Search

Japan is a country of high specific diversity of Onchocerca with eight species, the adults of two not yet known. Onchocerca dewittei japonica, a common filarial parasite of wild boar, had been proved to be the agent of five zoonotic onchocerciasis in Kyushu island with morphological and molecular studies. The sixth case, at Hiroshima in the main island, was identified to the same Onchocerca species, based on adult characters observed on histological sections. To consolidate the identification, mitochondrial cytochrome c oxidase subunit 1 (CO1) gene analysis was attempted with the formalin-fixed, paraffin-embedded parasite specimen. The sequence (196 bp) of a CO1 gene fragment of the parasite successfully PCR-amplified agreed well with those of O. dewittei japonica registered in GenBank, confirming the morphological identification. Moreover a comparison with the CO1 gene sequences of six other Onchocerca species in GenBank excluded the possibility that Onchocerca sp. from wild boar and Onchocerca sp. type A from cattle in Japan, were the causative agents in this case. Mitochondrial DNA analysis proved to be a valuable tool to support the morphological method for the discrimination of zoonotic Onchocerca species in a histological specimen.

Wild female black flies attracted to a man or an idling automobile were collected at Oita, Japan where five cases of zoonotic onchocerciasis had occurred. Among the five Simulium species captured, 2% of Simulium bidentatum, the predominant species, were infected with filarial larvae. There were at least two types of infective larvae, types A and B, based on morphometric observation. Moreover, molecular analysis of the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene revealed that types A and B were represented by a single unknown species of Onchocerca and two species, i.e., Onchocerca dewittei japonica from wild boar, the causative agent of zoonotic onchocerciasis in Japan, and an undescribed Onchocerca sp. from wild boar, respectively. Phylogenetic analysis based on the sequences of the mitochondrial 12S ribosomal RNA (12S rRNA) gene also showed that type A is likely to be an unknown species of Onchocerca. Natural infection of black flies with infective larvae of O. dewittei japonica and O. sp. was demonstrated for the first time. The present study strongly suggests that S. bidentatum plays a role as a vector in the transmission of zoonotic onchocerciasis due to O. dewittei japonica in Japan.

In order to clarify the genetic differences between Onchocerca dewittei japonica, the causative agent of zoonotic onchocerciasis in Japan and a related undescribed Onchocerca sp., both parasitizing wild boar (Sus scrofa) of which the infective larval stages are indistinguishable from each other, we compared the sequences of the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene region from four infective larvae (recovered from experimentally infected black flies), one microfilaria, and one adult of O. dewittei japonica, and from one infective larva (recovered from an experimentally infected black fly), one microfilaria, and a pool of several microfilariae of O. sp. The length of the CO1 gene region was 649 bp for all samples but there was a difference of 8.8 to 9.4% in the sequences between the two species although there were intraspecific variations of 0 to 0.5%. The CO1 sequences of O. sp. did not correspond to any of those deposited in the databases. Our study provides evidence that O. dewittei japonica and O. sp. are genetically different from each other.

Seasonal and daily biting activity patterns, and natural filarial infections of adult black flies attracted to human bait were investigated at Ban Pang Faen, a rural area in Chiang Mai Province in northern Thailand. Collections were carried out twice a month from 06-00 to 18-00 hours from January 2005 to February 2006. Among ten Simulium species collected, S. nodosum and S. asakoae were predominant occupying 57.3% and 37.2% of the total 16, 553 females, respectively. These two predominant species showed different patterns in seasonal abundance: majority of S. nodosum (86.7%) were collected in hot season (from mid February to mid May), while most of S. asakoae (74.5%) were collected in rainy season (from mid May to mid October). For the daily biting activity, S. nodosum had two patterns: the main one was unimodal with a peak from 17-00 to 18-00, and the other was bimodal and had the major peak from 16-00 to 18-00 and the minor one from 07-00 to 09-00. The pattern of S. asakoae was mostly unimodal with a peak from 06-00 to 10-00. The filarial larvae found in S. nodosum and S. asakoae were morphologically different from each other. The short and thick infective larvae found in S. asakoae differed from all known filarial larvae; it is suggested that they might be a bird parasite, Splendidofilariinae or Lemdaninae. The infection of the mammophilic S. nodosum with large Onchocerca type infective larvae was confirmed in this area. Natural filarial infections were found in each month (except December) in either S. nodosum or S. asakoae or in both. Monthly infection rates with all stages of larvae were 0.6-5.0% for S. nodosum, and 1.0-4.0% for S. asakoae. It is suggested that people in this village are exposed to the risk of infection with zoonotic filariae throughout the year.

Histological examination of a nodule removed from the back of the hand of a 58-year-old woman from Oita, Kyushu, Japan showed an Onchocerca female sectioned through the posterior region of the worm (ovaries identifiable) and young (thin cuticle). Six Onchocerca species are enzootic in that area: O. gutturosa and O. lienalis in cattle, O. suzukii in serows (Capricornis crispus), O. skrjabini and an Onchocerca sp. in Cervus nippon nippon, and O. dewittei japonica in wild boar (Sus scrofa leucomystax). Diagnostic charactets of female Onchocerca species, such as the cuticle and its ridges, change along the body length. Tables of the histologic morphology of the mid- and posterior body-regions of the local species are presented. In addition, it was observed that transverse ridges arose and thickened during the adult stage (examination of fourth stage and juvenile females of O. volvulus). The specimen described in this report, with its prominent and widely spaced ridges, was identified as O. d. japonica. Four of the 10 zoonotic cases of onchocerciasis reported worldwide were from Oita, three of them being caused by O. d. japonica, the prevalence of which in local wild boar was 22 of 24 (92 %).

Toshinori Nishizawa,1,2 Kosuke Ishizuka,3 Yuki Otsuka,4 Toshiyuki Nakanishi,5 Akira Kawashima,6 Taiju Miyagami,7 Shun Yamashita8,9 1Department of General Internal Medicine, St Luke’s International Hospital, Tokyo, Japan; 2Department of Global Health Promotion, Tokyo Medical and Dental University, Tokyo, Japan; 3Department of General Medicine, Yokohama City University School of Medicine, Kanagawa, Japan; 4Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; 5Department of Emergency and General Medicine, Nerima Hikarigaoka Hospital, Tokyo, Japan; 6Department of General Internal Medicine, National Center for Global Health and Medicine, Tokyo, Japan; 7Department of General Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan; 8Department of General Medicine, Saga University Hospital, Saga, Japan; 9Education and Research Center for Community Medicine, Faculty of Medicine, Saga University, Saga, JapanCorrespondence: Kosuke Ishizuka, Department of General Medicine, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan, Tel +81-45-787-2800, Fax +81-45-350-2728, Email e103007c@yokohama-cu.ac.jpAbstract: Case reports provide scientific knowledge and opportunities for new clinical research. However, it is estimated that less than 5% of cases presented by Japanese generalists at academic conferences are published due to various barriers such as the complex process of writing articles, conducting literature searches, the significant time required, the reluctance to write in English, and the challenge of selecting appropriate journals for publication. Therefore, the purpose of this opinion paper is to provide clinicians with practical tips for writing case reports that promote diagnostic excellence. In recent years, clinical practitioners have been striving for diagnostic excellence and optimal methods to accurately and comprehensively understand the patient’s condition. To write a case report, it is essential to be mindful of the elements of diagnostic excellence and consider the quality of the diagnostic reasoning process. We (the authors) are seven academic generalists who are members of the Japanese Society of Hospital General Medicine (JSHGM) – Junior Doctors Association, with a median of 7 years after graduation and extensive experience publishing case reports in international peer-reviewed journals. We conducted a narrative review and discussed ways to write case reports to promote diagnostic excellence, leveraging our unique perspectives as academic generalists. Our review did not identify any reports addressing the critical points in writing case reports that embody diagnostic excellence. Therefore, this report proposes a methodology that describes the process involved in writing diagnostic excellence-promoting case reports and provides an overview of the lessons learned. Based on our review and discussion, we explain the essential points for promoting diagnostic excellence through case reports categorized into seven components of clinical reasoning. These strategies are useful in daily clinical practice and instrumental in promoting diagnostic excellence through case reports.Keywords: case reports, clinical reasoning, diagnostic excellence

Yuya Yokota, Yuki Otsuka, Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, JapanCorrespondence: Yuki Otsuka, Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan, Tel +81-86-235-7342, Fax +81-86-235-7345, Email otsuka@s.okayama-u.ac.jp

Masaki Tago,1 Risa Hirata,1 Naoko E Katsuki,1 Yuki Otsuka,2 Taro Shimizu,3 Yosuke Sasaki,4 Kiyoshi Shikino,5 Takashi Watari,6 Hiromizu Takahashi,7 Kazunobu Une,8 Toshio Naito,7 Fumio Otsuka,2 Rachel Thompson,9 Susumu Tazuma8,10 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; 3Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, Tochigi, Japan; 4Department of General Medicine and Emergency Care, Toho University School of Medicine, Tokyo, Japan; 5Department of General Medicine, Chiba University Hospital, Chiba, Japan; 6General Medicine Center, Shimane University Hospital, Izumo, Japan; 7Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 8Department of Critical Care and General Medicine, Onomichi General Hospital, Hiroshima, Japan; 9Executive Team, Snoqualmie Valley Hospital, Snoqualmie, WA, USA; 10JR Hiroshima Hospital, Hiroshima, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpIntroduction: Hospitalists in Japan have been at the forefront of the COVID-19 pandemic. However, contributions of Japanese hospitalists during the COVID-19 pandemic and hospitalists’ awareness of crisis management education remain unclear.Material and Methods: We conducted a questionnaire survey to investigate the role of Japanese hospitalists during the COVID-19 pandemic. The questionnaire was conducted using email and Google Forms targeting the chairpersons of facilities certified by the Japanese Society of Hospital General Medicine (JSHGM). Members of the academic committee of the JSHGM and several hospitals conducted a narrative review and determined the questions for the survey in a discussion.Results: We conducted descriptive statistics based on the responses of 97 hospitals that agreed to participate in this survey. In total, 91.8% of general medicine departments in the included hospitals were involved in the medical care of COVID-19 patients. Furthermore, in 73.2% of hospitals, hospitalists were involved in infection control for COVID-19 inside or outside the hospital. Our survey revealed that Japanese hospitalists were responsible for COVID-19 treatment in over 60% of hospitals and contributed to hospital management, infection control, and vaccination. In total, 79.4% of hospitals answered that “training of personnel who can provide practical care for emerging infectious diseases is necessary”, 78.4% indicated that “the establishment of an infection control system in advance to prepare emerging infectious diseases in the hospital is necessary”, and 74.2% stated that “the establishment of an educational system for responding to emerging infectious diseases is necessary.”.Conclusion: In conclusion, during the pandemic, in addition to inpatient care, Japanese hospitalists provided outpatient care for COVID-19, which is the role of primary care physicians in other countries. Furthermore, Japanese hospitalists who experienced the COVID-19 pandemic expressed the need for personnel development and education to prepare for future emerging infectious disease pandemics.Keywords: COVID-19 pandemic, hospitalist, hospital management

Xin Gao,1 Xuemei He,1 Hiroyuki Oshima,2 Daisuke Miyatake,2 Yukio Otsuka,2 Kota Kato,3 Chunxiao Cai,4 Tomasz Wojtkowski,5 Nan Song,6 Yuichiro Kaneko,7 Aixin Shi1 1Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Clinical Pharmacology and Exploratory Development, Astellas Pharma Inc., Tokyo, Japan; 3Analysis & Pharmacokinetics Research Labs., Astellas Pharma Inc., Ibaraki, Japan; 4Development Medical Department, Astellas (China) Investment Co., Ltd, Beijing, People’s Republic of China; 5Data Science Development, Astellas Pharma US, Inc., Northbrook, IL, USA; 6Development Division Biostatistics and Statistical Programming, Astellas (China) Investment Co., Ltd, Beijing, People’s Republic of China; 7Biostatistics Group, Japan-Asia Data Science, Development, Astellas Pharma Inc, Tokyo, JapanCorrespondence: Aixin Shi, Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, 100730, People’s Republic of China, Tel +86-10-85133632, Email aixins0302@126.comObjective: To investigate the pharmacokinetics and safety of peficitinib (Janus kinase inhibitor for the treatment of rheumatoid arthritis) in healthy Chinese subjects following single and multiple doses.Methods: This open-label, randomized study was conducted at one site in China. Subjects received peficitinib 50, 100 or 150 mg as a single dose on Day 1 (fasted) and once daily from Days 8 to 13 in the multiple-dose period (fed). Blood samples were collected before administration each day, and up to 72h post administration. Pharmacokinetic assessments included area under the concentration curve (AUC), half-life (t1/2), maximum concentration (Cmax), and time to maximum concentration (tmax) of peficitinib and its metabolites (H1, H2 and H4). Treatment-emergent adverse events (TEAEs) were evaluated.Results: Thirty-six subjects were enrolled (12 per dose group). After a single dose of peficitinib, median tmax was 1.0– 1.5h and mean t1/2 was 7.4– 13.0h for all doses. In the multiple-dose period, median tmax was 1.5– 2.0h. Dose-proportional increases in Cmax and AUC24h were observed for peficitinib and its metabolites following single and multiple doses, with minimal drug accumulation. The major metabolite was H2, with a systemic exposure of > 150% of the parent AUC. Drug-related TEAEs were experienced by 5 (13.9%) and 12 (33.3%) subjects in the single- and multiple-dose periods, respectively. Following multiple doses of peficitinib, TEAEs were more frequent in higher than lower dose groups but were mild in severity with no related discontinuation or death.Conclusion: Following single and multiple doses of peficitinib in healthy Chinese subjects, peficitinib demonstrated rapid absorption and was well tolerated at all doses.Clinicaltrials.gov Identifier: NCT04143477.Keywords: rheumatoid arthritis, treatment, dose-proportionality, tsDMARDs

Equatorial Plasma Bubbles (EPBs) can generate ionospheric scintillation at GHz frequencies used in the Global Navigation Satellite System (GNSS). Emerging at any longitude following sunset and typically moving eastward, monitoring the EPBs is essential for space weather services. Using three GNSS receivers positioned at the same latitude (∼0°N) but separated in longitudes (∼9°, ∼16°, and ∼25°) and the 47 MHz Equatorial Atmosphere Radar (EAR) in Indonesia, our study delineates the zonal extent of eastward‐traveling post‐sunset EPB inducing ionospheric GNSS scintillation. Typically, the scintillation occurrences detected by a ground receiver concentrate between 19 and 01 local time (LT), with a peak incidence observed at 21 LT. Furthermore, an experiment combining EAR observations with GNSS receiver data allowed for the determination of the linear change in the speed of eastward‐traveling EPB inducing scintillation during this time period. Interestingly, the longitudinal range of eastward‐traveling EPBs increased with higher solar flux (F10.7) levels. Our findings suggest that EPB can induce scintillation up to a longitudinal distance of approximately 25° from the onset location at sunset to the eastern midnight region, particularly in F10.7 ranging from 90 to 150 solar flux units. Moreover, experiments using longitudinally separated GNSS receivers indicated that scintillations during 19–01 LT originate from post‐sunset EPBs within a longitudinal range extending 25° to the west. In conclusion, our research provides valuable insight into the ability of eastward‐traveling EPB to induce GNSS scintillation within a longitudinal range of 25°, thereby enhancing EPB and scintillation monitoring and prediction in regional space weather services. Plain Language Summary: Many modern technologies rely on Global Navigation Satellite Systems (GNSS). GNSS refers to satellites constellations, including Global Positioning Systems, that send signals from space to the receivers on the ground, providing positioning and timing data. However, GNSS signals can be disrupted by natural phenomena in the Earth's ionosphere, a layer of charged particles in the upper atmosphere. One such phenomenon is the Equatorial Plasma Bubble (EPB) occurring at night, which can cause fluctuations or scintillations in GNSS signals, leading to errors in positioning and timing. Understanding how EPBs affect GNSS is essential for maintaining the reliability of navigation systems and ensuring the smooth operation of various technological applications that rely on GNSS data. EPBs usually move eastward and can cause scintillation in the longitude where they are generated and in other longitudes. Previous studies have not determined how far eastward‐traveling EPB can induce scintillation. Our recent discovery shows that EPBs can induce scintillation within a longitudinal range of up to 25°. This insight is essential for mitigating the adverse effects of EPBs on GNSS applications in regional or longitudinal sectors. Key Points: A ground GNSS receiver typically detects scintillations due to Equatorial Plasma Bubbles (EPBs) from 19 to 01 local time (LT) with the peak occurrence at 21 LTThe furthest longitudinal range of EPB inducing GNSS scintillation depends on solar flux (F10.7) levelEPBs can cause GNSS scintillation within a 25° longitudinal range at F10.7 levels of 90–150 solar flux units [ABSTRACT FROM AUTHOR]

We analyze daytime quiet‐time MSTIDs between 2013 and 2015 at the geomagnetic equatorial and low latitude regions of the Chilean and Argentinian Andes using keograms of detrended total electron content (dTEC). The MSTIDs had a higher occurrence rate at geomagnetic equatorial latitudes in the June solstice (winter) and spring (SON). The propagation directions changed with the season: summer (DJF) [southeast, south, southwest, and west], winter (JJA) [north and northeast], and equinoxes [north, northeast, south, southwest, and west]. In addition, the MSTIDs at low latitudes observed between 8:00 and 12:00 UT occur more often during the December solstice and propagate northwestward and northeastward. After 12:00 UT, they are mostly observed in the equinoxes and June solstice. Their predominant propagation directions depend on the season: summer (all directions with a preference for northeastward), autumn (MAM) [north and northeast], winter (north and northeast), and spring (north, northeast, and southwest). The MSTID propagation direction at different latitudes was explained by the location of the possible sources. Besides, we calculated MSTIDs parameters at geomagnetic low latitudes over the Andes Mountains and compared them with those estimated at the geomagnetic equatorial latitudes. We found that the former is smaller on average than the latter. Also, our observations validate recent model results obtained during geomagnetically quiet‐time as well as daytime MSTIDs during winter over the south of South America. These results suggest that secondary or high‐order gravity waves (GWs) from orographic forcing are the most likely source of these MSTIDs. Key Points: Quiet‐time daytime MSTIDs were observed at equatorial and low‐geomagnetic latitudes over the Chilean and Argentinian Andes MountainsMSTIDs observed during summer at equatorial latitudes are most likely generated by higher‐order gravity waves from the Amazon regionEquatorial and low‐geomagnetic latitude wintertime MSTIDs over the Andes may be secondary or higher‐order gravity waves [ABSTRACT FROM AUTHOR]