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Shigeki?Kinuhata Yasuhiko?TakemotoEmail author Mariko?Senda Shiho?Nakai Erika?Tsumura Tatsuyuki?Otoshi Sadahiko?Hiratani Kazuo?Fukumoto Hiroki?Namikawa Yoshihiro?Tochino Mina?Morimura Taichi?Shuto Sadahiko?Uchimoto 《Asia Pacific family medicine》2018,17(1):6
Background
Detecting and treating dementia at an early stage are important. Although the Revised Hasegawa Dementia Scale (HDS-R) is commonly used to detect dementia, it takes about 10 min to complete. In contrast, the 1-min animal test (OMAT) takes only 1 min to complete and may be a helpful screening test for general practitioners in deciding whether to proceed with administering further diagnostic tests such as the HDS-R. We sought to examine the relationship between the OMAT and HDS-R scores, and determine the cut-off OMAT score that balanced the sensitivity and specificity in identifying HDS-R-positive patients.Methods
A total of 122 consecutive patients with diabetes who visited the outpatient clinic at the Fujiidera Municipal Hospital were enrolled. The patients underwent the OMAT and HDS-R on the same day. Tests were conducted in a single-blinded manner. The relationship between the OMAT and HDS-R scores was examined using Spearman’s rank correlation. Receiver operating characteristic curve analysis was performed to identify the optimal cut-off score of OMAT that will determine whether to proceed with further diagnostic tests.Results
A strong positive correlation between the OMAT and HDS-R scores was observed (r?=?0.70). The sensitivity and specificity of OMAT using cut-off scores of 12/13, 13/14, and 14/15 for HDS-R-positive patients were 0.87 and 0.66, 1.00 and 0.51, and 1.00 and 0.40, respectively among all the subjects. Similar results were obtained in a subgroup of subjects aged?≥?65 years.Conclusions
A cut-off score of 13/14 on the OMAT balanced the sensitivity closest to 1.00 and allowed for the highest specificity for the HDS-R not only among all the patients, but also among just the patients aged?≥?65 years. The OMAT may be an optimal screening test to determine whether to proceed with further diagnosis using HDS-R.Trial registration UMIN UMIN000025260. This study is retrospectively registered on December 13th, 2016953.
Integration of mechanistic and pharmacokinetic information to derive oral reference dose and margin‐of‐exposure values for hexavalent chromium
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Chad M. Thompson Christopher R. Kirman Sean M. Hays Mina Suh Seneca E. Harvey Deborah M. Proctor Julia E. Rager Laurie C. Haws Mark A. Harris 《Journal of applied toxicology : JAT》2018,38(3):351-365
The current US Environmental Protection Agency (EPA) reference dose (RfD) for oral exposure to chromium, 0.003 mg kg?1 day?1, is based on a no‐observable‐adverse‐effect‐level from a 1958 bioassay of rats exposed to ≤25 ppm hexavalent chromium [Cr(VI)] in drinking water. EPA characterizes the confidence in this RfD as “low.” A more recent cancer bioassay indicates that Cr(VI) in drinking water is carcinogenic to mice at ≥30 ppm. To assess whether the existing RfD is health protective, neoplastic and non‐neoplastic lesions from the 2 year cancer bioassay were modeled in a three‐step process. First, a rodent physiological‐based pharmacokinetic (PBPK) model was used to estimate internal dose metrics relevant to each lesion. Second, benchmark dose modeling was conducted on each lesion using the internal dose metrics. Third, a human PBPK model was used to estimate the daily mg kg?1 dose that would produce the same internal dose metric in both normal and susceptible humans. Mechanistic research into the mode of action for Cr(VI)‐induced intestinal tumors in mice supports a threshold mechanism involving intestinal wounding and chronic regenerative hyperplasia. As such, an RfD was developed using incidence data for the precursor lesion diffuse epithelial hyperplasia. This RfD was compared to RfDs for other non‐cancer endpoints; all RfD values ranged 0.003–0.02 mg kg?1 day?1. The lowest of these values is identical to EPA's existing RfD value. Although the RfD value remains 0.003 mg kg?1 day?1, the confidence is greatly improved due to the use of a 2‐year bioassay, mechanistic data, PBPK models and benchmark dose modeling. 相似文献
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The aim of endodontic treatment is to eliminate infection from the root canal by cleaning and shaping. Multiple factors, such as a broken instrument or anatomical variations in root canals, lead to treatment failure. This article describes a mandibular canine with two canals and two foramina. It is presented here to raise awareness of the importance of an improved access cavity in detecting excess canals. 相似文献
956.
Peter Agre Carolyn Bertozzi Mina Bissell Kevin P. Campbell Richard D. Cummings Umesh R. Desai Mary Estes Terence Flotte Guy Fogleman Fred Gage David Ginsburg Jeffrey I. Gordon Gerald Hart Vincent Hascall Laura Kiessling Stuart Kornfeld John Lowe John Magnani Lara K. Mahal Ruslan Medzhitov Richard J. Roberts Robert Sackstein Rita Sarkar Ronald Schnaar Nancy Schwartz Ajit Varki David Walt Irving Weissman 《The Journal of clinical investigation》2016,126(2):405-408
This position statement originated from a working group meeting convened on April 15, 2015, by the NHLBI and incorporates follow-up contributions by the participants as well as other thought leaders subsequently consulted, who together represent research fields relevant to all branches of the NIH. The group was deliberately composed not only of individuals with a current research emphasis in the glycosciences, but also of many experts from other fields, who evinced a strong interest in being involved in the discussions. The original goal was to discuss the value of creating centers of excellence for training the next generation of biomedical investigators in the glycosciences. A broader theme that emerged was the urgent need to bring the glycosciences back into the mainstream of biology by integrating relevant education into the curricula of medical, graduate, and postgraduate training programs, thus generating a critical sustainable workforce that can advance the much-needed translation of glycosciences into a more complete understanding of biology and the enhanced practice of medicine. 相似文献
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Since synaptic plasticity is regarded as a potential mechanism for memory formation and learning, there is growing interest in the study of its underlying mechanisms. Recently several evolutionary models of cellular development have been presented, but none have been shown to be able to evolve a range of biological synaptic plasticity regimes. In this paper we present a biologically plausible evolutionary cellular development model and test its ability to evolve different biological synaptic plasticity regimes. The core of the model is a genomic and proteomic regulation network which controls cells and their neurites in a 2D environment. The model has previously been shown to successfully evolve behaving organisms, enable gene related phenomena, and produce biological neural mechanisms such as temporal representations. Several experiments are described in which the model evolves different synaptic plasticity regimes using a direct fitness function. Other experiments examine the ability of the model to evolve simple plasticity regimes in a task -based fitness function environment. These results suggest that such evolutionary cellular development models have the potential to be used as a research tool for investigating the evolutionary aspects of synaptic plasticity and at the same time can serve as the basis for novel artificial computational systems. 相似文献
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