マウスガードの自律神経活動への影響 : 瞳孔フラッシュ応答による定量的評価

Background:Recently, it has been reported that mouth guards (MGs), which reduce the incidence and severity of traumatic oral injuries in contact sports, may actually affect sports performance. We have observed that a majority of subjects showed improved dynamic visual acuity during head rotation when using a MG, but subjects who were unwilling to use a MG showed the opposite effect. Thus, we hypothesized that unpleasant sensations due to MGs may decrease sports performance.Methods:In this study, we measured autonomic nervous system activity to evaluate unpleasant sensations objectively and quantitatively by measuring the pupillary flash response (PFR) and heart rate variability (HRV), before, during, and after wearing 3- and 5-mm-thick custom-made MGs in 10 healthy subjects.Results:It was found that the 5-mm MG had a higher incidence of unpleasant sensations (50% of subjects) than did the 3-mm MG (10%). PFR (not HRV) analysis showed that both sympathetic and parasympathetic nervous system activities increased in subjects with unpleasant sensations.Conclusions:We suggest that the unpleasant sensation induced this unusual autonomic nervous system response, which could not be detected by traditional methods such as HRV analysis. By using PFR analysis, it is possible to make MGs without unpleasant sensations for better sports performance.博士（医学）・乙第1306号・平成24年11月27日Copyright © 2012 Japanese Stomatological Society. Published by Elsevier Japan K

The estimated GFR, but not the stage of diabetic nephropathy graded by the urinary albumin excretion, is associated with the carotid intima-media thickness in patients with type 2 diabetes mellitus: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>To study the relationship between the intima-media thickness (IMT) of the carotid artery and the stage of chronic kidney disease (CKD) based on the estimated glomerular filtration rate (eGFR) and diabetic nephropathy graded by the urinary albumin excretion (UAE) in the patients with type 2 diabetes mellitus.</p> <p>Methods</p> <p>A cross-sectional study was performed in 338 patients with type 2 diabetes mellitus. The carotid IMT was measured using an ultrasonographic examination.</p> <p>Results</p> <p>The mean carotid IMT was 1.06 ± 0.27 mm, and 42% of the subjects showed IMT thickening (≥ 1.1 mm). Cerebrovascular disease and coronary heart disease were frequent in the patients with IMT thickening. The carotid IMT elevated significantly with the stage progression of CKD (0.87 ± 0.19 mm in stage 1, 1.02 ± 0.26 mm in stage 2, 1.11 ± 0.26 mm in stage 3, and 1.11 ± 0.27 mm in stage 4+5). However, the IMT was not significantly different among the various stages of diabetic nephropathy. The IMT was significantly greater in the diabetic patients with hypertension compared to those without hypertension. The IMT positively correlated with the age, the duration of diabetes mellitus, and the brachial-ankle pulse wave velocities (baPWV), and negatively correlated with the eGFR. In a stepwise multivariate regression analysis, the eGFR and the baPWV were independently associated with the carotid IMT.</p> <p>Conclusions</p> <p>Our study is the first report showing a relationship between the carotid IMT and the renal parameters including eGFR and the stages of diabetic nephropathy with a confirmed association between the IMT and diabetic macroangiopathy. Our study further confirms the importance of intensive examinations for the early detection of atherosclerosis and positive treatments for hypertension, dyslipidaemia, obesity, as well as hyperglycaemia are necessary when a reduced eGFR is found in diabetic patients.</p

Long-term effect of metformin on blood glucose control in non-obese patients with type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>We aimed to investigate the long-term effect of metformin on the blood glucose control in non-obese patients with type 2 diabetes mellitus.</p> <p>Methods</p> <p>A retrospective study was performed in 213 patients with type 2 diabetes mellitus under the administration of metformin for more than one year. The clinical parameters were investigated for 3 years. The obese and non-obese individuals were defined as a body mass index (BMI) of 25 kg/m²or over (<it>n </it>= 105) and a BMI of less than 25 kg/m²(<it>n </it>= 108), respectively.</p> <p>Results</p> <p>HbA1c levels were significantly decreased compared with those at the baseline time. The course of HbA1c was similar between the non-obese and the obese groups, while the dose of metformin required to control blood glucose was significantly lower in the non-obese group than in the obese group. The reductions in HbA1c were 1.2% and 1.1% at 12 months, 0.9% and 0.9% at 24 months, and 0.8% and 1.0% at 36 months in the non-obese and obese groups, respectively. BMI did not change during the observation periods. Approximately half of all patients required no additional antidiabetic agents or a reduction in other treatments after the initiation of metformin in either of the two groups.</p> <p>Conclusions</p> <p>The present study demonstrated the long-term beneficial effect of metformin in non-obese (BMI < 25 kg/m²) diabetic patients. This effect appears to be maintained even after the observation period of this study, because metformin was limited to a relatively low dose in the non-obese group and the observed worsening in glycemic control over time can probably be attenuated by increasing the dose of metformin.</p

A Bayesian Approach to Strong Lens Finding in the Era of Wide-area Surveys

The arrival of the Vera C. Rubin Observatory's Legacy Survey of Space and Time (LSST), Euclid-Wide and Roman wide area sensitive surveys will herald a new era in strong lens science in which the number of strong lenses known is expected to rise from $\mathcal{O}(10^3)$ to $\mathcal{O}(10^5)$. However, current lens-finding methods still require time-consuming follow-up visual inspection by strong-lens experts to remove false positives which is only set to increase with these surveys. In this work we demonstrate a range of methods to produce calibrated probabilities to help determine the veracity of any given lens candidate. To do this we use the classifications from citizen science and multiple neural networks for galaxies selected from the Hyper Suprime-Cam (HSC) survey. Our methodology is not restricted to particular classifier types and could be applied to any strong lens classifier which produces quantitative scores. Using these calibrated probabilities, we generate an ensemble classifier, combining citizen science and neural network lens finders. We find such an ensemble can provide improved classification over the individual classifiers. We find a false positive rate of $10^{-3}$ can be achieved with a completeness of $46\%$, compared to $34\%$ for the best individual classifier. Given the large number of galaxy-galaxy strong lenses anticipated in LSST, such improvement would still produce significant numbers of false positives, in which case using calibrated probabilities will be essential for population analysis of large populations of lenses.Comment: Submitted to MNRAS, 14 pages, 9 figures. Comments welcom

Associations in tumor infiltrating lymphocytes between clinicopathological factors and clinical outcomes in estrogen receptor-positive/human epidermal growth factor receptor type 2 negative breast cancer

The value of assessing tumor infiltrating lymphocytes (TILs) in estrogen receptor (ER) positive/human epidermal growth factor receptor type 2 (HER2) negative breast cancer has yet to be determined. In the present study, a total of 184 cases with early distant recurrence detected within 5 years following the primary operation, 134 with late distant recurrence diagnosed following 5 years or longer and 321 controls without recurrence for >10 years following starting the initial treatment for ER-positive/HER2 negative breast cancer, registered in 9 institutions, were analyzed. The distributions of TILs and their clinical relevance were investigated. TIL distributions did not differ significantly among the early, late and no recurrence groups, employing a 30% cut-off point as a dichotomous variable. In those who had received adjuvant chemotherapy as well as endocrine therapy, a trend toward higher TIL proportions was detected when the early recurrence group was compared with the no recurrence group employing the 30% cut-off point (P=0.064). The TIL distributions were significantly associated with nodal metastasis (P=0.004), ER status (P=0.045), progesterone receptor (PgR) status (P=0.002), tumor grade (P=0.021), and the Ki67 labeling index (LI) (P=0.002) in the no recurrence group and with the Ki67 LI in the recurrence groups (P=0.002 in early recurrence group, P=0.023 in late recurrence group). High TIL distributions also predicted shorter survival time following the detection of recurrence (P=0.026). However, these prognostic interactions were not significant in multivariate analysis (P=0.200). The present retrospective study demonstrated no significant interaction between TIL proportions and the timing of recurrence. However, higher TIL proportions were observed in breast cancer patients with aggressive biological phenotypes, which tended to be more responsive to chemotherapy. The clinical relevance of stromal TILs for identifying patients who would likely benefit from additional therapies merits further investigation in a larger patient population

VEGF\u3csub\u3e164\u3c/sub\u3e-Mediated Inflammation is Required for Pathological, but Not Physiological, Ischemia-Induced Retinal Neovascularization

Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological retinal neovascularization. In the current paper, the mechanisms of physiological and pathological neovascularization are compared and contrasted. During pathological neovascularization, both the absolute and relative expression levels for VEGF164 increased to a greater degree than during physiological neovascularization. Furthermore, extensive leukocyte adhesion was observed at the leading edge of pathological, but not physiological, neovascularization. When a VEGF164-specific neutralizing aptamer was administered, it potently suppressed the leukocyte adhesion and pathological neovascularization, whereas it had little or no effect on physiological neovascularization. In parallel experiments, genetically altered VEGF164-deficient (VEGF120/188) mice exhibited no difference in physiological neovascularization when compared with wild-type (VEGF+/+) controls. In contrast, administration of a VEGFR-1/Fc fusion protein, which blocks all VEGF isoforms, led to significant suppression of both pathological and physiological neovascularization. In addition, the targeted inactivation of monocyte lineage cells with clodronate-liposomes led to the suppression of pathological neovascularization. Conversely, the blockade of T lymphocyte–mediated immune responses with an anti-CD2 antibody exacerbated pathological neovascularization. These data highlight important molecular and cellular differences between physiological and pathological retinal neovascularization. During pathological neovascularization, VEGF164 selectively induces inflammation and cellular immunity. These processes provide positive and negative angiogenic regulation, respectively. Together, new therapeutic approaches for selectively targeting pathological, but not physiological, retinal neovascularization are outlined