Expressed emotion (EE) research has been productive in investigating the influence of the interpersonal environment on a range of disorders. The majority of EE research on the influence of carers has been carried out in the west. This is the first EE study of the carers of people with dementia in Japan. The aim of this study was to investigate the relationships between EE status and aspect of burden through cross-cultural comparison of the two countries, Japan and England, with large cultural and linguistic differences. Comparisons were made between samples of EE of carers of dementia and schizophrenic patients. In total, data on 80 carer/relative-patient dyads were collected and examined: (1) 20 Japanese carers of people with dementia (JD), (2) 20 English carers of patients with Alzheimer's disease (ED), (3) 20 Japanese relatives of patients with schizophrenia (JS), and (4) 20 English relatives of patients with schizophrenia (ES). The Camberwell Family Interview was administered in each country to ascertain levels of EE. Large differences between Japan and England were found in the frequency of critical comments, in which ES>ED>JS>JD. EE correlated significantly with burden in the JD sample alone. With an operational cut-off of 2CC (CC, critical comments), EE correlated significantly with cognitive impairment as well as with clinical severity in the JD sample. There was a tendency for lower expression of both positive and negative emotional reactions towards family members in the Japanese sample. The results of this study indicate that EE is an appropriate measure for use with carers of sufferers of dementia and can be utilized across different cultures. However, flexibility with the cut-offs may be required in Eastern cultures. This needs to be tested on larger samples with sensitivity to illness and cross-cultural differences.

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Dynamic light scattering (DLS) is a well-known technique for measuring the size of nanoparticles from the diffusion coefficient. We developed a new DLS technique with high sensitivity and used it as a detection tool in microchemical applications. We found a step-like downward change in the diffusion coefficient of nanoparticles just by starting a slight flow in the fluid channel. Because the diffusion coefficient is defined by the ratio of the force due to the chemical potential gradient to the frictional coefficient for the particle by a solvent, we propose that the frictional coefficient increased significantly. This result suggests that nanoscale friction under liquid motion differs from that under a steady state.

Previously we identified two alternative first exons (exon N1 and exon L1) coding for 5′ untranslated regions of human aromatic l‐amino acid decarboxylase (AADC) and found that their alternative usage produced two types of mRNAs in a tissue‐specific manner. To determine the cis‐acting element regulating the tissue‐specific expression of human AADC, we produced three kinds of transgenic mice harboring 5′ flanking regions of the human AADC gene fused to the bacterial chloramphenicol acetyltransferase (CAT) gene. The transgene termed ACA contained −7.0 kb to −30 bp in exon N1, including the entire exon L1; ACN contained −3.6 kb to −30 bp in exon N1; and ACL contained −2.8 kb to −42 bp in exon L1. The ACA transgenic mice expressed CAT at extremely high levels in peripheral nonneuronal tissues, such as pancreas, liver, kidney, small intestine, and colon, that contained endogenous high AADC activity, whereas CAT immunoreactivity was not detected in either catecholaminergic or serotonergic neurons in the CNS. Thus, it was suggested that the ACA transgene contained the major part of cis‐regulatory elements for the expression of AADC in peripheral nonneuronal tissues. On the other hand, the ACN transgenic mice moderately expressed CAT in various tissues except for the lung and liver, and the ACL transgenic mice showed moderate CAT expression only in the kidney.

AIMSHMG-CoA reductase inhibitors are available for use in low density lipoprotein-cholesterol (LDL-C) lowering therapy. The purposes of this study were to develop a population pharmacodynamic (PPD) model to describe the time course for the LDL-C lowering effects of statins and assess the efficacy of combination therapy based on electronic medical records. METHODSPatient backgrounds, laboratory tests and prescribed drugs were collected retrospectively from electronic medical records. Patients who received atorvastatin, pitavastatin or rosuvastatin were enrolled. A physiological indirect response model was used to describe the changes observed in LDL-C concentrations. The PPD analysis was performed using NONMEM 7.2.0 with the first order conditional estimation method with interaction (FOCE-INTER). RESULTSAn indirect response Imax model, based on the 2863 LDL-C concentrations of 378 patients, successfully and quantitatively described the time course for the LDL-C lowering effects of three statins. The combination of ezetimibe, a cholesterol absorption inhibitor, decreased the LDL synthesis rate (Kin) by 10.9%. A simulation indicated that the combined treatment of ezetimibe with rosuvastatin (2.5 mg day CONCLUSIONSA newly constructed PPD model supported previous evidence for the beneficial effects of ezetimibe combined with rosuvastatin. In addition, the established framework is expected to be applicable to other drugs without pharmacokinetic data in clinical practice. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• There is currently no population pharmacodynamic model to describe the time course for the low density lipoproteincholesterol (LDL-C) lowering effects of statins with regards to covariate factors (e.g. co-medicated drugs), which may enhance clinical efficacy, based on information obtained from electronic medical records in a general hospital. WHAT THIS STUDY ADDS• The indirect response model successfully and quantitatively described the time course for the LDL-C lowering effects of statins (atorvastatin, pitavastatin and rosuvastatin) and the efficacy of ezetimibe.• Patients with higher baseline LDL-C concentrations are recommended to receive a combination with ezetimibe rather than an increased dose of rosuvastatin.• The established framework is expected to be applicable to other drugs without pharmacokinetic data in clinical practice and may detect influential factors for drug therapy.

Background An administrative database covering a whole population such as the national database in Japan may be used to estimate the nationwide prevalence of diseases including rheumatoid arthritis (RA) when a well-validated definition of the disease is available. In Japan, the record linkage between the administrative database and medical charts in hospitals is strictly prohibited. A “hospital-based” validation study is one of few possible validation studies where claims kept inside the study hospital are rearranged into the database structure. Methods We selected random samples of 19,734 patients from approximately 1.6 million patients who received medical care between February 2018 and January 2019 in one of the 64 hospitals of the Tokushukai Medical Group. We excluded patients whose observation period was less than 365 days and identified 334 patients who met the definition of “possible cases of RA” whose medical charts were then independently evaluated by two rheumatologists. In a sensitivity analysis, we assessed bias due to misclassifying some patients with RA who did not meet the definition of “possible cases of RA” as a patient with no RA. Results The kappa coefficient between the two rheumatologists was 0.80. The prevalence of RA in the study population was estimated to be 0.56%. We found that [condition code of RA] and ([any disease-modifying antirheumatic drug] or [oral corticosteroid with no systemic autoimmune diseases (other than RA) and no polymyalgia rheumatica]) had a relatively high sensitivity (approximately 73%) and a high positive predictive value (approximately 80%). In a sensitivity analysis, we found that when some patients with RA who did not meet the definition of “possible cases of RA” were misclassified as a patient with no RA, then this would lead to underestimation of the prevalence of the definition-positive patients and the adjusted prevalence. Conclusions We recommend using the claims-based definition of RA (found in the current validation study) to estimate the prevalence of RA in Japan. We also suggest estimating the adjusted prevalence using the quantitative bias analysis method, since the prevalence of the disease in the “hospital-based” validation study is different from that in the administrative database. Trial registration The current study is not a clinical trial and hence not subject to trial registration.

Although the existence of three different cDNA forms of human GTP cyclohydrolase I (GCH I) have been reported (Togari et al., 1992), the full-length sequence of any human GCH I cDNA involving poly (A) tail has not yet been documented. In the present study, we first isolated a full-length cDNA clone encoding human GCH I type 1 from human pheochromocytoma cDNA library. The length of the cDNA insert was 2,921 base pairs including poly (A) tail. RNA blot analysis showed a single mRNA species of 4.0 kb in human pheochromocytoma tissue.

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