Embolic Material Migration as the Predominant Contributing Factor to Prognostic Deterioration Following Combined Tumor Resection and Preoperative Embolization.

Introduction Preoperative embolization can potentially facilitate surgical resection of challenging tumors in the intracranial and facial regions; however, its clinical efficacy remains controversial, mainly due to potential morbidity risks. We explored negative factors of the combined treatment of preoperative embolization and tumor resection that affect neurological prognosis. Method This retrospective study used clinical data from 132 consecutive tumors that underwent combined treatment at multiple facilities between January 2016 and May 2021. Basic patient information, tumor characteristics, and treatment details were assessed to identify predictors of deterioration as measured using the modified Rankin scale (mRS) score at three months post-treatment. Results Among the 126 eligible combined treatments, a deterioration in the postoperative mRS score was observed in 19/126 (15.1%). Complications related to embolization and tumor resection occurred in 8/126 (6.3%) and 19/125 (15.2%) of procedures, respectively. Multivariate analyses indicated significant associations between migration of embolic material (adjusted odds ratio 13.80; 95% confidence interval 1.25-152.52; p=0.03), elevated intraoperative blood loss (p=0.04), and deterioration of postoperative mRS score. Embolic material migration was identified as the primary prognostic factor for the deterioration of score. An analysis of 192 procedures, excluding those that exclusively used coils, identified embolization targeting the accessory meningeal artery (p=0.046) and the third segment of the internal maxillary artery (p=0.03) as a risk factor for embolic material migration. Conclusions Embolic material migration is the predominant factor associated with declining neurological outcome that persists into the chronic phase after combined treatment. Given that preoperative embolization is a supplementary treatment option, a thorough understanding of vascular anatomy and striving safe procedure are critical.

Biallelic variants in LARS1 induce steatosis in developing zebrafish liver via enhanced autophagy.

BACKGROUND: Biallelic pathogenic variants of LARS1 cause infantile liver failure syndrome type 1 (ILFS1), which is characterized by acute hepatic failure with steatosis in infants. LARS functions as a protein associated with mTORC1 and plays a crucial role in amino acid-triggered mTORC1 activation and regulation of autophagy. A previous study demonstrated that larsb-knockout zebrafish exhibit conditions resembling ILFS. However, a comprehensive analysis of larsb-knockout zebrafish has not yet been performed because of early mortality. METHODS: We generated a long-term viable zebrafish model carrying a LARS1 variant identified in an ILFS1 patient (larsb-I451F zebrafish) and analyzed the pathogenesis of the affected liver of ILFS1. RESULTS: Hepatic dysfunction is most prominent in ILFS1 patients during infancy; correspondingly, the larsb-I451F zebrafish manifested hepatic anomalies during developmental stages. The larsb-I451F zebrafish demonstrates augmented lipid accumulation within the liver during autophagy activation. Inhibition of DGAT1, which converts fatty acids to triacylglycerols, improved lipid droplets in the liver of larsb-I451F zebrafish. Notably, treatment with an autophagy inhibitor ameliorated hepatic lipid accumulation in this model. CONCLUSIONS: Our findings suggested that enhanced autophagy caused by biallelic LARS1 variants contributes to ILFS1-associated hepatic dysfunction. Furthermore, the larsb-I451F zebrafish model, which has a prolonged survival rate compared with the larsb-knockout model, highlights its potential utility as a tool for investigating the pathophysiology of ILFS1-associated liver dysfunction.

Effect of nonsense-mediated mRNA decay factor SMG9 deficiency on premature aging in zebrafish.

SMG9 is an essential component of the nonsense-mediated mRNA decay (NMD) machinery, a quality control mechanism that selectively degrades aberrant transcripts. Mutations in SMG9 are associated with heart and brain malformation syndrome (HBMS). However, the molecular mechanism underlying HBMS remains unclear. We generated smg9 mutant zebrafish (smg9oi7/oi7) that have a lifespan of approximately 6 months or longer, allowing for analysis of the in vivo function of Smg9 in adults in more detail. smg9oi7/oi7 zebrafish display congenital brain abnormalities and reduced cardiac contraction. Additionally, smg9oi7/oi7 zebrafish exhibit a premature aging phenotype. Analysis of NMD target mRNAs shows a trend toward increased mRNA levels in smg9oi7/oi7 zebrafish. Spermidine oxidase (Smox) is increased in smg9oi7/oi7 zebrafish, resulting in the accumulation of byproducts, reactive oxygen species, and acrolein. The accumulation of smox mRNA due to NMD dysregulation caused by Smg9 deficiency leads to increased oxidative stress, resulting in premature aging.

Hepatic extracellular ATP/adenosine dynamics in zebrafish models of alcoholic and metabolic steatotic liver disease.

Steatotic liver disease (SLD) is a burgeoning health problem predominantly associated with excessive alcohol consumption, which causes alcohol-related liver disease (ALD), and high caloric intake, which results in metabolic dysfunction-associated SLD (MASLD). The pathogenesis of ALD and MASLD, which can progress from steatohepatitis to more severe conditions such as liver fibrosis, cirrhosis, and hepatocellular carcinoma, is complicated by several factors. Recently, extracellular ATP and adenosine (Ado), as damage-associated molecular patterns, were reported to promote inflammation and liver fibrosis, contributing to SLD pathogenesis. Here, we explored the in vivo dynamics of hepatic extracellular ATP and Ado during the progression of steatohepatitis using a genetically encoded GPCR-activation-based sensor (GRAB) in zebrafish models. We established hepatocyte-specific GRABATP and GRABAdo in zebrafish and investigated the changes in in vivo hepatic extracellular ATP and Ado levels under ALD or MASLD conditions. Disease-specific changes in hepatocyte extracellular ATP and Ado levels were observed, clearly indicating a correlation between hepatocyte extracellular ATP/Ado dynamics and disease progression. Furthermore, clodronate, a vesicular nucleotide transporter inhibitor, alleviated the MASLD phenotype by reducing the hepatic extracellular ATP and Ado content. These findings provide deep insights into extracellular ATP/Ado dynamics in disease progression, suggesting therapeutic potential for ALD and MASLD.

DHCR7 links cholesterol synthesis with neuronal development and axonal integrity.

The DHCR7 enzyme converts 7-DHC into cholesterol. Mutations in DHCR7 can block cholesterol production, leading to abnormal accumulation of 7-DHC and causing Smith-Lemli-Opitz syndrome (SLOS). SLOS is an autosomal recessive disorder characterized by multiple malformations, including microcephaly, intellectual disability, behavior reminiscent of autism, sleep disturbances, and attention-deficit/hyperactivity disorder (ADHD)-like hyperactivity. Although 7-DHC affects neuronal differentiation in ex vivo experiments, the precise mechanism of SLOS remains unclear. We generated Dhcr7 deficient (dhcr7-/-) zebrafish that exhibited key features of SLOS, including microcephaly, decreased neural stem cell pools, and behavioral phenotypes similar to those of ADHD-like hyperactivity. These zebrafish demonstrated compromised myelination, synaptic anomalies, and neurotransmitter imbalances. The axons of the dhcr7-/- zebrafish showed increased lysosomes and attenuated autophagy, suggesting that autophagy-related neuronal homeostasis is disrupted.

Cardiac manifestations of human ACTA2 variants recapitulated in a zebrafish model.

The ACTA2 gene encodes actin α2, a major smooth muscle protein in vascular smooth muscle cells. Missense variants in the ACTA2 gene can cause inherited thoracic aortic diseases with characteristic symptoms, such as dysfunction of smooth muscle cells in the lungs, brain vessels, intestines, pupils, bladder, or heart. We identified a heterozygous missense variant of Gly148Arg (G148R) in a patient with a thoracic aortic aneurysm, dissection, and left ventricular non-compaction. We used zebrafish as an in vivo model to investigate whether or not the variants might cause functional or histopathological abnormalities in the heart. Following the fertilization of one-cell stage embryos, we injected in vitro synthesized ACTA2 mRNA of wild-type, novel variant G148R, or the previously known pathogenic variant Arg179His (R179H). The embryos were maintained and raised for 72 h post-fertilization for a heart analysis. Shortening fractions of heart were significantly reduced in both pathogenic variants. A histopathological evaluation showed that the myocardial wall of ACTA2 pathogenic variants was thinner than that of the wild type, and the total cell number within the myocardium was markedly decreased in all zebrafish with pathogenic variants mRNAs. Proliferating cell numbers were also significantly decreased in the endothelial and myocardial regions of zebrafish with ACTA2 variants compared to the wild type. These results demonstrate the effects of ACTA2 G148R and R179H on the development of left ventricle non-compaction and cardiac morphological abnormalities. Our study highlights the previously unknown significance of the ACTA2 gene in several aspects of cardiovascular development.

A pH imbalance is linked to autophagic dysregulation of inner ear hair cells in Atp6v1ba-deficient zebrafish.

V-ATPase is an ATP hydrolysis-driven proton pump involved in the acidification of intracellular organelles and systemic acid-base homeostasis through H+ secretion in the renal collecting ducts. V-ATPase dysfunction is associated with hereditary distal renal tubular acidosis (dRTA). ATP6V1B1 encodes the B1 subunit of V-ATPase that is integral to ATP hydrolysis and subsequent H+ transport. Patients with pathogenic ATP6V1B1 mutations often exhibit an early onset of sensorineural hearing loss. However, the mechanisms underlying this association remain unclear. We employed morpholino oligonucleotide-mediated knockdown and CRISPR/Cas9 gene editing to generate Atp6v1ba-deficient (atp6v1ba-/-) zebrafish as an ortholog model for ATP6V1B1. The atp6v1ba-/- zebrafish exhibited systemic acidosis and significantly smaller otoliths compared to wild-type siblings. Moreover, deficiency in Atp6v1ba led to degeneration of inner ear hair cells, with ultrastructural changes indicative of autophagy. Our findings indicate a critical role of ATP6V1B1 in regulating lysosomal pH and autophagy in hair cells, and the results provide insights into the pathophysiology of sensorineural hearing loss in dRTA. Furthermore, this study demonstrates that the atp6v1ba-/- zebrafish model is a valuable tool for further investigation into disease mechanisms and potential therapies for acidosis-related hearing impairment.

"The microcatheter contrast injection technique": A novel technique to detect the proximal end of a thrombus in mechanical thrombectomy.

Background: An aspiration catheter needs to attach to a thrombus in order to achieve first-pass recanalization by mechanical thrombectomy (MT) for acute ischemic stroke (AIS), particularly that using a direct aspiration first pass technique. The meniscus sign, which is defined as meniscoid contrast opacification indicating the proximal edge of a thrombus, has been suggested to contribute to successful recanalization. In some cases, the meniscus sign is not detected following an injection of contrast medium through a guiding catheter. To precisely identify the location of a thrombus, we use "the microcatheter contrast injection (MCI) technique," which accurately shows the proximal edge of a thrombus. We herein introduce this novel technique and discuss its efficacy in MT. Methods: In cases without the meniscus sign, a microcatheter was advanced to the distal end of contrast opacification, and contrast medium was injected through the microcatheter to detect the meniscus sign. An aspiration catheter was then advanced to the thrombus indicated by the meniscus sign and slowly withdrawn under aspiration. Results: 29 patients underwent MT for AIS using the MCI technique. Even in cases without the meniscus sign on initial angiography, the MCI technique accurately revealed the proximal edge of the thrombus. Moreover, middle cerebral artery occlusion due to atherosclerotic stenosis and displacement of the aspiration catheter and thrombus axis were detected using this technique. Conclusions: The MCI technique may effectively reveal the exact site of a thrombus and increase the success rate of first-pass recanalization.

Transvenous embolization for an intraosseous clival arteriovenous fistula via a proper access route guiding a three-dimensional fusion image: illustrative case.

BACKGROUND: Intraosseous clival arteriovenous fistulas (AVFs), in which the shunt drains extracranially from the posterior and anterior condylar veins rather than from the cavernous sinus (CS), are rare. Targeting embolization of an intraosseous clival AVF is challenging because of its complex venous and skull base anatomy; therefore, a therapeutic strategy based on detailed preoperative radiological findings is required to achieve a favorable outcome. Here, the authors report the successful targeted embolization of an intraosseous clival AVF using an ingenious access route. OBSERVATIONS: A 74-year-old woman presented with left-sided visual impairment, oculomotor nerve palsy, and right facial pain. A fusion image of three-dimensional rotational angiography and cone-beam computed tomography revealed a left CS dural AVF and a right intraosseous clival AVF. The shunt flow of the clival AVF drained extracranially from the posterior and anterior condylar veins via the intraosseous venous route. Transvenous embolization was performed by devising suboccipital, posterior condylar, and intraosseous access routes. The symptoms resolved after the bilateral AVFs were treated. LESSONS: Accurate diagnosis and proper transvenous access based on detailed intraosseous and craniocervical venous information obtained from advanced imaging modalities are key to resolving intraosseous clival AVF.

Complications and outcomes of carotid artery stenting in high-risk cases.

OBJECTIVES: Carotid artery stenting is sometimes adapted for some at-risk cases; however, appropriate treatment timing with stroke onset is controversial. This study aims to identify factors that have an impact on complications and outcomes, especially in patients at high risk. MATERIALS AND METHODS: We examined the characteristics of 152 consecutive patients treated by carotid artery stenting between January 2018 and March 2022 and retrospectively analyzed the risk factors for complications and poor outcomes (modified-Rankin-Scale deterioration), such as patient background, carotid artery stenting risks (access route tortuosity, severe calcification, vulnerable plaque, estimated glomerular filtration rate <30 mL/min/1.73 m2, etc.), characteristics of the stenosis, details of treatment, and treatment timing. RESULTS: The average North American Symptomatic Carotid Endarterectomy Trial criteria score was 68.3% and the lesion length was 20.5±9.7mm. Among patients, 107 (70.4%) had a carotid artery stenting risk. In high-risk carotid artery stenting cases, symptomatic complications occurred in 32 (30.0%), and the 90-day modified Rankin scale score deteriorated in 15 cases (14.0%). Multivariate analysis showed that cases with triple antithrombotic therapy (p=0.003), stenting within 7 days (p=0.0032), and after 28+ days (p=0.0035) of stroke onset were independently associated factors for complications. CONCLUSIONS: This study showed that among risk factors, triple antithrombotic therapy in particular was a risk factor for perioperative complications. Carotid artery stenting for patients with stroke after 28 days of onset affects the prognosis. Therefore, although further study is warranted, waiting more than one month for treatment in patients requiring carotid artery stenting is a potential risk.

Zebrafish as a Useful Model System for Human Liver Disease.

Liver diseases represent a significant global health challenge, thereby necessitating extensive research to understand their intricate complexities and to develop effective treatments. In this context, zebrafish (Danio rerio) have emerged as a valuable model organism for studying various aspects of liver disease. The zebrafish liver has striking similarities to the human liver in terms of structure, function, and regenerative capacity. Researchers have successfully induced liver damage in zebrafish using chemical toxins, genetic manipulation, and other methods, thereby allowing the study of disease mechanisms and the progression of liver disease. Zebrafish embryos or larvae, with their transparency and rapid development, provide a unique opportunity for high-throughput drug screening and the identification of potential therapeutics. This review highlights how research on zebrafish has provided valuable insights into the pathological mechanisms of human liver disease.

Behavioral and neurological effects of Vrk1 deficiency in zebrafish.

Vaccinia-related kinase 1 (VRK1) is a serine/threonine kinase, for which mutations have been reported cause to neurodegenerative diseases, including spinal muscular atrophy, characterized by microcephaly, motor dysfunction, and impaired cognitive function, in humans. Partial Vrk1 knockdown in mice has been associated with microcephaly and impaired motor function. However, the pathophysiological relationship between VRK1 and neurodegenerative disorders and the precise mechanism of VRK1-related microcephaly and motor function deficits have not been fully investigated. To address this, in this study, we established vrk1-deficient (vrk1-/-) zebrafish and found that they show mild microcephaly and impaired motor function with a low brain dopamine content. Furthermore, vrk1-/- zebrafish exhibited decreased cell proliferation, defects in nuclear envelope formation, and heterochromatin formation in the brain. To our knowledge, this is the first report demonstrating the important role of VRK1 in microcephaly and motor dysfunction in vivo using vrk1-/- zebrafish. These findings contribute to elucidating the pathophysiological mechanisms underlying VRK1-mediated neurodegenerative diseases associated with microcephaly.

De novo progressive dural arteriovenous fistula with putamen hemorrhage associated with long-term Down syndrome: A case report and literature review.

Dural arteriovenous fistula (DAVF) is considered an acquired change in blood flow related to factors such as craniotomy, trauma, and infection. However, several factors related to its development remain unknown. Here, we present a case of a 48-year-old man with Down syndrome and Eisenmenger syndrome. He had a history of craniotomy for multiple brain abscesses, followed by the occurrence of a de novo straight sinus (StS) DAVF within the last 2 years. The patient presented with right putamen hemorrhage due to venous congestion by a StS DAVF. The shunt flow was occluded by transarterial embolization using Onyx. Several studies have reported on DAVF models induced by venous congestion and hypoxemia. In this case, local venous congestion due to craniotomy for multiple brain abscesses was considered as one of the causes of DAVF. Complication of venous thrombosis or chronic hypoxemia due to Eisenmenger syndrome might have led to its progression. Especially in DAVF cases with Down syndrome, concomitant symptoms such as hypoxemia due to congenital heart failure and coagulopathy could worsen the disease state progressively.

Artificial cerebrospinal fluid restores aspirin-inhibited physiological hemostasis through recovery of platelet aggregation function.

BACKGROUND: Optimal hemostasis provides safety and reliability during neurosurgery which improves surgical outcomes. Previously, artificial cerebrospinal fluid (aCSF) and its component sodium bicarbonate were found to facilitate physiological hemostasis by amplifying platelet aggregation. This study aimed to verify whether aCSF amplifies platelet-dependent hemostasis in the presence of antiplatelet agents. METHODS: We prepared platelet-rich plasma (PRP) or washed platelets using aspirin (acetylsalicylic acid, (ASA)) or normal saline (NS). We evaluated samples treated with a commercially available aCSF solution or NS for amplification of aggregation, activation of integrin αIIbß3, phosphatidylserine (PS) exposure, P-selectin (CD62P) expression, and formation of microparticles (MPs). We assessed the effect of aCSF on in vivo hemostasis in the presence of ASA by measuring the tail bleeding time in ASA-or NS-injected C57BL/6 N mice. RESULTS: Compared with NS, aCSF amplified ASA-inhibited platelet aggregation by recovering platelet activation including PS exposure, MP release, CD62P expression, and integrin αIIbß3 activation. When using washed platelets, aCSF almost completely counteracted the inhibition of platelet aggregation by ASA. Prolonged bleeding time from the amputated tail of ASA-injected mice was significantly shortened by the treatment with aCSF compared to NS. Sodium bicarbonate also directly amplified ASA-inhibited platelet aggregation. CONCLUSIONS: aCSF and sodium bicarbonate facilitate physiological hemostasis through the recovery of inhibited platelet aggregation even in the presence of ASA. The utilization of aCSF in the operative field may be advantageous for facilitating hemostasis in patients with impaired platelet function and contribute to improving outcomes of neurosurgery.

Preoperative tumor embolization prolongs time to recurrence of meningiomas: a retrospective propensity-matched analysis.

BACKGROUND: Meningiomas are often embolized preoperatively to reduce intraoperative blood loss and facilitate tumor resection. However, the procedure is controversial and its effects have not yet been reported. We evaluated preoperative embolization for meningiomas and its effect on postoperative outcome and recurrence. METHODS: We retrospectively reviewed the medical records of 186 patients with WHO grade I meningiomas who underwent surgical treatment at our hospital between January 2010 and December 2020. We used propensity score matching to generate embolization and no-embolization groups (42 patients each) to examine embolization effects. RESULTS: Preoperative embolization was performed in 71 patients (38.2%). In the propensity-matched analysis, the embolization group showed favorable recurrence-free survival (RFS) (mean 49.4 vs 24.1 months; Wilcoxon p=0.049). The embolization group had significantly less intraoperative blood loss (178±203 mL vs 221±165 mL; p=0.009) and shorter operation time (5.6±2.0 hours vs 6.8±2.8 hours; p=0.036). There were no significant differences in Simpson grade IV resection (33.3% vs 28.6%; p=0.637) or overall perioperative complications (21.4% vs 11.9%; p=0.241). Tumor embolization prolonged RFS in a subanalysis of cases who experienced recurrence (n=39) among the overall cases before variable control (mean RFS 33.2 vs 16.0 months; log-rank p=0.003). CONCLUSIONS: After controlling for variables, preoperative embolization for meningioma did not improve the Simpson grade or patient outcomes. However, it might have effects outside of surgical outcomes by prolonging RFS without increasing complications.

Measuring concerns about the COVID-19 vaccine among Japanese internet users through search queries.

With the increasing availability of the COVID-19 vaccines, vaccination has been rapidly promoted globally as a countermeasure against the spread of COVID-19. In Japan, vaccination was first introduced in February 2021. However, the amount of concern towards vaccination differs between individuals, and topics of concern include adverse reactions and side effects. This study investigated attitudes toward vaccines or vaccination during the COVID-19 pandemic across different Japanese prefectures, using Yahoo! JAPAN search queries. We first defined a vaccine concern index (VCI) by aggregating the search counts of vaccine-related queries from Yahoo! JAPAN users before examining VCI across all Japanese prefectures, accounting for gender and age. Our results demonstrated that VCI tended to be lower in more populated areas, and VCI was higher in their 20s to 40s than older people, especially in female users. Furthermore, there was a significant positive correlation (Spearman's Rank correlation coefficient [Formula: see text] = 0.60, [Formula: see text]) between VCI and prefectural vaccination rate, suggesting that web searching of adverse vaccine reactions may precede actual vaccination. This could reflect the information-seeking behavior of individuals who are accepting of vaccinations.

Ankle2 deficiency-associated microcephaly and spermatogenesis defects in zebrafish are alleviated by heterozygous deletion of vrk1.

Autosomal recessive primary microcephaly (MCPH) is a rare congenital disorder characterized by a below average brain volume at birth and is associated with neurodevelopmental disorders such as growth retardation and intellectual disability. Mutations in ANKLE2 have been identified as one of the causes of MCPH (MCPH16). ANKLE2 is a target molecule of the Zika virus NS4a protein that interferes with ANKLE2 function, resulting in severe microcephaly. ANKLE2 is essential for organizing the nuclear envelope and chromatin structures during the mitotic-end process via barrier to autointegration factor (BAF) dephosphorylation. However, the precise mechanism by which the loss of ANKLE2 function causes the pathogenesis of microcephaly remains unclear. In this study, we generated Ankle2-deficient zebrafish (ankle2-/-) with a significant reduction in brain size compared with that of their control siblings. The ankle2-/- brain showed a significant decrease in the number of radial glial progenitor cells, suggesting that Ankle2 deficiency in zebrafish causes neurogenesis defects. Furthermore, ankle2-/- male zebrafish showed infertility owing to defects in spermatogenesis. Notably, microcephaly was overcome by vrk1 morpholino knockdown or vrk1 heterozygous deletion. In addition, spermatogenesis in ankle2-/- zebrafish males was partially restored by the vrk1 heterozygous deletion, although infertility was not resolved. These results indicate that ANKLE2 and VRK1 coordinate with each other for BAF phosphorylation to maintain normal mitosis during neurogenesis and spermatogenesis.

Availability of tracheal shift in the chest X-ray image as pre-treatment evaluation of mechanical thrombectomy.

BACKGROUND: The use of mechanical thrombectomy (MT) for treatment of acute large vessel occlusion has recently increased. Prompt and timely guiding catheter (GC) induction is necessary to improve prognosis of MT and reduce the time for recanalization. However, difficulties in GC induction are encountered in some patients. This GC induction depends mainly on the aortic arch structure. Therefore, this study focused on assessing presence of tracheal shift on chest X-ray images as pre-treatment evaluation method for GC induction due to its wide availability as an indicator for status of the mediastinum. METHODS: We retrospectively examined 33 patients who underwent MT at our facilities between April 2017 and March 2021. The patients were divided into two groups according to presence or absence of tracheal shift on chest X-ray images. Background characteristics and treatment courses in these two groups were compared. RESULTS: Among 33 patients, tracheal shift was observed on the chest X-ray images of 14 patients. Furthermore, tracheal shift was positively correlated with the time of GC induction (32.9 min vs. 11.6 min, [p < 0.05]) and the female sex (p = 0.03). Additionally, tracheal shift exhibited correlations with multiple risk factors of atherosclerosis (p = 0.04). CONCLUSIONS: In patients with tracheal shift, GC induction could be expectedly difficult. Therefore, advanced disinfection of the right upper arm and affected side of the neck during MT in preparation for changing an approach route is required.

Reconstructive embolization for contralateral vertebral artery dissecting aneurysm that developed after internal trapping of ruptured vertebral artery dissection: A case report and literature review.

Background: It is not well-known that contralateral vertebral artery dissecting aneurysms (VADA) may be newly revealed after parental artery occlusion for unilateral VADA. However, the optimal treatment strategies and perioperative management have not been established. In this report, we present the case of a patient who required reconstructive embolization in the subacute stage for contralateral VADA developed after endovascular internal trapping of the ruptured VADA. Case Description: A 61-year-old man developed subsequent disturbance of consciousness. Head CT showed a diffuse and symmetrical SAH. 3DCT revealed a fusiform aneurysm of the left intracranial vertebral artery with bleb formation. We performed emergency endovascular parent artery occlusion of the left vertebral artery. A digital subtraction angiography on postoperative day 16 showed continued occlusion of the left VA, and a fusiform aneurysm was noted at the right VA. We performed reconstructive embolization and the patient eventually recovered with minimal persistent symptoms. Conclusion: Since the outcomes of contralateral VAD complicated by infarction or hemorrhage are poor, and most cases develop within 7-14 days after endovascular internal trapping for unilateral VAD, performing bilateral radiographic reinspection within this time frame is recommended for early detection and preventive treatment of possible contralateral VADs.

Vrk2 deficiency elicits aggressive behavior in female zebrafish.

Vaccinia-related kinase 2 (VRK2) is a serine/threonine kinase initially identified in highly proliferative cells such as thymocytes and fetal liver cells, and it is involved in cell proliferation and survival. VRK2 is also expressed in the brain; however, its molecular function in the central nervous system is mostly unknown. Many genome-wide association studies (GWASs) have reported that VRK2 is a potential candidate molecule for neuropsychiatric diseases such as schizophrenia in humans. However, the pathophysiological relationship between VRK2 and neuropsychiatric disorders has not been fully investigated. In this study, we evaluated vrk2-deficient (vrk2-/- ) zebrafish and found that vrk2-/- female zebrafish showed aggressive behavior and different social preference compared with control (vrk2+/+ ) zebrafish, with low gamma-aminobutyric acid (GABA) content in the brain and high density of neuronal dendrites when compared to vrk2+/+ zebrafish. These findings suggest that female vrk2-/- zebrafish were indeed a model of malbehavior characterized by aggression and social interaction, which can be attributed to the low levels of GABA content in their brain.