Immune-mediated cerebellar ataxias: Clinical diagnosis and treatment based on immunological and physiological mechanisms

Hiroshi Mitoma,Mario manto,Marios Hadjivassiliou 대한파킨슨병및이상운동질환학회 2021 Journal Of Movement Disorders Vol.14 No.1

Since the first description of immune-mediated cerebellar ataxias (IMCAs) by Charcot in 1868, several milestones have been reached in our understanding of this group of neurological disorders. IMCAs have diverse etiologies, such as gluten ataxia, postinfectious cerebellitis, paraneoplastic cerebellar degeneration, opsoclonus myoclonus syndrome, anti-GAD ataxia, and primary autoimmune cerebellar ataxia. The cerebellum, a vulnerable autoimmune target of the nervous system, has remarkable capacities (collectively known as the cerebellar reserve, closely linked to plasticity) to compensate and restore function following various pathological insults. Therefore, good prognosis is expected when immune-mediated therapeutic interventions are delivered during early stages when the cerebellar reserve can be preserved. However, some types of IMCAs show poor responses to immunotherapies, even if such therapies are introduced at an early stage. Thus, further research is needed to enhance our understanding of the autoimmune mechanisms underlying IMCAs, as such research could potentially lead to the development of more effective immunotherapies. We underscore the need to pursue the identification of robust biomarkers.

Critical Thinking and Scientific Writing Skills of Non-Anglophone Medical Students: a Model of Training Course

Edward Barroga,Hiroshi Mitoma 대한의학회 2019 Journal of Korean medical science Vol.34 No.3

There are currently very limited reports on the strengths and weaknesses of Japanese medical students in processing (i.e., searching, reading, synthesizing, writing, editing, refining) and presenting medical content based on scholarly journal articles. We developed and offered a 3-week group independent research course in English as a summer elective named “Improving Medical English Skills and Creating English Medical Content (PPT and video) Based on Medical Journal Articles” to our fourth-year Japanese medical students who follow a 6-year medical curriculum as the target audience. Herein, we describe the specific strengths and weaknesses of 6 students who chose and completed the course. Thereafter, we assessed the possible reasons underlying these weaknesses, pondered on the potential implications of such weaknesses on the critical thinking, logical reasoning, and communication skills of Japanese medical students, and suggested approaches to further enhance these skills. The assessments, implications, and suggestions given may provide medical educators new insights on how to newly organize educational and clinical programs to address such weaknesses, improve searching, reading, writing, editing, and presentation skills, enhance critical thinking and logical reasoning abilities, and gain in-depth knowledge essential for effectively appraising and communicating medical content.

Antioxidant Opuntia ficus-indica Extract Activates AHR-NRF2 Signaling and Upregulates Filaggrin and Loricrin Expression in Human Keratinocytes

Takeshi Nakahara,Chikage Mitoma,Akiko Hashimoto-Hachiya,Masakazu Takahara,Gaku Tsuji,Hiroshi Uchi,Xianghong Yan,Junichi Hachisuka,Takahito Chiba,Hitokazu Esaki,Makiko Kido-Nakahara,Masutaka Furue 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.10

Opuntia ficus-indica (OFI) is a cactus species widely used as an anti-inflammatory, antilipidemic, and hypoglycemic agent. It has been shown that OFI extract (OFIE) inhibits oxidative stress in animal models of diabetes and hepatic disease; however, its antioxidant mechanism remains largely unknown. In this study, we demonstrated that OFIE exhibited potent antioxidant activity through the activation of nuclear factor erythroid 2-related factor 2 (NRF2) and the downstream antioxidant enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), which inhibited the generation of reactive oxygen species in keratinocytes challenged with tumor necrosis factor α or benzo[α]pyrene. The antioxidant capacity of OFIE was canceled in NRF2 knockdown keratinocytes. OFIE exerted this NRF2-NQO1 upregulation through activation of the aryl hydrocarbon receptor (AHR). Moreover, the ligation of AHR by OFIE upregulated the expression of epidermal barrier proteins: filaggrin and loricrin. OFIE also prevented TH2 cytokine-mediated downregulation of filaggrin and loricrin expression in an AHRdependent manner because it was canceled in AHR knockdown keratinocytes. Antioxidant OFIE is a potent activator of AHRNRF2-NQO1 signaling and may be beneficial in treating barrier-disrupted skin disorders.

Improving Scientific Writing Skills and Publishing Capacity by Developing University-Based Editing System and Writing Programs

Edward Barroga,Hiroshi Mitoma 대한의학회 2019 Journal of Korean medical science Vol.34 No.1

Scholarly article writing and publishing in international peer-reviewed journals can become an overwhelming task for many medical, nursing, and healthcare professionals in a university setting, especially in countries whose native language is not English. To help improve their scientific writing skills and publishing capacity, a university-based editing system and writing programs can be developed as educational platforms. These are delivered by a team of specialist editors composed of tenured faculty members who have a strong medical background and extensive experience in teaching courses on medical research, editing, writing, and publishing. For the editing system, the specialist editors provide comprehensive editing, personalized consultation, full editorial support after peer review, guidance with online submissions/resubmissions, and detailed editorial review at different stages of the manuscript writing. In addition, the specialist editors can develop writing programs such as medical writing and editing internships, academic courses in medical writing or research study designs and reporting standards, special interactive lectures and sessions on predatory publishing, seminars on updated editorial guidance of global editorial associations, academic visits on medical writing and editing, medical writing mentoring program, networking programs in scholarly communication, and publication resources in medical writing and scholarly publishing. These editing system and writing programs can serve as integrated platforms for improving scientific writing skills and publishing capacity by providing continuing education in medical writing, editing, publishing, and publication ethics.

Immobilization and volume reduction of heavy metals in municipal solid waste fly ash using nano-size calcium and iron-dispersed reagent

Mallampati, Srinivasa Reddy,Mitoma, Yoshiharu,Simion, Cristian,Lee, Byoung Ho Informa UK (Taylor Francis) 2015 Journal of the Air & Waste Management Association Vol.65 No.10

Dynamic immobilization of simulated radionuclide ¹³³Cs in soil by thermal treatment/vitrification with nanometallic Ca/CaO composites

Mallampati, Srinivasa Reddy,Mitoma, Yoshiharu,Okuda, Tetsuji,Simion, Cristian,Lee, Byeong Kyu Elsevier 2015 JOURNAL OF ENVIRONMENTAL RADIOACTIVITY Vol.139 No.-

<P><B>Abstract</B></P> <P>Although direct radiation induced health impacts were considered benign, soil contamination with <SUP>137</SUP>Cs, due to its long-term radiological impact (30 years half-life) and its high biological availability is of a major concern in Japan in the aftermath of the Fukushima nuclear power plant disaster. Therefore <SUP>137</SUP>Cs reduction and immobilization in contaminated soil are recognized as important problems to be solved using suitable and effective technologies. One such thermal treatment/vitrification with nanometallic Ca/CaO amendments is a promising treatment for the ultimate immobilization of simulated radionuclide <SUP>133</SUP>Cs in soil, showing low leachability and zero evaporation. Immobilization efficiencies were 88%, 95% and 96% when the <SUP>133</SUP>Cs soil was treated at 1200 °C with activated carbon, fly ash and nanometallic Ca/CaO additives. In addition, the combination of nanometallic Ca/CaO and fly ash (1:1) enhanced the immobilization efficiency to 99%, while no evaporation of <SUP>133</SUP>Cs was observed. At lower temperatures (800 °C) the leachable fraction of Cs was only 6% (94% immobilization). Through the SEM–EDS analysis, decrease in the amount of Cs mass percent detectable on soil particle surface was observed after soil vitrified with <I>n</I>Ca/CaO + FA. The <SUP>133</SUP>Cs soil was subjected to vitrified with <I>n</I>Ca/CaO + FA peaks related to Ca, crystalline phases (CaCO<SUB>3</SUB>/Ca(OH)<SUB>2</SUB>), wollastonite, pollucite and hematite appeared in addition to quartz, kaolinite and bentonite, which probably indicates that the main fraction of enclosed/bound materials includes Ca-associated complexes. Thus, the thermal treatment with the addition of nanometallic Ca/CaO and fly ash may be considered potentially applicable for the remediation of radioactive Cs contaminated soil at zero evaporation, relatively at low temperature.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Vitrification with nanometallic Ca/CaO is a promising treatment for Cs in soil. </LI> <LI> Dynamic Cs immobilization and zero evaporation were done by nanometallic Ca/CaO. </LI> <LI> By SEM analysis the amount of cesium detectable on soil particle surface decreases. </LI> <LI> Leachable cesium concentrations reduced, lower than the standard regulatory limit. </LI> <LI> Nanometallic Ca/CaO is unique amendment for the remediation of Cs in soil. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>SEM–EDS element maps of <SUP>133</SUP>Cs contaminated soil before and after thermal treatment at 1200 °C with different addictives. Color intensity for Cs is from 0 to 100 (low to high).</P> <P>[DISPLAY OMISSION]</P>

Heterogeneous nano-Fe/Ca/CaO catalytic ozonation for selective surface hydrophilization of plastics containing brominated and chlorinated flame retardants (B/CFRs): separation from automobile shredder residue by froth flotation

Mallampati, S. R.,Lee, B. H.,Mitoma, Y.,Simion, C. Springer 2017 Environmental Science and Pollution Research Vol. No.

<P>One method of weakening the inherently hydrophobic surface of plastics relevant to flotation separation is heterogeneous nano-Fe/Ca/CaO catalytic ozonation. NanoFe/Ca/CaO-catalyzed ozonation for 15 min efficiently decreases the surface hydrophobicity of brominated and chlorinated flame retardant (B/CFR)-containing plastics (such as acrylonitrile-butadienestyrene (ABS), high-impact polystyrene (HIPS), and polyvinyl chloride (PVC)) in automobile shredder residue (ASR) to such an extent that their flotation ability is entirely depressed. Such a hydrophilization treatment also stimulates the ABS, HIPS, and PVC surface roughness, wetting of the surface, and the thermodynamic equilibrium conditions at the surface and ultimately changes surface polarity. SEM-EDS, AFM, and XPS analyses of the PVC and ABS surfaces demonstrated a marked decrease in [Cl/Br] and a significant increase in the number of hydrophilic groups, such as C-O, C=O, and (C= O)-O. Under froth flotation conditions at 50 rpm, about 99.5% of ABS and 99.5% of HIPS in ASR samples settled out, resulting in a purity of 98 and 98.5 % for ABS and HIPS in ASR samples, respectively. Furthermore, at 150 rpm, we also obtained 100 % PVC separation in the settled fraction, with 98 % purity in ASR. Total recovery of non-B/CFR-containing plastics reached nearly 100 % in the floating fraction. The amount of nano-Fe/Ca/ CaO reagent employed during ozonation is very small, and additional removal of surface contaminants from the recycled ASR plastic surfaces by ozonation makes the developed process simpler, greener, and more effective.</P>

Dual mechanochemical immobilization of heavy metals and decomposition of halogenated compounds in automobile shredder residue using a nano-sized metallic calcium reagent

Mallampati, S. R.,Lee, B. H.,Mitoma, Y.,Simion, C. Springer Science + Business Media 2016 Environmental Science and Pollution Research Vol.23 No.22

<P>Simultaneous immobilization of heavy metals and decomposition of halogenated organic compounds in different fractions of automobile shredder residue (ASR) were achieved with a nano-sized metallic calcium through a 60-min ball milling treatment. Heavy metal (HM) immobilization and chlorinated/brominated compound (CBC) decomposition efficiencies both reached 90-100 %, after ball milling with nanometallic calcium/calcium oxide (Ca/CaO) dispersion, regardless of ASR particle size (1.0, 0.45-1.0, and 0.250 mm). Concentrations of leachable HMs substantially decreased to a level lower than the regulatory standard limits (Co and Cd 0.3 mg L-1; Cr 1.5 mg L-1; Fe, Pb, and Zn 3.0 mg L-1; Mn and Ni 1 mg L-1) proposed by the Korean hazardous waste elution standard regulatory threshold. Scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS) element maps/spectra showed that while the amounts of HMs and CBCs detectable in ASR significantly decreased, the calcium mass percentage increased. X-ray powder diffraction (XRD) patterns indicate that the main fraction of enclosed/bound materials on ASR includes Ca-associated crystalline complexes that remarkably inhibit HM desorption and simultaneously transform dangerous CBCs into harmless compounds. The use of a nanometallic Ca/CaO mixture in a mechanochemical process to treat hazardous ASR (dry conditions) is an innovative approach to remediate cross-contaminated residues with heavy metals and halogenated compounds.</P>

Evaluation of heavy metals in hazardous automobile shredder residue thermal residue and immobilization with novel nano-size calcium dispersed reagent

Lee, Chi-Hyeon,Truc, Nguyen Thi Thanh,Lee, Byeong-Kyu,Mitoma, Yoshiharu,Mallampati, Srinivasa Reddy Elsevier 2015 Journal of hazardous materials Vol.296 No.-

<P><B>Abstract</B></P> <P>This study was conducted to synthesize and apply a nano-size calcium dispersed reagent as an immobilization material for heavy metal-contaminated automobile shredder residues (ASR) dust/thermal residues in dry condition. Simple mixing with a nanometallic Ca/CaO/PO<SUB>4</SUB> dispersion mixture immobilized 95–100% of heavy metals in ASR dust/thermal residues (including bottom ash, cavity ash, boiler and bag filter ash). The quantity of heavy metals leached from thermal residues after treatment by nanometallic Ca/CaO/PO<SUB>4</SUB> was lower than the Korean standard regulatory limit for hazardous waste landfills. The morphology and elemental composition of the nanometallic Ca/CaO-treated ASR residue were characterized by field emission scanning election microscopy combined with electron dispersive spectroscopy (FE-SEM/EDS). The results indicated that the amounts of heavy metals detectable on the ASR thermal residue surface decreased and the Ca/PO<SUB>4</SUB> mass percent increased. X-ray diffraction (XRD) pattern analysis indicated that the main fraction of enclosed/bound materials on ASR residue included Ca/PO<SUB>4</SUB>− associated crystalline complexes, and that immobile Ca/PO<SUB>4</SUB> salts remarkably inhibited the desorption of heavy metals from ASR residues. These results support the potential use of nanometallic Ca/CaO/PO<SUB>4</SUB> as a simple, suitable and highly efficient material for the gentle immobilization of heavy metals in hazardous ASR thermal residue in dry condition.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Nanometallic Ca/CaO/PO<SUB>4</SUB> for heavy metals immobilization in ASR residue. </LI> <LI> Heavy metals immobilization in dry condition attained about 95–100%. </LI> <LI> Remaining heavy metals were lower than the Korean standard regulatory limit. </LI> <LI> The amounts of heavy metals detectable on the ASR dust surface decreased. </LI> <LI> Nanometallic Ca/CaO/PO<SUB>4</SUB> has a promising potential for heavy metal remediation. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Schematic representation of possible mechanisms determining the heavy metals immobilization efficiencyof ASR dust/thermal residues after treatment with nanometallic Ca/CaO/PO<SUB>4</SUB>.</P> <P>[DISPLAY OMISSION]</P>