Search

Although opioids are useful narcotic analgesics in clinical settings, their misuse and addiction in the United States of America and other countries are rapidly increasing. Therefore, the development of abuse-deterrent formulations is an urgent issue. We herein investigated how to select the ratio of an opioid and the opioid receptor antagonist, naloxone in abuse-deterrent formulations for mice. The conditioned place preference (CPP) test was used to evaluate the rewarding effects of abused drugs. The opioids morphine (30 μmol/kg), oxycodone (3 μmol/kg), fentanyl (0.4 μmol/kg), and buprenorphine (0.5 μmol/kg) significantly induced place preference in mice. We also examined the optimal ratio of naloxone and opioids to inhibit the rewarding effects of the latter. Naloxone (3-5 μmol/kg) effectively inhibited place preference induced by the opioids tested. We calculated theoretical drug doses that exerted the same pharmacodynamic effects based on two parameters: μ-opioid receptor binding affinity and blood-brain barrier (BBB) permeability. Theoretical doses were very close to the drug doses at which mice showed place preference. Therefore, the CPP test is useful as a behavioral method for evaluating abuse-deterrent formulations of opioids mixed with an antagonist. The ratio of naloxone with opioids, at which mice did not show place preference, may be an effective index for developing abuse-deterrent formulations. Ratios may be calculated for other opioids based on μ-opioid receptor binding affinity and BBB permeability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that may have influenced the work reported in this manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Objectives: Rigorous and transparent management strategies for conflicts of interest and clinical practice guidelines with the best available evidence are necessary for the development of nephrology guidelines. However, there was no study assessing financial and nonfinancial conflicts of interest, quality of evidence underlying the Japanese guidelines for CKD, and conflict of interest policies for guideline development., Design, Setting, Participants, & Measurements: This cross-sectional study examined financial and nonfinancial conflicts of interest among all 142 authors of CKD guidelines issued by the Japanese Society of Nephrology using a personal payment database from all 92 major Japanese pharmaceutical companies between 2016 and 2019 and self-citations by guideline authors. Also, the quality of evidence and strength of recommendations underlying the guidelines and conflicts of interest policies of Japanese, US, and European nephrology societies were evaluated., Results: Among 142 authors, 125 authors (88%) received $6,742,889 in personal payments from 56 pharmaceutical companies between 2016 and 2019. Four-year combined median payment per author was $8258 (interquartile range, $2230‒$51,617). The amounts of payments and proportion of guideline authors with payments remained stable during and after guideline development. The chairperson, vice chairperson, and group leaders received higher personal payments than other guideline authors. Of 861 references in the guidelines, 69 (8%) references were self-cited by the guideline authors, and 76% of the recommendations were on the basis of low or very low quality of evidence. There were no fully rigorous and transparent conflicts of interest policies for nephrology guideline authors in the United States, Europe, and Japan., Conclusions: Most of the Japanese CKD guideline recommendations were on the basis of low quality of evidence by the guideline authors tied with pharmaceutical companies, suggesting the need for better financial conflicts of interest management., (Copyright © 2022 by the American Society of Nephrology.)

Background: Magnetic resonance imaging-guided focused ultrasound thalamotomy is approved by the U.S. Food and Drug Administration for treatment of essential tremor. Although this incisionless technology creates an ablative lesion, it potentially avoids serious complications of open stereotactic surgery., Objective: To determine the safety profile of magnetic resonance imaging-guided focused ultrasound unilateral thalamotomy for essential tremor, including frequency, and severity of adverse events, including serious adverse events., Methods: Analysis of safety data for magnetic resonance imaging-guided focused ultrasound thalamotomy (186 patients, five studies)., Results: Procedure-related serious adverse events were very infrequent (1.6%), without intracerebral hemorrhages or infections. Adverse events were usually transient and were commonly rated as mild (79%) and rarely severe (1%). As previously reported, abnormalities in sensation and balance were the commonest thalamotomy-related adverse events., Conclusion: The overall safety profile of magnetic resonance imaging-guided focused ultrasound thalamotomy supports its role as a new option for patients with medically refractory essential tremor. © 2018 International Parkinson and Movement Disorder Society., (© 2018 International Parkinson and Movement Disorder Society.)

Mycobacterium avium complex (MAC) infections are increasing annually in many countries. MAC strains are the most common nontuberculous mycobacterial pathogens isolated from respiratory samples and predominantly consist of two species, Mycobacterium avium and Mycobacterium intracellulare. The aim of this study was to analyze the molecular epidemiology and genetic backgrounds of clinical MAC isolates collected from The Netherlands, Germany, United States, Korea and Japan. Variable numbers of tandem repeats (VNTR) analysis was used to examine the genetic relatedness of clinical isolates of M. avium subsp. hominissuis (n=261) and M. intracellulare (n=116). Minimum spanning tree and unweighted pair group method using arithmetic averages analyses based on the VNTR data indicated that M. avium subsp. hominissuis isolates from Japan shared a high degree of genetic relatedness with Korean isolates, but not with isolates from Europe or the United States, whereas M. intracellulare isolates did not show any specific clustering by geographic origin. The findings from the present study indicate that strains of M. avium subsp. hominissuis, but not M. intracellulare, exhibit geographical differences in genetic diversity and imply that MAC strains may have different sources, routes of transmission and perhaps clinical manifestations., (Copyright © 2015 Elsevier B.V. All rights reserved.)

This study sought to determine the multicenter reproducibility of magnetic resonance imaging (MRI) and the compatibility of different scanner platforms in assessing carotid plaque morphology and composition. A standardized multi-contrast MRI protocol was implemented at 16 imaging sites (GE: 8; Philips: 8). Sixty-eight subjects (61 ± 8 years; 52 males) were dispersedly recruited and scanned twice within 2 weeks on the same magnet. Images were reviewed centrally using a streamlined semiautomatic approach. Quantitative volumetric measurements on plaque morphology (lumen, wall, and outer wall) and plaque tissue composition [lipid-rich necrotic core (LRNC), calcification, and fibrous tissue] were obtained. Inter-scan reproducibility was summarized using the within-subject standard deviation, coefficient of variation (CV) and intraclass correlation coefficient (ICC). Good to excellent reproducibility was observed for both morphological (ICC range 0.98-0.99) and compositional (ICC range 0.88-0.96) measurements. Measurement precision was related to the size of structures (CV range 2.5-4.9 % for morphology, 36-44 % for LRNC and calcification). Comparable measurement variability was found between the two platforms on both plaque morphology and tissue composition. In conclusion, good to excellent inter-scan reproducibility of carotid MRI can be achieved in multicenter settings with comparable measurement precision between platforms, which may facilitate future multicenter endeavors that use serial MRI to monitor atherosclerotic plaque progression.

Image-guided hepatic biopsies have been performed safely and accurately for a number of years. The advantages of sonographic or CT guidance in avoiding major vital structures, such as large vessels, the gallbladder, or pleura, have been confirmed many times. However, the safety and accuracy of certified nurse practitioners' performing these biopsies have not been described. The authors describe a retrospective review of 418 image-guided hepatic biopsies that demonstrated no significant difference in accuracy or complication rates between biopsies performed by certified nurse practitioners and those performed by radiologists in a single-institution, multihospital academic setting. Appropriately trained advanced practice providers can perform image-guided hepatic biopsies safely and accurately., (Copyright © 2014 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Schizophrenia is a devastating neuropsychiatric disorder with genetically complex traits. Genetic variants should explain a considerable portion of the risk for schizophrenia, and genome-wide association study (GWAS) is a potentially powerful tool for identifying the risk variants that underlie the disease. Here, we report the results of a three-stage analysis of three independent cohorts consisting of a total of 2,535 samples from Japanese and Chinese populations for searching schizophrenia susceptibility genes using a GWAS approach. Firstly, we examined 115,770 single nucleotide polymorphisms (SNPs) in 120 patient-parents trio samples from Japanese schizophrenia pedigrees. In stage II, we evaluated 1,632 SNPs (1,159 SNPs of p<0.01 and 473 SNPs of p<0.05 that located in previously reported linkage regions). The second sample consisted of 1,012 case-control samples of Japanese origin. The most significant p value was obtained for the SNP in the ELAVL2 [(embryonic lethal, abnormal vision, Drosophila)-like 2] gene located on 9p21.3 (p = 0.00087). In stage III, we scrutinized the ELAVL2 gene by genotyping gene-centric tagSNPs in the third sample set of 293 family samples (1,163 individuals) of Chinese descent and the SNP in the gene showed a nominal association with schizophrenia in Chinese population (p = 0.026). The current data in Asian population would be helpful for deciphering ethnic diversity of schizophrenia etiology.

Introduction: Quality of information available over the Internet has been a cause for concern. Our goal was to evaluate the quality of information available on lung cancer in the United States and Japan and assess the differences between the two., Methods: We conducted a prospective, observational Web review by searching the word "lung cancer" in Japanese and English, using Google Japan (Google-J), Google United States (Google-U), and Yahoo Japan (Yahoo-J). The first 50 Web sites displayed were evaluated from the ethical perspective and for the validity of the information. The administrator of each Web site was also investigated., Results: Ethical policies were generally well described in the Web sites displayed by Google-U but less well so in the sites displayed by Google-J and Yahoo-J. The differences in the validity of the information available was more striking, in that 80% of the Web sites generated by Google-U described the most appropriate treatment methods, whereas less than 50% of the Web sites displayed by Google-J and Yahoo-J recommended the standard therapy, and more than 10% advertised alternative therapy. Nonprofit organizations and public institutions were the primary Web site administrators in the United States, whereas commercial or personal Web sites were more frequent in Japan., Conclusion: Differences in the quality of information on lung cancer available over the Internet were apparent between Japan and the United States. The reasons for such differences might be tracked to the administrators of the Web sites. Nonprofit organizations and public institutions are the up-and-coming Web site administrators for relaying reliable medical information.

Introduction: The main purpose of this study was to develop soft-tissue cephalometric standards for Yemeni men and compare them with the cephalometric standards of normal North American white people., Methods: Fifty Yemeni men (ages, 20-27 years; mean, 23.1 years) with normal occlusion were selected. With double selection by orthodontists and laypersons, a subsample of esthetically pleasing subjects was selected. Lateral cephalometric radiographs of all subjects were analyzed according to the Legan-Burstone and the Holdaway analyses., Results: The Yemeni esthetically pleasing subjects (YPG) and the remaining subjects (YNG) showed significant differences with respect to mandibular prognathism, lower face-throat angle, nasolabial angle, mentolabial sulcus depth, and interlabial gap, when compared with the Legan-Burstone norms for white Americans; the YPG also had significantly less obtuse facial convexity angle than the YNG. Most values of both Yemeni groups were generally within the range of the values reported by Holdaway, except for 3 variables: skeletal profile convexity, basic upper-lip thickness, and H-angle, which were all significantly larger than those of Holdaway; the YPG showed less skeletal profile convexity than the YNG., Conclusions: These results show that the soft-tissue facial profiles of white Yemenis and Americans are different in certain respects; these racial differences must be considered during diagnosis and treatment planning. These results should serve as a useful reference for orthodontists and maxillofacial surgeons who treat Yemeni patients and also contribute to more satisfactory diagnosis and treatment planning for them.

Background: Linkage with 18p11 is one of the replicated findings in molecular genetics of bipolar disorder. Because mitochondrial dysfunction has been suggested in bipolar disorder, NDUFV2 at 18p11, encoding a subunit of the complex I, reduced nicotinamide adenine dinucleotide (NADH)ubiquinone oxidoreductase, is a candidate gene for this disorder. We previously reported that a polymorphism in the upstream region of NDUFV2, -602G> A, was associated with bipolar disorder in Japanese subjects; however, functional significance of -602G> A was not known., Methods: We screened the further upstream region of NDUFV2. We performed a case-control study in Japanese patients with bipolar disorder and control subjects and a transmission disequilibrium test in 104 parent and proband trios of the National Institute of Mental Health (NIMH) Genetics Initiative pedigrees. We also performed the promoter assay to examine functional consequence of the -602G> A polymorphism., Results: The -602G> A polymorphism was found to alter the promoter activity. We found that the other haplotype block surrounding -3542G> A was associated with bipolar disorder. The association of the haplotypes consisting of -602G> A and -3542G> A polymorphisms with bipolar disorder was seen both in Japanese case-control samples and NIMH trios., Conclusion: Together these findings indicate that the polymorphisms in the promoter region of NDUFV2 are a genetic risk factor for bipolar disorder by affecting promoter activity.

Purpose: To study a comparison of problems arising in pulmonary rehabilitation programs in North America, Europe, and Tokyo., Methods: The survey instrument was a 13-item questionnaire sent in December 1994 to institutions in North America (n = 178), Europe (n = 179), and Tokyo (n = 399)., Results: Response rates were 51%, 40%, and 51% for North America, Europe, and Tokyo, respectively. Pulmonary rehabilitation programs were available at 56% of hospitals in North America and 74% in Europe, but at only 20% of hospitals in Tokyo. Most PRPs were conducted in an outpatient setting in North American (98%), whereas both outpatient (55%) and inpatient programs (65%) were adopted in Europe. Although the type of lung disease for which patients in both North America and Europe were referred to PRPs was mainly chronic obstructive pulmonary disease, this accounted for only 34% of referrals in Tokyo. However, referrals for primary tuberculosis sequelae (P = 0.028) and bronchiectasis (P = 0.021) were more common in Europe, similar to the situation in Tokyo. The following PRP items were available at significantly higher rates in North America than in Europe, and most were unavailable in Tokyo: family education, psychological support, nutritional instruction, treadmill, bicycle ergometer, walking training, and increasing the activity of daily living., Conclusion: Pulmonary rehabilitation programs in North America are more multidimensional. However, target diseases differ among North America, Europe, and Tokyo. Pulmonary rehabilitation programs in Tokyo differed from those in North America and Europe and were poorly programmed. Problems arising in PRPs in the three regions include lack of staff and insufficient reimbursement.

Antibiotic susceptibilities of twelve borrelial isolates from skin of patients with erythema migrans (EM) and ticks (Ixodes persulcatus and I. ovatus) in Japan were examined by in vitro microdilution MIC method and macrodilution MBC method. Nine EM isolates and 3 tick isolates were susceptible to amoxicillin, erythromycin, and minocycline. MICs for Japanese isolates were 0.038-0.30 microgram/ml, < 0.012 microgram/ml, and < 0.012-0.05 microgram/ml, respectively. MBCs were as follows: 0.038-0.88 microgram/ml, < 0.012-0.10 microgram/ml, and < 0.025-0.78 microgram/ml, respectively. These antibiotics could be recommended for treatment of patients in early stage of Lyme disease in Japan.