神経ブロック時の眼窩下神経の形態学的変化

A high dose local anesthetic, 5% lidocaine, and a semi-permanent neurolytic agent, 99% alcohol, were infused at the infraorbital foramen. The purpose of the paper is the progression in morphological change was observed light microscopically and electron, from nerve injury to regeneration. Immediately after drug injection, there were no significant changes seen in either the alcohol or lidocaine treated groups. One day after drug injection, both the alcohol treated group and the lidocaine treated group showed almost complete destruction of the myelinated nerve fibers within the fascicle. In the alcohol treated group, this damaged state persisted for 1 month post-injection. In the lidocaine treated group, however, there was a 50% reduction in the number of damaged myelinated fibres by the 3 day post-injection. In the alcohol treated group, it was observed that between 2 months and 3 months post-injection. 75% of the myelinated nerve fibers were less than 5μm in diameter, while 20% were thick myelinated nerve fibers greater than 5μm. 6 months after the injection, it was observed that 70% of myelinated nerve fibers were of thick diameter, whilst 30% were thin. These values were very similar to those seen in the control group. In the lidocaine treated group, it was observed that from 1 week to 6 months post-injection, the percentage of myelinated nerve fibers less than 5μm gradually decreased, while the percentage of fibers greater than 5μm increased. Approximately 5% of the fibres remained damaged. Our results demonstrate that the percentage of thick myelinated nerve fibers increased between 3 months and 6 months post-injection. This period correlates well with the period of time taken for clinical re-block administration. This correlation suggests that it takes a set amount of time for regenerative nerve fibers within the fascicle to grow to a length exceeding 5μm and become functional. This further suggests that sensory function is regained even before the ratio of thick and thin myelinated nerve fibers returns to normal levels

A novel underuse model shows that inactivity but not ovariectomy determines the deteriorated material properties and geometry of cortical bone in the tibia of adult rats

Our goal in this study was to determine to what extent the physiologic consequences of ovariectomy (OVX) in bones are exacerbated by a lack of daily activity such as walking. We forced 14-week-old female rats to be inactive for 15 weeks with a unique experimental system that prevents standing and walking while allowing other movements. Tibiae, femora, and 4th lumbar vertebrae were analyzed by peripheral quantitative computed tomography (pQCT), microfocused X-ray computed tomography (micro-CT), histology, histomorphometry, Raman spectroscopy, and the three-point bending test. Contrary to our expectation, the exacerbation was very much limited to the cancellous bone parameters. Parameters of femur and tibia cortical bone were affected by the forced inactivity but not by OVX: (1) cross-sectional moment of inertia was significantly smaller in Sham-Inactive rat bones than that of their walking counterparts; (2) the number of sclerostin-positive osteocytes per unit cross-sectional area was larger in Sham-Inactive rat bones than in Sham-Walking rat bones; and (3) material properties such as ultimate stress of inactive rat tibia was lower than that of their walking counterparts. Of note, the additive effect of inactivity and OVX was seen only in a few parameters, such as the cancellous bone mineral density of the lumbar vertebrae and the structural parameters of cancellous bone in the lumbar vertebrae/tibiae. It is concluded that the lack of daily activity is detrimental to the strength and quality of cortical bone in the femur and tibia of rats, while lack of estrogen is not. Our inactive rat model, with the older rats, will aid the study of postmenopausal osteoporosis, the etiology of which may be both hormonal and mechanical

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

EM-Based Inference of True Labels Using Confidence Judgments

We have developed a method for accurately inferring true labels from labels provided by crowdsourcing workers, with the aid of self-reported confidence judgments in their labels. Although confidence judgments can be useful information for estimating the quality of the provided labels, some workers are overconfident about the quality of their labels while others are underconfident. To address this problem, we extended the Dawid-Skene model and created a probabilistic model that considers the differences among workers in their accuracy of confidence judgments. Results of experiments using actual crowdsourced data showed that incorporating workers' confidence judgments can improve the accuracy of inferred labels