Hypertension, cerebral Amyloid, aGe Associated Known neuroimaging markers of cerebral small vessel disease Undertaken with stroke REgistry (HAGAKURE) prospective cohort study: Baseline characteristics and association of cerebral small vessel disease with prognosis in an ischemic stroke cohort.

Introduction: Cerebral small vessel disease (SVD) is one of the leading causes of stroke; each neuroimaging marker of SVD is correlated with vascular risk factors and associated with poor prognosis after stroke. However, longitudinal studies investigating the association between comprehensive SVD burden scoring system, "total SVD score" - which encompasses the established neuroimaging markers of lacunae, cerebral microbleeds (CMBs), white matter hyperintensities (WMH) including periventricular hyperintensities, and perivascular spaces in basal ganglia- and clinical outcomes are limited. The aim of this study is to determine the association between SVD burden and long-term prognosis in patients with ischemic stroke. Methods and design: This prospective, single-center, observational study enrolled patients with acute ischemic stroke, including cerebral infarction and transient ischemic attack. Magnetic resonance imaging scans were performed, and then total SVD score (range, 0-4) was calculated. We recorded baseline characteristics and evaluated the relationships of long-term outcomes to SVD neuroimaging markers and total SVD score. Stroke recurrence was thought as primary outcome. Hazard ratios (HRs) of events during follow-up were calculated using Cox proportional hazards modeling with adjustments for age, sex, hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation, and smoking. Cumulative event rates were estimated using the Kaplan-Meier method. Results: Consecutive 564 acute ischemic stroke patients were enrolled according to inclusion and exclusion criteria. A total of 467 participants with first-ever ischemic stroke were analyzed (median age 75.0 [interquartile range, 64.0-83.0] years, 59.3% male). Total SVD score was 0 point in 47 individuals (12.0%), 1 point in 83 (21.2%), 2 points in 103 (26.3%), 3 points in 85 (21.7%), and 4 points in 73 (18.7%). Twenty-eight recurrent stroke events were identified during follow-up. Total SVD score ≥ 2, presence of CMBs, and moderate-to-severe WMH were associated with increased risk of recurrent stroke events (HR 9.31, 95% confidence interval [CI] 2.33-64.23; HR 2.81, 95% CI 1.08-7.30; HR 2.90, 95% CI 1.22-6.88, respectively). Conclusion: The accumulation of SVD biomarkers as determined by total SVD score offered a reliable predictor of stroke recurrence. This study established a firm understanding of SVD prognosis in clinical settings.

Low-Dose Phosphodiesterase III Inhibitor Reduces the Vascular Amyloid Burden in Amyloid-ß Protein Precursor Transgenic Mice.

A previous study reported that relatively high-dose cilostazol (0.3%) promoted the drainage of cerebrovascular amyloid-ß (Aß) protein in Aß Precursor Protein (APP) transgenic mice overexpressing vasculotropic Aß. We investigated whether lower-dose cilostazol can decrease micro-hemorrhages and Aß deposition in the brain using APP transgenic mice. At baseline, 14-month-old female Tg2576 mice were randomly assigned to a control group (vehicle), aspirin group (0.01% aspirin), or cilostazol group (0.01% cilostazol). The severity of cerebral micro-hemorrhages (i.e., number), area of senile plaque, and severity of vascular amyloid burden (quantified with cerebral amyloid angiopathy (CAA) score (=number of Aß-positive vessels × severity of amyloid burden of Aß-positive vessels) were evaluated in the brain of mice aged 15 and 21-23 months. At 15 months, no differences were shown in each pathological change among the three groups. At 21-23 months, there were no differences in the severity of cerebral micro-hemorrhages or area of senile plaque among the three groups. However, the CAA score was significantly lower in the cilostazol compared to the control group (p = 0.046, Mann-Whitney U test), although no difference was seen between the control and aspirin group. Our study showed that lower-dose cilostazol could reduce the vascular amyloid burden without increasing cerebral micro-hemorrhages in APP transgenic mice.

Pre-critical MRI findings of an Alzheimer's disease patient with pathologically proven cerebral amyloid angiopathy related lobar hemorrhage.

An 85-year-old woman with untreated hypertension was admitted with a disturbance of consciousness. On admission, brain CT revealed a lobar intracerebral hemorrhage with a midline shift. An intracranial hematoma was evacuated via a life-saving craniotomy. Definite pathological findings of amyloid-ß deposition in the excised hematoma (strong in anti-amyloid ß40 immunostain, but weak in anti- amyloid ß42) indicated cerebral amyloid angiopathy (CAA). She had been diagnosed with Alzheimer's disease at a regional memory clinic one month before symptom onset based on MRI findings of medial temporal lobe atrophy as well as CAA-related features of multiple strictly lobar cerebral microbleeds in the occipital lobe, cortical superficial siderosis and >20 enlarged perivascular spaces in the centrum semiovale. This experience suggests that comprehensive interpretation of such CAA-related findings on MRI might help to improve the management of cardiovascular risk factors for Alzheimer's disease.

Periodontal regeneration with 0.3% basic fibroblast growth factor (FGF-2) for a patient with aggressive periodontitis: a case report.

This case report describes the clinical efficacy of treatment with basic fibroblast growth factor (FGF-2) for periodontal regeneration. A patient with aggressive periodontitis participated in a clinical trial involving administration of 0.3% FGF-2 in comparison with a placebo control. To evaluate the efficacy of FGF-2, standardized radiographs were taken before surgery and at 12, 24, and 36 weeks after FGF-2 treatment. The rate of increase in alveolar bone height was 86.9% at 36 weeks. The 6-year postoperative radiograph showed significant development of alveolar bone in comparison with the first visit. FGF-2 treatment may be effective for periodontal regeneration in cases of aggressive periodontitis. (J Oral Sci 58, 137-140, 2016).

Microarray analysis of the developing rat mandible.

To analyze the molecular events that occur in the developing mandible, we examined the expression of 8803 genes from samples taken at different time points during rat postnatal mandible development. Total RNA was extracted from the mandibles of 1-day-old, 1-week-old, and 2-week-old rats. Complementary RNA (cRNA) was synthesized from cDNA and biotinylated. Fragmented cRNA was hybridized to RG-U34A GeneChip arrays. Among the 8803 genes tested, 4344 were detectable. We identified 148 genes with significantly increased expression, and 19 genes with significantly decreased expression. A comprehensive analysis appears to be an effective method of studying the complex process of development.

Effects of ipriflavone on bone augmentation within a titanium cap in rabbit calvaria.

Ipriflavone (7-isopropoxyisoflavone, IP), a drug used in the treatment of osteoporosis, may promote bone formation during bone remodeling. IP has been shown to accelerate both the activity of, and formation of mineralized nodules by a human osteosarcoma cell line at an early stage. However, the direct effects of IP on bone augmentation have not been investigated. The purpose of this study was to determine whether IP induces bone augmentation within a titanium cap in rabbit calvaria at an early stage. Five adult male Japanese white rabbits were used. One cap (test site) was packed with IP in a collagen gel, and the other (control site) was packed with the collagen gel alone. After the one- and three-month healing periods, we measured the newly generated tissue and bone within the titanium caps. The amount of newly generated tissue within the titanium caps of the control sites was higher than the tests sites after one month and three months. However, the percentage of newly generated bone/bone marrow in the newly generated tissue at the test sites was higher than for the control sites after one month and three months. These results suggest that IP affects the quality of bone augmentation at an early stage.