Interdisciplinary therapy for severe periodontitis with Angle Class II Division 1 malocclusion : A case report with 7-year follow-up

Background: Previous studies have suggested that occlusal discrepancy is a risk factor contributing to periodontal disease. 1-3 Occlusal discrepancy could increase the risk of infrabony defects. This is a case of a patient with severe periodontitis who exhibited many infrabony defects in the molar region due to malocclusion-induced trauma. Here, we report the 7-year prognosis of the patient after periodontal regenerative and comprehensive orthodontic therapies for functional recovery with implant prosthodontics. Case Description: A 54-year-old female presented with the chief complaint of masticatory disturbance. In the molar region, significant tooth mobility, deep periodontal pockets, and infrabony defects were observed. She had excessive overjet, resulting in collapse of anterior guidance. Malocclusion was considered to be an exacerbating factor of the infrabony defects. After initial periodontal therapy, we performed periodontal regenerative therapy in the mandibular molar regions. We carefully placed implants in a position in the maxillary molar region that would ensure an appropriate anterior dental relationship after orthodontic treatment. Comprehensive orthodontic treatment was subsequently performed using implants as anchoring units. Then, definitive surgery was performed on the mandibular molars before placing the final prosthesis. A favorable periodontal condition and a stable occlusion have been maintained for the 7-year post-treatment period. Practical Implications: Comprehensive and interdisciplinary treatment enables stable occlusion and establishment of periodontal tissue and peri-implant tissues with high cleansability, even in patients with severe periodontitis and malocclusion. In the present case, a favorable long-term treatment outcome can be expected

グリコケノデオキシコール酸による培養マウス胆管上皮でのアポトーシス誘導およびアポトーシス関連蛋白の発現

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1414号，学位授与年月日：平成12年3月31日,学位授与年：200

Comprehensive treatment for severe periodontitis with pathologic tooth migration−related bimaxillary protrusion : A case report with 3-year follow-up

Background: Patients with severe periodontitis often experience pathologic tooth migration (PTM), which impairs esthetics and leads to occlusal disharmony (e.g., premature contacts and/or traumatic occlusion) that can further exacerbate periodontitis. Here, we describe a patient who exhibited severe periodontitis with PTM-related bimaxillary protrusion. This report includes 3-year clinical outcomes following periodontal regenerative therapy, implant-anchored orthodontic therapy, and implant prosthodontics intended to achieve both functional and esthetic improvements. Case Description: A 63-year-old woman presented with the chief complaint of upper anterior tooth mobility. Clinical examination revealed excessive tooth mobility, deep periodontal pockets, and infrabony defects in all teeth. All teeth exhibited PTM; the mandibular anterior teeth exhibited marked protrusion caused by the progression of periodontitis. After initial periodontal therapy, periodontal regenerative therapy was performed in all molar regions. At 9 and 6 months postoperatively, comprehensive orthodontic treatment was initiated for the mandible and maxilla, respectively, using orthodontic anchorage devices to achieve acceptable functional occlusion. After orthodontic treatment, staged guided bone regeneration was performed and dental implants were placed in the severely resorbed maxillary anterior ridge. This comprehensive treatment yielded favorable periodontal conditions, stable occlusion, and good esthetic outcomes. Practical Implications: Favorable esthetics, stable occlusion, and highly cleansable periodontal tissues were achieved with well-planned interdisciplinary and comprehensive treatment, although the patient had severe periodontitis and PTM-related bimaxillary protrusion

Mechanism of Voriconazole-Induced Transient Visual Disturbance: Reversible Dysfunction of Retinal ON-Bipolar Cells in Monkeys

PURPOSE. To investigate the mechanism of voriconazole-induced transient visual disturbance in humans. METHODS. Standard full-field electroretinograms (ERGs) were recorded from monkeys treated intravenously with voriconazole. In addition, photopic ERGs elicited by long-duration stimuli (ON-OFF response) were also recorded from monkeys receiving intravenous voriconazole or intravitreal 2-amino-4-phosphonobutyric acid (APB). RESULTS. Characteristic changes were observed in the waveform of the standard full-field ERGs obtained immediately after dosing of voriconazole as follows: electronegative combined rod-cone response (markedly attenuated b-wave and oscillatory potentials), undetectable rod response (eliminated b-wave); slightly abnormal single-flash cone response (flattened appearance in the bottom of the a-wave, mildly attenuated b-wave); and slightly abnormal 30 Hz flicker (mildly attenuated b-wave). The above changes fully recovered to baseline 24 hours after each dosing, along with a decrease in plasma voriconazole concentration. In addition, the change in the waveform of the ON-OFF response recorded in voriconazole-treated monkeys was quite similar to that recorded in APB-treated monkeys as follows: the b-wave was eliminated or prominently attenuated; and the a-and d-waves were not apparently attenuated. V oriconazole is a triazole antifungal agent with potent activity against a broad spectrum of clinically significant pathogens. 1-3 Voriconazole has been generally well tolerated in clinical trials 4 and postmarketing surveillances 5-7 with frequently reported adverse events of transient visual disturbances, which are described as enhanced/altered light perception, photopsia, photophobia, blurred vision, or color vision changes without any abnormality in the fundus oculi. Very few studies have focused on the detailed effect of voriconazole on retinal function, although the retina is generally considered to be the site of the visual disturbances because reversible decreases in the amplitude of the electroretinogram (ERG) were noted in voriconazole-treated humans. METHODS Animals A total of ten cynomolgus monkeys (Macaca fascicularis) between three and eight years of age were used in this study. The animals were housed individually in stainless steel cages in an animal study room where the environmental condition was set as follows: room temperature, 24°C; relative humidity, 60%; illumination, 12-hour lighting (7:00 to 19:00) at 150 to 300 luces. The animals were fed 100 g per animal per day of pellet food for monkeys (PS; Oriental Yeast Co., Ltd., Tokyo, Japan). Tap water from a feed-water nozzle was supplied ad libitum to the animals. All experimental procedures adhered to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research, and were approved by the Institutional Animal Care Committee of DaiichiSankyo Co. Ltd. Drug Administration Voriconazole (VFEND for Intravenous Use; Pfizer Inc., New York, NY) was dissolved in physiologic saline. The dose formulation was administered intravenously at a rate of 0.2 mL/kg per minute for ten minutes to six animals with increasing doses of 0, 3, 6 and 12 mg/kg at intervals of one week or more, and the standard full-field ERGs were recorded as described below. Several months after the 12 mg/kg dosing, voriconazole was administered to three animals at 0 mg/kg and to another three animals at 6 mg/kg in the same manner, and the photopic ERG elicited by a long-duration stimulus (the ON-OFF response) was recorded as described below. Intravitreal injection of 2-amino-4-phosphonobutyric acid (APB) (Sigma-Aldrich; St. Louis, MO) was also conducted in two animals several weeks after the last dosing of voriconazole mentioned above. The techniques for intravitreal injection have been described in detail elsewhere

De Novo Mutations in GNAO1, Encoding a Gαo Subunit of Heterotrimeric G Proteins, Cause Epileptic Encephalopathy

Heterotrimeric G proteins, composed of α, β, and γ subunits, can transduce a variety of signals from seven-transmembrane-type receptors to intracellular effectors. By whole-exome sequencing and subsequent mutation screening, we identified de novo heterozygous mutations in GNAO1, which encodes a Gαo subunit of heterotrimeric G proteins, in four individuals with epileptic encephalopathy. Two of the affected individuals also showed involuntary movements. Somatic mosaicism (approximately 35% to 50% of cells, distributed across multiple cell types, harbored the mutation) was shown in one individual. By mapping the mutation onto three-dimensional models of the Gα subunit in three different complexed states, we found that the three mutants (c.521A>G [p.Asp174Gly], c.836T>A [p.Ile279Asn], and c.572_592del [p.Thr191_Phe197del]) are predicted to destabilize the Gα subunit fold. A fourth mutant (c.607G>A), in which the Gly203 residue located within the highly conserved switch II region is substituted to Arg, is predicted to impair GTP binding and/or activation of downstream effectors, although the p.Gly203Arg substitution might not interfere with Gα binding to G-protein-coupled receptors. Transient-expression experiments suggested that localization to the plasma membrane was variably impaired in the three putatively destabilized mutants. Electrophysiological analysis showed that Gαo-mediated inhibition of calcium currents by norepinephrine tended to be lower in three of the four Gαo mutants. These data suggest that aberrant Gαo signaling can cause multiple neurodevelopmental phenotypes, including epileptic encephalopathy and involuntary movements

CNVs in Three Psychiatric Disorders

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25–0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD

Population‑based prostate‑specific antigen screening for prostate cancer may have an indirect effect on early detection through opportunistic testing in Kusatsu City, Shiga, Japan

Prostate cancer is the most common genitourinary cancer in men. Population-based serum prostate-specific antigen (PSA) testing is used to screen men for the early detection of asymptomatic prostate cancer. The present study compared the features of patients with prostate cancer in Kusatsu City, the only municipality in Shiga Prefecture of Japan to implement organized PSA screening, with those in other municipalities. The target population for organized PSA screening by mail invitation was men ≥50 years. Patients were pathologically diagnosed via prostate biopsy because of elevated serum PSA. This multicenter observational study was subsequently conducted in 14 hospitals. The following information was extracted from patient records: age, reason for PSA testing, initial PSA level, Gleason score, clinical stage, and place of residence. Risk classification was defined as low, intermediate, high, and advanced. Each patient was stratified according to their city/town. A total of 984 patients diagnosed with prostate cancer in Shiga in 2012 and 2017 were analyzed, of which 955 (97%) were opportunistically tested, with the remaining 29 (3%) assessed by organized screening. In Kusatsu, 93 patients were diagnosed, of whom 26 (28%) were detected by organized screening. By contrast, only three of 891 patients (0.3%) were detected by organized screening in other municipalities. Of patients in Kusatsu, cases identified by opportunistic testing had a higher initial PSA value (P=0.010) than those identified by organized screening. However, patients detected through opportunistic testing in Kusatsu City were younger (P=0.034), had a lower PSA value (P=0.001), and improved risk classification (P<0.001) than those in other municipalities. It was concluded that more patients were diagnosed with early-stage cancer by organized PSA screening. Furthermore, population-based PSA screening in Kusatsu City may have indirectly affected early detection, even by opportunistic testing