Neurocognitive and psychiatric disorders-related axonal degeneration in Parkinson's disease

Neurocognitive and psychiatric disorders have significant consequences for quality of life in patients with Parkinson's disease (PD). In the current study, we evaluated microstructural white matter (WM) alterations associated with neurocognitive and psychiatric disorders in PD using neurite orientation dispersion and density imaging (NODDI) and linked independent component analysis (LICA). The indices of NODDI were compared between 20 and 19 patients with PD with and without neurocognitive and psychiatric disorders, respectively, and 25 healthy controls using tract-based spatial statistics and tract-of-interest analyses. LICA was applied to model inter-subject variability across measures. A widespread reduction in axonal density (indexed by intracellular volume fraction [ICVF]) was demonstrated in PD patients with and without neurocognitive and psychiatric disorders, as compared with healthy controls. Compared with patients without neurocognitive and psychiatric disorders, patients with neurocognitive and psychiatric disorders exhibited more extensive (posterior predominant) decreases in axonal density. Using LICA, ICVF demonstrated the highest contribution (59% weight) to the main effects of diagnosis that reflected widespread decreases in axonal density. These findings suggest that axonal loss is a major factor underlying WM pathology related to neurocognitive and psychiatric disorders in PD, whereas patients with neurocognitive and psychiatric disorders had broader axonal pathology, as compared with those without. LICA suggested that the ICVF can be used as a useful biomarker of microstructural changes in the WM related to neurocognitive and psychiatric disorders in PD.     

Multiplexed genome editing by in vivo electroporation of Cas9 ribonucleoproteins effectively induces endometrial carcinoma in mice

Synergistic effects among multiple gene mutations are involved in cancer development and progression. However, developing genetically modified mouse models to analyze various combinations of mutations is extremely labor-intensive and time-consuming. To address these problems, we developed a novel method for in vivo multiplexed genome editing of the murine uterus to model human endometrial carcinoma (EMC). To do this, we injected a CRISPR-Cas9 ribonucleoprotein complex into the uterine cavity of adult female mice, followed by electroporation. Evaluation of reporter mice demonstrated that genome editing occurred specifically in uterine epithelial cells, which are the origin of EMCs. Simultaneous targeting of Pten/Trp53/Lkb1, or targeting of Pten/Lkb1 along with the Ctnnb1ΔEx3 mutation, resulted in efficient generation of invasive tumors in wild-type females within 3 months. This novel method will enable rapid and easy validation of many combinations of gene mutations that lead to endometrial carcinogenesis.     

Effects of root morphology on stress distribution at the root apex

It is thought that the stress concentration at the root apex caused by orthodontic force induces root resorption. The purpose of this study was to investigate stress distribution at the root in cases of deviated root shapes using finite element models (FEMs). To clarify this, five three-dimensional FEMs divided by deviated root shape (normal, short, blunt, bent root apex, pipette shape) were constructed and, experimental orthodontic forces, applied in a vertical (intrusive) and horizontal (lingual) direction to the tooth axis. In the short-root model, significant stress was concentrated at the middle of the root. The blunt-shaped root model showed no significant stress concentration at the root. In the models with a bent or pipette-shaped root, significant stress was concentrated at the root apex. During orthodontic force application, stress concentration was observed in the root of the models with short, bent, and pipette-shaped roots, indicating that attention must be paid to root shape during orthodontic treatment.     

A clinical and morphological study of cervical hypersensitivity.

One-hundred five teeth with clinically diagnosed cervical hypersensitive dentin were studied using scanning electron microscopy on replica models and electrical impedance. Thirty-two percent of the teeth were in male patients in their 40s. Maxillary premolars comprised 31%; maxillary incisors, 27%; mandibular premolars, 17%; and mandibular incisors, 15%. Scanning electron microscopy of the models of hypersensitive spots showed enlarged dentinal tubules, agglutinated dentinal tubules, belt-like groups of agglutinated dentinal tubules, and tubule morphology not clearly visible. The electrical impedance of the cervical hypersensitive dentin ranged from 15 to 150 ohms, with an average of 54 ohms. There was a significantly high correlation between the dentinal tubule morphology and dentin hypersensitivity.     

Effect of lifestyle on periodontal disease status in diabetic patients

Lifestyle and socioeconomic status have been associated with the disease status of diabetic patients. However, there have been few reports on the relationship between these factors and the periodontal condition of diabetics. We assessed the association between disease status and lifestyle of diabetic patients and clinical features of advanced periodontitis such as deep probing depths and severe alveolar bone loss. Fifty-seven diabetic patients were examined in this study. Clinical assessment of probing pocket depth and radiographic alveolar bone loss was performed. Data regarding diabetic status and lifestyle of the diabetic patients were also recorded and statistically analysed by logistic regression. Drinking habits and high values of hemoglobin A1c (HbA1c) (>9.0%) were significantly associated with deep probing depth. The odds ratios (OR) of these factors were 7.72 (95% confidence interval (CI), 1.80 to 33.19), and 6.10 (95% CI = 1.23 to 30.25), respectively. Presence of complications such as retinopathy (OR = 8.86, 95% CI, 1.99 to 39.40), irascible behaviour (OR = 8.40, 95% CI = 1.33 to 53.17) and high value of HbA1c (OR = 4.94, 95% CI = 1.14 to 21.46) were significantly related to mean advanced alveolar bone loss. Only the high value of HbA1c (OR = 3.53, 95% CI = 1.06 to 11.73) was detected as a significant factor related to advanced periodontitis, characterised by more than 50% mean alveolar bone loss, or two or more teeth with probing depth greater than 6 mm. In conclusion, drinking habit and irascible behaviour are correlated with the periodontal disease condition of diabetic patients, in addition to a high value of HbA1c (>9.0%). Lifestyle and psychosocial stress may affect the periodontal disease status of diabetic patients.