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Motor-evoked potential (MEP) monitoring by transcranial electrical stimulation (TES) is important for intraoperative motor function assessment in neurosurgery; however, false-negative results sometimes occur, and these findings should be interpreted with caution. Herein, we report an interesting MEP change resulting from a pons transection. The patient was a boy aged 5 years and 2 months. He underwent multiple craniotomies for cerebellar anaplastic ependymoma and was already paralyzed in the right upper and lower limbs. Therefore, we decided to remove the recurrent lesion from the left anterior pons. MEPs were recorded on both the right and left sides after the start of surgery but disappeared 1 h 30 min after the start of surgery in the TES on the operative side, even when the stimulation intensity was increased. The contralateral TES consistently recorded stable MEPs throughout the surgery. The tumor was completely resected on imaging. Immediately postoperatively, the patient experienced flaccid paralysis on the right side of the body, which recovered to preoperative levels over time. A transcranial MEP cannot be derived if the corticospinal tract is transected at the pons. Transcranial MEP findings may accurately reflect the corticospinal tract function if the injury is caudal to the pons. [ABSTRACT FROM AUTHOR]

Trigeminal neuralgia causes excruciating pain in patients. Microvascular decompression is indicated for drug-resistant s trigeminal neuralgia. Unlike facial spasms, any part of the nerve can be the culprit, not only the root entry zone. Intraoperative monitoring does not yet exist for trigeminal neuralgia. We successfully used intermittent stimulation of the superior cerebellar artery during surgery and confirmed the disappearance of the trigeminal nerve motor branch reaction after the release of the compression. Intermittent direct stimulation of the culprit blood vessel using the motor branch of the trigeminal nerve may assist in intraoperative monitoring of decompression during trigeminal nerve vascular decompression surgery. [ABSTRACT FROM AUTHOR]

In Gram-positive bacteria, sophisticated machineries to acquire the heme group of hemoglobin (Hb) have evolved to extract the precious iron atom contained in it. In the human pathogen Streptococcus pyogenes, the Shr protein is a key component of this machinery. Herein we present the crystal structure of hemoglobin-interacting domain 2 (HID2) of Shr bound to Hb. HID2 interacts with both, the protein and heme portions of Hb, explaining the specificity of HID2 for the heme-bound form of Hb, but not its heme-depleted form. Further mutational analysis shows little tolerance of HID2 to interfacial mutations, suggesting that its interaction surface with Hb could be a suitable candidate to develop efficient inhibitors abrogating the binding of Shr to Hb. [ABSTRACT FROM AUTHOR]

Although patients with symptomatic Rathke's cleft cysts (RCCs) receive surgical treatment, recurrence sometimes occurs after surgery. However, the mechanism underlying recurrence remains unclear. We evaluated the outcomes of RCC decompression over a long-term follow-up period. We retrospectively reviewed the medical records of 35 patients with symptomatic RCC who underwent endonasal endoscopic surgery (EES) at our institution between 2008 and 2023. Patients' characteristics, intraoperative findings, and postoperative follow-up outcomes were evaluated. A univariate regression model was used to identify the predictors of recurrence. The median patient age was 48.0 years, and 74.2% of the patients were female. The mean follow-up duration was 94.7 ± 47.6 months. Cyst content recurrence was observed in 15 patients (42.8%). Five patients (14.2%) with symptomatic recurrence underwent reoperation. Postoperative vision improved in all 23 patients (100%); headaches improved in 20 patients (90.9%). A new hormonal deficit occurred in two patients (5.7%). Complications included intraoperative cerebrospinal fluid (CSF) leak in 10 patients (28.5%), postoperative CSF leak in two patients (5.7%), permanent diabetes insipidus in two patients (5.7%), and postoperative infection in three patients (8.5%). Univariate analyses revealed that the position of the anterior pituitary lobe (p = 0.019) and preoperative visual disturbances (p = 0.008) significantly affected recurrence after surgery. Although EES was efficient, the recurrence rate was relatively high over a long-term period. The anterior pituitary lobe position and preoperative visual disturbances were significantly associated with recurrence. The anterior-inferior position can predict a high risk of recurrence before surgery. [ABSTRACT FROM AUTHOR]

Background: Careful examination of motor-evoked potential (MEP) findings is critical to the safety of intraoperative neuromonitoring during neurosurgery. We reviewed the intraoperative MEP findings in a pediatric patient who had undergone hemispherotomy for refractory epilepsy. Case description: The patient was a 4-year-and-2-month-old boy with extensive right cerebral hemisphere, drug-resistant epilepsy, left upper and lower extremity paralysis, and cognitive impairment. We examined intraoperative MEP results both before and after hemispherotomy. Post-hemispherotomy and MEPs were successfully elicited through transcranial electrical stimulation (TES) but not via direct cortical stimulation on the right side. Furthermore, TES on the right side, following hemispherotomy, led to a reduction in the MEP amplification effect resulting from tetanic stimulation of the left unilateral median and tibial nerves. Conversely, we observed the effects of MEP amplification during TES on the left side after tetanic stimulation of these nerves. Postoperatively, the patient underwent magnetic resonance imaging and electroencephalogram examinations, confirming the anatomical and electrophysiological completeness of the dissection. Notably, the seizures disappeared, and no apparent complications were observed. Conclusion: Collectively, our findings suggest that TES can still activate deep structures and elicit MEPs, even in cases where the corticospinal connections to the posterior limb of the internal capsule are entirely severed. Thalamo-cortical interactions may affect the MEP amplification, observed during tetanic stimulation. Injury to the corticospinal tracts of the white matter may be obscured on conventional MEP findings; however, it may be identified by MEP changes in tetanic stimulation. [ABSTRACT FROM AUTHOR]

The phenomenon of ischemic postconditioning (PostC) is known to be neuroprotective against ischemic reperfusion (I/R) injury. One of the key processes in PostC is the opening of the mitochondrial ATP-dependent potassium (mito-KATP) channel and depolarization of the mitochondrial membrane, triggering the release of calcium ions from mitochondria through low-conductance opening of the mitochondrial permeability transition pore. Mitochondrial calcium uniporter (MCU) is known as a highly sensitive transporter for the uptake of Ca2+ present on the inner mitochondrial membrane. The MCU has attracted attention as a new target for treatment in diseases, such as neurodegenerative diseases, cancer, and ischemic stroke. We considered that the MCU may be involved in PostC and trigger its mechanisms. This research used the whole-cell patch-clamp technique on hippocampal CA1 pyramidal cells from C57BL mice and measured changes in spontaneous excitatory post-synaptic currents (sEPSCs), intracellular Ca2+ concentration, mitochondrial membrane potential, and N-methyl-d-aspartate receptor (NMDAR) currents under inhibition of MCU by ruthenium red 265 (Ru265) in PostC. Inhibition of MCU increased the occurrence of sEPSCs (p = 0.014), NMDAR currents (p < 0.001), intracellular Ca2+ concentration (p < 0.001), and dead cells (p < 0.001) significantly after reperfusion, reflecting removal of the neuroprotective effects in PostC. Moreover, mitochondrial depolarization in PostC with Ru265 was weakened, compared to PostC (p = 0.004). These results suggest that MCU affects mitochondrial depolarization in PostC to suppress NMDAR over-activation and prevent elevation of intracellular Ca2+ concentrations against I/R injury. [ABSTRACT FROM AUTHOR]

Xenophagy, a type of selective autophagy, is a bactericidal membrane trafficking that targets cytosolic bacterial pathogens, but the membrane homeostatic system to cope with bacterial infection in xenophagy is not known. Here, we show that the endosomal sorting complexes required for transport (ESCRT) machinery is needed to maintain homeostasis of xenophagolysosomes damaged by a bacterial toxin, which is regulated through the TOM1L2–Rab41 pathway that recruits AAA-ATPase VPS4. We screened Rab GTPases and identified Rab41 as critical for maintaining the acidification of xenophagolysosomes. Confocal microscopy revealed that ESCRT components were recruited to the entire xenophagolysosome, and this recruitment was inhibited by intrabody expression against bacterial cytolysin, indicating that ESCRT targets xenophagolysosomes in response to a bacterial toxin. Rab41 translocates to damaged autophagic membranes via adaptor protein TOM1L2 and recruits VPS4 to complete ESCRT-mediated membrane repair in a unique GTPase-independent manner. Finally, we demonstrate that the TOM1L2–Rab41 pathway-mediated ESCRT is critical for the efficient clearance of bacteria through xenophagy. Xenophagy targets cytosolic bacteria, but their membrane homeostatic system is not known. Here the authors show that the ESCRT machinery repairs xenophagic membrane damaged by a bacterial toxin, which is regulated by the TOM1L2–Rab41 that recruits VPS4. [ABSTRACT FROM AUTHOR]

Purpose: Delayed hyponatremia can occur after pituitary surgery, resulting in prolonged hospitalization. However, the influence of surgical factors after such a procedure has not been well established. The impact of surgery and related factors on delayed hyponatremia was investigated. Methods: This was a retrospective analysis of 137 consecutive patients who underwent transsphenoidal surgery for a nonfunctioning pituitary adenoma between 2008 and 2019. Preoperative (demographics, comorbidities), intraoperative (resection extent, operation time, blood loss volume, cerebrospinal fluid leak, tumor consistency), and postoperative [hematoma, meningitis, diabetes insipidus (DI), hormonal assessment] data were collected, with statistical analysis of each factor performed. Results: Among the 137 patients, delayed hyponatremia occurred in 31 (22.6%). Multivariate analysis revealed that those with hypertension had a significantly higher likelihood of avoiding delayed hyponatremia (p = 0.004). Although no correlations of direct surgical factors with delayed hyponatremia were found, multivariate analysis of indirect surgical factors showed that presence of a firm tumor, transient DI, and meningitis were significantly associated with delayed hyponatremia (p = 0.014, 0.001, and 0.047, respectively). There was also a significant association of severe hyponatremia with appearance of symptoms (p = 0.002). Conclusion: There was a tendency for hypertension to be associated with delayed hyponatremia avoidance, with indirect surgical factors including tumor consistency, transient DI, and meningitis found to have an influence on delayed hyponatremia. It was concluded that attention should be given to non-hypertensive patients with a firm tumor, transient DI, or meningitis after pituitary surgery, as delayed hyponatremia may occur. [ABSTRACT FROM AUTHOR]

Ischemic postconditioning (PostC) is known to reduce cerebral ischemia/reperfusion (I/R) injury; however, whether the opening of mitochondrial ATP-dependent potassium (mito-KATP) channels and mitochondrial permeability transition pore (mPTP) cause the depolarization of the mitochondrial membrane that remains unknown. We examined the involvement of the mito-KATP channel and the mPTP in the PostC mechanism. Ischemic PostC consisted of three cycles of 15 s reperfusion and 15 s re-ischemia, and was started 30 s after the 7.5 min ischemic load. We recorded N-methyl-d-aspartate receptors (NMDAR)-mediated currents and measured cytosolic Ca2+ concentrations, and mitochondrial membrane potentials in mouse hippocampal pyramidal neurons. Both ischemic PostC and the application of a mito-KATP channel opener, diazoxide, reduced NMDAR-mediated currents, and suppressed cytosolic Ca2+ elevations during the early reperfusion period. An mPTP blocker, cyclosporine A, abolished the reducing effect of PostC on NMDAR currents. Furthermore, both ischemic PostC and the application of diazoxide potentiated the depolarization of the mitochondrial membrane potential. These results indicate that ischemic PostC suppresses Ca2+ influx into the cytoplasm by reducing NMDAR-mediated currents through mPTP opening. The present study suggests that depolarization of the mitochondrial membrane potential by opening of the mito-KATP channel is essential to the mechanism of PostC in neuroprotection against anoxic injury. [ABSTRACT FROM AUTHOR]

Cerebral hyperperfusion syndrome (CHS) is a serious complication following carotid artery stenting (CAS). Staged angioplasty (AP) could potentially prevent CHS and hyperperfusion phenomenon (HPP) after revascularization. However, methods for measuring the effects of staged AP on cerebral hemodynamic reserve have not been established. Here, we evaluated whether indocyanine green kinetics and near-infrared spectroscopy (ICG-NIRS) with hypocapnia induced by hyperventilation can detect the effects of staged AP on hemodynamic reserve to prevent CHS after CAS. Participants comprised 44 patients at high risk of CHS, whose ipsilateral cerebrovascular reactivity (CVR) was impaired on preoperative single photon emission computed tomography (SPECT). Patients were divided into a staged AP group (n=13) and a regular CAS group (n=31). In the staged AP group, stenting was performed 3 weeks after staged AP. In the regular CAS group, 16 cases (52%) showed HPP, and five (16%) presented with CHS after CAS, while no HPP or CHS occurred in the staged AP group (p=0.001). Changes in blood flow index (BFI) and time to peak (TTP) ratio during hypocapnia calculated from ICG-NIRS indicated a significant linear relationship with preprocedural CVR on SPECT (r=−0.710, 0.632, respectively; p<0.0001 each). BFI and TTP ratios during hypocapnia were significantly improved after staged AP (p<0.001 each). Furthermore, significant linear correlations were observed between BFI and TTP ratio during hypocapnia and postoperative asymmetry index AI (r=0.405, −0.475, respectively; p<0.01 each). Hypocapnia induced by hyperventilation under ICG-NIRS appears useful for detecting the effects of staged AP on hemodynamic reserve in patients at high risk of CHS. [ABSTRACT FROM AUTHOR]

Balloon test occlusion (BTO) is a useful examination for evaluating ischemic tolerance to internal carotid artery (ICA) occlusion. The aim of this study was to investigate the relationships between intraoperative motor evoked potential (MEP) monitoring and the results of preoperative BTO. Between 2013 and 2017, 32 patients undergoing surgery under general anesthesia with intraoperative MEP monitoring, in whom preoperative BTO was performed, were identified. A receiver operator characteristic (ROC) analysis was performed to determine the appropriate cutoff value of MEP amplitude for BTO-positive. Furthermore, the accuracy of MEP monitoring for BTO-positive was compared with electroencephalogram (EEG) and somatosensory evoked potential (SEP) monitoring. Four of 32 (12.5%) patients were BTO-positive. The cutoff value of MEP amplitude for BTO-positive was a > 80% reduction from the baseline level, which showed sensitivity of 100% and specificity of 100%. Thus, the sensitivity and specificity for BTO-positive were significantly higher for MEP than for EEG (100% and 72.0%, p = 0.02) in 28 patients, but they were not significantly different compared with SEP (33.3% and 100%, p = 0.48) in 21 patients. MEP monitoring might be one of the alternatives for evaluating ischemic tolerance to ICA occlusion during surgery. The cutoff value of MEP amplitude was a > 80% reduction. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the incidence of intraprocedural motor-evoked potential (MEP) changes and to correlate them with intraprocedural ischemic complications and postprocedural neurological deficits in patients after endovascular intracranial aneurysm treatment. This study analyzed data from 164 consecutive patients who underwent endovascular coil embolization to treat intracranial aneurysms under transcranial MEP monitoring. We analyzed associations between significant changes in MEP defined as > 50% decrease in amplitude, and intraprocedural complications as well as postoperative neurological deficits. Factors associated with postprocedural neurological deficits were also assessed. The treated aneurysms were predominantly located in the anterior circulation (71%). Fourteen (9%) were located at perforators or branches that supplied the pyramidal tract. Intraprocedural complications developed in eight (5%) patients, and four of eight (50%) patients occurred postprocedural neurological deficits. Significant intraprocedural MEP changes occurred during seven of eight endovascular procedures associated with intraprocedural complications and salvage procedures were performed immediately. Among these changes, four transient MEP changes, recovered within 10 min, were not associated with postprocedural neurological deficits, whereas three permanent MEP changes were associated with postprocedural neurological deficits and mRS ≥ 1 at discharge. Aneurysms located at perforators/branches supplying the pyramidal tract, and permanent intraprocedural MEP changes were associated with postprocedural neurological deficits. We conclude that intraprocedural transcranial MEP monitoring can reliably identify ischemic changes and can initiate prompt salvage procedures during endovascular aneurysm treatment. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have recently made significant progression in multiple clinical trials targeting several clinical disorders and in the modulation of immune responses. In the present study, we isolated human adipose tissue-derived stem cells (ADSCs) by direct membrane migration method without using enzymatic digestion via collagenase, and tried to extract adequate number of cells for clinical application. Hydroxyapatite-treated nonwoven fabric membrane made up of synthetic macromolecular fiber materials, polyethylene and polyester terephthalene was used. Expansion culture of ADSCs having plastic flask adherent characteristic in serum-free condition was successfully established, and adequate number of cells were obtained for clinical application. They were found to be positive for CD44, CD73, CD90 and CD105 and negative for CD11b, CD34, CD45, CD80 and HLA-DR. The resulting immunological marker profile satisfied the immunophenotype of previously reported MSCs. Also, microscopic findings demonstrated trilineage differentiation into adipogenic, osteogenic and chondrogenic cells as the characteristics of MSCs. The isolation by nonwoven fabric membrane and expanded cells under serum-free condition satisfied the criteria of MSCs, as proposed by the International Society for Cellular Therapy. Our direct membrane migration method without enzyme digestion is useful as ADSCs can be obtained from small pieces of adipose tissue and expanded under serum-free culture condition. This method was considered to be feasible for clinical application. [ABSTRACT FROM AUTHOR]

Laser speckle flowgraphy (LSFG) is a noninvasive technique that can measure relative blood flow velocity in the optic fundus contributed by the ophthalmic artery, the main first branch originating from the internal carotid artery (ICA). The aim of this study was to assess the feasibility of ocular blood flow measurement by LSFG to detect ischemic stress due to carotid clamping during carotid endarterectomy (CEA). Nineteen patients undergoing CEA with ocular blood flow measurement by LSFG and intraoperative monitoring (IOM) were prospectively enrolled between August 2016 and March 2019. The mean blur rate (MBR) of ocular blood flow by LSFG, representing relative blood flow of the branch of the retinal artery originating from the optic nerve head, was compared between before and after carotid clamping during CEA. The correlation between the reduction ratio of MBR and the regional saturation oxygen (rSO2) index by near infrared spectroscopy was investigated. Ocular blood flow measurement by LSFG could not be performed in one patient with a severe cataract. In the other 18 patients, LSFG could be performed in all 106 sessions during surgery. The MBR reduction ratio between before and after carotid clamping ranged from − 12 to 100%. The MBR reduction ratio was positively correlated with the rSO2 index (r = 0.694, 95% confidence interval: 0.336–0.877, p = 0.001). The MBR reduction ratio of ocular blood flow by LSFG after carotid clamping was significantly correlated with the rSO2 index. The ocular blood flow by LSFG could be considered an adjunct modality for evaluating cerebral ischemic tolerance during CEA. [ABSTRACT FROM AUTHOR]

Cranioplasty complications after decompressive craniectomy (DC) in infants are not fully recognized. We aimed to devise and assess the efficacy of a hinge and floating DC (HFDC) technique for treating infantile acute subdural hematoma. Five infants, aged 2–20 months, were included. Intracranial pressure was controlled below 20 mmHg, no additional surgery was required, and there was no incidence of surgical site infection or bone graft resorption. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of our unique therapy for treating post-intraventricular hemorrhagic hydrocephalus (PIVHH) in low birth weight infants (LBWls) through an early stage fibrinolytic therapeutic strategy involving urokinase (UK) injection into the lateral ventricle, called the "Ventricular Lavage (VL) therapy." Methods: Overall, 43 consecutive infants with PIVHH were included. Most were extremely LBWIs (n = 39). Other cases included very LBWIs (n = 2) and full-term infants (n = 2). VL therapy involved continuous external ventricular drainage (EVD) management using a very fine catheter and intermittent slow injection of 6000 IU of UK every 3–6 h to actively dissolve hematomas. Results: Early EVD management (within 3 weeks of IVH onset) was performed in 25 infants, with combination VL therapy in 21 infants. Five initiated late EVD management (≥ 3 weeks after IVH onset); the remaining 13 were treated conservatively for several weeks, delaying surgical intervention. Eighteen of 21 (86%) infants who received VL therapy did not require permanent shunt surgery. There were no serious complications, including the absence of secondary hemorrhage and infection. Two-thirds of the infants treated in the late stages required permanent shunt, and various shunt-related complications frequently occurred. A good outcome occurred in 13/17 infants in the early treatment group, despite most subjects having an IVH grade IV, and in 6/15 in the late treatment group. Conclusions: Permanent shunt surgery needs were dramatically reduced following early VL therapy, and functional outcomes were favorable. VL therapy might be a promising strategy that could lead to the development of new treatments for PIVHH. [ABSTRACT FROM AUTHOR]

Background and purpose: Poststroke epilepsy is a common problem in clinical practice. This study aimed to determine the predictors of poststroke epilepsy and to identify the risk factors. Methods: A total of 436 patients were enrolled for this study. Baseline characteristics were recorded. Patients were followed up for 3 years. According to the occurrence of late seizures (i.e., seizure occurring 8 days or later after the stroke), the patients were separated into two groups: a seizure group and a seizure-free group. Baseline characteristics were compared between the groups. Univariate and multivariate Cox regression analysis was used to identify the risk factors for occurrence of poststroke epilepsy. The study was registered in the University Hospital Medical Information Network Center Clinical Trials Registry (registration number UMIN000009659, date 28/December/2012). Results: Among the 436 patients, 26 developed late seizures—an incidence rate of 5.96%. In univariate analysis, female, subarachnoid hemorrhage, hemorrhagic lesion, lesion affecting the cortex, lesion affecting the frontal lobe, and absence of comorbidities were the significant risk factors for occurrence of epilepsy. In multivariate analysis, the independent predictors of poststroke epilepsy were hemorrhagic lesion (hazard ratio (HR) = 3.03) and lesion location in the cortex (HR = 4.64). The incidence of poststroke epilepsy in patients with both two risk factors was 15.4%. Conclusions: Poststroke epilepsy occurs in almost 6% of patients within 3 years after stroke onset. Hemorrhagic stroke and subcortical lesion appear to be significantly associated with likelihood of developing epilepsy. Thus, prophylactic administration of antiepileptic drugs could be useful for stroke patients with these two risk factors. [ABSTRACT FROM AUTHOR]

We describe a rare case of extradural schwannoma in the upper cervical spine compressing the dominant internal jugular vein (IJV) presenting with atypical headaches. A 50-year-old woman complained of a subcutaneous neck mass associated with atypical headaches. Radiological examinations revealed the right IJV was compressed anteriorly by C2 extradural mass and occluded with markedly dilated collateral cerebral venous drainage through deep cervical veins. Subtotal removal was performed via the posterolateral approach and the atypical headaches resolved immediately. This case demonstrates that extradural schwannoma in the upper cervical spine could compress the IJV and manifest as cerebral venous circulation disturbances. [ABSTRACT FROM AUTHOR]

Group A Streptococcus (GAS) secretes deoxyribonucleases and evades neutrophil extracellular killing by degrading neutrophil extracellular traps (NETs). However, limited information is currently available on the interaction between GAS and NETs in the pathogenicity of GAS pharyngitis. In this study, we modified a mouse model of GAS pharyngitis and revealed an essential role for DNase in this model. After intranasal infection, the nasal mucosa was markedly damaged near the nasal cavity, at which GAS was surrounded by neutrophils. When neutrophils were depleted from mice, GAS colonization and damage to the nasal mucosa were significantly decreased. Furthermore, mice infected with deoxyribonuclease knockout GAS mutants (∆spd, ∆endA, and ∆sdaD2) survived significantly better than those infected with wild-type GAS. In addition, the supernatants of digested NETs enhanced GAS-induced cell death in vitro. Collectively, these results indicate that NET degradation products may contribute to the establishment of pharyngeal infection caused by GAS. [ABSTRACT FROM AUTHOR]

Invading microbial pathogens can be eliminated selectively by xenophagy. Ubiquitin-mediated autophagy receptors are phosphorylated by TANK-binding kinase 1 (TBK1) and recruited to ubiquitinated bacteria to facilitate autophagosome formation during xenophagy, but the molecular mechanism underlying TBK1 activation in response to microbial infection is not clear. Here, we show that bacterial infection increases Ca2+ levels to activate TBK1 for xenophagy via the Ca2+-binding protein TBC1 domain family member 9 (TBC1D9). Mechanistically, the ubiquitin-binding region (UBR) and Ca2+-binding motif of TBC1D9 mediate its binding with ubiquitin-positive bacteria, and TBC1D9 knockout suppresses TBK1 activation and subsequent recruitment of the ULK1 complex. Treatment with a Ca2+ chelator impairs TBC1D9–ubiquitin interactions and TBK1 activation during xenophagy. TBC1D9 is also recruited to damaged mitochondria through its UBR and Ca2+-binding motif, and is required for TBK1 activation during mitophagy. These results indicate that TBC1D9 controls TBK1 activation during xenophagy and mitophagy through Ca2+-dependent ubiquitin-recognition. Xenophage, or autophagy directed against pathogens, might be involved in the clearance of bacterial infection, but the mechanism is unclear. Here, the authors show that ubiquitinated bacteria are bound by TBC1D9 via a Ca2+-dependent interaction to induce downstream activation of TBK1 signalling and xenophagy, as well as mitophagy. [ABSTRACT FROM AUTHOR]

Understanding the risks of contrast-induced encephalopathy (CIE), a serious complication of contrast agents, is crucial in endovascular treatment. We present the case of a 73-year-old woman who developed CIE in the medulla and cervical cord during coil embolization for unruptured left basilar-superior cerebellar artery and basilar artery tip aneurysms. The CIE was identified via neuromonitoring. In this case, spinal cord ischemia might have occurred due to reduced perfusion pressure after inserting the distal access catheter (DAC) in the vertebral artery. Multiple injections of contrast medium via the DAC during coil embolization likely contributed to an unusual form of CIE. Extreme caution is warranted during endovascular treatments involving the posterior circulation, due to the relatively high incidence of contrast-mediated encephalopathy, which can lead to severe consequences such as perforator infarction. Neuromonitoring is very useful for the early detection of neurological changes, particularly because intraoperative angiography may not reveal all irregularities. [ABSTRACT FROM AUTHOR]

A 14-year-old boy experienced sudden headache in the left parietal region, without any history of head trauma. Approximately 40 ml of hematoma was aspirated using a 22-gauge needle, and scalp swelling immediately disappeared. However, the swelling recurred bilaterally 2 weeks later. Left external carotid angiography revealed a reticular shadow consistent with subgaleal hematoma from a branch of bilateral superficial temporal arteries, without any arteriovenous shunts. The patient was successfully treated using the combination of hematoma aspiration and embolization of the superficial temporal artery. The combination of aspiration of hematoma and embolization may be effective for refractory non-traumatic subgaleal hematoma. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to identify the correlation between the location of the internal carotid artery (ICA) and the need for an orbitozygomatic approach (OZA) when approaching a basilar apex (BX) aneurysm. Materials and methods: By imaging the virtual trajectory to access the basilar artery (BA) through the ICA, the correlations among the height of the BX, the height and lateral breadth of the bifurcation of the ICA, and the need for removal of the orbital rim or zygomatic arch were investigated using three-dimensional computed tomography angiography (3DCTA) data of approximately 80 random samples not limited to BX aneurysms. Furthermore, the utility of 3D simulation to determine the need for the OZA was verified using data from five patients with BX aneurysms. Results: The height of the bifurcation of the ICA was inversely correlated and the height of the BX was positively correlated with the need for the OZA (both p < 0.017). Among patients undergoing surgery, clipping was successfully performed without the OZA in two patients in whom the distance from the simulated skull point on the extended line from the BX through the bifurcation of the ICA was more than 4 cm from the zygoma and orbital rim. Conclusions: It is necessary to determine the spatial relationship between the basilar artery and the ICA to decide whether the OZA is needed for surgery. Correlations of the height of the ICA and BX with the need for the OZA were not very strong individually, though they were significant. Therefore, simulation using 3DCTA appears to be important for planning the surgical approach for the treatment of BX aneurysms. [ABSTRACT FROM AUTHOR]

Nitrogen-containing bisphosphonates (N-BPs), which prevent bone resorption, exert direct and γδT cell (GDT)-mediated antitumor effects against several tumor cell types, including glioblastoma (GBM). However, limited information is available regarding the antitumor effects of N-BPs in GBM. Specifically, the antitumor effects of minodronate (MDA), a third-generation N-BP, in GBM are yet unclear. This study aimed to investigate the antitumor effects of MDA in GBM in vitro and in vivo. We performed growth inhibition and apoptosis detection assays using the GBM cell lines U87MG and U138MG. Apoptosis inhibition assays were also conducted. In vivo xenograft assays were performed in highly immunodeficient NOD.Cg-Prkdc Il2rg/Jic mice subcutaneously implanted with U87MG and U138MG cells. Growth inhibition and apoptosis detection assays demonstrated that MDA inhibited GBM cell growth via apoptosis, which was markedly enhanced by ex vivo expanded GDT. A pan-caspase inhibitor, z-VAD-fmk, inhibited MDA-induced U138MG apoptosis and MDA/GDT-induced U87MG and U138MG apoptosis. But z-VAD-fmk increased MDA-induced U87MG apoptosis. MDA/GDT-mediated apoptosis was blocked by the anti-T cell receptor (TCR) Vγ9, mevalonate pathway inhibitor, granzyme B inhibitor, and antitumor necrosis factor (TNF)-α. In vivo xenograft assays showed that combined intraperitoneal administration of MDA/GDT induced antitumor effects on unestablished U87MG-derived subcutaneous tumors. MDA exerted direct and GDT-mediated anti-GBM apoptotic effects in a caspase-dependent manner. GDT recognized MDA-exposed GBM cells via TCRVγ9 and induced apoptosis via granzyme B and TNF-α release. Because MDA elicited anti-GBM effects in synergy with GDT in vivo, a combination of MDA and ex vivo-generated GDT could be an effective treatment in patients with GBM. [ABSTRACT FROM AUTHOR]

Purpose: Periprocedural ischemic stroke is one problem associated with carotid artery stenting (CAS). This study was designed to assess whether preoperative statin therapy reduces the risk of periprocedural ischemic complications with CAS. Methods: In this prospective study at 11 centers, patients with carotid artery stenosis (symptomatic ≥50 %, asymptomatic ≥80 %) and a high risk of carotid endarterectomy but without previous statin treatments were divided into two groups by low-density lipoprotein cholesterol (LDL-C) levels. With LDL-C ≥120 mg/dl, the pitavastatin-treated (PS) group received pitavastatin at 4 mg/day. With LDL-C <120 mg/dl, the non-PS group received no statin therapy. After 4 weeks, both groups underwent CAS. Frequencies of new ipsilateral ischemic lesions on diffusion-weighted imaging within 72 h after CAS and cerebrovascular events (transient ischemic attack, stroke, or death) within 30 days were assessed. Results: Among the 80 patients enrolled, 61 patients (PS group, n = 31; non-PS group, n = 30) fulfilled the inclusion criteria. New ipsilateral ischemic lesions were identified in 8 of 31 patients (25.8 %) in the PS group and 16 of 30 patients (53.3 %) in the non-PS group ( P = 0.028). Cerebrovascular events occurred in 0 patients in the PS group and in 3 of 30 patients (10.0 %) in the non-PS group ( P = 0.071). Multivariate analyses demonstrated the pitavastatin treatment ( β = 0.74, 95 % confidence interval 0.070-1.48, P = 0.042) to be an independent factor for decreasing post-CAS ischemic lesions. Conclusion: Pretreatment with pitavastatin significantly reduced the frequency of periprocedural ischemic complications with CAS. [ABSTRACT FROM AUTHOR]

The oral microbiota change dramatically with each part of the oral cavity, even within the same mouth. Nevertheless, the microbiota associated with peri-implantitis and periodontitis have been considered the same. To improve our knowledge of the different communities of complex oral microbiota, we compared the microbial features between peri-implantitis and periodontitis in 20 patients with both diseases. Although the clinical symptoms of peri-implantitis were similar to those of periodontitis, the core microbiota of the diseases differed. Correlation analysis revealed the specific microbial co-occurrence patterns and found some of the species were associated with the clinical parameters in a disease-specific manner. The proportion of Prevotella nigrescens was significantly higher in peri-implantitis than in periodontitis, while the proportions of Peptostreptococcaceae sp. and Desulfomicrobium orale were significantly higher in periodontitis than in peri-implantitis. The severity of the peri-implantitis was also species-associated, including with an uncultured Treponema sp. that correlated to 4 clinical parameters. These results indicate that peri-implantitis and periodontitis are both polymicrobial infections with different causative pathogens. Our study provides a framework for the ecologically different bacterial communities between peri-implantitis and periodontitis, and it will be useful for further studies to understand the complex microbiota and pathogenic mechanisms of oral polymicrobial diseases. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a highly aggressive brain tumor for which novel therapeutic approaches, such as immunotherapy, are urgently needed. Zoledronate (ZOL), an inhibitor of osteoclastic activity, is known to stimulate peripheral blood-derived γδT cells and sensitize tumors to γδT cell-mediated killing. To investigate the feasibility of γδT cell-based immunotherapy for patients with GBM, we focused on the killing of GBM cell lines by γδT cells and the molecular mechanisms involved in these cell-cell interactions. Peripheral blood mononuclear cells were expanded in ZOL and interleukin (IL)-2 for 14 days, and γδT cells were enriched in the expanded cells by the immunomagnetic depletion of αβT cells. Gliomas are resistant to NK cells but susceptible to lymphokine-activated killer cells and some cytotoxic T lymphocytes. When the γδT cell-mediated killing of three GBM cell lines (U87MG, U138MG and A172 cells) and an NK-sensitive leukemia cell line (K562 cells) were tested, 32 % U87MG, 15 % U138MG, 1 % A172, and 50 % K562 cells were killed at an effector:target ratio of 5:1. The γδT cell-mediated killing of all three GBM cell lines was significantly enhanced by ZOL and this ZOL-enhanced killing was blocked by an anti-T cell receptor (TcR) antibody. These results indicated that TcR γδ is crucial for the recognition of ZOL-treated GBM cells by γδT cells. Since the low level killing of GBM cells by the γδT cells was enhanced by ZOL, γδT cell-targeting therapy in combination with ZOL treatment could be effective for patients with GBM. [ABSTRACT FROM AUTHOR]

Background: To evaluate a broad-range real-time polymerase chain reaction (PCR) targeting the bacterial 16S rRNA gene for detection of bacterial DNA in infectious endophthalmitis. Methods: The bacterial 16S rRNA gene was measured by quantitative real-time PCR. For the assay, bacterial DNA was prepared from 12 Gram-positive and 4 Gram-negative strains. To determine the optimum method for DNA extraction, four extraction procedures were selected by using DNA extraction program cards with and without the use of lysozyme. To evaluate PCR sensitivity, PCR fragments were amplified from Staphylococcus aureus and Escherichia coli DNA. Results: DNA extraction using the Bacteria card without enzymes resulted in detection of all the tested strains at concentrations ≥10 copies/mL. Extraction with the Bacteria card with lysozyme resulted in detection of all the tested strains at concentrations ≥10 copies/mL, indicative of no significant difference between the two procedures. DNA extraction using the Virus card, both with and without enzymes, resulted in reduced efficiency of detection of all strains compared with use of the Bacteria card. The PCR could detect as few as 1-10 colony-forming units (CFU) in diluted vitreous samples per reaction, and all tested bacterial species known to cause endophthalmitis were detected. Conclusions: Bacterial 16S-specific PCR can comprehensively detect the main causative bacteria of clinically suspected endophthalmitis. [ABSTRACT FROM AUTHOR]

Purpose: Serum atrial natriuretic peptide (ANP) that is elevated after aneurysmal subarachnoid hemorrhage (SAH) causes diuresis and natriuresis (cerebral salt wasting) and might exacerbate delayed ischemic neurological deficit (DIND). We investigated relationships among hyponatremia, serum ANP elevation, and the onset of DIND after SAH. Materials and methods: Thirty-nine consecutive patients (15 women and 24 men) with SAH were assigned to a normonatremia group or a group that developed hyponatremia after SAH. Serum ANP and brain natriuretic peptide were assessed after SAH. All patients remained normovolemic and normotensive. We attributed DIND to vasospasm only in the absence of other causes and when supported by cerebral angiography. Results: Hyponatremia developed after SAH in 11 patients (28.2%), among whom serum ANP concentrations at 0 and 3 days thereafter were significantly increased. Furthermore, DIND developed in five (45.5%) and two (7.1%) hyponatremic and normonatremic patients, respectively ( P < 0.05). The serum ANP levels on day 0 after SAH were higher in Hunt and Kosnik grades 3-4 than in 1-2 and in Fisher groups 3-4 than in 1-2 ( P < 0.05). Conclusions: Increasing serum ANP concentrations were independently associated with hyponatremia resulting in DIND. Early treatment of hyponatremia might prevent DIND in patients after SAH. [ABSTRACT FROM AUTHOR]

Objective: To introduce reliable and minimally invasive virtual surgical planning for superficial temporal artery to middle cerebral artery (STA–MCA) bypass surgery using three-dimensional (3-D) rotational reconstruction digital subtraction angiography (DSA). Methods: Twenty-eight consecutive patients (11 women and 17 men) with cerebrovascular insufficiency due to internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion ( n = 16), ICA or MCA stenosis ( n = 6), and moyamoya or moyamoya-like disease ( n = 6) underwent rotational DSA. Anatomical locations of the appropriate donor branch of the STA, the most suitable recipient of MCA and squamous sutures on the skull surface, were visualized using 3-D reconstruction imaging. Localization of the minicraniotomy, the skin incision on top of the superficial temporal artery branch, and the anastomosis point were accurately determined by virtual surgical planning. Results: According to preoperative assessments, the minimum necessary skin incision and small craniotomy were successfully achieved. The preselected artery was found without additional craniotomy and anastomosed at the putative point in all patients. Perioperative complications did not arise and all bypasses remained patent on follow-up. Conclusion: Preoperative 3-D virtual surgical planning assessments are exactly consistent with operative findings. Such assessments avoid unnecessary manipulation and simplify the surgical procedure. This imaging technique is helpful for planning STA–MCA bypass surgery. [ABSTRACT FROM AUTHOR]

Autophagy degrades unnecessary organelles and misfolded protein aggregates, as well as cytoplasm-invading bacteria. Nevertheless, the bacteria Listeria monocytogenes efficiently escapes autophagy. We show here that recruitment of the Arp2/3 complex and Ena/VASP, via the bacterial ActA protein, to the bacterial surface disguises the bacteria from autophagic recognition, an activity that is independent of the ability to mediate bacterial motility. L. monocytogenes expressing ActA mutants that lack the ability to recruit the host proteins initially underwent ubiquitylation, followed by recruitment of p62 (also known as SQSTM1) and LC3, before finally undergoing autophagy. The ability of ActA to mediate protection from ubiquitylation was further demonstrated by generating aggregate-prone GFP–ActA–Q79C and GFP–ActA–170* chimaeras, consisting of GFP (green fluorescent protein), the ActA protein and segments of polyQ or Golgi membrane protein GCP170 (ref. 6). GFP–ActA–Q79C and GFP–ActA–170* formed aggregates in the host cell cytoplasm, however, these ActA-containing aggregates were not targeted for association with ubiquitin and p62. Our findings indicate that ActA-mediated host protein recruitment is a unique bacterial disguise tactic to escape from autophagy. [ABSTRACT FROM AUTHOR]

No filter protection devices for carotid artery stenting (CAS) have been formally approved for use in Japan; however, as of April 2008, the Angioguard XP (AGXP) was approved. This article describes our initial results using the AGXP during CAS for the treatment of carotid artery stenosis. A group of 15 patients (14 men) with a mean age of 72.3 years (range 53–81 years) were treated by CAS using the AGXP. Among them, 10 were symptomatic with >50% stenosis of the common or internal carotid artery (ICA), and 5 were asymptomatic with >70% stenosis. The rates of technical success, periprocedural stroke, ICA flow impairment, filter movement, and development of new ischemic lesions on diffusion-weighted imaging (DWI) were assessed. CAS using the AGXP was successful in all cases. There was one minor stroke, and flow impairment occurred in six patients. Filter movement averaged 1.9 vertebral bodies. DWI showed new ipsilateral ischemic lesions in eight of the patients. Initial clinical experience using the AGXP for CAS has been generally sufficient. However, attention must be paid to three problems when using the AGXP: the filter may move after placement; the filter may disturb blood flow in the ICA; and debris may pass around the filter. [ABSTRACT FROM AUTHOR]

Propionibacterium acnes is one of the most commonly implicated etiologic agents of sarcoidosis. We previously reported a complete genome sequence of the C1 strain of P. acnes as a clinical isolate from subcutaneous granulomatous inflammatory lesions in a patient with sarcoidosis. In the present study, we initially searched for genetic profiles specific to the C1 strain by core genome analysis and multiple genome alignment with database sequences from 76 and 9 P. acnes strains, respectively. The analysis revealed that the C1 strain was phylogenetically independent and carried an 18.8-kbp transposon sequence unique to the sarcoid isolate. The unique composite transposon comprised a novel insertion sequence and extrinsic genes from bacteria other than P. acnes. Multilocus sequence typing using 24 sarcoid and 36 non-sarcoid isolates revealed a total of 28 sequence types (STs), including ST26, which was most frequently found without specificity for sarcoid isolates. All 13 ST26 isolates exhibited cell-invasiveness and were confirmed to carry the novel insertion sequence and 4 of the 27 extrinsic CDSs in the transposon, with one exception. ST26 of P. acnes with the composite transposon is the most unique strain detected to date and should be further examined as a causative strain of sarcoidosis. [ABSTRACT FROM AUTHOR]

Polymicrobial diseases are caused by combinations of multiple bacteria, which can lead to not only mild but also life-threatening illnesses. Periodontitis represents a polymicrobial disease; Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, called 'the red complex', have been recognized as the causative agents of periodontitis. Although molecular interactions among the three species could be responsible for progression of periodontitis, the relevant genetic mechanisms are unknown. In this study, we uncovered novel interactions in comparative genome analysis among the red complex species. Clustered regularly interspaced short palindromic repeats (CRISPRs) of T. forsythia might attack the restriction modification system of P. gingivalis, and possibly work as a defense system against DNA invasion from P. gingivalis. On the other hand, gene deficiencies were mutually compensated in metabolic pathways when the genes of all the three species were taken into account, suggesting that there are cooperative relationships among the three species. This notion was supported by the observation that each of the three species had its own virulence factors, which might facilitate persistence and manifestations of virulence of the three species. Here, we propose new mechanisms of bacterial symbiosis in periodontitis; these mechanisms consist of competitive and cooperative interactions. Our results might shed light on the pathogenesis of periodontitis and of other polymicrobial diseases. [ABSTRACT FROM AUTHOR]