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We reported a case of a 22-months child with hemolytic uremic syndrome associated with encephalopathy. As the cause of this case, the involvements of verotoxin 1 and 2 caused by O157: the H7 strain of the enterohemorrhagic Escherichia coli and rotavirus were presumed. We administered brain hypothermic therapy and steroid pulse therapy in the intensive care unit, but we were not able to save his life and the child died on the 6th day from the onset. [ABSTRACT FROM AUTHOR]

Lissencephaly is a rare brain malformation characterized by abnormal neuronal migration during cortical development. In this study, we performed a comprehensive genetic analysis using next-generation sequencing in 12 unsolved Japanese lissencephaly patients, in whom PAFAH1B1, DCX, TUBA1A, and ARX variants were excluded using the Sanger method. Exome sequencing (ES) was conducted on these 12 patients, identifying pathogenic variants in CEP85L, DYNC1H1, LAMC3, and DCX in four patients. Next, we performed genome sequencing (GS) on eight unsolved patients, and structural variants in PAFAH1B1, including an inversion and microdeletions involving several exons, were detected in three patients. Notably, these microdeletions in PAFAH1B1 could not to be detected by copy number variation (CNV) detection tools based on the depth of coverage methods using ES data. The density of repeat sequences, including Alu sequences or segmental duplications, which increase the susceptibility to structural variations, is very high in some lissencephaly spectrum genes (PAFAH1B1, TUBA1A, DYNC1H1). These missing CNVs were due to the limitations of detecting repeat sequences in ES-based CNV detection tools. Our study suggests that a combined approach integrating ES with GS can contribute to a higher diagnostic yield and a better understanding of the genetic landscape of the lissencephaly spectrum., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

We report our findings in a 5-year-old Japanese girl with unilateral optic neuritis who was seropositive for anti-myelin-oligodendrocyte glycoprotein (MOG) antibody. Functional and microstructural changes were assessed longitudinally for 3.5 years by serial recordings of the pattern visual evoked potentials (pVEPs) and optical coherence tomography (OCT) during the acute and chronic phases. On the initial visit, the best-corrected visual acuity (BCVA) in the right eye was light perception. She was treated with 450 mg of intravenous methylprednisolone pulses followed by a gradual tapering of the oral prednisolone. The visual acuity decreased to no light perception, and plasmapheresis combined with high-dose intravenous immunoglobulin therapy was performed. The BCVA quickly improved to 1.0, and no recurrence was detected for approximately four years. The implicit times of N75, P100, and N145 of the pVEPs and peripapillary retinal nerve fiber (pRNFL) thickness in the OCT images were measured during the course of the disease process. The pRNFL thickness of the right eye decreased and was less than one-half of the baseline value at one year and then stabilized. In contrast, the optic pathway function assessed by pVEPs improved. The implicit times of the N75 and P100 components of the right eye were shortened and stabilized at approximately one year. However, the implicit times in the right eye were still longer than that of the left eye. Our findings documented the course of the function and structures of an eye with anti-MOG antibody-positive optic neuritis. This information should be helpful for the understanding of the pathology and prognosis of this disease entity. Further analysis of the pVEPs and structural changes in more cases is needed., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tachibana et al.)

Background: This study evaluated the efficacy and safety of eculizumab, a terminal complement C5 inhibitor, in juvenile generalized myasthenia gravis (gMG)., Methods: Adolescents aged 12 to 17 years with refractory anti-acetylcholine receptor (AChR) antibody-positive gMG received eculizumab (weekly induction [one to two doses of 600 mg or four doses of 900 mg] followed by maintenance doses [300 to 1200 mg] every two weeks for up to 26 weeks) in a phase 3, open-label multicenter study (NCT03759366). Change from baseline to week 26 in Quantitative Myasthenia Gravis (QMG) total score (primary end point) and secondary end points including Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score, Myasthenia Gravis Composite score, Myasthenia Gravis Foundation of America postintervention status, EuroQol 5-Dimensions (Youth) and Neurological Quality-of-Life Pediatric Fatigue questionnaire scores, as well as pharmacokinetics, pharmacodynamics, and safety, were recorded., Results: Eleven adolescents (mean ± S.D. age 14.8 ± 1.8 years) were enrolled; 10 completed the primary evaluation period. Least-squares mean changes from baseline at week 26 were -5.8 (standard error [SE] 1.2; P = 0.0004) for QMG total score and -2.3 (SE 0.6; P = 0.0017) for MG-ADL total score. Overall, the primary and all secondary efficacy end point analyses met statistical significance from the first assessment and were sustained throughout. Complete terminal complement inhibition was sustained through 26 weeks in all patients. Treatment-emergent adverse events were all mild/moderate and predominantly unrelated to eculizumab., Conclusions: Eculizumab was effective in reducing disease burden and was well tolerated in adolescents with refractory AChR antibody-positive gMG., Competing Interests: Declaration of competing interest Dr. Brandsema has received research funding from Alexion, AstraZeneca Rare Disease, Momenta/Janssen, and Argenx; individual consulting fees from Momenta/Janssen and Argenx; and support in attending meetings from Alexion, AstraZeneca Rare Disease. Dr. Ginsberg reports that Alexion, AstraZeneca Rare Disease, sponsored the current research and associated costs including the provision of equipment needed for the conduct of the study. Dr. Rao has received research funding from Alexion, AstraZeneca Rare Disease, and NS Pharma; individual consulting fees from Biogen, AveXis/Novartis, Genentech/Roche, Sarepta Therapeutics, NS Pharma, Scholar Rock, PTC Therapeutics, and Regenxbio; honoraria from Biogen, AveXis/Novartis, Genentech/Roche, PTC therapeutics, France Foundation, and the Muscular Dystrophy Association; travel assistance from Cure SMA, NS Pharma, Biogen, AveXis/Novartis, and France Foundation, Neuropedicon; honoraria for attending advisory boards or data safety meetings from Capricor and Watermark, and expert testimony fees. Dr. Ruzhansky has received research funding from Argenx, Alexion, AstraZeneca Rare Disease, Alnylam, Corbus, UCB/Ra, Momenta Janssen, MGNet, and the Myasthenia Gravis Foundation of America; individual consulting fees from Guidepoint and GLG; honoraria from WebMD; support in attending meetings from MUSC and MGNet; and honoraria for attending advisory boards or data safety meetings from Argenx, Alexion, AstraZeneca Rare Disease, Amylyx, Immunovant, UCB/Ra, and Guidepoint. Dr. Suresh has received payment for speaking from Takeda Pharmaceuticals and for participating in advisory boards or data safety meetings from Alexion, AstraZeneca Rare Disease, and Argenx. Dr. Howard has received research support (paid to his institution) from Alexion, AstraZeneca Rare Disease, Argenx, BVBA, Cartesian Therapeutics, the Centers for Disease Control and Prevention (Atlanta, GA, USA), the Myasthenia Gravis Foundation of America, the Muscular Dystrophy Association, the National Institutes of Health (including the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases), PCORI, Ra Pharmaceuticals (now UCB Pharma), and Takeda Pharmaceuticals; honoraria from Alexion, AstraZeneca Rare Disease, Argenx, BVBA, Immunovant Inc, Ra Pharmaceuticals (now UCB Pharma), Regeneron Pharmaceuticals, Sanofi US, and Viela Bio Inc (now Horizon Therapeutics); and nonfinancial support from Alexion, AstraZeneca Rare Disease, Argenx, BVBA, Ra Pharmaceuticals (now UCB Pharma), and Toleranzia AB. Drs. Frick, Hicks, and Liao are employees of and own stock in Alexion, AstraZeneca Rare Disease. No other disclosures were reported., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pleomorphic lung cancer is a very rare type of cancer and very few cases have been reported in the literature. We present a case of pleomorphic lung cancer in a patient with history of IgA nephropathy on hemodialysis., Competing Interests: The authors state that the study was conducted without any commercial or financial relationships that could be interpreted as a conflict of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Parents' psychological stress during the perinatal and neonatal periods continues to increase in an environment of declining birthrates, aging populations, and shrinking family sizes. The increase in child abuse and neglect cases, most likely by inexperienced and insufficiently knowledgeable parents, necessitates education on childcare and intervention techniques in nursing and midwifery training. In particular, attachment formation early in life between mother and infant is crucial. To accurately teach sensitive and comprehensive information on intervention techniques for mother-child attachment formation, realistic videos, and educational materials are necessary. Although pseudoeducational materials are available, they might be limited in explaining complex realism, particularly to support breastfeeding that involves both parents and child and that encourages interaction between the two. In a previous study in a common marmoset (Callithrix jacchus) model, we experimentally controlled infant feeding and nurturing through 24 h of constant sensing and collected 1 month of quantitative data on psychological indices that possibly translated to psychological development. Age-dependent dynamic visualization of these data by multivariate analyses inferred causal relationships between early parental feeding and psychobiological rhythm formation. In the same primate model, we identified a spontaneous case of breastfeeding failure in which the father inhibited his neonatal infant's feeding and the mother appeared to abandon nurturing, leading to clinically significant weight loss in the infant. Thus, we explored intervention techniques to promote mother-infant interaction. The mother was trained to allow the infant to spontaneously explore her breast. Initially, the mother refused to display the feeding pose potentially due to pain associated with breast engorgement. Massage was used to soften the breast and feeding was reintroduced. We hypothesize that activation of instinctive attachment formation mechanisms by encouraging spontaneity in each parent and child is the key to successful feeding intervention.

Background: Early treatment may improve the prognosis of acute encephalopathy (AE). However, methods for early diagnosis have not yet been established. In this paper, we examined methods for the early diagnosis of AE., Methods: We extracted data on patients with febrile status epilepticus from the electronic medical records in our department between March 2016 and April 2021. Among these, 79 patients who underwent continuous electroencephalography (cEEG) were included in this study. Patients who exhibited psychomotor retardation or abnormal brain magnetic resonance imaging findings were assigned to Group E (n = 20), and the remaining patients were the control group (Group C, n = 59). The following tests were compared retrospectively between these two groups on admission: cEEG, serum hepatic function tests, and blood coagulation tests., Results: The percentage of patients who exhibited high-amplitude slow waves or flat waves on cEEG at the time of admission was statistically significantly higher in Group E than in Group C (p < 0.01). Moreover, the percentage of patients whose high-amplitude slow waves or flat brain waves on admission disappeared within 6 h after an initial episode of convulsion was statistically significantly lower in Group E than in Group C (p < 0.01). Furthermore, all the items in the coagulation and the hepatic function tests were statistically significantly different in Group E from those in Group C (p < 0.05)., Conclusion: These results showed that cEEG together with hepatic function and coagulation tests may be useful for the differential diagnosis of AE., (© 2023 Japan Pediatric Society.)

Background: The consumption of Jerusalem artichoke has multiple beneficial effects against diabetes and obesity., Objective: The aim of this study was to determine the effect of a single administration of Jerusalem artichoke tubers on postprandial glycemia and the concentrations of incretin hormones in humans., Method: Grated Jerusalem artichoke was administered prior to a meal (Trial 1; white rice for prediabetic participants, n = 10). Dose-dependent effect of Jerusalem artichoke (Trial 2; white rice for prediabetic participants, n = 4) and effect prior to the fat-rich meal were also investigated (Trial 3; healthy participants, n = 5) in this pilot study. Circulating glucose, insulin, triglyceride, glucagon, active glucagon-like peptide-1 (GLP-1), and active glucose-dependent insulinotropic polypeptide (GIP) concentrations were subsequently measured in all the trials., Results: Jerusalem artichoke significantly reduced the glucose and GIP concentrations after the consumption of either meal in Trial 1 and Trial 3, whereas there were no differences in the insulin, glucagon, and active GLP-1 concentrations. Also, there was no significant difference in the triglyceride concentration after the ingestion of the fat-rich meal in Trial 3. The glucose and GIP-lowering effects were dose-dependent, and the consumption of at least 100 g of Jerusalem artichoke was required to have these effects in Trial 2., Conclusion: This study demonstrates that a single administration of Jerusalem artichoke tubers reduces postprandial glucose and active GIP concentrations in prediabetic and healthy individuals., (© 2022 Hirokazu Takahashi et al.)

Background: Taro (Colocasia esculenta cv. Daikichi) is believed to be one of the earliest cultivated tuber crops and it is a staple food in many parts of the world. The mother corm and side cormels (daughter and granddaughter tubers) form the major consumed parts; however, the former is rarely preferred. Taro is mainly cultivated using either unflooded or flooding cultivation, under dryland-rainfed and wetland-irrigated conditions, respectively. Although flooding cultivation has several advantages, such as lower risk of diseases, weeds, and insect pests, contributing to increased tuber yield, its effects on the quality characteristics of the tubers are largely unknown. In this study, the effects of controlled flooding cultivation on the quality of mother corm and side cormels were investigated. Their taste, color, physical properties, antioxidant activity, and starch, oxalic acid, nitrate ion, arabinogalactan (AG)/AG protein (AGP), γ-aminobutyric acid (GABA), and total polyphenol content was compared with those under unflooded cultivation., Results: Flooding cultivation increased polyphenol levels and antioxidant activity and decreased oxalate, nitrate ion, GABA, and AG/AGP levels. Flooding cultivation also reduced the harshness and increased the hardness and stickiness of steamed mother corm paste, generally discarded under unflooded cultivation, thus rendering it suitable for consumption., Conclusion: Controlled flooding cultivation has economic advantages and the potential to improve the quality of cultivated taro. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Objective: Self-stigma is the internalization of negative public attitudes and is often experienced by patients with epilepsy (PWE). Greater self-stigma is associated with lower self-esteem and hinders therapeutic behavior. The study aims were to develop the Epilepsy Self-Stigma Scale (ESSS) to assess self-stigma in PWE and to examine the scale's reliability and validity., Methods: We created a test scale based on items from an existing stigma scale and the results of a previous qualitative analysis we conducted. We recruited 200 outpatients from departments specializing in epilepsy (psychiatry, neurology, and pediatric neurology) at four facilities in Tokyo and Saitama prefecture, Japan, between September and December 2020. Participants also completed the Rosenberg Self-Esteem Scale (RSES) and Beck Depression Inventory (BDI-II)., Results: Questionnaires were returned from 102 participants (response rate: 51%). After excluding two participants with incomplete questionnaires, data for 100 participants were analyzed (53 women, 47 men; mean age [standard deviation]: 39.86 [17.45] years). Exploratory factor analysis extracted eight items loading on three factors: internalization of stigma, societal incomprehension, and confidentiality. Cronbach's α for all items and each factor demonstrated acceptable internal consistency (α = 0.76-0.87). Test-retest reliability was confirmed using data from 21 participants who completed the scale twice (r = 0.72 to 0.90). ESSS total scores and subscale scores correlated with RSES and BDI-II scores (r = -0.30 to 0.55). The ESSS demonstrated substantial constructive validity. However, total scores did not significantly correlate with objective physician assessment of self-stigma., Significance: The results showed that the eight-item ESSS has high reliability and validity. This scale could facilitate the examination of factors associated with self-stigma in PWE, which could inform the development of effective interventions for reducing stigma., (© 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Thrombosis is a characteristic complication in coronavirus disease 2019 (COVID-19). Since coagulopathy has been observed over the entire clinical course, thrombosis might be a clue to understanding the specific pathology in COVID-19. Currently, there is limited epidemiological data of COVID-19-associated thrombosis in the Japanese population and none regarding variant strains of SARS-CoV-2. Here, we elucidate the risk factors and the pattern of thrombosis in COVID-19 patients. Methods: The patients consecutively admitted to Tokyo Medical and Dental University Hospital with COVID-19 were retrospectively analyzed. SARS-CoV-2 variants of concern/interest (VOC/VOI) carrying the spike protein mutants E484K, N501Y, or L452R were identified by PCR-based analysis. All thrombotic events were diagnosed by clinical symptoms, ultrasonography, and/or radiological tests. Results: Among the 516 patients, 32 patients experienced 42 thromboembolic events. Advanced age, severe respiratory conditions, and several abnormal laboratory markers were associated with the development of thrombosis. While thrombotic events occurred in 13% of the patients with a severe respiratory condition, those events still occurred in 2.5% of the patients who did not require oxygen therapy. Elevated D-dimer and ferritin levels on admission were independent risk factors of thrombosis (adjusted odds ratio 9.39 and 3.11, 95% confidence interval 2.08-42.3, and 1.06-9.17, respectively). Of the thrombotic events, 22 were venous, whereas 20 were arterial. While patients with thrombosis received anticoagulation and antiinflammatory therapies with a higher proportion, the mortality rate, organ dysfunctions, and bleeding complications in these patients were higher than those without thrombosis. The incidence of thrombosis in COVID-19 became less frequent over time, such as during the replacement of the earlier strains of SARS-CoV-2 by VOC/VOI and during increased use of anticoagulatory therapeutics. Conclusion: This study elucidated that elevated D-dimer and ferritin levels are useful biomarkers of thrombosis in COVID-19 patients. The comparable incidence of arterial thrombosis with venous thrombosis and the development of thrombosis in less severe patients required further considerations for the management of Japanese patients with COVID-19. Further studies would be required to identify high-risk populations and establish appropriate interventions for thrombotic complications in COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Oba, Hosoya, Amamiya, Mitsumura, Kawata, Sasaki, Kamiya, Yamamoto, Ando, Shimada, Shirai, Okamoto, Tateishi, Endo, Aiboshi, Nosaka, Yamanouchi, Ugawa, Nagaoka, Oi, Tao, Maejima, Tanaka, Tanimoto, Takeuchi, Tohda, Hirakawa, Sasano, Arai, Otomo, Miyazaki and Yasuda.)

Objective: The current study aimed to identify and compare the clinical characteristics of human parechovirus type 3 (HPeV3)-associated acute encephalitis/encephalopathy (HPeV3E/E) between infants with abnormal brain magnetic resonance imaging (MRI) findings (typical, or MRI-positive HPeV3E/E) and those with MRI-negative findings (MRI-negative HPeV3E/E)., Methods: This is a retrospective study on patients with HPeV3 infection, and a two-step questionnaire survey performed on 837 hospitals in Japan between 2014 and 2016., Results: We identified 240 infants with HPeV3 infection, of which 34 had been clinically-diagnosed HPeV3E/E (cHPeV3E/E). However, detailed clinical data were provided by 32 of the 34 patients. Among these 32, 23 had undergone MRI and were categorized into two groups, MRI-positive (n = 17) and -negative (n = 6). There were no significant intergroup differences in clinical lab results or symptoms, except for gastrointestinal symptoms that were only present in the MRI-negative patients. The MRI-positive group showed white matter involvement on brain MRI during the acute phase, and 8 patients presented with lesions on follow-up MRI. Furthermore, 4 (50%) of the 8 patients had neurological sequelae., Conclusion: Clinical characteristics of cHPeV3E/E patients with and without lesions on brain MRI showed no significant differences. Therefore, considering the difficulty in distinguishing febrile infants with cHPeV3E/E from those with a sepsis-like illness, during an HPeV3 infection epidemic, it is imperative to frequently perform brain MRI in febrile infants presenting with severe disease for the early diagnosis of HPeV3E/E presenting with brain lesions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

The cardinal symptom of acute encephalopathy is impairment of consciousness of acute onset during the course of an infectious disease, with duration and severity meeting defined criteria. Acute encephalopathy consists of multiple syndromes such as acute necrotizing encephalopathy, acute encephalopathy with biphasic seizures and late reduced diffusion and clinically mild encephalitis/encephalopathy with reversible splenial lesion. Among these syndromes, there are both similarities and differences. In 2016, the Japanese Society of Child Neurology published 'Guidelines for the Diagnosis and Treatment of Acute Encephalopathy in Childhood', which made recommendations and comments on the general aspects of acute encephalopathy in the first half, and on individual syndromes in the latter half. Since the guidelines were written in Japanese, this review article describes extracts from the recommendations and comments in English, in order to introduce the essence of the guidelines to international clinicians and researchers., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

The use of home-based image sensors for biological and environmental monitoring provides novel insight into health and development but it is difficult to evaluate people during their normal activities in their home. Therefore, we developed a low-cost infrared (IR) technology-based motion, location, temperature and thermal environment detection system that can be used non-invasively for long-term studies in the home environment. We tested this technology along with the associated analysis algorithm to visualize the effects of parental care and thermal environment on developmental state change in a non-human primate model, the common marmoset ( Callithrix jacchus ). To validate this system, we first compared it to a manual analysis technique and we then assessed the development of circadian rhythms in common marmosets from postnatal day 15-45. The semi-automatically tracked biological indices of locomotion velocity (BV) and body surface temperature (BT) and the potential psychological index of place preference toward the door (BD), showed age-dependent shifts in circadian phase patterns. Although environmental variables appeared to affect circadian rhythm development, principal component analysis and signal superimposing imaging methods revealed a novel phasic pattern of BD-BT correlation day/night switching in animals older than postnatal day 38 (approximately equivalent to one year of age in humans). The origin of this switch was related to earlier development of body temperature (BT) rhythms and alteration of psychological behavior rhythms (BD) around earlier feeding times. We propose that this cost-effective, inclusive sensing and analytic technique has value for understanding developmental care conditions for which continual home non-invasive monitoring would be beneficial and further suggest the potential to adapt this technique for use in humans.

Background: We previously reported the nationwide, epidemiological data of acute encephalopathy in Japan during 2007-2010. Here we conducted the second national survey of acute encephalopathy during 2014-2017, and compared the results between the two studies to elucidate the trends in the seven years' interval as well as the influence of changes in pediatric viral infections and guidelines for acute encephalopathy in Japan., Methods: The Research Committee on Acute Encephalopathy supported by the Japanese Government sent a questionnaire to 507 hospitals throughout Japan, and collected the responses by mail., Results: A total of 1115 cases from 267 hospitals reportedly had acute encephalopathy during April 2014-June 2017. In this study, the age at onset was younger, the ratios of recently established syndromes, such as acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS), were higher, and the ratio of influenza-associated encephalopathy was lower, than in the previous study. The age at onset of influenza-associated encephalopathy was lower, and that of HHV-6/7-associated encephalopathy higher, compared to the first survey. The outcomes of entire acute encephalopathy remained unchanged., Conclusion: Some of these changes reflected the recent trends of viral infectious diseases including 2009 influenza pandemic, and others the standardization of the diagnosis of acute encephalopathy in Japan., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Holoprosencephaly (HPE) is a congenital malformation with an estimated prevalence of 0.10-6.06 per 10 000 births but with no nationwide data specific to Japan., Methods: This nationwide retrospective questionnaire survey was conducted from 2011 to 2013. All 467 training hospitals for perinatal and neonatal care certified by the Japan Society of Perinatal and Neonatal Medicine were contacted. The birth prevalence rate (BPR) was assessed from the primary survey and clinical characteristics from the secondary survey., Results: We received valid responses from 253 hospitals in the primary survey (54.6%). Of 390 342 live births, 60 were diagnosed with HPE (23 males and 37 females), resulting in an actual BPR of 1.54 per 10 000 live births. The point estimate for HPE cases was 100 (95% confidence interval [CI]: 80.7-120), and the estimated BPR of HPE was calculated to be 0.32 per 10 000 live births (95% CI: 0.26-0.38) based on 3 117 853 live births according to Japanese national statistics during the study period. In the secondary survey, we obtained data for 49 cases (19 males and 30 females). Of these, 20 were alobar (40.8%), 20 were semilobar (40.8%), five were lobar (10.4%), and four were of unknown type. Genetic examination was performed in 37 of the 49 HPE patients and revealed that chromosomes 13, 18, and 7 were affected in eight, six, and four patients, respectively., Conclusions: This is the most extensive survey on holoprosencephaly to date in Japan. The estimated BPR was consistent with that reported in previous research., (© 2019 Japan Pediatric Society.)

There has been long taxonomic debate on mulberry species (genus Morus) because the classification of mulberry species has relied on morphological characteristics. Although attempts for classifying mulberry species using molecular markers have been performed, phylogenetic relationships among diploid mulberry species remain unclear. In this study, we aim to investigate the genetic relationship between 54 diploid mulberry varieties belonging to seven different Morus species (M. alba, M. indica, M. bombycis, M. acidosa, M. latifolia, M. kagayamae, and M. rotundiloba) and one unspecified Morus species ('Enbu') using genome-wide SNP discovery and phylogenetic analysis via double-digest restriction site-associated DNA sequencing (ddRAD-seq). Genome-wide 2229 homozygous SNPs of 54 mulberry varieties in the eight species were identified by ddRAD-seq. Results of the phylogenetic analysis identified only three clear monophyletic clades in two Japanese native species, M. acidosa and M. kagayamae, which are found on different geographically isolated islands and a Thai species, M. rotundiloba, whereas the other species were non-monophyletic. Varieties of M. bombycis, another Japanese native species, were roughly classified into three groups. Of these, two M. bombycis groups were monophyletic with M. acidosa and M. kagayamae, respectively, while another M. bombycis group was not monophyletic. Varieties of M. indica, an Indian native species, were classified into two different monophyletic clades. Of these, one clade was clearly monophyletic with an indigenous variety in Kenya, 'Enbu', while another clade was monophyletic with M. rotundiloba and one M. latifolia variety. There were no clear monophyletic clades within M. alba and M. latifolia varieties, which could be a result of several hybridization events after their introductions from China to Japan. Our results suggested that it was difficult to clearly classify the hybridized mulberry varieties even with genome-wide DNA markers. In addition to phylogenetic analysis, we also evaluated morphological characteristics of mulberry leaves for each variety. The results of morphological evaluation indicated that leaf tip ratio may correlate to genetic difference among the two M. bombycis groups in monophyletic clades and another M. bombycis group in non-monophyletic clades. These results suggested that leaf tip ratio might be used for evaluating hybridization of M. bombycis varieties. Over all, our results may provide new insights into taxonomic debate of mulberry species., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to evaluate the clinical outcomes of implant-retained obturator rehabilitation after maxillectomy, based on quality of life (QOL) and masticatory function., Study Design: The present study included 12 patients who underwent dental implant surgery after maxillectomy. Oral health-related QOL and masticatory function before and after completion of implant-retained obturator rehabilitation were evaluated., Results: Oral Health Impact Profile-Short Form (OHIP-14) scores showed significant differences in the domain for functional limitation (before, 4.08 ± 2.47; after, 1.33 ± 0.98; P < .01); physical pain (before, 2.75 ± 2.05; after, 0.42 ± 0.51; P < .01); physical disability (before, 3.24 ± 2.11; after, 1.33 ± 1.30; P < .01), psychological disability (before, 3.83 ± 2.48; after, 1.67 ± 2.50; P < .01); social disability (before, 2.17 ± 1.75; after, 1.08 ± 1.38; P < .05); handicap (before, 3.17 ± 1.90; after, 1.08 ± 1.00; P < .01); and total score (before, 22.41 ± 10.17; after, 8.83 ± 6.82; P < .01) Furthermore, masticatory function score was significantly higher after completing implant-retained obturator rehabilitation (before, 38.75 ± 22.97; after, 69.17 ± 21.41; P < .01)., Conclusions: Implant-retained obturator rehabilitation contributed to improved masticatory function and oral health-related QOL after maxillectomy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The catechin content in green tea leaves varies according to cultivation conditions such as intensity of solar radiation, temperature, and precipitation, and thus, there is ambiguity about the best harvest time for obtaining optimal functional effects. In this study, the Yabukita (ordinary) and Benifuki varieties, which contain methylated catechin, were used to determine the difference in green tea catechins according to harvest times and tea manufacturing processes. Caffeine determination was also carried out to provide information about green tea intake for all age-groups of children and pregnant women. Determining the quantity of each catechin was difficult because of degradation, polymerization, and isomerization that had occurred during heat-drying in the refining process. In addition, the absorption of catechin compounds was tested using miniature swine because of their functional and physiological similarity to humans. Benifuki tea leaves contained epigallocatechin-3-(3"-O-methyl) gallate (EGCg3"Me) instead of epigallocatechin-3-(4"-O-methyl) gallate (EGCg4"Me). However, EGCg4"Me was detected during the entire intake period, but EGCg3"Me was not detected in the blood of miniature swine fed Benifuki tea. It is possible that the position of the methyl group was modified by the pig metabolism. Furthermore, caffeine from both Yabukita and Benifuki tea varieties was found to be easily accumulated in miniature swine. These results suggest that nonrefined September-October picking tea (autumn and winter tea) of the Benifuki variety is preferable over the Yabukita variety for consumption by children and pregnant women owing to its lower caffeine content and higher content of methylated catechin., Competing Interests: The authors declare that they do not have any conflict of interest.

Background: Two recent large randomized controlled trials did not show the superiority of high-frequency oscillatory ventilation (HFOV) in adults with ARDS. These two trials had differing results, and possible causes could be the different oscillators used and their different settings, including inspiratory time % (IT%). The aims of this study were to obtain basic data about the ventilation characteristics in two adult oscillators and to elucidate the effect of the oscillator and IT% on ventilation efficiency., Methods: The Metran R100 or SensorMedics 3100B was connected to an original lung model internally equipped with a simulated bronchial tree. The actual stroke volume (aSV) was measured with a flow sensor placed at the Y-piece. Carbon dioxide (CO 2 ) was continuously insufflated into the lung model ([Formula: see text]CO 2 ), and the partial pressure of CO 2 (PCO 2 ) in the lung model was monitored. Alveolar ventilation ([Formula: see text]A; L/min) was estimated as [Formula: see text]CO 2 divided by the stabilized value of PCO 2 . [Formula: see text]A was evaluated with several stroke volume settings in the R100 (IT = 50%) or several airway pressure amplitude settings in the 3100B (IT = 33%, 50%) at a frequency of 6 and 8 Hz, a mean airway pressure of 25 cmH 2 O, and a bias flow of 30 L/min. Assuming that [Formula: see text]A = frequency a  × aSV b , values of a and b were determined. Ventilation efficiency was calculated as [Formula: see text]A divided by actual minute ventilation., Results: The relationship between aSV and [Formula: see text]A or ventilation efficiency were different depending on the oscillator and IT%. The values of a and b were 0 < a < 1 and 1 < b < 2 and were different for three conditions at both frequencies. [Formula: see text]A and ventilation efficiency were highest with R100 (IT = 50%) and lowest with 3100B (IT = 33%) for high aSV ranges at both frequencies., Conclusions: In this lung model study, ventilation characteristics were different depending on the oscillator and IT%. Ventilation efficiency was highest with R100 (IT = 50%) and lowest with 3100B (IT = 33%) for high aSV ranges.

Background: Bias flow (BF) is essential to maintain mean airway pressure (MAP) and to washout carbon dioxide (CO 2 ) from the oscillator circuit during high-frequency oscillatory ventilation (HFOV). If the BF rate is inadequate, substantial CO 2 rebreathing could occur and ventilation efficiency could worsen. With lower ventilation efficiency, the required stroke volume (SV) would increase in order to obtain the same alveolar ventilation with constant frequency. The aim of this study was to assess the effect of BF rate on ventilation efficiency during adult HFOV., Methods: The R100 oscillator (Metran, Japan) was connected to an original lung model internally equipped with a simulated bronchial tree. The actual SV was measured with a flow sensor placed at the Y-piece. Carbon dioxide (CO 2 ) was continuously insufflated into the lung model ([Formula: see text]CO 2 ), and the partial pressure of CO 2 (PCO 2 ) in the lung model was monitored. Alveolar ventilation ([Formula: see text]A) was estimated as [Formula: see text]CO 2 divided by the stabilized value of PCO 2 . [Formula: see text]A was evaluated by setting SV from 80 to 180 mL (10 mL increments, n = 5) at a frequency of 8 Hz, a MAP of 25 cmH 2 O, and a BF of 10, 20, 30, and 40 L/min (study 1). Ventilation efficiency was calculated as [Formula: see text]A divided by the actual minute volume. The experiment was also performed with an actual SV of 80, 100, and 120 mL and a BF from 10 to 60 L/min (10 L/min increments: study 2)., Results: Study 1: With the same setting SV, the [Formula: see text]A with a BF of 20 L/min or more was significantly higher than that with a BF of 10 L/min. Study 2: With the same actual SV, the [Formula: see text]A and the ventilation efficiency with a BF of 30 L/min or more were significantly higher than those with a BF of 10 or 20 L/min., Conclusions: Increasing BF up to 30 L/min or more improved ventilation efficiency in the R100 oscillator.

BACKGROUND Psoriasis is known as the most frequent disease treated by long-term topical steroids. It is also known that patients with thick, chronic plaques require the highest potency topical steroids. However, the treatment is limited to up to four weeks due to risk of systemic absorption. CASE REPORT An 80-year-old man was diagnosed with type 2 diabetes 16 years before, and was being administered insulin combined with alpha glucosidase inhibitor. He was diagnosed with plaque psoriasis and his oral steroid treatment was switched to topical steroid treatment due to lack of improvement and poorly controlled blood glucose level. The hypoglycemic events improved after the psoriatic lesions improved. CONCLUSIONS Control of blood glucose level is difficult at the very beginning of topical steroid treatment for psoriasis especially if a patient is receiving insulin treatment. Intense monitoring of blood glucose level during initiation of topical steroid treatment is necessary to prevent unfavorable complications.

Background: This study aimed to clarify the characteristics of acute encephalopathic episodes in patients with congenital adrenal hyperplasia (CAH), which we termed "CAH-associated encephalopathy (CAHE).", Methods: This retrospective study was conducted using a questionnaire as a nationwide survey of patients with CAH with acute encephalopathy and related episodes., Results: Fifteen patients were recruited on the bases of clinical data that supported a diagnosis of CAHE. Fourteen patients displayed seizures at onset, and 12 patients exhibited refractory seizures. Deep coma lasting >24h was noted in 12 patients. Neuroimaging studies revealed some heterogeneous features. Diffuse or focal edematous lesions in the cerebrum, which produce high signal intensity on diffusion-weighted magnetic resonance imaging or low density on computer tomography, were found in the acute period in all 15 patients. In the chronic period, 14 patients survived, 11 of whom had some degree of neurological sequelae. Moreover, various degrees of cerebral shrinkage were observed in 11 of 14 surviving patients. Surprisingly, there were no abnormal neuroimaging findings in the basal ganglia, brainstem, and cerebellum in any patient., Conclusion: Our results indicated that patients with CAH have a risk of developing CAHE, and thus, they should be followed closely because not only status epilepticus or deep coma but also minor symptoms, such as fever and nausea, may lead to CAHE. Because CAHE may feature some heterogeneous encephalopathic episodes, further validation is needed to clarify its etiology., (Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Neurodevelopmental disorders (NDDs) are highly prevalent and severely debilitating brain illnesses caused by aberrant brain growth and development. Resulting in cognitive, social, motor, language and affective disabilities, common NDDs include autism spectrum disorder (ASD), intellectual disability, communication/speech disorders, motor/tic disorders and attention deficit hyperactivity disorder. Affecting neurogenesis, glia/neuronal proliferation and migration, synapse formation and myelination, aberrant neural development occurs over a substantial period of time. Genetic, epigenetic, and environmental factors play a key role in NDD pathogenesis. Animal models are an indispensable tool to study NDDs. Paralleling clinical findings, we comprehensively evaluate various preclinical tests and models which target key (social, cognitive, motor) neurobehavioral domains of ASD and other common NDDs. Covering both traditional (rodent) and alternative NDD models, we outline the emerging areas of research and emphasize how preclinical models play a key role in gaining translational and mechanistic insights into NDDs and their therapy., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Chloramphenicol (CP) is recently one of the rarely-used antibiotics. In this study, we present four patients with intractable bacterial meningitis, who were successfully treated with CP and discuss the therapeutic indications of CP in these pediatric cases. The patients were diagnosed as bacterial meningitis at the ages ranging from 2 months to 1 year and 4 months. The causative organisms found in three of the patients were H. influenzae and in the fourth patient, S. pneumoniae. According to the microbial sensitivity tests, these organisms were highly sensitive to antibiotics including ceftriaxone, meropenem and/or panipenem/betamipron. Treatment with these antibiotics was initially effective; however, recurrences of meningitis appeared in all patients. Administration of CP (100 mg/kg/day) started between the 11th and the 58th days, and was continued for 9 days up to 19 days. Their fever had disappeared within four days after the administration of CP, and it was confirmed that all patients completely recovered from meningitis. Two of the patients developed a mild degree of anemia, but soon recovered after the discontinuation of CP. None of them had neurological sequela. We recommend CP as one of the choices for the treatment of intractable bacterial meningitis.

Introduction: Neurodevelopmental disorders (NDDs) are common and severely debilitating. Their chronic nature and reliance on both genetic and environmental factors makes studying NDDs and their treatment a challenging task., Areas Covered: Herein, the authors discuss the neurobiological mechanisms of NDDs, and present recommendations on their translational research and therapy, outlined by the International Stress and Behavior Society. Various drugs currently prescribed to treat NDDs also represent a highly diverse group. Acting on various neurotransmitter and physiological systems, these drugs often lack specificity of action, and are commonly used to treat multiple other psychiatric conditions. There has also been relatively little progress in the development of novel medications to treat NDDs. Based on clinical, preclinical and translational models of NDDs, our recommendations cover a wide range of methodological approaches and conceptual strategies., Expert Opinion: To improve pharmacotherapy and drug discovery for NDDs, we need a stronger emphasis on targeting multiple endophenotypes, a better dissection of genetic/epigenetic factors or "hidden heritability," and a careful consideration of potential developmental/trophic roles of brain neurotransmitters. The validity of animal NDD models can be improved through discovery of novel (behavioral, physiological and neuroimaging) biomarkers, applying proper environmental enrichment, widening the spectrum of model organisms, targeting developmental trajectories of NDD-related behaviors and comorbid conditions beyond traditional NDDs. While these recommendations cannot be addressed all in once, our increased understanding of NDD pathobiology may trigger innovative cross-disciplinary research expanding beyond traditional methods and concepts.

Educational treatment to support social development of children with autism spectrum disorder (ASD) is an important topic in developmental psychiatry. However, it remains difficult to objectively quantify the socio-emotional development of ASD children. To address this problem, we developed a novel analytical method that assesses subjects' complex behaviors using multivariate analysis, 'Behavior Output analysis for Quantitative Emotional State Translation' (BOUQUET). Here, we examine the potential for psycho-cognitive ASD therapy based on comparative evaluations of clinical (human) and experimental (animal) models. Our observations of ASD children (vs. their normally developing siblings) and the domestic chick in socio-sensory deprivation models show the importance of unimodal sensory stimulation, particularly important for tactile- and auditory-biased socialization. Identifying psycho-cognitive elements in early neural development, human newborn infants in neonatal intensive care unit as well as a New World monkey, the common marmoset, also prompted us to focus on the development of voluntary movement against gravity. In summary, striking behavioral similarities between children with ASD and domestic chicks' socio-sensory deprivation models support the role of multimodal sensory-motor integration as a prerequisite step for normal development of socio-emotional and psycho-cognitive functions. Data obtained in the common marmoset model also suggest that switching from primitive anti-gravity reflexes to complex voluntary movement may be a critical milestone for psycho-cognitive development. Combining clinical findings with these animal models, and using multivariate integrative analyses may facilitate the development of effective interventions to improve social functions in infants and in children with neurodevelopmental disorders.

We present characteristic magnetic resonance imaging (MRI) features in a pediatric female patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Muscle weakness developed at 8 years old and fluctuated during the clinical course over 7 years. Electrophysiological studies showed a demyelination pattern with moderately delayed nerve conduction velocity, as well as dispersion phenomenon. MRI showed marked changes in thickening of the spinal nerve roots and their peripheral nerves in the lumber and brachial plexuses, as well as in the bilateral trigeminal nerves. It is suggested that these MRI features are characteristic and strongly supportive of the diagnosis of CIDP with a prolonged clinical course., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

We report a 4-year-old boy with generalized seizures with abrupt falling and unresponsive staring provoked by somatosensory stimuli of the face. Ictal manifestation comprised a sudden fall immediately after wiping the face, followed by unresponsive staring for around 10 seconds, during which time the video-EEG recorded paroxysmal 3-Hz diffuse spike-wave complexes, which were followed by high-voltage 3.5 to 4-Hz delta wave discharges, predominantly appearing in the bilateral frontal areas. Seizures were not controlled by clonazepam, valproate or levetiracetam, but were successfully treated with lamotrigine added to valproate. This type of generalized reflex seizure has so far not been reported in the literature. [Published with video sequence].

Staphylococcus lugdunensis is a known pathogen of infective endocarditis, but not of urinary tract infection. We report a previously healthy neonate without congenital anomalies of the kidney and urinary tract who developed urinary tract infection due to Staphylococcus lugdunensis, illustrating that Staphylococcus lugdunensis can cause urinary tract infection even in those with no urinary tract complications., (© 2015 Japan Pediatric Society.)

As a diurnal experimental primate, the common marmoset (Callithrix jacchus) has recently contributed to numerous kinds of studies of neurobiological psychiatry as an essential pre-clinical model. The marmoset matures sexually within one or two years after birth. Thus, we can observe how the primate learns and develops psycho-cognitive functions through experiences in experimental environment for a much shorter period compared to that of humans. Longer daylight exposure may affect psychological development of children. In our research, we focus on raising marmosets under constant daylight from birth until various ages. In order to quantitatively evaluate the development of higher-ordered psychological functions, we designed a system of socio-behavioral tests and multivariate correlation analysis methods based on principal component analysis. With reference to the call and typical body movement expressed during a particular social context, we statistically inferred the emotional features of the subjects. In the current literature, we review our published results showing increased alert behaviors by constant light, and then, attempted to extend our additional analysis to seek age-dependent susceptibility to constant light. We then present the neurobiological mechanisms with reference to previous research reports. The current review suggests possible existence of a susceptible period earlier than three to five month-old in the environment-induced developmental disorder model, supposedly like attention deficit hyperactive disorders (ADHD) or oppositional defiant disorder (ODD)., (Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Behaviour is one of the most powerful objective signals that connotes psychological functions regulated by neuronal network systems. This study searched for simple behaviours using smartphone sensors with three axes for measuring acceleration, angular speed and direction. We used quantitative analytic methodology of pattern recognition for work contexts, individual workers and seasonal effects in our own longitudinally recorded data. Our 13 laboratory members were involved in the care of common marmosets and domestic chicks, which lived in separate rooms. They attached a smartphone to their front waist-belts during feeding and cleaning in five care tasks. Behavioural characteristics such as speed, acceleration and azimuth, pitch, and roll angles were monitored. Afterwards, participants noted subjective scores of warmth sensation and work efficiency. The multivariate time series behavioral data were characterized by the subjective scores and environmental factors such as room temperature, season, and humidity, using the linear mixed model. In contrast to high-precision but stress-inducing sensors, the mobile sensors measuring daily behaviours allowed us to quantify the effects of the psychological states and environmental factors on the behavioural traits., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Multidimensional diagnosis plays a central role in infant developmental care, which leads to the prediction of future disabilities. Information consolidated from objective and subjective, early and late, central and peripheral data may reveal neuro-pathological mechanisms and realize earlier and more precise preventive intervention. In the current study, we retrospectively searched correlating factors to the following neurological and behavioral development of 'Head Control' and 'Roll Over' using multivariate correlation analysis of differ-ent diagnostic domains over age, subject/object information of the patients who were previously admitted in our neonatal intensive care unit (NICU) and could be developmentally followed up in our outpatient clinic. Based on the hematologic and biochemical data, MRI brain anatomy during NICU hospitalization, we characterized all the acquired data distribution from 31 infants with either 'appeared neurologically normal (ANN, n = 21)’ or 'appeared neurologically abnormal (ANA, n = 10)’ pro tempore, with a physician's clinical judgment before discharge. Besides single factor comparisons between ANN and ANA, we examined their development difference by using the multidimensional information processing, principal component analysis (PCA). The diagnostic predictors of neuro-behavioral development were selected by regression analysis with variable selection. It resulted that hematological and brain anatomical factors seemed correlated to both ‘Head Control’ and ‘Roll Over’. This report suggested certain possibility of the cross-domain translational approach between subjective and objective developmental information through multivariate analyses, with candidate markers preliminarily to be evaluated in further studies., (Copyright © 2014 The Authors. Published by Elsevier B.V.)