Verification of optimal conditions for the scattering correction of 123I-FP-CIT SPECT on a single-photon emission tomography system with a two-detector whole-body cadmium-zinc-telluride semiconductor detector.

To identify the optimal scattering correction for 123I-FP-CIT SPECT (DAT-SPECT) using a two-detector whole-body cadmium-zinc-telluride semiconductor detector (C-SPECT) system with a medium-energy high-resolution sensitivity (MEHRS) collimator. The C-SPECT system with the MEHRS collimator assessed image quality and quantification using a striated phantom. Different reconstruction methods and scattering correction settings were compared, including filtered back projection (FBP) and ordered subset expectation maximization (OSEM). Higher %contrast and %CV values were observed > 10% subwindow (SW) for all conditions, with no significant differences between images without scattering correction and those < 7% SW. The FBP images show a greater increase in %CV > 10% SW than the OSEM images. The specific binding ratio in the radioactivity ratio of 8:1 was higher than the true value under all conditions. The C-SPECT system with an MEHRS collimator provided accurate scattering suppression and enabled high-quality imaging for DAT-SPECT. Careful setting of the scattering correction is essential for total count accuracy.

Clinical results of 30 consecutive patients of carotid artery stenosis treated with CASPER stent placement: 1-year follow-up and in-stent findings on intravascular ultrasound examination immediately and 6 months after treatment.

BACKGROUND: The CASPER stent is expected to reduce periprocedural ischemic complications, but there is concern about restenosis in the early period. One-year follow-up results of CASPER stenting and findings on intravascular ultrasound (IVUS) immediately and 6 months after treatment are evaluated. METHODS: Thirty consecutive patients were treated with CASPER stents for carotid artery stenosis. IVUS was performed immediately after stenting, and MRI and carotid ultrasonography were performed the next day, at 1 week, at 2 weeks, and then every 3 months. One-year follow-up results were evaluated. Twenty-five patients underwent follow-up angiography and IVUS after 6 months and their findings were investigated. RESULTS: All patients were treated without complications during the intraoperative and periprocedural periods. After 6 months, all 25 patients with follow-up angiography and IVUS showed various degrees of intimal formation on IVUS and 8 of them had ≥50% stenosis on angiography. Three of the 30 patients required retreatment within 6 months because of severe restenosis. In these patients, the inner layer of the stent was deformed toward the inside due to intimal hyperplasia on follow-up IVUS, and there was dissociation between the inner and outer layers. All but the 3 of 30 patients with 1-year follow-up did not lead to symptomatic cerebrovascular events or retreatment. CONCLUSIONS: The CASPER stent appears to be effective for preventing periprocedural ischemic complications. IVUS showed various degrees of intimal formation within 6 months after treatment, and it is possible that the CASPER stent is structurally prone to intimal formation or hyperplasia.

Factors related to insufficient hemostasis using the EXOSEAL vascular closure device with five-minutes compression for femoral artery punctures after neuro-endovascular therapy: A retrospective, single-center experience.

OBJECTIVES: The aim was to identify the factors related to inadequate hemostasis with five minutes of manual compression using the EXOSEAL vascular closure device (VCD), and to evaluate the optimal time to hemostasis (TTH). METHODS: A total of 119 consecutive patients who underwent neuro-endovascular therapy via common femoral arterial puncture between February 2019 and August 2021 were included. These patients underwent hemostasis using an EXOSEAL with manual compression for five minutes. In this retrospective study, the 119 patients were divided into two groups: (1) achieved hemostasis with five minutes (n = 76); and (2) required more than five minutes to achieve hemostasis (n = 43, Add group). In both groups, patient's characteristics, endovascular procedures, and closure procedures were assessed. RESULTS: On univariable analysis, activated clotting time (ACT), multiple antiplatelets, closure with an under-sized EXOSEAL VCD (U-VCD), endovascular procedure, and use of a 7Fr. VCD were significantly associated with additional compression (p < 0.05). On multivariate logistic regression analysis, the following three factors were found to be associated with additional compression: pre-closure ACT (adjusted OR, 0.136; 95% CI, 1.017-1.056; p < 0.001); multiple antithrombotics (adjusted OR, 12.843; 95% CI, 3.458-47.693; p < 0.001); and closure with a U-VCD (adjusted OR, 5.653; 95% CI, 1.751-18.151; p = 0.004). On the receiver-operating characteristic curve analysis for prediction of the need for additional compression, the cutoff point for pre-closure ACT was calculated to be 268 s. In the Add group, mean TTH was 9.8 ± 1.5 min. CONCLUSION: Multiple antiplatelets and closure with a U-VCD may increase the risk of insufficient hemostasis with five-minutes compression using an EXOSEAL VCD for femoral puncture sites if the pre-closure ACT is greater than 268 s. In these patients, mean TTH was 9.8 ± 1.5 min.

Cerebral Aneurysm Coil Embolization with a Coil-Assisted Technique Using a Small-Diameter Helical Coil.

Objective: We introduce a coil-assisted technique using a small diameter helical coil to preserve a branch artery in the aneurysm neck or dome during coil embolization of a cerebral aneurysm. Case Presentations: We report three cases that were treated with the coil-assisted technique. Using this method, the branch artery was preserved with a small diameter helical coil that was placed to support another frame coil. The first case was a ruptured internal carotid artery-posterior communicating artery (IC-Pcom) aneurysm, the second case was a ruptured anterior communicating artery aneurysm, and the third case was an unruptured IC-Pcom aneurysm, with branching of the Pcom, A2, and Pcom, respectively, from the neck or dome of the aneurysm. We were able to preserve the branch artery in all cases. Conclusion: This technique is feasible and safe for coil embolization of intracranial branch-incorporated aneurysms. The technique is especially useful for preserving branch arteries that are difficult to preserve by conventional techniques.

Clinical Evaluations of the Ischemic Core in Acute Ischemic Stroke Using Modified Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Scores by Ischemic Reversibility Using the Signal Intensity.

Objective: Early recanalization of acute stroke caused by large vessel occlusion (LVO) may improve high signal intensity (HSI) on diffusion-weighted imaging (DWI). In this study, we investigated whether subtraction of reversible ischemic lesions (RIL) from the HSI lesions on DWI improves the diagnostic accuracy for the ischemic core. Methods: A total of 35 patients from April 2013 and December 2019 were included in this study. These patients presented acute ischemic stroke due to anterior circulation LVO and underwent thrombectomy. All patients underwent DWI within 48 hours after thrombectomy. HSI ratios were calculated, and compared between ischemic lesions and contralateral normal tissue. Ischemic lesions with improvement in the HSI ratio from initial to postoperative DWI were defined as RIL. Based on a receiver operating characteristic (ROC) curve analysis that compared the HSI ratio of all ischemic lesions, the cutoff value of HSI ratio of RILs was calculated. Results: In all, 127 ischemic lesions were identified in 35 patients. HSI ratios of RILs were significantly lower than those of irreversible ischemic lesions (IILs) (p <0.0001). Based on a ROC curve analysis that compared the HSI ratio of all 127 lesions, the cutoff value of the HSI ratio of RILs was 1.4. After applying this cutoff value to the 127 ischemic lesions of the 35 patients, 20 patients (57%) were identified as having RILs with a HSI ratio of <1.4. In this 20 patients, the postoperative National Institutes of Health Stroke Scale (NIHSS) score at 24 hours was significantly lower (p = 0.007) and improvement in the NIHSS score was significantly higher (p = 0.018) than in the other patients. Conclusion: A HSI ratio of <1.4 on preoperative DWI may reflect ischemic reversibility. In this study, the HSI ratio correlated with clinical findings associated with cerebral ischemia, and our method may be useful in assessing ischemic cores.

Renal Artery Injury Caused by a 0.035-Inch Guidewire in Navigating a Guiding Sheath during Coil Embolization: A Case Report of Rescue Embolization with n-Butyl-2-Cianoacrylate.

Objective: We report renal artery injury by a guidewire during coil embolization of a cerebral artery aneurysm, which was successfully treated by transarterial embolization using n-butyl-2-cianoacrylate (NBCA). Case Presentation: A 65-year-old woman underwent coil embolization for an unruptured cerebral aneurysm, resulting in its complete occlusion. However, her blood pressure decreased during embolization and postoperative abdominal computed tomography (CT) revealed a retroperitoneal hematoma. Intraoperative video revealed that the 0.035-inch guidewire had passed deeply into the right renal artery when the guiding sheath was navigated into the abdominal aorta, suggesting renal artery perforation. Transarterial embolization using NBCA was performed immediately, which resulted in hemostasis. Conclusion: Although renal artery perforation with a guidewire is a rare complication, it can have severe consequences. Early diagnosis with prompt and definitive hemostasis is important.

Simple and Reproducible Microcatheter Shaping Method for Coil Embolization of Medially-directed Paraclinoid Internal Carotid Artery Aneurysms.

Objective: It is important to guarantee intra-aneurysmal stability of microcatheters during coil embolization. We developed a simple and reproducible microcatheter shaping method for medially-directed paraclinoid internal carotid artery aneurysms. Methods: An injection needle cap was used to make a smooth curve on the mandrel, which was first wound around the back end of the cap to create a primary curve. Next, a secondary curve was created using near the tip of the cap. Thus, a two-dimensional (2D), pigtail-shaped mandrel with a two-stage curve was created. The pigtail-shaped mandrel was inserted from the tip of a straight microcatheter and heat-shaped using a heat gun. Lastly, a microcatheter having a curve whose tip was approximately 6 mm longer than that of the preshaped J was created. We evaluated the ease of navigating the microcatheter into the aneurysm and its stability during coil embolization. Results: In all, 34 consecutive medially-directed paraclinoid internal carotid artery aneurysms were treated using the shaped catheters. It took 50-300 seconds (intermediate value: 90 seconds) from inserting the microcatheter with a microguide wire to navigate and place it into an aneurysm. There were no cases that required reshaping of the microcatheters during navigation into the aneurysm. There were no cases that resulted in kickback of the microcatheters from the aneurysm during coil placement, and microcatheter stability was good until the end of the procedure. In all, 12 cases required the balloon-assisted technique and three cases required stent-assisted coiling. The angiographic outcomes immediately after embolization were as follows: 25 cases (73.5%) with complete occlusion; 3 cases (8.8%) with dome filling; and 6 cases (17.6%) with a neck remnant. There were no perioperative complications. Conclusion: The shaping method with a pigtail-shaped mandrel using an injection needle cap is simple and reproducible, and is useful for medially-directed paraclinoid internal carotid artery aneurysms.

[Tentorial Dural Arteriovenous Fistula Presenting with Ocular Symptoms:A Case Report].

Tentorial dural arteriovenous fistula(dAVF)is classified as Cognard 4 with a high risk of aggressive feature, such as intracranial hemorrhage, venous infarction, and intracranial hypertension. We report a rare case presenting with ocular symptoms caused by tentorial dAVF. A 59-year-old man presented with progressive chemosis and exophthalmos of his left eye. Angiography showed a tentorial dAVF that was primarily fed by the middle meningeal artery and the meningohypophyseal artery. The AVF drained into the superior ophthalmic vein and the cerebellar cortical vein via an enlarged petrosal vein. Because transarterial Onyx embolization resulted in incomplete obliteration of the fistula, he underwent microsurgery via a suboccipital approach to obliterate the shunt. Postoperative angiography showed complete obliteration of the shunt. His ocular symptoms rapidly cured. We present this rare case and discuss the pathomechanism associated with the development of ocular symptoms secondary to a tentorial dAVF from the viewpoint of microvascular anatomy.

The ABBA motif binds APC/C activators and is shared by APC/C substrates and regulators.

The anaphase-promoting complex or cyclosome (APC/C) is the ubiquitin ligase that regulates mitosis by targeting specific proteins for degradation at specific times under the control of the spindle assembly checkpoint (SAC). How the APC/C recognizes its different substrates is a key problem in the control of cell division. Here, we have identified the ABBA motif in cyclin A, BUBR1, BUB1, and Acm1, and we show that it binds to the APC/C coactivator CDC20. The ABBA motif in cyclin A is required for its proper degradation in prometaphase through competing with BUBR1 for the same site on CDC20. Moreover, the ABBA motifs in BUBR1 and BUB1 are necessary for the SAC to work at full strength and to recruit CDC20 to kinetochores. Thus, we have identified a conserved motif integral to the proper control of mitosis that connects APC/C substrate recognition with the SAC.

The mitotic checkpoint complex binds a second CDC20 to inhibit active APC/C.

The spindle assembly checkpoint (SAC) maintains genomic stability by delaying chromosome segregation until the last chromosome has attached to the mitotic spindle. The SAC prevents the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase from recognizing cyclin B and securin by catalysing the incorporation of the APC/C co-activator, CDC20, into a complex called the mitotic checkpoint complex (MCC). The SAC works through unattached kinetochores generating a diffusible 'wait anaphase' signal that inhibits the APC/C in the cytoplasm, but the nature of this signal remains a key unsolved problem. Moreover, the SAC and the APC/C are highly responsive to each other: the APC/C quickly targets cyclin B and securin once all the chromosomes attach in metaphase, but is rapidly inhibited should kinetochore attachment be perturbed. How this is achieved is also unknown. Here, we show that the MCC can inhibit a second CDC20 that has already bound and activated the APC/C. We show how the MCC inhibits active APC/C and that this is essential for the SAC. Moreover, this mechanism can prevent anaphase in the absence of kinetochore signalling. Thus, we propose that the diffusible 'wait anaphase' signal could be the MCC itself, and explain how reactivating the SAC can rapidly inhibit active APC/C.

Mad2 and the APC/C compete for the same site on Cdc20 to ensure proper chromosome segregation.

The spindle assembly checkpoint (SAC) is essential to ensure proper chromosome segregation and thereby maintain genomic stability. The SAC monitors chromosome attachment, and any unattached chromosomes generate a "wait anaphase" signal that blocks chromosome segregation. The target of the SAC is Cdc20, which activates the anaphase-promoting complex/cyclosome (APC/C) that triggers anaphase and mitotic exit by ubiquitylating securin and cyclin B1. The inhibitory complex formed by the SAC has recently been shown to inhibit Cdc20 by acting as a pseudosubstrate inhibitor, but in this paper, we show that Mad2 also inhibits Cdc20 by binding directly to a site required to bind the APC/C. Mad2 and the APC/C competed for Cdc20 in vitro, and a Cdc20 mutant that does not bind stably to Mad2 abrogated the SAC in vivo. Thus, we provide insights into how Cdc20 binds the APC/C and uncover a second mechanism by which the SAC inhibits the APC/C.

[Two cases of Nocardia farcinica brain abscess].

Brain abscess caused by Nocardia is a relatively rare disease, but its prognosis is poor, with the fatality being 3 times as high as that of other types of brain abscess. Nocardiosis caused by N. farcinica has higher fatality rates than nocardiosis caused by the other bacteria of the genus Nocardia. We report two cases of brain abscess caused by N. farcinica. Case 1: 72-year-old immunocompetent man. In this case, the disease healed in response to burr hole drainage and treatment with antibiotics (pazufloxacin, ciprofloxacin). Case 2: A 78-year-old woman with a history of liver cirrhosis. This patient received burr hole drainage and treatment with multiple antibiotics (sulfamethoxazole/trimethoprim, pazufloxacin, meropenem, amikacin, minocycline, and linezolid). Her brain abscess tended to alleviate but her general condition worsened, leading to death. N. farcinica is often resistant to multiple antibiotics. For treatment of brain abscess caused by this bacterium, it is essential to perform pathogen identification and a drug sensitivity test immediately, and to select optimum antibiotics, taking into account the general condition of individual patients.

How APC/C-Cdc20 changes its substrate specificity in mitosis.

Progress through mitosis requires that the right protein be degraded at the right time. One ubiquitin ligase, the anaphase-promoting complex or cyclosome (APC/C) targets most of the crucial mitotic regulators by changing its substrate specificity throughout mitosis. The spindle assembly checkpoint (SAC) acts on the APC/C co-activator, Cdc20 (cell division cycle 20), to block the degradation of metaphase substrates (for example, cyclin B1 and securin), but not others (for example, cyclin A). How this is achieved is unclear. Here we show that Cdc20 binds to different sites on the APC/C depending on the SAC. Cdc20 requires APC3 and APC8 to bind and activate the APC/C when the SAC is satisfied, but requires only APC8 to bind the APC/C when the SAC is active. Moreover, APC10 is crucial for the destruction of cyclin B1 and securin, but not cyclin A. We conclude that the SAC causes Cdc20 to bind to different sites on the APC/C and this alters APC/C substrate specificity.

A mutual inhibition between APC/C and its substrate Mes1 required for meiotic progression in fission yeast.

The anaphase-promoting complex/cyclosome (APC/C) is a cell-cycle-regulated essential E3 ubiquitin ligase; however, very little is known about its meiotic regulation. Here we show that fission yeast Mes1 is a substrate of the APC/C as well as an inhibitor, allowing autoregulation of the APC/C in meiosis. Both traits require a functional destruction box (D box) and KEN box. We show that Mes1 directly binds the WD40 domain of the Fizzy family of APC/C activators. Intriguingly, expression of nonubiquitylatable Mes1 blocks cells in metaphase I with high levels of APC/C substrates, suggesting that ubiquitylation of Mes1 is required for partial degradation of cyclin B in meiosis I by alleviating Mes1 inhibitory function. Consistently, a ternary complex, APC/C-Fizzy/Cdc20-Mes1, is stabilized by inhibiting Mes1 ubiquitylation. These results demonstrate that the fine-tuning of the APC/C activity, by a substrate that is also an inhibitor, is required for the precise coordination and transition through meiosis.

Fission yeast Mes1p ensures the onset of meiosis II by blocking degradation of cyclin Cdc13p.

Meiosis is a special form of nuclear division to generate eggs, sperm and spores in eukaryotes. Meiosis consists of the first (MI) and the second (MII) meiotic divisions, which occur consecutively. MI is reductional, in which homologous chromosomes derived from parents segregate. MI is supported by an elaborate mechanism involving meiosis-specific cohesin and its protector. MII is equational, in which replicated sister-chromatids separate as in mitosis. MII is generally considered to mimic mitosis in mechanism. However, fission yeast Mes1p is essential for MII but dispensable for mitosis. The mes1-B44 mutant arrests before MII. Transcription of mes1 is low in vegetative cells and boosted in a narrow window between late MI and late MII. The mes1 mRNA undergoes meiosis-specific splicing. Here we show that Mes1p is a factor that suppresses the degradation of cyclin Cdc13p at anaphase I. Mes1p binds to Slp1p, an activator of APC/C (anaphase promoting complex/cyclosome), and counteracts its function to engage Cdc13p in proteolysis. Inhibition of APC/C-dependent degradation of Cdc13p by Mes1p was reproduced in a Xenopus egg extract. We therefore propose that Mes1p has a key function in saving a sufficient level of MPF (M-phase-promoting factor) activity required for the execution of MII.

Fission yeast Rhp51 is required for the maintenance of telomere structure in the absence of the Ku heterodimer.

The Schizosaccharomyces pombe Ku70-Ku80 heterodimer is required for telomere length regulation. Lack of pku70+ results in telomere shortening and striking rearrangements of telomere-associated sequences. We found that the rearrangements of telomere-associated sequences in pku80+ mutants are Rhp51 dependent, but not Rad50 dependent. Rhp51 bound to telomere ends when the Ku heterodimer was not present at telomere ends. We also found that the single-stranded G-rich tails increased in S phase in wild-type strains, while deletion of pku70+ increased the single-stranded overhang in both G2 and S phase. Based on these observations, we propose that Rhp51 binds to the G-rich overhang and promotes homologous pairing between two different telomere ends in the absence of Ku heterodimer. Moreover, pku80 rhp51 double mutants showed a significantly reduced telomere hybridization signal. Our results suggest that, although Ku heterodimer sequesters Rhp51 from telomere ends to inhibit homologous recombination activity, Rhp51 plays important roles for the maintenance of telomere ends in the absence of the Ku heterodimer.