is a rare complication that can result in catastrophic events, such as death. However, vascular access complications cannot be completely prevented despite the introduction of ultrasound-guided punctures. Here, we present a case of a patient with symptomatic paroxysmal atrial fibrillation that required catheter ablation.

Safety evaluation of sinus patency after stereotactic radiosurgery for transverse-sigmoid sinus dural arteriovenous fistulas: implications of treatment options for patients with Borden type I fistulas.

OBJECTIVE: This study aimed to assess the efficacy and safety of stereotactic radiosurgery (SRS) in treating transverse-sigmoid sinus dural arteriovenous fistulas (TSS DAVFs), and to investigate post-SRS sinus patency, focusing on the risk factors associated with treated sinus occlusion. METHODS: Data from 34 patients treated with SRS between January 2006 and April 2023 were analyzed. Detailed angioarchitecture was confirmed using digital subtraction angiography before SRS. Angiography of the ipsilateral internal carotid artery and vertebral artery was performed to evaluate whether the involved side of the TSS was used for normal venous drainage. TSS stenosis was defined as sinus diameter < 50% of the normal proximal diameter. DAVF shunt obliteration, TSS occlusion, neurological status, and adverse events were also evaluated. RESULTS: Of the 34 patients, 21 had Borden type I and 14 had Borden type II DAVFs. The median age at SRS was 64 years (interquartile range 54-71 years), and the follow-up period was 31 months (interquartile range 15-94 months). Complete shunt obliteration was achieved in 24 (70.6%) patients. The cumulative 2-, 3-, and 5-year shunt obliteration rates were 49.6%, 71.2%, and 86.0%, respectively. Borden type I had higher obliteration rates (60.5%, 83.1%, and 94.4%, respectively) than Borden type II (41.7%, 51.4%, and 75.7%, respectively; p = 0.034). TSS occlusion occurred in 5 patients (14.7%). The cumulative 1-, 5-, and 10-year TSS occlusion rates were 2.9%, 8.3%, and 23.6%, respectively, across the entire cohort. All occlusions occurred exclusively in the sinuses that were not used for normal venous drainage. Cox proportional analyses revealed that TSS stenosis and the sinus not being used for normal venous drainage were significantly associated with a greater risk of TSS occlusion after SRS (HR 9.44, 95% CI 1.01-77.13; p = 0.049). CONCLUSIONS: SRS is effective and safe for TSS DAVF and results in favorable shunt obliteration, symptom improvement, and low complication rates. TSS occlusion after SRS is asymptomatic and is limited to sinuses that are not used for normal venous drainage.

Genomic repertoires linked with pathogenic potency of arthritogenic Prevotella copri isolated from the gut of patients with rheumatoid arthritis.

OBJECTIVES: Prevotella copri is considered to be a contributing factor in rheumatoid arthritis (RA). However, in some non-Westernised countries, healthy individuals also harbour an abundance of P. copri in the intestine. This study investigated the pathogenicity of RA patient-derived P. copri (P. copri RA) compared with healthy control-derived P. copri (P. copri HC). METHODS: We obtained 13 P. copri strains from the faeces of patients with RA and healthy controls. Following whole genome sequencing, the sequences of P. copri RA and P. copri HC were compared. To analyse the arthritis-inducing ability of P. copri, we examined two arthritis models (1) a collagen-induced arthritis model harbouring P. copri under specific-pathogen-free conditions and (2) an SKG mouse arthritis model under P. copri-monocolonised conditions. Finally, to evaluate the ability of P. copri to activate innate immune cells, we performed in vitro stimulation of bone marrow-derived dendritic cells (BMDCs) by P. copri RA and P. copri HC. RESULTS: Comparative genomic analysis revealed no apparent differences in the core gene contents between P. copri RA and P. copri HC, but pangenome analysis revealed the high genome plasticity of P. copri. We identified a P. copri RA-specific genomic region as a conjugative transposon. In both arthritis models, P. copri RA-induced more severe arthritis than P. copri HC. In vitro BMDC stimulation experiments revealed the upregulation of IL-17 and Th17-related cytokines (IL-6, IL-23) by P. copri RA. CONCLUSION: Our findings reveal the genetic diversity of P. copri, and the genomic signatures associated with strong arthritis-inducing ability of P. copri RA. Our study contributes towards elucidation of the complex pathogenesis of RA.

Genetics of brain arteriovenous malformations and cerebral cavernous malformations.

Cerebrovascular malformations comprise abnormal development of cerebral vasculature. They can result in hemorrhagic stroke due to rupture of lesions as well as seizures and neurological defects. The most common forms of cerebrovascular malformations are brain arteriovenous malformations (bAVMs) and cerebral cavernous malformations (CCMs). They occur in both sporadic and inherited forms. Rapidly evolving molecular genetic methodologies have helped to identify causative or associated genes involved in genesis of bAVMs and CCMs. In this review, we highlight the current knowledge regarding the genetic basis of these malformations.

Hypertensive disorders of pregnancy in moyamoya disease: A single institution experience.

OBJECTIVE: The characteristics of pregnancy and delivery in patients with moyamoya disease (MMD) remain unclear. We retrospectively investigated perinatal outcomes in patients with MMD to evaluate the risks associated to this condition. MATERIALS AND METHODS: Clinical data of women with MMD who delivered at the University of Tokyo Hospital between 2000 and 2021 were collected. Maternal characteristics including genetic data, obstetric complications, method of delivery and anesthesia, neonatal outcomes, neurological events during pregnancy, delivery, and postpartum course, were reviewed. RESULTS: Thirteen pregnancies with MMD were identified. The median maternal age was 30 years. The initial clinical symptoms were identified as transient ischemic attack, infarction, and headache. Eight patients had a history of bypass surgery. The median gestational age at delivery was 37 weeks. DNA samples were collected from five patients, responsible for six pregnancies. Of these six cases, five had the RNF213 c.14429G > A (p.Arg4810Lys) heterozygous variant. Of the 13 pregnancies, seven had hypertensive disorder of pregnancy (HDP). Additionally, three of five pregnancy cases with RNF213 p.Arg4810Lys heterozygous variant presented with HDP. Nine patients underwent cesarean section, and four delivered vaginally with epidural anesthesia. One case of ischemic stroke was confirmed during the postpartum period. Regarding newborns, neither Apgar scores lower than 7 nor neonatal intensive care unit admissions were reported. CONCLUSIONS: This study suggests that the frequency of HDP is higher in patients with MMD compared to those with normal pregnancies. Strict blood pressure control should be performed in patients with MMD during pregnancy and postpartum period.

Reliability and sensitivity to altered hemodynamics measured with resting-state fMRI metrics: Comparison with 123I-IMP SPECT.

Blood oxygenation level-dependent (BOLD) contrast is sensitive to local hemodynamic changes and thus is applicable to imaging perfusion or vascular reactivity. However, knowledge about its measurement characteristics compared to reference standard perfusion imaging is limited. This study longitudinally evaluated perfusion in patients with steno-occlusive disease using resting-state functional MRI (rsfMRI) acquired before and within nine days of anterior circulation revascularization in patients with large cerebral artery steno-occlusive diseases. The reliability and sensitivity to longitudinal changes of rsfMRI temporal correlation (Rc) and time delay (TDc) relative to the cerebellar signal were examined voxel-wise in comparison with single-photon emission CT (SPECT) cerebral blood flow (CBF) using the within-subject standard deviation (Sw) and intraclass correlation coefficients (ICCs). For statistical comparisons, the standard deviation (SD) of longitudinal changes within the cerebellum, the number of voxels with significant changes in the left middle cerebral artery territory ipsilateral to surgery, and their average changes relative to the cerebellar SD were evaluated. The test-retest reliability of the fMRI metrics was also similarly evaluated using the human connectome project (HCP) healthy young adult dataset. The test-retest time interval was 31 ± 18 days. Test-retest reliability was significantly higher for SPECT (cerebellar SD: -2.59 ± 0.20) than for fMRI metrics (cerebellar SD: Rc, -2.34 ± 0.24, p = 0.04; TDc, -2.19 ± 0.21, p = 0.003). Sensitivity to postoperative changes, which was evaluated as the number of voxels, was significantly higher for fMRI TDc (8.78 ± 0.72) than for Rc (7.42 ± 1.48, p = 0.03) or SPECT CBF (6.88 ± 0.67, p < 0.001). The ratio between the average Rc, TDc, and SPECT CBF changes within the left MCA target region and cerebellar SD was also significantly higher for fMRI TDc (1.21 ± 0.79) than Rc (0.48 ± 0.94, p = 0.006) or SPECT CBF (0.23 ± 0.57, p = 0.001). The measurement variability of time delay was also larger than that of temporal correlation in HCP data within the cerebellum (t = -8.7, p < 0.001) or in the whole-brain (t = -27.4, p < 0.001) gray matter. These data suggest that fMRI time delay is more sensitive to the hemodynamic changes than SPECT CBF, although the reliability is lower. The implication for fMRI connectivity studies is that temporal correlation can be significantly decreased due to altered hemodynamics, even in cases with normal CBF.

Arterial Transit Time-Based Multidelay Combination Strategy Improves Arterial Spin Labeling Cerebral Blood Flow Measurement Accuracy in Severe Steno-Occlusive Diseases.

BACKGROUND: Although perfusion imaging plays a key role in the management of steno-occlusive diseases, the clinical usefulness of arterial spin labeling (ASL) is limited by technical issues. PURPOSE: To examine the effect of arterial transit time (ATT) prolongation on cerebral blood flow (CBF) measurement accuracy and identify the best CBF measurement protocol for steno-occlusive diseases. STUDY TYPE: Prospective. POPULATION: Moyamoya (n = 10) and atherosclerotic diseases (n = 8). FIELD STRENGTH/SEQUENCE: A 3.0T/3DT1 -weighted and ASL. ASSESSMENT: Hadamard-encoded multidelay ASL scans with/without vessel suppression (VS) and single-delay ASL scans with long-label duration (LD) and long postlabeling delay (PLD), referred to as long-label long-delay (LLLD), were acquired. CBF measurement accuracy and its ATT dependency, measured as the correlation between the relative CBF measurement difference (ASL-single-photon emission computed tomography [SPECT]) and ATT, were compared among 1) Combo (incorporating multidelay and LLLD data based on ATT), 2) standard (LD/PLD = 1333/2333 msec), and 3) LLLD (LD/PLD = 4000/4000 msec) protocols, using whole-brain voxel-wise correlation with reference standard SPECT CBF. The effect of VS on CBF measurement accuracy was also assessed. STATISTICAL TESTS: Pearson's correlation coefficient, repeated-measures analysis of variance, t-test. P< 0.05 was considered significant. RESULTS: Pearson's correlation coefficients between ASL and SPECT CBF measurements were as follows: Combo = 0.55 ± 0.09; standard = 0.52 ± 0.12; LLLD = 0.41 ± 0.10. CBF measurement was least accurate in LLLD and most accurate in Combo. VS significantly improved overall CBF measurement accuracy in the standard protocol and in moyamoya patients for the Combo. ATT dependency analysis revealed that, compared with Combo, the standard and LLLD protocols showed significantly lower and negative and significantly higher and positive correlations, respectively (standard = -0.12 ± 0.04, Combo = -0.04 ± 0.03, LLLD = 0.17 ± 0.03). DATA CONCLUSION: By using ATT-corrected CBF derived from LD/PLD = 1333/2333 msec as a base and by compensating underestimation in delayed regions using multidelay scans, the ATT-based Combo strategy improves CBF measurement accuracy compared with single-delay protocols in severe steno-occlusive diseases. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Reliability and Sensitivity to Longitudinal CBF Changes in Steno-Occlusive Diseases: ASL Versus 123 I-IMP-SPECT.

BACKGROUND: Noninvasive cerebral blood flow (CBF) monitoring using arterial spin labeling (ASL) magnetic resonance imaging is useful for managing large cerebral artery steno-occlusive diseases. However, knowledge about its measurement characteristics in comparison with reference standard perfusion imaging is limited. PURPOSE: To evaluate perfusion in a longitudinal manner in patients with steno-occlusive disease using ASL and compare with single-photon emission computed tomography (SPECT). STUDY TYPE: Prospective. POPULATION: Moyamoya (n = 10, eight females) and atherosclerotic diseases (n = 2, two males). FIELD STRENGTH/SEQUENCE: 3.0 T; gradient-echo three-dimensional T1 -weighted and spin-echo ASL. ASSESSMENT: Multi-delay ASL and [123 I]-iodoamphetamine SPECT CBF measurements were performed both before and within 9 days of anterior-circulation revascularization. Reliability and sensitivity to whole-brain voxel-wise CBF changes (ΔCBF) and their postlabeling delay (PLD) dependency with varied PLDs (in milliseconds) of 1000, 2333, and 3666 were examined. STATISTICAL TESTS: Reliability and sensitivity to ΔCBF were examined using within-subject standard deviation (Sw) and intraclass correlation coefficients (ICCs). For statistical comparisons, standard deviation of longitudinal ΔCBF within the hemisphere contralateral to surgery, and the ratio between it and average ΔCBF within the ipsilateral regions of interest were subjected to paired t tests, respectively. P < 0.05 was considered statistically significant. RESULTS: ASL test-retest time interval was 31 ± 18 days. Test-retest reliability was significantly lower for SPECT (0.16 ± 0.02) than ASL (0.13 ± 0.04). Sensitivity to postoperative changes was significantly higher for ASL (2.71 ± 2.79) than SPECT (0.27 ± 0.62). Test-retest reliability was significantly higher for a PLD of 2333 (0.13 ± 0.04) than 3666 (0.19 ± 0.05), and sensitivity to ΔCBF was significantly higher for PLDs of 1000 (2.53 ± 2.50) and 2333 than 3666 (0.79 ± 1.88). ICC maps also showed higher reliability for ASL than SPECT. DATA CONCLUSION: Higher test-retest reliability led to better ASL sensitivity than SPECT for postoperative ΔCBF. ASL test-retest reliability and sensitivity to ΔCBF were higher with a PLD of 2333. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Revisitation of imaging features of skull base chondrosarcoma in comparison to chordoma.

PURPOSE: Pre-surgical diagnosis of skull base chondrosarcoma (SBC) is often challenging due to the resemblance to chordoma. The goal of this study was to develop an optimal method for predicting SBC diagnosis. METHODS: This retrospective study included patients with histologically diagnosed SBC and skull base chordoma. Their clinical and radiologic features were compared, and the predictive factors of SBC were examined. RESULTS: Forty-one patients with SBC and 41 with chordoma were included. Most SBCs exhibited hypointensity (25, 64.1%) or isointensity (12, 30.8%) on T1-weighted images, and hyperintensity (34, 87.1%) or mixed intensity (5, 12.8%) on T2-weighted images. MRI contrast enhancement was usually avid or fair (89.7%) with "arabesque"-like pattern (41.0%). The lateral/paramidline location was more common in SBC than in chordoma (85.4% vs. 9.8%; P < 0.01), while midline SBCs (14.6%) were also possible. Multivariate analysis demonstrated that higher apparent diffusion coefficient (ADC) value (unit odds ratio 1.01; 95% confidence interval 1.00-1.02; P < 0.01) was associated with an SBC diagnosis. An ADC value of ≥ 1750 × 10-6 mm2/s demonstrated a strong association with an SBC diagnosis (odds ratio 5.89 × 102; 95% confidence interval 51.0-6.80 × 103; P < 0.01) and yielded a sensitivity of 93.9%, specificity of 97.4%, positive predictive value of 96.9%, and negative predictive value of 95.0%. CONCLUSION: The ADC-based method is helpful in distinguishing SBC from chordoma and readily applicable in clinical practice. The prediction accuracy increases when other characteristics of SBC, such as non-midline location and arabesque-like enhancement, are considered together.

The optimal management of ruptured basilar artery dissecting aneurysms: a case series and scoping review.

The natural history of ruptured basilar artery dissecting aneurysms (BADAs) remains unclear compared to that of ruptured vertebral artery dissecting aneurysms (VADAs). In this study, we investigated the natural history and optimal management of ruptured BADAs. We identified 17 patients with ruptured BADA among 4586 patients with aneurysmal subarachnoid hemorrhage (SAH) treated in seven participating hospitals. A scoping literature review was undertaken to investigate prognostic factors. Six patients among the profiled patients (35.3%) died, all with poor SAH grades (World Federation of Neurological Societies Grade IV and V). Rebleeding after admission was observed in three patients (17.6%) with poor SAH grades. Aggressive treatment and conservative management were initiated in seven and ten patients, respectively. Patients with good SAH grades had significantly higher favorable treatment outcomes than those with poor grades (83.3% vs. 9.1%, P = 0.005). Moreover, based on a scoping review of 158 cases with ruptured BADA, including the patients from our series, approximately 90% of patients with good SAH grades had favorable outcomes. A good SAH grade and no rebleeding after admission were favorable prognostic factors (P < 0.0001 and P = 0.002, respectively). The rebleeding rates were 20.2%, 13.3%, and 6.3% for dilated, pearl and string, and stenotic lesions, respectively. We concluded that the natural history of isolated ruptured BADAs may be better than that of VADAs. Although definitive treatment, if possible, is undoubtedly important, conservative management with careful radiological follow-up for morphological changes might be a viable option for patients in good clinical condition and with non-dilated lesions.

Identification of interleukin-16 production on tumor aggravation in hepatocellular carcinoma by a proteomics approach.

BACKGROUND: Cytokines play an important role in the immune response, angiogenesis, cell growth, and differentiation in hepatocellular carcinoma (HCC). OBJECTIVE: We performed a comprehensive study to identify tumor-related cytokines and pathways involved in HCC pathogenesis. METHODS: Cytokine production was evaluated in human HCC tissues and adjacent non-tumor tissues using an antibody-based protein array technique. We compared cytokine expression in HCC tissues with that of hepatic hemangioma (HH), liver metastasis of colorectal cancer, and noncancerous liver tissues from transplantation donors. The protein levels and localization of the candidate cytokines were analyzed by western blotting and immunohistochemistry. RESULTS: Increased expression of interleukin (IL)-1 receptor antagonist, macrophage migration inhibitory factor, and IL-16 was observed in HCC and paired adjacent non-tumor tissues compared with noncancerous livers. In addition, there were increased IL-16 levels in HCC tissues compared with HH. IL-16 treatment significantly increased cell proliferation in vitro. The expression of extracellular signal-regulated kinase (ERK)1/2 and cyclin D1 was markedly increased in cells from two HCC cell lines, Huh7 and HepG2, in a dose- and time-dependent manner. Phosphorylated to total ERK1/2 ratio was increased in Huh7 cells following IL-16 50 ng/ml, but not HepG2 cells. ERK phosphorylation have occurred earlier than protein accumulation at 48 h. Pretreatment with the ERK inhibitor, FR18024, or an anti-IL-16 antibody reduced the increase in IL-16 production in HCC cells. CONCLUSIONS: These results suggest that cell proliferation induced by IL-16 is mediated through the ERK pathway, thus, we identified a new factor associated with HCC tumor growth.

Complete Lymphadenectomy Around the Entire Superior Mesenteric Artery Improves Survival in Artery-First Approach Pancreatoduodenectomy for T3 Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Artery-first approach pancreatoduodenectomy (AFA-PD) is an important technique for treating pancreatic ductal adenocarcinoma (PDAC). However, it remains unknown whether performing complete lymphadenectomy around the entire superior mesenteric artery (SMA) is associated with better outcomes. In this retrospective study, we aimed to investigate whether this approach improved overall and recurrence-free survival in patients with PDAC. METHODS: We identified 88 patients with T3 PDAC who underwent PD at St. Marianna University School of Medicine, Kawasaki, Japan, between April 2005 and October 2017. Two groups were defined: an "AFA-PD group" (n = 45) who had undergone AFA-PD in addition to complete lymphadenectomy around the entire SMA, and a "conventional PD group" (n = 43) in whom complete lymphadenectomy had not been performed (conventional group). Univariate and multivariate survival analyses were performed to identify risk factors for overall and disease-free survival. RESULTS: The AFA-PD group had a longer median survival time (40.3 vs. 22.6 months; p = 0.0140) and a higher 5-year survival rate (40.3% vs. 5.9%, p = 0.005) than the conventional PD group. Multivariate analysis showed that AFA-PD with complete lymphadenectomy around the entire SMA was an independent factor for improved overall survival (p = 0.022). Recurrences around the SMA were significantly less frequent in the AFA-PD group than in the conventional group (22.2% vs. 44.2%, p = 0.041). CONCLUSIONS: AFA-PD with complete lymphadenectomy around the entire SMA can prevent recurrences around the SMA and may prolong overall survival in patients with PDAC.

Analysis of water distribution in delipidated human hair by small-angle neutron scattering (SANS).

OBJECTIVE: It is known that damaged hair has a part of its internal structure damaged, and its water absorption and desorption behavior are different. In recent years, it has been reported that internal lipids play an important role in the adsorption and desorption of water to the hair. Therefore, we investigate whether the water distribution in hair and the amount of internal lipids are related. METHODS: To investigate the effect of internal lipid on water distribution, we prepare human hair samples with and without a partial lack of internal lipids. Internal lipids have been removed using formic acid. The distribution of D2 O in the hair is investigated using small angle neutron scattering (SANS) under the wet and dry conditions of each hair sample. RESULTS: It is found from the obtained SANS data that formic acid-treated hairs tended to have fewer 40Å-sized water clusters that were periodically present along the fibre axis in the wet condition. On the other hand, in the dry condition, there were no differences in water distribution between samples. CONCLUSION: These observations are believed to have been caused by the reduction of 40Å-sized water clusters existing on the constituents removed by formic acid treatment, especially the hydrophobic (lipid) constituent tissues. Consequently, it is clarified that internal lipids are deeply involved in the state of water distribution on hair in wet conditions.

OBJECTIF: il est de connaissance notoire que les cheveux abîmés présentent une structure interne en partie endommagée et des différences dans leurs propriétés d'absorption et de désorption de l'eau. Ces dernières années, des rapports ont fait état du rôle important joué par les lipides internes dans l'adsorption et la désorption de l'eau sur les cheveux. Par conséquent, nous étudions l'existence d'un lien éventuel entre la répartition de l'eau dans les cheveux et la quantité de lipides internes. MÉTHODES: pour étudier l'effet des lipides internes sur la répartition de l'eau, nous préparons des échantillons de cheveux humains caractérisés ou non par une carence partielle en lipides internes. Les lipides internes ont été éliminés à l'aide d'acide formique. L'étude de la répartition de D2O dans les cheveux passe par la technique de diffusion de neutrons aux petits angles (SANS), dans les conditions humides et sèches correspondant à chaque échantillon de cheveux. RÉSULTATS: les données obtenues par la technique SANS révèlent, pour les cheveux traités à l'acide formique, une tendance moindre aux clusters d'eau de 40 ångströms périodiquement présents le long de l'axe des fibres en condition humide. En revanche, en condition sèche, aucune différence n'a été observée dans la répartition de l'eau entre les échantillons. CONCLUSION: ces observations auraient pour cause la réduction des clusters d'eau de 40 ångströms présents sur les composants éliminés par le traitement à l'acide formique, en particulier sur les tissus des composants hydrophobes (les lipides). Par conséquent, des précisions ont été apportées sur la forte implication des lipides internes dans l'état de répartition de l'eau sur les cheveux dans des conditions humides.

[How Do We Perform Imaging Tests before Treating Cerebral Aneurysms?]

Acquiring appropriate preoperative images is an important step in the treatment of cerebral aneurysms. Despite recent advances in contrast-enhanced CT and MRI, catheter angiography remains the standard of care in preoperative imaging tests for both ruptured and unruptured intracranial aneurysms. Three-dimensional rotational angiography can provide a clear view of vascular structure around the aneurysm in an intuitive manner, including the small perforators. For ruptured aneurysms, the treatment modality(i.e., surgical clipping or endovascular embolization)is usually based on emergent contrast CT and catheter angiography findings. For unruptured aneurysms, integrated assessment involving CT, MRI, and angiography is often useful in multimodal treatment decision making.

Effect of Deep-Defects Excitation on Mechanical Energy Dissipation of Single-Crystal Diamond.

The ultrawide band gap of diamond distinguishes it from other semiconductors, in that all known defects have deep energy levels that are less active at room temperature. Here, we present the effect of deep defects on the mechanical energy dissipation of single-crystal diamond experimentally and theoretically up to 973 K. Energy dissipation is found to increase with temperature and exhibits local maxima due to the interaction between phonons and deep defects activated at specific temperatures. A two-level model with deep energies is proposed to explain well the energy dissipation at elevated temperatures. It is evident that the removal of boron impurities can substantially increase the quality factor of room-temperature diamond mechanical resonators. The deep energy nature of the defects bestows single-crystal diamond with outstanding low intrinsic energy dissipation in mechanical resonators at room temperature or above.

A long side chain imidazolium-based graft-type anion-exchange membrane: novel electrolyte and alkaline-durable properties and structural elucidation using SANS contrast variation.

Newly designed styrylimidazolium-based grafted anion-exchange membranes (StIm-AEMs), in which imidazolium ionic groups are attached to styrene at the far side from the graft chains, were prepared by radiation-induced graft polymerization of p-(2-imidazoliumyl) styrene onto poly(ethylene-co-tetrafluoloethylene) (ETFE) films, followed by N-alkylation and ion-exchange reactions. StIm-AEM having an ion exchange capacity (IEC) of 0.54 mmol g-1 with a grafting degree (GD) of ∼18%, possesses practical conductivity (>50 mS cm-1) even with a very low water uptake (∼10%) and high stability over 600 h in a 1 M KOH solution at 80 °C. There exists a critical IEC (IECc) in the range of 0.7-0.8 mmol g-1 over which the membrane showed high water uptake, which resulted in pronounced susceptibility to hydrolysis. Using small-angle neutron scattering technique with a contrast variation method, we found the hydrophilic phase in StIm-AEMs with IECs lower and higher than IECc shows "reverse-micelles" with water domains dispersed in the polymer matrix and "micelles" with graft polymer aggregates dispersed in the water matrix, respectively. The further analysis of micelle structures using the hard-sphere liquid model and Porod limit analysis reveals that the interfacial structures of ionic groups are essential for the electrochemical properties and durability of StIm-AEMs. In addition, StIm-AEM with an IEC of 0.95 mmol g-1 and the maximum power density of 80 mW cm-2 in the hydrazine hydrate fuel cell test, exhibited long-term durability under constant current (8.0 mA) up to 455 h, which, thus far, is the best durability at 80 °C for platinum-free alkaline-type liquid fuel cells.

Vasoactive intestinal peptide increases apoptosis of hepatocellular carcinoma by inhibiting the cAMP/Bcl-xL pathway.

Vasoactive intestinal peptide (VIP) is a modulator of inflammatory responses. VIP receptors are expressed in several tumor types, such as colorectal carcinoma. The study described herein was conducted to confirm the presence of VIP and its receptors (VPAC1 and VPAC2) in surgically resected hepatocellular carcinoma (HCC) tissues and in the HCC cell line Huh7. The mechanism responsible for apoptosis of HCC cells was then examined because VIP treatment (10-10  M) significantly suppressed proliferation of Huh7 cells. In examining apoptosis-related proteins, we found caspase-3 to be significantly increased and Bcl-xL and cyclic AMP (cAMP) response element-binding protein (CREB) to be significantly decreased in Huh7 cells cultured with VIP. Furthermore, the CREB level and phosphorylation were reduced. These effects were reversed by the addition of VIP receptor antagonist or cAMP antagonist Rp-cAMPS. Pretreatment with cAMP analogue blocked the increased apoptosis, suggesting that VIP induces apoptosis via a PKA-independent signaling mechanism. Our data indicate that VIP prevents the progression of HCC by apoptosis through the cAMP/Bcl-xL pathway.

Necklace-like microstructure in shallow-quenched aqueous solutions of poly(n-isopropylacrylamide), detected by advanced small-angle neutron scattering methods.

The microstructure of aqueous poly(N-isopropyl acrylamide) (PNIPA) gel and solution was investigated by small-angle neutron scattering (SANS) in the vicinity of the gel volume phase transition at TV (= 34 °C). The SANS technique was reinforced by refractive neutron lenses and perfect single crystals in order to get access to µm length scales. At 31 °C SANS shows Ornstein-Zernike (OZ) type scattering in the swollen gel which at 32 °C starts to deviate from the OZ-formalism, exhibiting excess scattering and at the wave number qc≅ 5 × 10-3Å-1 a crossover to Porod's asymptotic q-4 power law. For shallow quenches of ΔT < 1.0 K above TV the excess scattering intensity is further increasing whereas qc is shifting toward lower values. Based on this observation and analysis of the SANS q-profiles, we propose a necklace-like microstructure consisting of PNIPA-rich globules of R≅ 100 Å size which are connected by swollen PNIPA chains and stabilized for more than a day by pinning of chain connectivity. The formation of PNIPA globules near TV is discussed in terms of partially cooperative dehydration which is crucial to explain the "miscibility square phase behavior" of aqueous PNIPA solutions. Globule-like structure was also found in aqueous PNIPA solution of size slightly larger than in gels. At deeper quenches of gels above TV (ΔT > 1.0 K) the globules are aggregating to larger objects of R≅ 0.24 µm size as determined from a strong intensity upturn in the small q-region of USANS.

Size-tunable MRI-visible nitroxide-based magnetic mixed micelles: preparation, stability, and theranostic application.

Metal-free magnetic mixed micelles (mean diameter: 16 nm) composed of biocompatible surfactant Tween 80 and hydrophobic pyrrolidine-N-oxyl radical were prepared by mixing them in phosphate-buffered saline. The magnetic mixed micelles were characterized by dynamic light scattering and small angle neutron scattering measurements. The stability of the micelles is found to depend on the length of alkyl side chain in the nitroxide compounds and degree of unsaturation in the hydrophobic chain in the surfactant. The size of the mixed micelle can be tuned by changing the molar ratio of Tween 80 and nitroxyl radical. In view of theranostic application of the micelle, the cytotoxicity and stability in a physiological environment was investigated; the mixed micelle exhibited no cytotoxicity, high colloidal stability and high resistance towards reduction by large excess ascorbic acid. The in vitro and in vivo magnetic resonance imaging (MRI) revealed sufficient contrast enhancement in the proton longitudinal relaxation time (T 1) weighted images. In addition, hydrophobic fluorophores and an anticancer drug are stably encapsulated in the mixed micelles and showed fluorescence (FL) upon reduction by ascorbic acid and cytotoxicity to cancer cells, respectively. For example, the paclitaxel-loaded mixed micelles efficiently suppressed cancer cell growth. Furthermore, they were found to give higher MRI contrast (higher r 1 value) in vitro than the micelles without paclitaxel. The magnetic mixed micelles presented here are promising theranostic agents in nanomedicine due to their high biocompatibility and high resistivity towards reduction as well as functioning as a drug carrier in therapy and MR or FL imaging probe in diagnosis.