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Preparation of drug metabolites at the milligram scale is essential for determining the structure and toxicity of drug metabolites. However, their preparation using recombinant proteins and human liver microsomes (HLM) is often difficult because of technical and ethical issues. Reproducing human drug metabolism in food-derived microorganisms may be useful for overcoming these challenges. In this study, we identified an unknown metabolite of the anaesthetic drug lidocaine, which is metabolised by HLM. By screening for lidocaine metabolic activity in five types of foods (blue cheese, shiitake mushroom, natto, yoghurt, and dry yeast), we found that bacteria isolated from natto reproduced the lidocaine metabolic reaction that occurs in HLM. A fraction containing the unknown lidocaine metabolite was prepared through mass cultivation of a Bacillus subtilis standard strain, ethyl acetate extraction, open column chromatography, and HPLC purification. We identified the unknown metabolite as 3-(2,6-dimethylphenyl)-1-ethyl-2-methyl-4-imidazolidinone using NMR. Our results showed that food-derived microorganisms can produce large amounts of human drug metabolites via large-scale cultivation. Additionally, food microorganisms that can reproduce drug metabolism in humans can be used to examine drug metabolites at a low cost and without ethical issues.

Background: CDKL5 deficiency is caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene and clinically manifests often in females as drug-resistant intractable epilepsy and severe psychomotor retardation., Case Report: We report the case of a girl with a CDKL5 mutation born at 39 weeks without neonatal asphyxia. She developed epilepsy at age 1 month with myoclonus of the face and limbs, and non-rhythmic and irregular opsoclonus. She developed tonic seizures and epileptic spasms at 6 months of age and was diagnosed with symptomatic West syndrome and underwent adrenocorticotropic hormone therapy but her seizures were refractory. At the age of 4, she was introduced to our hospital and development was at 2 months of age. We diagnosed her with early myoclonic encephalopathy (EME) due to the remaining suppression-burst pattern observed on an electroencephalogram and her symptoms since onset were mainly myoclonus. At 14 years of age, mutational analysis revealed a CDKL5 mutation (c.380A > G:p.His127Arg). She was diagnosed with epileptic encephalopathy exhibiting clinical features of early myoclonic epilepsy caused by CDKL5 deficiency., Conclusions: Early onset epilepsy with severe psychomotor retardation without a known etiology may be caused by a mutation in CDKL5. More research investigating a genotype-phenotype correlation of CDKL5 mutations is necessary because clinical severity may be associated with the location and type of mutations., (Copyright © 2019 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Introduction: Epilepsy is considered to arise from dysfunction in neural networks. Recent advances in neuroimaging and its analysis have made it possible to investigate both functional and structural connectivity in the brain. The aim of this study was to elucidate alterations in the structural connectivity in children with localization-related epilepsy using the mathematical method of graph theoretical analysis., Methodology: Fifteen children with localization-related epilepsy (8 female subjects; mean age, 8.5±3.5years) as an epilepsy group and 23 children without a history of seizure (12 female subjects; mean age, 8.9±3.7years) as a control group underwent three-dimensional T1-weighted brain magnetic resonance imaging (MRI). Gray matter images segmented and spatially normalized from the MRIs of both groups were analyzed using statistical parametric mapping with the Graph Analysis Toolbox. We compared global networks (global efficiency, clustering coefficient and network strength) and regional networks (betweenness centrality and clustering) between patients and controls., Results: The global efficiency tended to be increased (p=0.081) and the global modularity was significantly increased (p=0.017) in the epilepsy group as compared with the control group. The epilepsy group showed locally decreased betweenness centrality mainly in the bilateral cingulate gyri, right perisylvian area, and bilateral precentral gyri, and locally increased clustering in the bilateral cingulate gyri, right perisylvian area, and medial frontal lobes as compared with the control group. The epilepsy group showed higher network resilience to random attack and targeted attack than the control group. Voxel-based morphometry did not show any difference between the two groups., Conclusions: We observed globally increased structural connectivity along with excessive network robustness in patients with localization-related epilepsy. Local abnormality of connectivity was observed mainly in the cingulate gyrus, perisylvian area, and precentral gyrus. This alteration in the structural connectivity without any morphometric changes may be related to the underlying epileptogenicity., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Tongue diagnosis is a noninvasive diagnosis and is traditionally one of the most important tools for physicians who practice Kampo (traditional Japanese) medicine. However, it is a subjective process, and its results can depend on the experience of the physician performing it. Previous studies have reported how to measure and evaluate the shape and color of the tongue objectively. Therefore, this study focused on the glossy component in order to quantify tongue moisture in tongue diagnosis. We hypothesized that moisture appears as a gloss in captured images and measured the amount of water on the tongue surface in 13 subjects. The results showed a high correlation between the degree of gloss and the amount of water on the tongue surface and suggested that the moisture on the tongue can be estimated by the degree of gloss in a captured image. Because the moisture level on the tongue changes during the course of taking photos, it became clear that we had to wait at least 3 minutes between photos. Based on these results, we established the tongue image analyzing system (TIAS), which can consistently record the gloss and color of the tongue surface simultaneously.

Osteomyelitis due to Mycobacterium bovis Bacille Calmette-Guerin (BCG) often develops in patients with interferon-γ receptor 1 (IFNγR1) deficiency. In these patients, susceptibility appears to be caused by impaired interleukin-12- and IFNγ-mediated immunity. Here we report the case of a one-year-old girl with dominant partial IFNγR1 deficiency who suffered from lymphadenitis and multiple sites of osteomyelitis due to BCG infection. She was allergic to isoniazid and rifampicin--the prescribed standard treatment--and required prior desensitization therapy. She was subsequently treated with these drugs, but her symptoms did not improve. IFNγ therapy was added to the antitubercular therapy, increasing the serum level of IFNγ and leading to the resolution of the lymphadenitis and osteomyelitis. In conclusion, high dose IFNγ therapy in combination with antitubercular drugs led to resolution of BCG infection in a patient with dominant partial IFNγ deficiency., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In traditional Japanese medicine (Kampo medicine), tongue color is important in discerning a patient's constitution and medical conditions. However, tongue color diagnosis is susceptible to the subjective factors of the observer. To investigate factors involved in tongue color diagnosis, both color discrimination and tongue color diagnosis were researched in 68 Kampo medical practitioners. Color discrimination was studied by the Farnsworth-Munsell 100 Hue test, and tongue color diagnosis was studied by 84 tongue images. We found that overall color discrimination worsened with aging. However, the color discrimination related to tongue color regions was maintained in subjects with 10 or more years of Kampo experience. On the other hand, tongue color diagnosis significantly differed between subjects with <10 years of experience and ≥10 years of experience. Practitioners with ≥10 years of experience could maintain a consistent diagnosis of tongue color regardless of their age.