Neuroradiological, genetic and clinical characteristics of histone H3 K27-mutant diffuse midline gliomas in the Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network): multicenter retrospective cohort.

This study aims to elucidate the clinical and molecular characteristics, treatment outcomes and prognostic factors of patients with histone H3 K27-mutant diffuse midline glioma. We retrospectively analyzed 93 patients with diffuse midline glioma (47 thalamus, 24 brainstem, 12 spinal cord and 10 other midline locations) treated at 24 affiliated hospitals in the Kansai Molecular Diagnosis Network for CNS Tumors. Considering the term "midline" areas, which had been confused in previous reports, we classified four midline locations based on previous reports and anatomical findings. Clinical and molecular characteristics of the study cohort included: age 4-78 years, female sex (41%), lower-grade histology (56%), preoperative Karnofsky performance status (KPS) scores ≥ 80 (49%), resection (36%), adjuvant radiation plus chemotherapy (83%), temozolomide therapy (76%), bevacizumab therapy (42%), HIST1H3B p.K27M mutation (2%), TERT promoter mutation (3%), MGMT promoter methylation (9%), BRAF p.V600E mutation (1%), FGFR1 mutation (14%) and EGFR mutation (3%). Median progression-free and overall survival time was 9.9 ± 1.0 (7.9-11.9, 95% CI) and 16.6 ± 1.4 (13.9-19.3, 95% CI) months, respectively. Female sex, preoperative KPS score ≥ 80, adjuvant radiation + temozolomide and radiation ≥ 50 Gy were associated with favorable prognosis. Female sex and preoperative KPS score ≥ 80 were identified as independent good prognostic factors. This study demonstrated the current state of clinical practice for patients with diffuse midline glioma and molecular analyses of diffuse midline glioma in real-world settings. Further investigation in a larger population would contribute to better understanding of the pathology of diffuse midline glioma.

Shear bond strength of ultraviolet-polymerized resin to 3D-printed denture materials: Effects of post-polymerization, surface treatments, and thermocycling.

PURPOSE: The purpose of this study is to compare the shear bond strength of ultraviolet (UV)-polymerized resin to 3D-printed denture materials, both with and without post-polymerization. Moreover, the effects of surface treatment and thermocycling on shear bond strength after post-polymerization were investigated. METHODS: Cylindrical 3D-printed denture bases and teeth specimens were prepared. The specimens are subjected to two tests. For Test 1, the specimens were bonded without any surface treatment or thermal stress for comparison with and without post-polymerization. In Test 2, specimens underwent five surface treatments: untreated (CON), ethyl acetate (EA), airborne particle abrasion (APA) with 50 µm (50-APA) and 110 µm alumina (110-APA), and tribochemical silica coating (TSC). A UV-polymerized resin was used for bonding. Half of the Test 2 specimens were thermocycled for 10,000 cycles. Shear bond strength was measured and analyzed using Kruskal-Wallis and Steel-Dwass tests (n = 8). RESULTS: In Test 1, post-polymerization significantly reduced shear bond strength of both 3D-printed denture materials (P < 0.05). No notable difference was observed between the denture teeth and the bases (P > 0.05). In Test 2, before thermocycling, the CON and EA groups exhibited low bond strengths, while the 50-APA, 110-APA, and TSC groups exhibited higher bond strengths. Thermocycling did not reduce bond strength in the latter groups, but significantly reduced bond strength in the EA group (P < 0.001). CONCLUSIONS: Post-polymerization can significantly reduce the shear bond strength of 3D-printed denture materials. Surface treatments, particularly APA and TSC, maintained bond strength even after thermocycling.

Occlusal disharmony transiently decrease cognition via cognitive suppressor molecules and partially restores cognitive ability via clearance molecules.

Occlusal disharmony has been reported to be affected not only by cytokine and steroid hormone secretion and sympathetic activation in peripheral organs, but also by neurotransmitter release in the central nervous system. However, little is known about whether occlusal disharmony can decrease cognitive ability. We hypothesized that hyperocclusion decreases cognition via Alzheimer's disease-associated molecule expression in the brain. The present study is aimed to elucidate the relationships among occlusal disharmony, cytokine and cognitive-regulated molecule expression in the brain, and the impairment of learning and memory cognition. We examined the effect of hyperocclusion on the relationships among cytokine expression, cognitive suppressor molecules in the hippocampus, and cognition in behavior using a hyperocclusion mouse model. Hyperocclusion dramatically increased interleukin-1ß expression in the serum and hippocampus 1 week after hyperocclusal loading in 2-month-old mice, but no effects in 12-month-old mice. The social and long-term cognitive abilities of the 2-month-old mice were transiently downregulated close to the level of the 12-month-old mice 1 week after hyperocclusion and recovered to close to basal level via the expression of cognitive suppressor clearing proteins. The expression levels of amyloid-ß and phosphorylated tau were significantly upregulated 1 week after hyperocclusal loading in the hippocampus of 2-month-old mice but were constant in 12-month-old mice. Occlusal disharmony-induced interleukin-1ß expression may contribute to accumulation of cognitive suppressor molecules such as amyloid-ß and phosphorylated tau and activate their clearance proteins, resulting in protection against transient dementia in young but not older individuals.

Development of an error-detection examination for conservative dentistry education.

OBJECTIVE: For dental students, textbooks and lectures provide basic knowledge, and simulated and actual clinical training provide learning in technical and communication skills. At our college, conservative dentistry is taught in the third and fourth years of a 6-year undergraduate degree. Clinical training is undertaken subsequently in the fifth year and includes cavity preparation and composite resin filling tasks. However, despite the clinical importance of a full understanding surrounding these procedures, sixth-year students occasionally provide incorrect answers regarding these procedures in assessments. Although they demonstrated a basic understanding of the procedures, they may have forgotten the acquired knowledge during their clinical training. Therefore, we developed an error-detection examination to evaluate and improve fifth-year students' knowledge. METHODS: Written detailed treatment procedures for standardized, typical, cases were presented to students. Some critical steps were intentionally written incorrectly, and students had to identify and correct these. After correcting the steps, students gave a presentation to their peers on their corrections. This was followed by a summary of the correct answers and a short lecture by the teacher. Students then completed a questionnaire investigating their experience of the examination. RESULTS: Students misunderstood some key treatment steps, such as pretreatment of composite resin filling, amalgam removal, and ceramic inlay fitting. The questionnaire revealed that this method of testing applied knowledge was new to students and helped them to identify knowledge gaps. The test also increased their motivation to study conservative dentistry. Students were open to taking similar tests in different areas. CONCLUSION: Although conservative dentistry is a basic field of dental treatment, mistakes in treatment can lead to early treatment failure or reduce the lifetime of a restored tooth. Therefore, students need to have a deep understanding of procedures. Error-detection examinations may help students identify knowledge gaps and provide useful feedback to teachers to identify areas that they should stress in earlier years.

IgG4-related small-sized occlusive vasculitis in Mikulicz's disease.

Mikulicz's disease is one of the IgG4-related diseases (IgG4-RDs) that involves the cardiovascular system; however, small-sized vasculitis is rare in IgG4-related diseases. A 64-year-old man presented with distal occlusive disease and developed left cerebrovascular infarction with occlusion of the middle cerebral artery and diseased temporal artery branches. He underwent superficial temporal artery-middle cerebral artery anastomosis surgery. Histology of the temporal artery biopsy showed smooth muscle cell proliferation with many IgG4-positive plasma cells. He then developed salivary gland inflammation, and Mikulicz's disease was diagnosed. Small-sized occlusive vasculitis was observed in this IgG4-RD. Low-dose corticosteroid therapy is effective in preventing progressive occlusive disease.

Effortful Processing Reduces the Attraction Effect in Multi-Alternative Decision Making: An Electrophysiological Study Using a Task-Irrelevant Probe Technique.

The attraction effect in multi-alternative decision making reflects the context-dependent violation of axioms that are considered fundamental to rational choice. This effect is believed to depend on relatively effortless and intuitive processing (System 1) rather than on effortful and elaborative processing (System 2). To investigate the relationship between cognitive resources and the attraction effect in detail, we used a task-irrelevant probe technique, wherein task-irrelevant auditory probes were presented while participants viewed each alternative in a decision-making task, and measured the electroencephalographic responses to the probes. Thirty participants solved 48 hypothetical purchase problems with three alternatives that differed in terms of two attributes. We found that, in the second epoch of the experimental trials (possibly corresponding to the evaluation and comparison stage), the mean N1 amplitudes of the event-related potentials elicited by the auditory probes were significantly smaller when participants chose the competitor (i.e., trials in which no attraction effect occurred) than when participants chose the target (i.e., trials in which an attraction effect may have occurred). This result suggests that the allocation of more cognitive resources to the alternatives disrupts the attraction effect. This finding supports the assumption that intuitive comparisons among alternatives executed by System 1 are critical for the occurrence of the attraction effect.

Application of a Minimally Invasive Liposuction Technique for Harvesting Fat during Transsphenoidal Surgery: A Technical Note.

Secure reconstruction in transsphenoidal surgery (TSS) is important for the prevention of the major and serious complication of postoperative cerebrospinal fluid (CSF) leak. Although abdominal fat can be safely and effectively used as a reconstruction tissue, harvesting it from the abdominal wall is traumatic and invasive, resulting in cosmetic problems. In this report, we present a method of harvesting abdominal fat using a minimally invasive liposuction technique to avoid cosmetic issues. Since 2016, we have been using fat harvested from the abdominal wall by suctioning with a dedicated syringe for reconstruction after TSS in selected cases. The liquefied fat obtained by the liposuction technique was wrapped with an oxycellulose sheet and changed its form to what we termed "fatty candy". In this form, the fat maintained its configuration and could be handled almost as easily as a conventional fat graft. In our experienced series, there was no case with wound complication nor postoperative or late-onset CSF leak during a postoperative follow-up of at least 3 months. The fat harvested by this simple and minimally invasive liposuction technique can be expected to provide an autologous graft that is adequate not only for prevention of cosmetic problems but also for prevention of postoperative CSF leak.

Micro-computed tomography for evaluating alveolar bone resorption induced by hyperocclusion.

PURPOSE: Occlusal trauma, resulting in the destruction of alveolar bone, is a form of periodontal disease caused by excessive mechanical stress (MS) during hyperocclusion. Previously, we showed that CC chemokine ligand (CCL) 2/CCR2 receptor axis plays a crucial role in MS-dependent osteoclastogenesis. However, in the previous work, we were unable to precisely measure changes in alveolar bone profiles. In the present study, we sought to establish a precise method for evaluating alveolar bone resorption induced by hyperocclusion using micro-computed tomography. METHODS: Under anesthesia, a stainless steel wire was attached to the molars of 5-week-old C57/BL6 wild-type (WT) mice, CCL2-/- mice, and CCR2-/-mice to induce occlusal force overload. At days 0 and 7, hard tissue samples were harvested and analyzed by micro-computed tomography. RESULTS: In the WT mice, bone mineral density of the alveolar bone was significantly decreased at day 7 as compared with day 0, with marked alveolar bone resorption observed. Similarly, significant alveolar bone resorption was observed in the CCL2-/- and CCR2-/- mice at day 7 as compared with day 0. CONCLUSIONS: Micro-computed tomographic images can be used to measure changes in bone mineral density in a mouse model of hyperocclusion. This method may be useful for further investigating bone changes in other periodontal disease research fields.

Hyperocclusion stimulates the expression of collagen type XII in periodontal ligament.

OBJECTIVES: It is known that excessive mechanical force exerted by hyperocclusion induces occlusal trauma. However, the mechanism of the process remains unclear. In the present study, we employed an in vivo hyperocclusion rodent model to examine morphological and biological mechanisms of occlusal trauma in periodontal ligament tissue. DESIGN: To investigate alveolar bone resorption, tooth sections were stained to detect osteoclasts. To investigate the relationship between hyperocclusion and the regeneration of the cell matrix, we examined the effect of hyperocclusal force on the expression of collagens using immunohistochemistry and quantitative PCR methods. RESULTS: The arrangement of collagen fibers in the furcation area of the teeth was undisturbed before hyperocclusion (control). Type I collagen was localized in the extracellular area at the furcation and there was faint expression and localization of type XII collagen in the periodontal ligament. The number of osteoclasts significantly increased in the furcation and lingual cervical regions on day 4 after hyperocclusion was induced. Type XII collagens were gradually up-regulated following the induction of hyperocclusion, in a time-dependent manner. Although type I collagen mRNA expression was stable before and after hyperocclusion, type XII collagen mRNA was significantly up-regulated on day 2 and day 4 after hyperocclusion treatment. CONCLUSIONS: Our findings indicate that hyperocclusal force predominantly up-regulates the expression of type XII collagen in periodontal tissue, but not type I collagen, suggesting that there is a mechanism for regeneration of periodontal tissues as a response to occlusal trauma.

The potential role of transient receptor potential type A1 as a mechanoreceptor in human periodontal ligament cells.

Transient receptor potential type A1 (TRPA1) is reported to be a Ca(2+) -permeable channel and is activated by cold temperatures and mechanical stimuli in the hair cells and in dorsal root ganglion. Using a DNA microarray, we found that TRPA1 was significantly up-regulated in human periodontal ligament (hPDL) cells 2 d after intermittent mechanical stimulation (iMS) loading compared with unloaded cells. Although hPDL cells are known to respond to mechanical stimulation induced by occlusal force, little is known about the expression and functional role of TRPA1 in these cells. Therefore, we investigated the effects of iMS on TRPA1 expression and its signaling pathway in hPDL cells. Intermittent mechanical stimulation loading up-regulated TRPA1 expression in hPDL cells in a time-dependent manner, but had no effect on other mechanoreceptors. Furthermore, iMS significantly increased the phosphorylation of mitogen-activated protein kinases (MAPKs), especially extracellular signal-regulated kinase 1/2 (ERK1/2) and p38, and the expression of C-C chemokine ligand 2 (CCL2). Transient receptor potential type A1 agonists also increased MAPK phosphorylation and the intracellular Ca(2+) concentration. By contrast, inhibition or silencing of TRPA1 partially suppressed iMS-induced MAPK phosphorylation. In summary, iMS during occlusion activates TRPA1 and MAPK signaling in periodontal ligament tissues, suggesting that TRPA1 regulates the mechanosensitivity of occlusal force via activation of MAPKs in hPDL cells.

[A multi-measure analysis of the similarity, attraction, and compromise effects in multi-attribute decision making].

In multi-attribute decision making, the similarity, attraction, and compromise effects warrant specific investigation as they cause violations of principles in rational choice. In order to investigate these three effects simultaneously, we assigned 145 undergraduates to three context effect conditions. We requested them to solve the same 20 hypothetical purchase problems, each of which had three alternatives described along two attributes. We measured their choices, confidence ratings, and response times. We found that manipulating the third alternative had significant context effects for choice proportions and confidence ratings in all three conditions. Furthermore, the attraction effect was the most prominent with regard to choice proportions. In the compromise effect condition, although the choice proportion of the third alternative was high, the confidence rating was low and the response time was long. These results indicate that the relationship between choice proportions and confidence ratings requires further theoretical investigation. They also suggest that a combination of experimental and modeling studies is imperative to reveal the mechanisms underlying the context effects in multi-attribute, multi-alternative decision making.

Microsurgical Maneuvers under Side-Viewing Endoscope in the Treatment of Skull Base Lesions.

The objective of the present study is to elucidate the feasibility of surgical maneuvers under the side-viewing endoscope during skull base tumor removal. The study focused on 51 patients who underwent tumor removal with the assistance of a side-viewing endoscope. The side-viewing endoscope enabled visualization and removal of residual tumors obscured by the skull base bone, cranial nerves, and other vital structures after a microscopic procedure. If the surgical field is surrounded by the dura or skull base tissue, not only curettage of a tumor but also semisharp dissection and bipolar coagulation are shown to be feasible. In the subarachnoid space, however, the primary feasible surgical maneuver was suctioning of the tumor. The extent of skull base resection could be reduced in 25 cases and additional tumor removal became possible in 47 cases. Application of the side-viewing endoscope enabled removal of the tumor compartment, the exposure of which has conventionally required an extensive skull base resection. This technique is a promising option for the treatment of skull base tumors.

Bilateral pallidal deep brain stimulation in primary Meige syndrome.

Primary Meige syndrome is an idiopathic movement disorder that manifests as craniofacial and often cervical dystonias. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has emerged as a powerful surgical option in the treatment of primary generalized or segmental dystonia. However, the experience with GPi-DBS in Meige syndrome is limited. We followed 5 patients with disabling Meige syndrome treated by bilateral GPi-DBS for 49 ± 43.7 (mean ± SD) months. All patients were assessed before surgery and at the last follow-up after surgery using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) which includes both the movement and disability scales. Bilateral GPi-DBS produced a sustained and long-lasting improvement in dystonia symptoms associated with Meige syndrome. At the last follow-up, the mean scores of BFMDRS movement and disability scales improved significantly by 84 ± 6.8% (range, 75-94%) and 89 ± 8.1% (range, 80-100%), respectively. Bilateral pallidal stimulation is a beneficial therapeutic option for long-term relief of the disabling dystonia symptoms in Meige syndrome.

Differential induction of collagens by mechanical stress in human periodontal ligament cells.

OBJECTIVE: Excessive mechanical stress (MS) during hyperocclusion is known to result in destruction of periodontal tissues and alveolar bone, leading to occlusal trauma. Collagens are extracellular matrix components that are encoded by more than 30 different genes. They are classified into three types: fibril-forming, fibril-associated with interrupted triple helices (FACIT), and non-fibril forming collagens. Although MS is known to affect COL I, little is known about its effects on other types of collagens in the periodontal ligament (PDL). We hypothesised that MS could induce expression of the three different types of collagens, thus protecting against occlusal trauma. DESIGN: The aim of this study was to investigate intermittent uniaxial stretching-induced collagen expression in PDL cells using DNA microarray, polymerase chain reaction, and western blotting analysis. We compared changes in collagen expression caused by MS stimulation and osteogenic stimulation, and examined relationships between expression of collagen and their digestive enzymes, matrix metalloproteases (MMPs). RESULTS: Expression of both fibril-forming and FACIT collagens was transiently decreased in the initial phase after MS, while the expression of non-fibril-forming collagens was gradually increased. MS for 3-7 days resulted in gradual upregulation of all three types of collagen. Furthermore, the expression of fibril- and non-fibril-forming collagens was reciprocally related to expression of MMPs. In contrast, expression of all three types of collagen was slightly upregulated during osteogenesis. CONCLUSION: The MS-induced expression patterns of fibril-forming and FACIT collagens suggest changes in the composition of the extracellular matrix to increase the resistance of PDL cells to hyperocclusal force.

[Percutaneous interventional treatment of vertebral artery stenosis with coronary stents: two case reports].

Two patients underwent percutaneous interventional treatment for vertebral artery stenosis using coronary stents. Vertebral angiography of Case 1 (78-year-old male) showed right ostial 100% obstruction and left ostial 99% stenosis. Balloon angioplasty and stent placement (Multilink 4.0 x 18 mm) were performed for the left vertebral artery. Vertebral angiography of Case 2 (64-year-old male) showed bilateral ostial severe stenoses (right 90%, left 99% + alpha). Balloon angioplasty and stent placement(Multilink 3.5 x 18 mm) were performed for the right vertebral artery. These two patients showed excellent angiographic results with no complication associated with stent placement. Vertebral artery angioplasty can be performed safely using coronary interventional equipment and techniques.

[Subarachnoid hemorrhage complicated with different manifestations of transient abnormal left ventricular wall motion: two case reports].

Two patients with subarachnoid hemorrhage presented with transient abnormal left ventricular wall motion. Case 1 was a 56-year-old man. Electrocardiography showed ST segment elevation in leads I, II, II, aVL, aVF, V3-V6. Echocardiography showed localized left ventricular hypokinesis around the apical area (takotsubo-like cardiomyopathy). Ejection fraction was 20% (1st hospital day). Troponin T was positive. Case 2 was a 48-year-old woman. Electrocardiography showed ST segment elevation in leads I, aVL, V2-V6 and ST segment depression in leads II, III, aVF, V1. Echocardiography showed diffuse left ventricular hypokinesis. Ejection fraction was 21% (1st hospital day). Troponin T was positive. These two patients had no history of cardiac disease, and coronary angiography showed no stenosis or obstruction. Catecholamine was given for 1 day(Case 1) and for about 2 weeks (Case 2). Pimobendane was given to Case 2. Ejection fraction was 57% in Case 1 (2nd hospital day) and 33% (6th hospital day), 43% (7th hospital day)and 58% (16th hospital day)in Case 2. The recovery period of left ventricular abnormal wall motion and the medication period were longer in Case 2 showing diffuse hypokinesis than in Case 1 showing takotsubo-like cardiomyopathy.

Differential gene expression of collagen-binding small leucine-rich proteoglycans and lysyl hydroxylases, during mineralization by MC3T3-E1 cells cultured on titanium implant material.

Titanium implants create a unique ultrastructure (composed of a collagenous zone with relatively disorganized fibril morphology) at the bone-implant interface. The objective of this study was to investigate the temporal mRNA expression patterns, using real-time polymerase chain reaction, of type I collagen (COLI) and regulators for collagen fibrillogenesis, collagen-binding small leucine-rich proteoglycans (SLRPs) and lysyl hydroxylases (LHs), during mineralization, by MC3T3-E1 cells cultured on titanium (Ti). Lysates of the cultures on Ti and on plastic wells (Pl) for 10-50 d were used for the quantification of calcium and mRNA. Although the onset of calcium accumulation in the cultures on Ti (30-40 d) was slower than that of cultures on Pl (20-30 d), the gene expression patterns during mineralization were similar in cells cultured on either material. COLI and fibromodulin were up-regulated just before the onset of mineralization and then down-regulated. Lumican and LH1 were up-regulated just before the onset of mineralization and then returned to the baseline level. Decorin and LH2 were up-regulated at the late mineralization stage. Biglycan was down-regulated once at the early mineralization stage and then returned to the original level. LH3 was maintained at a steady level throughout. This study suggests actual but distinct roles of SLRPs and LHs in the formation of a unique ultrastructure at the bone-implant interface.

[Connectionist modeling of higher-level cognitive processes].

Connectionist modeling is one approach to understanding human intelligence using simulated networks of neuron-like processing units. In this article, we report on recent progress in connectionist models that simulate empirical data of higher-level cognitive processes, these being memory, learning, language, thinking, cognitive development, and social cognition. We also review and summarize the advantages and disadvantages of these connectionist models. The computational framework of connectionist modeling has the potential to integrate specialized psychological findings of different areas using the same architectures and local functions of units and connections, inspired from neuroscience. In particular, the problems of dealing with structured information in distributed form, and doing tasks that require variable binding in connectionist networks are discussed from several different perspectives. As one possible solution to treat systematic mental representations properly, the symbolic connectionist model, which is a hybrid approach using symbolic representations and connectionist architectures, is explained. We argue that connectionist computer simulation offers significant benefits for today's psychological researches, and that connectionist modeling is likely to have an important influence on future studies.