Endovascular Treatment Strategy for Acute Basilar Artery Occlusion with Unexpected Right-Sided Aortic Arch.

A right-sided aortic arch (RAA) is a rare variant of the aortic arch found. We present a case of endovascular treatment (EVT) for acute basilar artery (BA) occlusion with an RAA. A 70-year-old man developed acute ischemic stroke due to BA occlusion. During urgent EVT for BA occlusion with an RAA, which was observed unexpectedly, navigation of the catheter to the target vessel was achieved as a result of an early change in the access route. Flexible treatment strategies are warranted for cases of unexpected anatomical variant in the fight against time for emergent cases, such as acute ischemic stroke.

Long-term recurrence after surgery for schwannoma of the cauda equina.

Background: Cauda equina tumors are rare primary spinal tumors. Histologically, the most common tumor arising from the cauda equina is a schwannoma. However, little is known about the long-term postoperative outcomes of cauda equina schwannoma. Here, we reviewed the median-to-long-term postoperative outcomes of eight of our own patients with schwannomas of the cauda equina. Methods: Between 2007 and 2020, we, retrospectively, reviewed eight patients with cauda equina schwannomas (CESs) undergoing nine operations at our institution. There were five males and three females averaging 56.5 years of age who were followed for over 40 postoperative months. The study included assessment of the following variables: the modified McCormick scale, tumor size, location, extent of resection, treatment of the tumor involving nerve roots, and postoperative observational follow-up. Results: Gross-total resection was achieved in all eight patients; none received adjuvant therapy. The involved nerve roots were completely sacrificed in seven patients and partially resected in one. During a median follow-up of 108 months, only one patient sustained a tumor recurrence 164 months following the index surgery. Conclusion: CESs may recur more than 10 years after the original surgery. Radical resection of the tumor, including complete removal of the involved nerve root during the index surgery, and long-term postoperative follow-up is, therefore, essential.

Gamma knife radiosurgery cured hydrocephalus in non-hemorrhagic brain stem arteriovenous malformation.

A 13-year-old boy, with a history of intermittent headache and transient diplopia, was found to have non-hemorrhagic cerebral arteriovenous malformation in the midbrain tegmental region associated with hydrocephalus. Gamma knife radiosurgery was performed at 16 Gy with 75% marginal dose. Posttreatment course was uneventful. Follow-up MR imaging at one year after the treatment revealed complete disappearance of the abnormal vascular flow voids. The size of each ventricle at the treatment and at one year after treatment were as follows; 60.2 cc and 20.9 cc in the lateral ventricles, 3.7 cc and 2.7 cc in the third ventricle. The hydrocephalus might be caused by obstructive mechanism but mostly by high venous pressure due to the shunt blood flow. The goal of treatment for hydrocephalus should be nidus obstruction and normalizing the vascular flow.

[Sellar and Parasellar Inflammatory Lesions with Impaired Visual Function:Clinical Features and Endoscopic Surgical Outcomes of Six Cases].

Accurate diagnosis and treatment of sellar and parasellar inflammatory lesions is difficult. We report six patients with sellar and parasellar inflammatory lesions and impaired visual function, who underwent endonasal endoscopic surgery. These patients included one with aspergillosis, one with hypertrophic pachymeningitis, one patient with abscess, and three with idiopathic granulomatous lesions. Following surgery and medication, visual function improved in patients with aspergillosis, hypertrophic pachymeningitis, and abscess. In patients with idiopathic granulomatous inflammation, visual function improved in one out of three patients. The treatment outcome for sellar and parasellar inflammatory lesions with impaired visual function depends on the surgery as well as on the reaction to postoperative medication. In the present study, the functional prognosis of patients with idiopathic granulomatous lesions was relatively poor when compared with that of patients with other inflammatory lesions.

An Aneurysm at the Origin of a Duplicated Middle Cerebral Artery Treated by Stent-Assisted Coiling Using the "Wrapped-Candy" Low-Profile Visualized Intraluminal Support (LVIS) Technique: A Technical Case Report and Review of the Literature.

BACKGROUND: Aneurysms at the origin of a duplicated middle cerebral artery (DMCA) are quite rare. Here, we report a patient with such an aneurysm successfully treated endovascularly using our novel "wrapped-candy" low-profile visualized intraluminal support (LVIS) technique. CASE DESCRIPTION: A 44-year-old woman underwent endovascular treatment for an unruptured wide-necked aneurysm at the origin of a DMCA that incorporated the origin of the DMCA into its neck. Stent-assisted coiling was performed using our newly developed "wrapped-candy" LVIS technique. To protect the origin of the DMCA and increase the stent metal density at the neck, an LVIS blue 3.5-mm × 22-mm stent was deployed by pushing the delivery wire aggressively to transform the visible wire components of the LVIS into a shape like "wrapped candy," maximizing the strut compaction at the neck of the aneurysm. Subsequently, the aneurysm component was coiled using a jailed microcatheter. The final procedural angiography demonstrated almost complete aneurysm occlusion with DMCA preservation. CONCLUSIONS: Stent-assisted coiling can be a feasible treatment for an unruptured, usually wide-necked, aneurysm at the origin of a DMCA. The wrapped-candy LVIS technique may be useful in more challenging morphologies such as wide-necked aneurysms that incorporate the branch origin into the aneurysm neck.

Potential energy landscape and thermodynamic transitions of coarse-grained protein models revealed by the multicanonical generalized hybrid Monte Carlo method.

In the present study, thermodynamic properties of coarse-grained protein models have been studied by an extended ensemble method. Two types of protein model were analyzed; one is categorized into a fast folder and the other into a slow folder. Both models exhibit the following thermodynamic transitions: the collapse transition between random coil states and spatially compact, but non-native states and the folding transition between the collapsed states and the folded native states. Caloric curve for the fast folder shows strong statistical ensemble dependence, while almost no ensemble dependence is found for the slow folder. Microcanonical caloric curve for the fast folder exhibits S-shaped temperature dependence on the internal energy around the collapse transition which is reminiscent of the van der Waals loop observed for the first order transition; at the transition temperature, the collapsed and random coil states coexist dynamically. The corresponding microcanonical heat capacity is found to have negative region around the transition. This kind of exotic behaviors could be utilized to distinguish fast folding proteins.

Double Stent Retriever (SR) Technique: A Novel Mechanical Thrombectomy Technique to Facilitate the Device-Clot Interaction for Refractory Acute Cerebral Large Vessel Occlusions.

BACKGROUND: Mechanical thrombectomy has become the standard treatment for acute ischemic stroke caused by large vessel occlusion; however, refractory occlusions still occur despite various thrombectomy procedures. The double stent retriever (SR) technique, which employs 2 SRs simultaneously at the occlusion, can be useful for such refractory occlusions. METHODS: We described 2 cases of refractory acute cerebral occlusion despite the use of conventional thrombectomy procedures that were both treated with the double SR technique. To discuss the technical aspects of how this easy-to-perform technique facilitates the device-clot interaction, we also evaluated radiographic findings of the SR strut during the procedure. RESULTS: In both cases, conventional thrombectomy procedures, including an SR alone, an aspiration catheter alone, and combined use of the SR and aspiration catheter, failed to recanalize the occlusion. The double SR technique was then performed with the stent-in-stent method in 1 patient and the parallel stent method in 1 patient. One pass of this technique retrieved hard clots and successfully recanalized the refractory occlusion in both cases. Intraprocedural radiographic images of these cases showed that the degree of stent expansion improved after deployment of the second SR compared with the first SR. CONCLUSIONS: Our radiographic findings suggested that adding a second SR facilitates the device-clot interaction at the occlusion site. The double SR technique may be an easy-to-perform thrombectomy technique to improve clot-capturing ability for the management of refractory acute cerebral artery occlusions.

[A Case of Multiple Brain Lesions Associated with Hydrophilic Polymer Allergy after Coil Embolization that Showed Repeated Progression and Regression].

A 41-year-old woman underwent coil embolization for subarachnoid hemorrhage associated with a ruptured anterior cerebral artery(A1)aneurysm. Approximately 3 weeks later, MRI revealed right cerebral white matter changes with extensive edema and enhancement lesions. Even though she was asymptomatic, we suspected an allergic reaction to the hydrophilic coating polymer and initiated steroid treatment. After tapering and discontinuing the steroid treatment, follow-up MRI revealed development of white matter lesions;thus, steroid treatment was reinitiated. Progression and regression of the lesions occurred repeatedly, and she was radiologically stable at almost 1 year after coiling. We speculated that these white matter lesions were foreign body granulomas that reacted to the hydrophilic coating of the endovascular device. Overall, an allergic reaction to hydrophilic coating polymer could occur as a delayed complication after coil embolization and that progression and regression of the lesions could repeatedly occur in rare cases.

Applications of MALDI mass spectrometry imaging for pharmacokinetic studies during drug development.

The concentration and distribution of a drug or its metabolites in tissues are key factors for understanding drug efficacy or toxicity. Conventional pharmacokinetic studies show that the plasma concentration of a drug is often unrelated to the intra-tissue concentration. Moreover, it is difficult to predict the distribution of a drug in tissues, particularly those with complex structures, even though the overall tissue concentration is measured by using homogenizing procedures. Mass spectrometry imaging (MSI) enables visualization of the spatial distribution and quantities of drugs in tissue sections without labeling, which can significantly impact on the development of new drugs and translational research. Recent advances in instrument technology and the knowledge accumulated to date could further improve the sensitivity, spatial resolution, and reproducibility of MSI. Here we present current applications of matrix-assisted laser desorption/ionization (MALDI)-MSI in pharmacokinetic imaging (PK-imaging) studies, give an overview of MALDI-MSI procedures, highlight the importance of internal standards, and give details of quantitative approaches. We also point out the need for standardizing MALDI-MSI techniques. PK-imaging using standardized MALDI-MSI methods, independent of instrument or technician expertise, is expected to contribute to acquiring reliable data in drug development and translational research in the future.

[A Case of Aplastic or Twig-like Middle Cerebral Artery with a Ruptured Aneurysm at an Anomalous Collateral Artery].

A 69-year-old man presented with sudden loss of consciousness and was admitted to our hospital. Computed tomography revealed diffuse subarachnoid hemorrhage. Digital subtraction angiography revealed occlusion of the left M1 segment, collateral arteries from the left A1 to the left M2 via twig-like networks, and a 6-mm aneurysm in the collateral arteries. Clipping surgery was performed on the 3rd hospital day. Vascular abnormalities of the middle cerebral artery with twig-like networks have been reported with an incidence of 0.11-0.17%. In addition, aneurysms are reported as complications in 40% of cases, suggesting hemodynamic stress and structural vulnerability. (Received January 16, 2018; Accepted June 21, 2018; Published September 1, 2018).

Development of a generalized hybrid Monte Carlo algorithm to generate the multicanonical ensemble with applications to molecular systems.

In the present paper, a generalized hybrid Monte Carlo method to generate the multicanonical ensemble has been developed, which is a generalization of the multicanonical hybrid Monte Carlo (HMC) method by Hansmann and co-workers [Chem. Phys. Lett. 259, 321 (1996)]. The generalized hybrid Monte Carlo (GHMC) method is an equations-of-motion guided Monte Carlo combined with partial momentum refreshment. We successfully applied our multicanonical GHMC to dense Lennard-Jones fluids and a coarse grained protein model. It is found that good computational efficiency can be gained in the case of the acceptance ratio around 60% for the models examined. While a large number of molecular dynamics (MD) steps in a single GHMC cycle is needed to yield good computational efficiency at a large mixing ratio of momenta with thermal noise vectors, corresponding to the original multicanonical HMC method, a small number of MD steps are enough to achieve good efficiency at a small mixing ratio. This property is useful to develop a composite algorithm combining the present GHMC method with other Monte Carlo moves.

Quantum structural fluctuation in para-hydrogen clusters revealed by the variational path integral method.

In this paper, the ground state of para-hydrogen clusters for size regime N ≤ 40 has been studied by our variational path integral molecular dynamics method. Long molecular dynamics calculations have been performed to accurately evaluate ground state properties. The chemical potential of the hydrogen molecule is found to have a zigzag size dependence, indicating the magic number stability for the clusters of the size N = 13, 26, 29, 34, and 39. One-body density of the hydrogen molecule is demonstrated to have a structured profile, not a melted one. The observed magic number stability is examined using the inherent structure analysis. We also have developed a novel method combining our variational path integral hybrid Monte Carlo method with the replica exchange technique. We introduce replicas of the original system bridging from the structured to the melted cluster, which is realized by scaling the potential energy of the system. Using the enhanced sampling method, the clusters are demonstrated to have the structured density profile in the ground state.

Variational path integral molecular dynamics and hybrid Monte Carlo algorithms using a fourth order propagator with applications to molecular systems.

In the present study, variational path integral molecular dynamics and associated hybrid Monte Carlo (HMC) methods have been developed on the basis of a fourth order approximation of a density operator. To reveal various parameter dependence of physical quantities, we analytically solve one dimensional harmonic oscillators by the variational path integral; as a byproduct, we obtain the analytical expression of the discretized density matrix using the fourth order approximation for the oscillators. Then, we apply our methods to realistic systems like a water molecule and a para-hydrogen cluster. In the HMC, we adopt two level description to avoid the time consuming Hessian evaluation. For the systems examined in this paper, the HMC method is found to be about three times more efficient than the molecular dynamics method if appropriate HMC parameters are adopted; the advantage of the HMC method is suggested to be more evident for systems described by many body interaction.

Efficient algorithms for semiclassical instanton calculations based on discretized path integrals.

Path integral instanton method is a promising way to calculate the tunneling splitting of energies for degenerated two state systems. In order to calculate the tunneling splitting, we need to take the zero temperature limit, or the limit of infinite imaginary time duration. In the method developed by Richardson and Althorpe [J. Chem. Phys. 134, 054109 (2011)], the limit is simply replaced by the sufficiently long imaginary time. In the present study, we have developed a new formula of the tunneling splitting based on the discretized path integrals to take the limit analytically. We have applied our new formula to model systems, and found that this approach can significantly reduce the computational cost and gain the numerical accuracy. We then developed the method combined with the electronic structure calculations to obtain the accurate interatomic potential on the fly. We present an application of our ab initio instanton method to the ammonia umbrella flip motion.

Identification of valproic acid glucuronide hydrolase as a key enzyme for the interaction of valproic acid with carbapenem antibiotics.

Plasma levels of valproic acid (VPA) are decreased by concomitant use with carbapenem antibiotics, such as panipenem (PAPM). One of the plausible mechanisms of this interaction is the inhibition of VPA glucuronide (VPA-G) hydrolysis by carbapenems in the liver. To elucidate this interaction mechanism, we purified VPA-G hydrolase from human liver cytosol, in which the hydrolytic activity was mainly located. After chromatographic purification, the VPA-G hydrolase was identified as acylpeptide hydrolase (APEH). APEH-depleted cytosol, prepared by an immunodepletion method, completely lacked the hydrolytic activity. These results demonstrate that APEH is a single enzyme involved in PAPM-sensitive VPA-G hydrolysis in cytosol. In addition, the hydrolytic activity of recombinant human APEH was inhibited by PAPM and the inhibition profile by typical esterase inhibitors (diisopropyl fluorophosphate, 5,5'-dithiobis(2-nitrobenzoic acid), p-chloromercuribenzoic acid, and d-saccharic acid 1,4-lactone) was similar to that of human liver cytosol. Cytosolic VPA-G hydrolase activity was slightly inhibited by cholinesterase and carboxylesterase inhibitors. beta-Glucuronidase activity remained in APEH-depleted cytosol, whereas VPA-G hydrolase activity was completely abolished. Thus, either cholinesterase, carboxylesterase, or beta-glucuronidase in cytosol would not be involved in VPA-G hydrolysis. Taken together, APEH plays a major role in the PAPM-sensitive VPA-G hydrolysis in the liver. These findings suggest that APEH could be a key enzyme for the drug interaction of VPA with carbapenems via VPA-G hydrolysis.

CS-8958, a prodrug of the novel neuraminidase inhibitor R-125489, demonstrates a favorable long-retention profile in the mouse respiratory tract.

CS-8958 is a prodrug of the pharmacologically active form R-125489, a selective neuraminidase inhibitor, and has long-acting anti-influenza virus activity in vivo. In this study, the tissue distribution profiles after a single intranasal administration of CS-8958 (0.5 micromol/kg of body weight) to mice were investigated, focusing especially on the retention of CS-8958 in the respiratory tract by comparing it with R-125489 and a marketed drug, zanamivir. After administration of [(14)C]CS-8958, radioactivity was retained in the respiratory tract over long periods. At 24 h postdose, the radioactivity concentrations after administration of [(14)C]CS-8958 were approximately 10-fold higher in both the trachea and the lung than those of [(14)C]R-125489 and [(14)C]zanamivir. The [(14)C]CS-8958-derived radioactivity present in these two tissues consisted both of unchanged CS-8958 and of R-125489 at 1 h postdose, while only R-125489, and no other metabolites, was detected at 24 h postdose. After administration of unlabeled CS-8958, CS-8958 was rapidly eliminated from the lungs, whereas the lung R-125489 concentration reached a maximum at 3 h postdose and gradually declined, with an elimination half-life of 41.4 h. The conversion of CS-8958 to R-125489 was observed in mouse trachea and lung S9 fractions and was inhibited by esterase inhibitors, such as diisopropylfluorophosphate and bis-p-nitrophenylphosphate. These results demonstrated that CS-8958 administered intranasally to mice was efficiently converted to R-125489 by a hydrolase(s) such as carboxylesterase, and then R-125489 was slowly eliminated from the respiratory tract. These data support the finding that CS-8958 has potential as a long-acting neuraminidase inhibitor, leading to significant efficacy as an anti-influenza drug by a single treatment.

Culture period-dependent change of function and expression of ATP-binding cassette transporters in Caco-2 cells.

The objective of this study was to determine an appropriate culture period to assess whether a compound of interest is transported by efflux transporters such as human multidrug resistance 1 (hMDR1), human multidrug resistance-associated protein 2 (hMRP2), and human breast cancer resistance protein (hBCRP) in Caco-2 cells. Caco-2 cells were cultured on a Transwell for 1 to 6 weeks. The expression of these transporters in the mRNA and protein levels was examined using a real-time polymerase chain reaction and Western blotting, respectively. Transcellular transport activities using digoxin, ochratoxin A, olmesartan, and estrone-3-sulfate were also examined. Except for digoxin, the permeability coefficient (P(app)) ratio of the three compounds at 2 weeks was the highest in the periods tested. The P(app) ratio of digoxin at 2 weeks was higher than that at 3 weeks. The temporal expression profile of each transporter in the mRNA level was similar to that in the protein level, and the functions of hMRP2 and hBCRP were roughly correlated with the expression in the mRNA and protein levels, but that of hMDR1 was not. These data suggest that among all the culture periods evaluated a 2-week culture is the best culture period for transport studies to identify whether a compound is a substrate for hMDR1, hMRP2, and hBCRP.

Development of high-performance cooling devices for space application by using flow boiling in narrow channels.

Heat generation density from semiconductor devices has been increasing with the rapid development of electronic technology. The cooling system using boiling two-phase phenomena has attracted much attention because of its high heat removal potential. To develop compact and high-performance cooling systems, we conducted experiments on the increase of critical heat flux (CHF) for flow boiling in narrow channels by improved liquid supply. A large surface of 150 mm in heated length and 30 mm in width with grooves of an apex angle of 90 degrees , 0.5-mm depth, and 1 mm in pitch was employed. A structure of narrow heated channel between parallel plates with an unheated auxiliary channel was devised and tested by using water for different combinations of gap sizes and volumetric flow rates, where inlet of the main heated channel and the outlet of auxiliary unheated channel were closed to prevent the flow instability observed frequently at low flow rate for parallel two channels. For the total volumetric flow rate more than 4.5 x 10(-5) m(3)/s, higher values of CHF large than 2 x 10(6) W/m(2) were obtained for gap size of 2 mm. For gap sizes of 2 mm and 5 mm at high volumetric flow rate larger than 6.0 x 10(-5) m(3)/s, or mass velocity based on the cross section are of main heated channel 958.1 kg/m(2)s and 383.2 kg/m(2) s, respectively, the extension of dry patches was observed at the upstream location of the main heated channel resulting in burnout not at the downstream but at the upstream. By the increase in total volumetric flow rate, the pressure drop increased because of increasing in the flow rate passing through the sintered metal porous plates connecting both channels. The values of pressure drop for gap size of 2 mm were higher than that for gap size of 5 mm. When the performance of the cooling system was evaluated on the basis of pump power, ignoring its variation in the efficiency with volumetric flow rate, that is, the power defined as the product of the pressure drop and the total volumetric flow rate, higher values of CHF were obtained for gap size of 5 mm as far as the same pump power was concerned.

Mechanism-based inhibition of human cytochrome P450 2B6 by ticlopidine, clopidogrel, and the thiolactone metabolite of prasugrel.

Mechanism-based inhibition of CYP2B6 in human liver microsomes by thienopyridine antiplatelet agents ticlopidine and clopidogrel and the thiolactone metabolites of those two agents plus that of prasugrel were investigated by determining the time- and concentration-dependent inhibition of the activity of bupropion hydroxylase as the typical CYP2B6 activity. By comparing the ratios of k(inact) (maximal inactivation rate constant)/K(I) (the inactivator concentration producing a half-maximal rate of inactivation), it was found that the thiolactone metabolite of prasugrel is 10- and 22-fold less potent, respectively, in the mechanism-based inhibition of CYP2B6 than ticlopidine and clopidogrel. The k(inact)/K(I) ratio of the thiolactone metabolite of ticlopidine was comparable with that of the parent compound, whereas this ratio for the thiolactone metabolite of clopidogrel was significantly smaller than that of clopidogrel. In conclusion, ticlopidine, its thiolactone metabolite, and clopidogrel were more potent mechanism-based inhibitors of CYP2B6 than the thiolactone metabolite of prasugrel.

Navigation for laparoscopic gastrectomy with 3-dimensional computed tomography (3D-CT).

BACKGROUND/AIMS: Early-stage gastric cancer is one relatively well-explored target for laparoscopic resection. Systemic lymphadenectomy is considered an essential component of gastrectomy, however, it may not be easy even with extensive experience. It is convenient for the laparoscopists, therefore, to be given preoperatively thorough information regarding the vessels anatomy of the celiac branches around the stomach for each patient. METHODOLOGY: Between July 2001 and January 2006, 41 patients with gastric carcinoma scheduled for surgery underwent 3-dimensional computed tomography (3D-CT) examination at Nagoya University Hospital. From the 3D-CT images, information regarding the vessels that are dissected during surgery for gastric cancer was obtained, and the branching patterns of those were analyzed. RESULTS: The left gastric artery and the right gastroepiploic artery were detected in all 41 cases, while the right gastric artery was detected only in 22 cases (53.7%). Variations in the origin of the left gastric and right gastroepiploic arteries were not observed. However, there was a considerable variation in the origin of the right gastric artery, with 50.0% branching from the proper hepatic artery, 22.7% from the left hepatic artery, and 13.6% from the gastroduodenal artery. In 4 cases (9.7%), the left hepatic artery was found to originate from the left gastric artery. CONCLUSIONS: Preoperative knowledge of the basic vascular patterns obtained through 3D-CT imaging is a useful guide to safely perform laparoscopic gastrectomy, although further improvements in the processing of more detailed imaging is needed.