Clinical Study of 14 Cases of Bone Augmentation with Selective Laser Melting Titanium Mesh Plates.

Additive manufacturing techniques are being used in the medical field. Orthopedic hip prostheses and denture bases are designed and fabricated based on the patient's computer-aided design (CAD) data. We attempted to incorporate this technique into dental implant bone augmentation. Surgical simulation was performed using patient data. Fourteen patients underwent bone augmentation using a selective laser melting (SLM) titanium mesh plate. The results showed no evidence of infection in any of the 14 patients. In 12 patients, only one fixation screw was used, and good results were obtained. The SLM titanium mesh plate was good adaptation in all cases, with bone occupancy greater than 90%. The average bone resorption of the marginal alveolar bone from the time of dental implant placement to the time of the superstructure placement was 0.69 ± 0.25 mm. Implant superstructures were placed in all cases, and bone augmentation with SLM titanium mesh plates was considered a useful technique.

Additional Embolization for Intra-aneurysmal Blood Flow Resumption after Stent-assisted Embolization of Cerebral Aneurysms.

Objective: Stent-assisted aneurysmal embolization (SAAE) is an effective treatment for aneurysms with a low risk of recurrence. In rare cases, retreatment is necessary due to recanalization of blood flow into the aneurysm. However, only a few studies have reported on retreatment. We examined the efficacy and complications of stent-assisted aneurysm embolization for large or wide-neck aneurysms at our hospital. Methods: Between July 2010 and June 2018, 293 patients underwent stent-assisted aneurysm embolization at our hospital. Among them, 12 (2 women, 10 men, mean age: 62 years) needed retreatment. We evaluated the initial treatment of these 12 patients, and the methods and results of their retreatment. Results: Six of the 12 retreated patients were treated using the simple technique. It was possible to treat nine patients (75%) without placing new stents, but three needed additional stents. We were able to guide the microcatheter into the aneurysm using the trans-cell technique even with two overlapping stents. We achieved complete embolism in seven patients (58%), and remnants were observed in the neck in five (42%) patients. No complications were associated with our surgery. We were able to perform follow-up for 10 patients and there was no recurrence. Conclusion: Embolization should be considered in recurrent cases after the initial stent-assisted coil embolization. We achieved good results and reduced the recurrence rate by selecting the appropriate treatment in each case.

Polycomb repression complex 2 is required for the maintenance of retinal progenitor cells and balanced retinal differentiation.

Polycomb repressive complexes maintain transcriptional repression of genes encoding crucial developmental regulators through chromatin modification. Here we investigated the role of Polycomb repressive complex 2 (PRC2) in retinal development by inactivating its key components Eed and Ezh2. Conditional deletion of Ezh2 resulted in a partial loss of PRC2 function and accelerated differentiation of Müller glial cells. In contrast, inactivation of Eed led to the ablation of PRC2 function at early postnatal stage. Cell proliferation was reduced and retinal progenitor cells were significantly decreased in this mutant, which subsequently caused depletion of Müller glia, bipolar, and rod photoreceptor cells, primarily generated from postnatal retinal progenitor cells. Interestingly, the proportion of amacrine cells was dramatically increased at postnatal stages in the Eed-deficient retina. In accordance, multiple transcription factors controlling amacrine cell differentiation were upregulated. Furthermore, ChIP-seq analysis showed that these deregulated genes contained bivalent chromatin (H3K27me3+ H3K4me3+). Our results suggest that PRC2 is required for proliferation in order to maintain the retinal progenitor cells at postnatal stages and for retinal differentiation by controlling amacrine cell generation.

WNT/ß-Catenin Signaling in Vertebrate Eye Development.

The vertebrate eye is a highly specialized sensory organ, which is derived from the anterior neural plate, head surface ectoderm, and neural crest-derived mesenchyme. The single central eye field, generated from the anterior neural plate, divides to give rise to the optic vesicle, which evaginates toward the head surface ectoderm. Subsequently, the surface ectoderm, in conjunction with the optic vesicle invaginates to form the lens vesicle and double-layered optic cup, respectively. This complex process is controlled by transcription factors and several intracellular and extracellular signaling pathways including WNT/ß-catenin signaling. This signaling pathway plays an essential role in multiple developmental processes and has a profound effect on cell proliferation and cell fate determination. During eye development, the activity of WNT/ß-catenin signaling is tightly controlled. Faulty regulation of WNT/ß-catenin signaling results in multiple ocular malformations due to defects in the process of cell fate determination and differentiation. This mini-review summarizes recent findings on the role of WNT/ß-catenin signaling in eye development. Whilst this mini-review focuses on loss-of-function and gain-of-function mutants of WNT/ß-catenin signaling components, it also highlights some important aspects of ß-catenin-independent WNT signaling in the eye development at later stages.

The effect of histidine on mental fatigue and cognitive performance in subjects with high fatigue and sleep disruption scores.

Our previous study reported that a dried bonito broth known in Japan as 'dashi' improved or ameliorated mood states, including fatigue, during the daily lives of human subjects. Histidine is an amino acid that is present in dried bonito broth, and we sought to evaluate whether histidine would affect feelings of fatigue in humans. We investigated the effects of histidine intake on the feeling of fatigue, mood states and mental task performance by performing a placebo-controlled, double-blind crossover trial. Twenty subjects with high fatigue and sleep disruption scores were asked to ingest histidine or a placebo every day for two weeks. The subjects' mood states were evaluated using the Profile of Mood States (POMS) scale and a visual analog scale (VAS) for eight feelings (fatigue, depression, carelessness, drowsiness, clear thinking, motivation, attentiveness and concentration). We also measured subjects' cognitive performance using the CogHealth test battery. The fatigue T-scores on the POMS test decreased significantly following histidine ingestion compared to placebo ingestion (p<0.05). After two weeks of histidine ingestion, the reaction time for the working memory task in the CogHealth test battery was significantly shorten compared to placebo ingestion. The VAS scores for clear thinking and for attentiveness were increased significantly following histidine ingestion compared to placebo ingestion (p<0.05). These results suggest that daily ingestion of histidine may ameliorate feelings of fatigue, increase performance during working memory tasks, and improve the clear thinking and attentiveness.

Genetic interaction between Pax6 and ß-catenin in the developing retinal pigment epithelium.

Wnt/ß-catenin signaling plays an essential role in the retinal pigment epithelium (RPE) determination. Since activity of Pax6 (together with Pax2) is also required for the RPE determination, we investigated a possible genetic interaction between Pax6 and Wnt/ß-catenin signaling pathway by analyzing Pax6, ß-catenin, and Pax6/ß-catenin conditional knockout mice. Although Pax6 inactivation alone had no impact on initial specification determined by the expression of Mitf and Otx2, melanin pigmentation was reduced in the RPE. This suggests that along with Mitf and Otx2, Pax6 is required for the full differentiation of RPE. Reporter gene assays in vitro suggest that hypopigmentation is at least in part due to the direct regulation of genes encoding enzymes involved in melanin synthesis by Pax6, Mitf, and ß-catenin. The RPE of a ß-catenin/Pax6 double mutant was differentiated into the neural retina; however, the tissue was thinner than that of the conditional ß-catenin mutant due to reduced proliferation. Together, our data demonstrate that Pax6 is required for the RPE differentiation by regulating pigmentation and accountable for hyperproliferation in the transdifferentiated RPE. In this context, Pax6 appears to function as a pleiotropic regulator, directing development of ocular tissues in concert with the signaling pathway and, at the same time, regulating expression of structural component of the eye, such as shielding pigment.

Lens morphogenesis is dependent on Pax6-mediated inhibition of the canonical Wnt/beta-catenin signaling in the lens surface ectoderm.

Lens formation in mouse is critically dependent on proper development of the retinal neuroectoderm that is located close beneath the head surface ectoderm. Signaling from the prospective retina triggers lens-specific gene expression in the surface-ectoderm. Supression of canonical Wnt/beta-catenin signaling in the surface ectoderm is one of the prerequisites for lens development because, as we show here, ectopic Wnt activation in the retina and lens abrogates lens formation. Wnt inhibiton is mediated by signals coming from the retina but its exact mechanism is unknown. We show that Pax6 directly controls expression of several Wnt inhibitors such as Sfrp1, Sfrp2, and Dkk1 in the presumptive lens. In accordance, absence of Pax6 function leads to aberrant canonical Wnt activity in the presumptive lens that subsequently impairs lens development. Thus Pax6 is required for down-regulation of canonical Wnt signaling in the presumptive lens ectoderm.

Spatial and temporal regulation of Wnt/beta-catenin signaling is essential for development of the retinal pigment epithelium.

Wnt/beta-catenin signaling is highly active in the dorsal retinal pigment epithelium (RPE) during eye development. To study the role of Wnt/beta-catenin signaling in the RPE development we used a conditional Cre/loxP system in mice to inactivate or ectopically activate Wnt/beta-catenin signaling in the RPE. Inactivation of Wnt/beta-catenin signaling results in transdifferentiation of RPE to neural retina (NR) as documented by downregulation of RPE-specific markers Mitf and Otx2 and ectopic expression of NR-specific markers Chx10 and Rx, respectively. In contrast, ectopic activation of Wnt/beta-catenin signaling results in the disruption of the RPE patterning, indicating that precise spatial and temporal regulation of Wnt/beta-catenin signaling is required for normal RPE development. Using chromatin immunoprecipitation (ChIP) and reporter gene assays we provide evidence that Otx2 and RPE-specific isoform of Mitf, Mitf-H, are direct transcriptional targets of Wnt/beta-catenin signaling. Combined, our data suggest that Wnt/beta-catenin signaling plays an essential role in development of RPE by maintaining or inducing expression of Mitf and Otx2.

Subtracted vortex centers path line method with cinematic angiography for measurement of flow speed in cerebral aneurysms.

BACKGROUND AND PURPOSE: The assessment of blood flow speed by imaging modalities is of increasing importance for endovascular treatment, such as stent implantation, of cerebral aneurysms. The subtracted vortex centers path line method (SVC method) utilizes image post-processing for determining flow quantitatively. In current practice, intra-aneurysmal flow in an in vitro model is visualized by laser sheet translumination and digitally recorded. In this study, we applied this method to cinematic angiography (CA), which is the preferred imaging method for endovascular interventions, to analyse hemodynamic changes. The SVC method was applied to the images and compared with results of the slipstream line method with colored fluid. METHODS: A transparent tubular model was constructed of silicone which included an aneurysm 10 mm in diameter and having a 5 mm neck on a straight parent artery with a diameter of 3.5 mm. The model was integrated into a pulsatile circulation system. By CA, successive images at 25 frames/s with injection of contrast were obtained. RESULTS AND CONCLUSION: Rotating vortexes of contrast, which advanced along the wall of the aneurysm, were observed in successive images of the aneurysm cavity. This phenomenon was also observed in the successive images with the slipstream line method. The speed of the vortex center was calculated and the results show that the vortex speed of CA was the same as that under the slipstream line method. This indicates the possibility of applying the SVC method to medical imaging equipment for analysis of the flow in aneurysms containing stent.

Wnt-mediated down-regulation of Sp1 target genes by a transcriptional repressor Sp5.

Wnt/beta-catenin signaling regulates many processes during vertebrate development. To study transcriptional targets of canonical Wnt signaling, we used the conditional Cre/loxP system in mouse to ectopically activate beta-catenin during central nervous system development. We show that the activation of Wnt/beta-catenin signaling in the embryonic mouse telencephalon results in the up-regulation of Sp5 gene, which encodes a member of the Sp1 transcription factor family. A proximal promoter of Sp5 gene is highly evolutionarily conserved and contains five TCF/LEF binding sites that mediate direct regulation of Sp5 expression by canonical Wnt signaling. We provide evidence that Sp5 works as a transcriptional repressor and has three independent repressor domains, called R1, R2, and R3, respectively. Furthermore, we show that the repression activity of R1 domain is mediated through direct interaction with a transcriptional corepressor mSin3a. Finally, our data strongly suggest that Sp5 has the same DNA binding specificity as Sp1 and represses Sp1 target genes such as p21. We conclude that Sp5 transcription factor mediates the downstream responses to Wnt/beta-catenin signaling by directly repressing Sp1 target genes.

Insoluble fiber is a major constituent responsible for lowering the post-prandial blood glucose concentration in the pre-germinated brown rice.

The intake of pre-germinated brown rice (PR) instead of white rice (WR) ameliorates the hyperglycemia. To clarify the mechanism(s) to decrease the post-prandial blood glucose concentration, the effect of water-soluble/oil-soluble fraction-depleted PR bran (termed as "DB"; which is destarched and defatted PR bran) on post-prandial blood glucose was compared with that of full-fat PR bran (PB) or WR. The test diets, WR diet, PB diet and DB diet which are containing identical amount of available carbohydrate (1.5 g) were fed to Wistar strain rats. Post-prandial blood glucose concentration and incremental area under the curve (IAUC) for DB diet were lower than those for WR diet, and there was no difference between the DB diet and PB diet. Changes in plasma insulin concentration and the IAUC obtained also revealed the same tendency as those observed in blood glucose concentration. These results indicate that the blood glucose-lowering effect of PB diet may be derived from the properties of PB involving substantially higher content of dietary fiber than WR, and that the potential benefit of intake of PR instead of WR in the prevention of diabetic vascular complications.

[Clinical study of multiple traumas with severe facial injury undergoing emergency endovascular treatment: significance of emergency embolization of the external carotid artery].

The outcome of multiple injures freqently depends on the priority of treatments, and the decision as to the procedures and timing of primary care is extremely important. We studied the patients with multiple trauma whounderwent emergency endovascular treatment for facial hemorrhage related to external carotid arterial injury. The subjects are 5 patients who underwent embolization of the external carotid artery by an endovascular approach among patients with multiple traumas who were brought to our hospital by ambulance. In these patients, the vital signs on arrival, interval between injury and intravascular surgery, type of brain injury, type and grade of concurrent injury and outcome were studied. Three patients showed hemorrhagic shock on arrival, and 1 patient showed hemorrhagic shock immediately after arrival. The mean interval between injury and endovascular surgery was 3.9 hours. All patients had skull base fracture, and abnormal intracranial lesions on initial CT including 4 focal injuries and 1 diffuse injury. Moderate to severe thoracic/abdominal injuries were noted in 3 patients. In the remaining 2 patients, there was no trauma in the thoracic or abdominal regions. Intraperitoneal hemorrhage with splenic injury was observed in 3 patients. In 3 of 4 patients died by hemorrhagic shock because of the delay of endvascular treatments. In trauma patients with persistent hemorrhage, emergency endovascular treatment should be considered as a primary survey for initial treatment without delay under intensive conservative treatment.

[Case of meningioma with extracranial extension through the internal jugular vein].

We report a case of posterior fossa meningioma extending into the cervical jugular vein, which was successfully resected. A 57-year old male with ataxia and mild hypogeusia was admitted to our hospital. MRI demonstrated a well-circumscribed large posterior fossa mass with extracranial extension through the internal jugular vein. Two-staged surgical treatment was then performed. The mass in the posterior fossa was removed at the first operation. The tumor was invading into the sigmoid sinus which was filled with tumor. The second operation for extracranial mass was performed 1 month later. Transcervically, the internal jugular vein obstructed by tumor was successfully removed. The post-operative course was uneventful and histopathological examination revealed the fibrous meningioma in the posterior fossa, but the intravenous portion of the tumor showed more atypical findings. Such a case is quite uncommon and the mechanism of tumor extension with different histological features is discussed.

[Ischemia of the sternocleidomastoid muscle following occipital artery embolization for dural arteriovenous fistula].

We report a case of localized ischemia of the sternocleidomastoid muscle (SCM) occurring after occipital artery embolization of a dural arteriovenous fistula (dAVF). A 45-year-old man presented intracerebral hemorrhage from a dAVF at the left transverse-sigmoid sinus. The dAVF had a high flow fistula from the left occipital artery (OA). Endovascular therapy was carried out one month later. Transarterial embolization of the OA was carried out prior to the transvenous approach to decrease the shunt flow. During obliteration of the proximal portion of the OA with fiber platinum coils and polyvinyl alcohol particles, the patient reported severe neck pain. The fistula was successfully embolized after transvenous packing of the left sigmoid sinus with detachable coils. The neck pain persisted for one week and disappeared after conservative treatment. T2-MR imaging 3 days after the embolization showed a hyperintensity in the left SCM. This ischemic lesion was probably induced by occlusion of the muscular branch of the OA. We discuss this common but rarely reported complication of OA embolization.

Distal-tip shape-consistency testing of steam-shaped microcatheters suitable for cerebral aneurysm coil placement.

BACKGROUND AND PURPOSE: Although the selection of microcatheter for endovascular aneurysmal treatment is one important factor in patient outcome, the use of steam shaping for achieving safe entry and stability during coil placement has not, to our knowledge, been systematically evaluated. The goal of this study was to compare the durability of distal microcatheter steam shaping in five different catheters with typical intraprocedural stresses that are similar to those encountered during aneurysm coil placement. METHODS: Distal tips of microcatheters were shaped into a 90 degrees turn with distal straight-segment lengths of 3, 5, or 7 mm by using steam, performed according to the instructions for use included with each catheter. In a water bath kept at body temperature, the changes in catheter tip angle were recorded and measured following microcatheter insertion into a guiding catheter, microguidewire insertion through the microcatheter, and Guglielmi detachable coil (GDC) placement through the microcatheter. RESULTS: The degree of distal microcatheter straightening with typical intraprocedural manipulations was more pronounced on braided microcatheters and on microcatheters with 3- or 5-mm distal-shaped segments. The degree of spontaneous recovery of the initially steamed shape was more pronounced with nonbraided catheters. The most significant single variable contributing to straightening of a steam-shaped catheter tip was the effect of microguidewire insertion. The catheter-tip straightening effect encountered with inserting GDCs was less than that encountered with microguidewire insertion. We demonstrated that the decreased catheter-tip angle encountered with a large-magnitude straightening stress spontaneously recovered once the stress was removed or when it was reduced to a smaller magnitude stress. CONCLUSION: Our study shows that, although braided microcatheters are suitable for maintaining durable configurations when long distal-tip lengths are permissible, nonbraided microcatheters demonstrate the most durable distal-tip configurations when short distal-tip lengths are called for. This may be one of significant factors in catheter choice for endovascular treatment of aneurysm.

Bilateral anomalous posterior inferior cerebellar artery-anterior inferior cerebellar artery anastomotic arteries associated with a ruptured cerebral aneurysm--case report.

A 50-year-old man presented with subarachnoid hemorrhage from a ruptured cerebral aneurysm arising from a left posterior inferior cerebellar artery (PICA)-anterior inferior cerebellar artery anastomotic artery manifesting as severe headache, obtundation, and quadriplegia. Conventional and three-dimensional digital subtraction angiography showed that the anastomotic complex was present bilaterally and both vertebral arteries terminated at the origin of the PICA. The identification of this anomalous vascular network allowed coil embolization of the broad-based aneurysm with occlusion of the parent artery. The patient had residual moderate disturbance of consciousness and quadriplegia before transfer for rehabilitation.

Primary intracerebral malignant fibrous histiocytoma in a child.

We report herein a rare case of pediatric intracerebral malignant fibrous histiocytoma (MFH). A 2-year-old boy gradually developed mild left hemiparesis and became somnolent. Magnetic resonance imaging upon admission revealed a well-enhanced mass lesion in the right frontotemporal operculum. Subtotal removal of the tumor was successfully performed using a right transsulcal and transcortical approach. The tumor developed as an extraaxial mass with brain adhesion to the arterial wall of the branch of the middle cerebral artery rather than to cerebral tissue. Pathological examination confirmed the presence of inflammatory-type MFH. Pediatric cases of intracerebral MFH are rare, and the possible origin of the tumor is discussed based on clinicopathological findings.

Rapid multiplex single nucleotide polymorphism genotyping based on single base extension reactions and color-coded beads.

A single nucleotide polymorphism (SNP) typing method using color-coded beads is promising because it is easy to use and inexpensive. However, the present protocols are not suitable for clinical and diagnostic applications because they need centrifugation for bead-washing. Here, we developed a simplified protocol without a bead-washing procedure that enables SNP typing of PCR amplified fragments in only 30 min.