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  1. Article: Role of the Gut Microbiota in Regulating Non-alcoholic Fatty Liver Disease in Children and Adolescents.

    Tokuhara, Daisuke

    Frontiers in nutrition

    2021  Volume 8, Page(s) 700058

    Abstract: Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in children and adolescents. Although obesity is the leading cause of NAFLD, the etiologies of NAFLD are multifactorial (e.g., high-fat diet, a lack of exercise, ... ...

    Abstract Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in children and adolescents. Although obesity is the leading cause of NAFLD, the etiologies of NAFLD are multifactorial (e.g., high-fat diet, a lack of exercise, gender, maternal obesity, the antibiotic use), and each of these factors leads to dysbiosis of the gut microbiota community. The gut microbiota is a key player in the development and regulation of the gut mucosal immune system as well as the regulation of both NAFLD and obesity. Dysbiosis of the gut microbiota promotes the development of NAFLD
    Language English
    Publishing date 2021-06-25
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2776676-7
    ISSN 2296-861X
    ISSN 2296-861X
    DOI 10.3389/fnut.2021.700058
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Challenges in developing mucosal vaccines and antibodies against infectious diarrhea in children.

    Tokuhara, Daisuke

    Pediatrics international : official journal of the Japan Pediatric Society

    2018  Volume 60, Issue 3, Page(s) 214–223

    Abstract: Infectious diarrhea in children can be life-threatening and imposes a large economic burden on healthcare systems, therefore more effective prophylactic and therapeutic drugs are needed urgently. Because most of the pathogens responsible for childhood ... ...

    Abstract Infectious diarrhea in children can be life-threatening and imposes a large economic burden on healthcare systems, therefore more effective prophylactic and therapeutic drugs are needed urgently. Because most of the pathogens responsible for childhood diarrhea infect the gastrointestinal mucosa, providing protective immunity at the mucosal surface is an ideal way to control pathogen invasion and toxic activity. Mucosal (e.g. oral, nasal) vaccines are superior to systemic (subcutaneous or intramuscular) vaccination for conferring both mucosal and systemic pathogen-specific immune responses. Therefore, great efforts has been focused on the development of cost-effective mucosal vaccines for the past 50 years. Recent progress in plant genetic engineering has revolutionized the production of inexpensive and safe recombinant vaccine antigens. For example, rice plant biotechnology has facilitated the development of a cold-chain-free rice-based oral subunit vaccine against Vibrio cholerae. Furthermore, this technology has led to the creation of a rice-based oral antibody for prophylaxis and treatment of rotavirus gastroenteritis. This review summarizes current perspectives regarding the mucosal immune system and the development of mucosal vaccines and therapeutic antibodies, particularly rice-based products, and discusses future prospects regarding mucosal vaccines for children.
    MeSH term(s) Antibodies/administration & dosage ; Child ; Diarrhea/immunology ; Humans ; Immunity, Mucosal/immunology ; Intestinal Mucosa/immunology ; Vaccination/methods ; Vaccines/immunology
    Chemical Substances Antibodies ; Vaccines
    Language English
    Publishing date 2018-03-02
    Publishing country Australia
    Document type Journal Article ; Review
    ZDB-ID 1470376-2
    ISSN 1442-200X ; 1328-8067
    ISSN (online) 1442-200X
    ISSN 1328-8067
    DOI 10.1111/ped.13497
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Cord Blood-Based Approach to Assess Candidate Vaccine Adjuvants Designed for Neonates and Infants.

    Tokuhara, Daisuke / Hikita, Norikatsu

    Vaccines

    2021  Volume 9, Issue 2

    Abstract: Neonates and infants are particularly susceptible to infections, for which outcomes tend to be severe. Vaccination is a key strategy for preventing infectious diseases, but the protective immunity achieved through vaccination typically is weaker in ... ...

    Abstract Neonates and infants are particularly susceptible to infections, for which outcomes tend to be severe. Vaccination is a key strategy for preventing infectious diseases, but the protective immunity achieved through vaccination typically is weaker in infants than in healthy adults. One possible explanation for the poor acquisition of vaccine-induced immunity in infants is that their innate immune response, represented by toll-like receptors, is immature. The current system for developing pediatric vaccines relies on the confirmation of their safety and effectiveness in studies involving the use of mature animals or adult humans. However, creating vaccines for neonates and infants requires an understanding of their uniquely immature innate immunity. Here we review current knowledge regarding the innate immune system of neonates and infants and challenges in developing vaccine adjuvants for those children through analyses of cord blood.
    Language English
    Publishing date 2021-01-27
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines9020095
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Symptomatic esophageal retention of a patency capsule due to extraesophageal compression from pulmonary artery stent grafts.

    Cho, Yuki / Tokuhara, Daisuke

    Pediatrics international : official journal of the Japan Pediatric Society

    2021  Volume 63, Issue 11, Page(s) 1392–1394

    MeSH term(s) Capsule Endoscopy ; Humans ; Intestinal Obstruction ; Pulmonary Artery/diagnostic imaging ; Stents/adverse effects
    Language English
    Publishing date 2021-07-04
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 1470376-2
    ISSN 1442-200X ; 1328-8067
    ISSN (online) 1442-200X
    ISSN 1328-8067
    DOI 10.1111/ped.14624
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Successful retrieval of a foreign body in an infant's right pulmonary artery using the new boomerang loop-snare technique: A case report.

    Kamisako, Atsufumi / Ikoma, Akira / Suzuki, Takayuki / Kakimoto, Nobuyuki / Suenaga, Tomohiro / Tokuhara, Daisuke / Sonomura, Tetsuo

    Radiology case reports

    2024  Volume 19, Issue 5, Page(s) 1965–1969

    Abstract: We report successful percutaneous retrieval of a foreign body located in an infant's right pulmonary artery using the new boomerang loop-snare technique. The case was an 18-month-old girl. A central venous catheter for chemotherapy was inserted from the ... ...

    Abstract We report successful percutaneous retrieval of a foreign body located in an infant's right pulmonary artery using the new boomerang loop-snare technique. The case was an 18-month-old girl. A central venous catheter for chemotherapy was inserted from the right subclavian vein during treatment for myelodysplastic syndrome at another hospital. A postprocedural chest X-ray showed a foreign body in her right lung, and contrast-enhanced computed tomography confirmed the linear foreign body was located in the right pulmonary artery. The patient was transferred to our hospital to retrieve the foreign body. Under cooperation with pediatric cardiologists, a 6 Fr sheath was inserted via the right femoral vein, and a guiding catheter was advanced into the right pulmonary artery. Owing to the risk of vascular injury when using endoscopic forceps, we decided to use the loop-snare technique. We successfully crossed over the foreign body using a steerable microcatheter and a long microguidewire. The microguidewire was reinserted into the guiding catheter, and a loop was created by grasping the end of the wire using a microsnare catheter, which was inserted coaxially within the guiding catheter. By pulling the microsnare catheter, we were able to pull the foreign body into the guiding catheter and successfully retrieved it. There were no complications, such as pulmonary artery injuries or thrombi. The recovered foreign body was a piece of a guidewire. The boomerang loop-snare technique using a small-diameter system is useful for the retrieval of a foreign body in infants.
    Language English
    Publishing date 2024-02-27
    Publishing country Netherlands
    Document type Case Reports
    ZDB-ID 2406300-9
    ISSN 1930-0433
    ISSN 1930-0433
    DOI 10.1016/j.radcr.2024.02.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: [MUCOSAL MULTI-ECOSYSTEM FOR THE PREVENTION AND TREATMENT OF MUCOSAL DISORDERS].

    Tokuhara, Daisuke / Kiyono, Hiroshi

    Arerugi = [Allergy

    2019  Volume 68, Issue 6, Page(s) 675–680

    MeSH term(s) Ecosystem ; Humans ; Mucous Membrane/pathology
    Language Japanese
    Publishing date 2019-08-01
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 974201-3
    ISSN 0021-4884
    ISSN 0021-4884
    DOI 10.15036/arerugi.68.675
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Analysis of cytokine profiles in sera of single and multiple infantile hemangioma.

    Sakata, Mariko / Kunimoto, Kayo / Kawaguchi, Ami / Inaba, Yutaka / Kaminaka, Chikako / Yamamoto, Yuki / Kakimoto, Nobuyuki / Suenaga, Tomohiro / Tokuhara, Daisuke / Jinnin, Masatoshi

    The Journal of dermatology

    2023  Volume 50, Issue 7, Page(s) 906–911

    Abstract: Infantile hemangiomas (IH) are benign vascular tumors that are common in infancy. They vary in growth, size, location, and depth, and although most lesions are relatively small, approximately one fifth of patients have multiple lesions. Risk factors for ... ...

    Abstract Infantile hemangiomas (IH) are benign vascular tumors that are common in infancy. They vary in growth, size, location, and depth, and although most lesions are relatively small, approximately one fifth of patients have multiple lesions. Risk factors for IH include female sex, low birth weight, multiple gestation, preterm birth, progesterone therapy, and family history, but the mechanism that causes multiple lesions is unclear. We hypothesized that blood cytokines are involved as a cause of multiple IHs, and tried to prove this using sera and membrane arrays from patients with single and multiple IHs. Serum samples were obtained from five patients with multiple lesions and four patients with a single lesion, none of which had received any treatment. Serum levels of 20 cytokines were measured using human angiogenesis antibody membrane array. Four of the 20 cytokines (bFGF, IFN-γ, IGF-I, and TGF-β1) were higher in the patients with multiple lesions than in those with single lesion, with statistically significant difference (p < 0.05). Notably, signal for IFN-γ was evident in all cases with multiple IHs, but was absent in cases with single IH. Although not significant, there was mild correlation between IFN-γ and IGF-I (r = 0.64, p = 0.065), and between IGF-I and TGF-β1 (r = 0.63, p = 0.066). bFGF levels were strongly and significantly correlated with the number of lesions (r = 0.88, p = 0.0020). In conclusion, blood cytokines could act as a cause of multiple IHs. This is a pilot study with a small cohort, so further large-scale studies are necessary.
    MeSH term(s) Humans ; Infant, Newborn ; Female ; Infant ; Transforming Growth Factor beta1 ; Hemangioma/pathology ; Insulin-Like Growth Factor I ; Pilot Projects ; Premature Birth ; Cytokines
    Chemical Substances Transforming Growth Factor beta1 ; Insulin-Like Growth Factor I (67763-96-6) ; Cytokines
    Language English
    Publishing date 2023-03-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 800103-0
    ISSN 1346-8138 ; 0385-2407
    ISSN (online) 1346-8138
    ISSN 0385-2407
    DOI 10.1111/1346-8138.16781
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Effects of obesity reduction on transient elastography-based parameters in pediatric non-alcoholic fatty liver disease.

    Isoura, Yoshiharu / Cho, Yuki / Fujimoto, Hiroki / Hamazaki, Takashi / Tokuhara, Daisuke

    Obesity research & clinical practice

    2020  Volume 14, Issue 5, Page(s) 473–478

    Abstract: Aim: To clarify the effects of obesity reduction on non-alcoholic fatty liver disease (NAFLD) in obese children.: Methods: Twenty-six obese pediatric NAFLD patients (median age, 13.0 years; range, 6.4-16.6 years), who underwent obesity management ... ...

    Abstract Aim: To clarify the effects of obesity reduction on non-alcoholic fatty liver disease (NAFLD) in obese children.
    Methods: Twenty-six obese pediatric NAFLD patients (median age, 13.0 years; range, 6.4-16.6 years), who underwent obesity management supported by regular hospital visits and/or hospital admission, were studied to explore how reductions in weight and body mass index (BMI) percentile affected two transient elastography-based parameters: controlled attenuation parameter (CAP) and liver stiffness (LS), which reflect the degree of hepatic fat deposition and liver fibrosis, respectively.
    Results: Univariate analysis revealed that CAP reduction was correlated positively with baseline CAP and reductions in weight and BMI percentile (r = 0.320-0.525), whereas LS reduction was correlated positively with baseline LS and reductions in weight, BMI percentile, aspartate transaminase, and alanine aminotransferase (r = 0.385-0.625). Multivariate analysis revealed that baseline CAP and reduction in weight were significantly associated with CAP reduction, whereas reduction in weight and alanine aminotransferase were significantly associated with LS reduction. Short-term weight control by hospital admission (24.9 ± 9.5 days) provided significantly higher reductions in weight and BMI percentile (both P < 0.001) and was associated with reductions of CAP and LS (P = 0.04 and 0.01) compared with regular hospital visit-supported self-directed weight management (0.9 ± 0.8 years).
    Conclusions: Weight reduction in obese pediatric NAFLD patients resulted in reduced hepatic fat deposition and liver stiffness. Weight control by short-term hospital admission is an alternative approach to regular hospital visit-supported self-directed weight management in NAFLD patients who fail to reduce obesity.
    MeSH term(s) Adolescent ; Alanine Transaminase ; Child ; Elasticity Imaging Techniques ; Humans ; Liver/pathology ; Liver Cirrhosis/pathology ; Non-alcoholic Fatty Liver Disease/therapy ; Pediatric Obesity/pathology ; Pediatric Obesity/therapy ; Weight Loss
    Chemical Substances Alanine Transaminase (EC 2.6.1.2)
    Language English
    Publishing date 2020-09-13
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2274031-4
    ISSN 1878-0318 ; 1871-403X
    ISSN (online) 1878-0318
    ISSN 1871-403X
    DOI 10.1016/j.orcp.2020.08.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: COVID-19 phobia in a boy with undiagnosed autism spectrum disorder: A case report.

    Sakamoto, Shoko / Miyawaki, Dai / Goto, Ayako / Harima, Yuji / Tokuhara, Daisuke / Inoue, Koki

    Medicine

    2021  Volume 100, Issue 22, Page(s) e26233

    Abstract: Rationale: Coronavirus disease 2019 (COVID-19) is affecting mental health profoundly. Previous studies have reported pandemic-related anxiety. Anxiety disorder and autism spectrum disorder (ASD) are common comorbidities. However, there has been no ... ...

    Abstract Rationale: Coronavirus disease 2019 (COVID-19) is affecting mental health profoundly. Previous studies have reported pandemic-related anxiety. Anxiety disorder and autism spectrum disorder (ASD) are common comorbidities. However, there has been no report of any patient with undiagnosed ASD who developed anxiety disorders caused by the COVID-19 pandemic. In this case report, we describe an 8-year-old Japanese boy with undiagnosed ASD who developed COVID-19 phobia, resulting in avoidant restrictive food intake disorder (ARFID).
    Patient concerns: As COVID-19 was highly publicized in the mass media and the risk of droplet infection was emphasized upon, the patient began to fear viral contamination from food, culminating in a refusal to eat or even swallow his saliva. He was admitted to a pediatric medical center in Osaka with life-threatening dehydration and was then referred to our child psychiatry department.
    Diagnosis: We diagnosed the patient with COVID-19 phobia resulting in ARFID. We identified ASD traits from his present social communication skills and developmental history.
    Interventions: We provided psychoeducation of ASD for the parents and administered supportive psychotherapy.
    Outcomes: Shortly after our intervention to relieve his ASD-related anxiety, his dysphagia improved.
    Lessons: Our findings suggest that children with undiagnosed ASD may develop COVID-19 phobia. In these cases, intervention for ASD may be more appropriate than starting treatment for anxiety disorders as the first-line option. COVID-19 is the biggest pandemic in the recent past, and more undiagnosed ASD patients who develop COVID-19 phobia may seek treatment. Clinicians should consider the underlying ASD in these patients and assess their developmental history and present social communication skills.
    MeSH term(s) Autism Spectrum Disorder/complications ; Autism Spectrum Disorder/psychology ; Avoidant Restrictive Food Intake Disorder ; COVID-19/psychology ; Child ; Humans ; Male ; Phobic Disorders/complications ; SARS-CoV-2
    Language English
    Publishing date 2021-06-04
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 80184-7
    ISSN 1536-5964 ; 0025-7974
    ISSN (online) 1536-5964
    ISSN 0025-7974
    DOI 10.1097/MD.0000000000026233
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Intrinsic Control of Surface Immune and Epithelial Homeostasis by Tissue-Resident Gut Stromal Cells.

    Kurashima, Yosuke / Tokuhara, Daisuke / Kamioka, Mariko / Inagaki, Yutaka / Kiyono, Hiroshi

    Frontiers in immunology

    2019  Volume 10, Page(s) 1281

    Abstract: The epithelial layer creates a chemical and physical barrier at the forefront of intestinal mucosa, and immune cells beneath the surface epithelium are poised to react to extrinsic factors, to maintain tissue homeostasis. Importantly, the nexus of ... ...

    Abstract The epithelial layer creates a chemical and physical barrier at the forefront of intestinal mucosa, and immune cells beneath the surface epithelium are poised to react to extrinsic factors, to maintain tissue homeostasis. Importantly, the nexus of epithelial-immune responses at mucosal surfaces is dexterously modulated by intrinsic stromal-mesenchymal cells. First, organogenesis of lymphoid tissues, including Peyer's patches, requires dynamic interplay between lymphoid cells and stromal cells, which have become known as "lymphoid organizers." Second, correct spatiotemporal interaction between these cell populations is essential to generate the infrastructure for gut immune responses. Moreover, immune cells at the intestinal barrier are functionally modulated by stromal cells; one such example is the stromal cell-mediated differentiation of innate immune cells, including innate lymphoid cells and mast cells. Ultimately, mucosal stromal cells orchestrate the destinations of epithelial and immune cells to maintain intestinal immune homeostasis.
    MeSH term(s) Animals ; Epithelial Cells/immunology ; Homeostasis/immunology ; Humans ; Immunity, Innate/immunology ; Intestinal Mucosa/immunology ; Lymphocytes/immunology ; Lymphoid Tissue/immunology ; Mast Cells/immunology ; Stromal Cells/immunology
    Language English
    Publishing date 2019-06-19
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2019.01281
    Database MEDical Literature Analysis and Retrieval System OnLINE

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