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Purpose: The 2HELPS2B score is an invaluable tool for assessing seizure risk in critically ill patients with unconsciousness. However, this can be challenging for non-epileptologists to use owing to its reliance on electroencephalogram (EEG) analysis. Thus, identifying clinical manifestations associated with high 2HELPS2B scores is crucial., Methods: We examined patients who underwent EEG for acute impaired consciousness in the emergency department between 2020 and 2022. We evaluated the clinical manifestations immediately prior to the EEG tests and identified those associated with a 2HELPS2B score ≥ 2. Additionally, we investigated clinical outcomes in accordance with these manifestations and the 2HELPS2B score., Results: A total of 78 patients were included in this study. While the median 2HELPS2B score was 1 (range: 0-6), 13 patients (16.6%) showed electrographic/electroclinical seizures or status epilepticus and 16 patients (20.5%) showed ictal-interictal continuum in their EEGs. Abnormal muscle tonus (p = 0.034) and eye deviation (p = 0.021) were Significantly associated with a 2HELPS2B score ≥ 2. The presence of these manifestations (p < 0.001) and a 2HELPS2B score ≥ 2 (p < 0.001) were both significantly associated with a favorable response to anti-seizure medication. Conversely, patients with a 2HELPS2B score ≥ 2 who exhibited these clinical manifestations were more likely to be non-dischargeable (p = 0.053), have prolonged intensive care unit stays (p = 0.002), or require extended ventilator use (p = 0.082)., Conclusion: Abnormal muscle tonus and eye deviation were significant manifestations compatible with a 2HELPS2B score ≥ 2 and may indicate an increased risk of seizures or the severity of the epileptic condition., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that there are no conflicts of interest to disclose, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Purpose: High-density surface electromyography (HD-sEMG) allows non-invasive analysis of motor unit (MU) activity and recruitment. This study examines MU recruitment features as well as action potential using HD-sEMG in the suprahyoid muscles of patients with Parkinson's disease (PD) and assesses alterations caused by cervical percutaneous interferential current stimulation., Methods: Electrical activity of the suprahyoid muscles during tongue elevation was measured using HD-sEMG. Maximum voluntary contraction (MVC) was measured, then the modified entropy, coefficient of variation, correlation coefficient, and root mean square (RMS) were examined. For comparison, HD-sEMG was also conducted on healthy controls. In addition, this study assessed the impact of cervical percutaneous interferential current stimulation on HD-sEMG in patients with PD (Hoehn-Yahr stages 2-4) over 8 weeks., Results: Twenty-two patients with PD (mean age 71.7 ± 6.0, 7 females) and 14 healthy controls (mean age 74.9 ± 6.1, 7 females) were included. The RMS at 60 % MVC was significantly lower in patients with PD than in healthy controls (p = 0.007). After cervical percutaneous interferential current stimulation, the correlation coefficients at 40 % and 60 % MVC significantly decreased (p = 0.040 and p = 0.048, respectively), and the RMS at 60 % MVC significantly increased (p = 0.035)., Conclusion: HD-sEMG of the suprahyoid muscles showed characteristic findings in patients with PD and was able to detect subtle changes due to electrical stimulation intervention. Thus, HD-sEMG could be a promising tool for evaluating swallowing-related muscle conditions and interventions., Competing Interests: Declaration of competing interest HM received honoraria from Eisai, Shionogi, Otsuka Pharmaceutical, and Sumitomo Pharma. The other authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Introduction/aims: The common presentations of statin intolerance are muscle-specific symptoms. Although statins are one type of drug reported to cause myasthenic worsening, myasthenic worsening has not been recognized as statin intolerance. The purpose of the present study is to investigate in a large cohort the safety profiles of statins in patients with myasthenia gravis (MG)., Methods: A total of 1710 consecutive patients with MG who visited sites associated with the Japan MG registry 2021 group between April and October 2021 were reviewed. Statin-associated myasthenic worsening was defined as worsening of any myasthenic symptoms on statin use and improvement of the symptom by stopping the statin or by undertaking additional treatment with patient and doctor confirmation., Results: Among the 400 patients who used statins, 8 (2%) patients experienced statin intolerance and 6 (1.5%) patients experienced myasthenic worsening. No patients developed MG on the statin. Ptosis was a main symptom of myasthenic worsening in 4 (67%) patients. Atorvastatin was used in all patients with statin-associated myasthenic worsening. The symptoms of statin intolerance and statin-associated myasthenic worsening were improved within 2 months and 3 months, respectively, in all patients by cessation of statin use., Discussion: Regarding statin-associated myasthenic worsening, prevalence was low, and severity was mild; with cessation of statin use, symptoms improved within a few months, and outcomes were generally good. Although statins can be used in MG patients with little concern, statin-associated myasthenic worsening should be noted in addition to the classical statin intolerance associated with statin use., Competing Interests: Declaration of competing interest T. Sugimoto declares no potential conflicts of interest related to this article. S. Suzuki received speakers' fees from Alexion Pharmaceuticals, the Japan Blood Products Organization, Asahi Kasei Medical, and Argenx and participated in advisory board meetings of Alexion Pharmaceuticals and Argenx. A. Uzawa has received honoraria from Alexion Pharmaceuticals and Argenx. T. Yamawaki declares no potential conflicts of interest related to this article. M, Masuda declares no potential conflicts of interest related to this article. N. Minami declares no potential conflicts of interest related to this article. N. Kawaguchi declare no financial or other conflicts of interest. T. Kubota reports honoraria for lectures from Alexon Pharmaceuticals. M. P. Takahashi reports unrestricted research grants from Japan Blood Products Organization, Astellas Pharma, Mitsubishi Tanabe Pharma and Pfizer, outside the submitted work, and has served as a paid Consultant for Alexion, Argenx, Sanofi, and UCB Pharma and received honoraria for lectures from Argenx, Alexion Pharmaceuticals and UCB Pharma. Y. Suzuki declares no potential conflicts of interest related to this article. G Watanabe declares no potential conflicts of interest related to this article. S. Konno declares no potential conflicts of interest related to this article. T. Kimura declares no potential conflicts of interest related to this article. M. Samukawa declares no potential conflicts of interest related to this article. K. Ishizuchi declares no potential conflicts of interest related to this article. H. Akamine declares no potential conflicts of interest related to this article. Y. Onishi declares no potential conflicts of interest related to this article. M. Yasuda declares no potential conflicts of interest related to this article. Y. Nagane has received honoraria from Alexion Pharmaceuticals, Argenx, the Japan Blood Products Organization, and UCB Pharma. H. Maruyama declares no potential conflicts of interest related to this article. H. Murai has served as a paid consultant for UCB Pharma, Argenx, Janssen Pharma, Viela Bio, Chugai Pharma, Hanall BioPharma, and Mitsubishi Tanabe Pharma, and has received speaker honoraria from Argenx, Alexion Pharmaceuticals, and the Japan Blood Products Organization. K. Utsugisawa has served as a paid consultant for UCB Pharma, Argenx, Janssen Pharma, Viela Bio, Chugai Pharma, Hanall BioPharma, Merck and Mitsubishi Tanabe Pharma, and has received speaker honoraria from Argenx, Alexion Pharmaceuticals, UCB Pharma and the Japan Blood Products Organization., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Giant somatosensory evoked potentials (SEPs) are observed in patients with cortical myoclonus. Short-latency components (SLC), are regarded as evoked epileptic activities or paroxysmal depolarization shifts (PDSs). This study aimed to reveal the electrophysiological significance of the middle-latency component (MLC) P50 of the SEPs., Methods: Twenty-two patients with cortical myoclonus having giant SEPs (patient group) and 15 healthy controls were included in this study. Waveform changes in SEPs before and after perampanel (PER) treatment were evaluated in the patient group. The wide range, time-frequency properties underlying the waveforms were compared between the groups., Results: After PER treatment, SLC was prolonged and positively correlated with PER concentration, whereas MLC showed no correlation with PER concentration. Time-frequency analysis showed a power increase (156 Hz in all patients, 624 Hz in benign adult familial myoclonus epilepsy patients) underlying SLC and a power decrease (156 Hz, 624 Hz) underlying MLC in the patient group., Conclusions: The high-frequency power increase in SLCs and decrease in MLCs clearly reflected PDS and subsequent hyperpolarization, respectively. This relationship was similar to that of interictal epileptiform discharges, suggesting that giant SEPs evoke epileptic complexes of excitatory and inhibitory components., Significance: MLCs of giant SEPs reflected inhibitory components., (Copyright © 2024. Published by Elsevier B.V.)

Fasciolosis is a food-borne parasitic disease, caused by the large liver fluke, Fasciola. Humans acquire infection by ingesting fresh or undercooked water plants, on which infective metacercaria encyst. In spite of the rarity of the disease in Japan, we encountered four successive fasciolosis patients within a short period, who were all living in the same area. The patients were 70-82 years old, three females and the husband of one of the female patients. They started complaining of non-specific symptoms, such as fever, general fatigue, appetite loss, and abdominal pain, almost at the same time. All patients showed prominent peripheral blood eosinophilia, and the medical imaging indicated multiple hepatic lesions. No parasite eggs or worms were detected in any of the patients. Diagnosis was made serologically and they were treated with praziquantel and/or triclabendazole. No cattle or sheep were farmed in the area, but the wild sika deer, Cervus nippon, inhabited adjacent to the residential area. The intermediate host snail, Austropeplea ollula, were found near the residence of the patients, and one of the collected snails was positive for F. hepatica/gigantica hybrid type rediae. Our report should alarm the medical professionals for this rare and unfamiliar parasitic disease., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Systemic transplantation of mesenchymal stem cells (MSCs) and conditioned medium derived from MSCs have been reported to recover bone loss in animal models of osteoporosis; however, the underlying mechanisms remain unclear. We recently reported that extracellular vesicles released from human mesenchymal stem cells (hMSCs) prevent senescence of stem cells in bisphosphonate-related osteonecrosis of the jaw model. In this study, we aimed to compare the effects of conditioned medium (hMSCs-CM) from early and late passage hMSCs on cellular senescence and to verify the benefits of CM from early passage hMSCs in mitigating the progression of osteoporosis through the prevention of cellular senescence. We investigated the distinct endocrine effects of early (P5) and late (P17) passage hMSCs in vitro, as well as the preventive benefits of early passage hMSCs-CM in osteoporosis model triggered by ovariectomy. Our results indicate that long-term cultured hMSCs contributed to the progression of inflammatory transcriptional programs in P5 hMSCs, ultimately impairing their functionality and enhancing senescence-related characteristics. Conversely, early passage hMSCs reversed these alterations. Moreover, early passage hMSCs-CM infused intravenously in a postmenopausal osteoporosis mouse model suppressed bone degeneration and prevented osteoporosis by reducing ovariectomy-induced senescence in bone marrow MSCs and reducing the expression of senescence-associated secretory phenotype-related cytokines. Our findings highlight the high translational value of early passage hMSCs-CM in antiaging intervention and osteoporosis prevention., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: We previously reported that nerve enlargement assessment by nerve ultrasonography of the intermediate upper limb is applicable for distinguishing demyelinating Charcot-Marie-Tooth disease (CMT) from chronic inflammatory demyelinating polyneuropathy (CIDP). However, differences in the severity and distribution patterns of lower extremity nerve enlargement have not been established for either disease. Therefore, we examined the utility of lower extremity nerve ultrasonography for differentiating between CMT and CIDP., Methods: Twelve patients with demyelinating CMT and 17 patients with CIDP were evaluated. The median, ulnar, tibial, and fibular nerves were evaluated in three regions: the distal upper extremity, intermediate upper extremity, and lower extremity. Of the 14 selected screening sites, the number of sites that exhibited nerve enlargement (enlargement site number, ESN) in each region was determined., Results: The screening ESNs in the intermediate region and lower extremities were greater in patients with demyelinating CMT than in patients with CIDP and greater than the ESN in the distal region (p = 0.010, p = 0.001, and p = 0.101, respectively). The ESNs in the intermediate region and lower extremities significantly differed among patients with typical CIDP, CIDP variants, and demyelinating CMT (p = 0.084 and p < 0.001). Among the 14 selected screening sites, the combined upper and lower extremity ESNs exhibited the highest AUC (0.92; p < 0.001)., Conclusions: Combining the upper and lower extremities for ultrasonographic nerve measurement more accurately distinguishes CIDP from demyelinating CMT., Competing Interests: Declaration of competing interest The authors declare that they have no potential conflicts of interest in relation to this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Thoracolumbar junctional kyphosis (TLJK) due to osteoporotic vertebral fracture (OVF) negatively impacts patients' quality of life. The necessity of pelvic fixation in corrective surgery for TLJK due to OVF remains controversial. This study aimed to: 1) evaluate the surgical outcomes of major corrective surgery for thoracolumbar junctional kyphosis due to osteoporotic vertebral fracture, and 2) identify the risk factors for distal junctional failure to identify potential candidates for pelvic fixation., Methods: Patients who underwent surgical correction (fixed TLJK>40°, OVF located at T11-L2, the lowermost instrumented vertebra at or above L5) were included. Sagittal vertical axis, pelvic tilt, pelvic incidence, thoracic kyphosis, lumbar lordosis (L1-S1), local kyphosis, and lower lumbar lordosis (L4-S1) were assessed. Proximal and distal junctional kyphosis (P/DJK) and failures (P/DJF) were evaluated. Pre/postoperative spinopelvic parameters were compared between DJF and non-DJF patients., Results: Thirty-one patients (mean age: 72.3 ± 7.9 years) were included. PJK was observed in five patients (16.1%), while DJK in 11 (35.5%). Twelve cases (38.7%) were categorized as failure. Among the patients with PJK, there was only one patient (20%) categorized as PJF and required an additional surgery. Contrary, all of eleven patients with DJK were categorized as DJF, among whom six (54.5%) required additional surgery for pelvic fixation. In comparisons between DJF and non-DJF patients, there was no significant difference in pre/postoperative LK (pre/post, p = 0.725, p = 0.950). However, statistically significant differences were observed in the following preoperative alignment parameters: SVA (p = 0.014), LL (p = 0.001), LLL (p = 0.006), PT (p = 0.003), and PI-LL (p < 0.001)., Conclusions: Spinopelvic parameters, which represent the compensatory function of lumbar hyperlordosis and pelvic retroversion, have notable impacts on surgical outcomes in correction surgery for TLJK due to OVF. Surgeons should consider each patient's compensatory function when choosing a surgical approach., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Resuming crop production in physically decontaminated fields affected by radiocesium ( 134 Cs and 137 Cs) releases is crucial for restoring impacted areas. However, surface soil excavation to reduce radiocesium may lead to lower crop yield due to the loss of fertile topsoil. This study aimed to assess the effects of cattle manure compost (CMC) application on soil properties, crop growth, and 137 Cs soil-to-crop transfer in a physically decontaminated field and pot experiment. Field trials were conducted during 2018-2022, with CMC (1 and 2 kg m -2  year -1 ) applied alongside conventional fertilization (CMC1 and CMC2 plots, respectively) in 2018-2019 and conventional fertilization alone in 2020-2022. Additionally, a pot experiment was used to evaluate the impact of CMC application in soil (1 kg m -2  year -1 for 5 years) on 137 Cs transfer. In the field trial during 2018-2019, CMC1 and CMC2 plots exhibited higher soybean shoot dry weight (DW) compared with plots receiving conventional fertilization and additional K fertilizer (+K 2 O). CMC application also improved soil nutrient content. The transfer factor of 137 Cs (TF- 137 Cs: plant 137 Cs activity concentration/soil 137 Cs activity concentration) followed the order CMC2 < CMC1 ≈ +K 2 O < conventional fertilization only (CF) and was negatively correlated with soil exchangeable K (Ex-K). During 2020-2022, when all plots received conventional fertilization alone, grain yields were higher in CMC1 and CMC2 plots than in the +K 2 O plot, with the lowest TF- 137 Cs in CMC2 plot followed by CMC1, +K 2 O, and CF plots. The pot experiment confirmed that CMC soil had a lower TF- 137 Cs and higher plant DW compared with CF soil with the same Ex-K level. Additionally, the soil exchangeable 137 Cs (Ex- 137 Cs) level was significantly lower in CMC soil than CF soil. These findings demonstrate the potential of CMC application to improve crop growth and reduce 137 Cs transfer in physically decontaminated fields., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Apolipoprotein E4 (APOE4), the strongest risk factor for late-onset Alzheimer's disease (AD), has been revealed to cause greater accumulation of extracellular amyloid β (Aβ) aggregates than does APOE3 in traditional transgenic mouse models of AD. However, concerns that the overexpression paradigm might have affected the phenotype remain. Amyloid precursor protein (APP)-knock-in (KI) mice, incorporating APP mutations associated with AD development, offer an alternative approach for overproducing pathogenic Aβ without needing overexpression of APP. Here, we present the results of comprehensive analyses of pathological and biochemical traits in the brains of APP-KI mice harboring APP-associated familial AD mutations (APP NL - G-F /NL - G-F mice) crossed with human APOE-KI mice. Immunohistochemical and biochemical analyses revealed the APOE genotype-dependent increase in Aβ pathology and glial activation, which was evident within 8 months in the mouse model. These results suggested that this mouse model may be valuable for investigating APOE pathobiology within a reasonable experimental time frame. Thus, this model can be considered in investigating the interaction between APOE and Aβ in vivo, which may not be addressed appropriately by using other transgenic mouse models., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takashi Kurashige reports financial support was provided by Takeda Science Foundation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Purpose: Several noninvasive tools assess swallowing disorders, including electronic stethoscope artificial intelligence (AI) analysis for remote diagnosis, with the potential for telemedicine. This study investigated the swallowing sound index in patients with Parkinson's disease (PD)., Methods: This single-arm, open-label trial assessed the impact of cervical percutaneous interferential current stimulation on swallowing in patients with PD classified as Hoehn-Yahr stages 2-4. Stimulation was conducted for 8 weeks. Baseline data were used to examine the link between the swallowing sound index and indicators such as videofluoroscopy (VF). Furthermore, we examined changes in the swallowing sound index after the intervention., Results: Twenty-five patients were included. The swallowing sound index in patients with PD was higher than that in those with amyotrophic lateral sclerosis but considerably lower than that in healthy controls. The number of patients with normal EAT-10 scores positively correlated with the swallowing sound index, whereas elevated C-reactive protein levels were negatively correlated with the swallowing sound index. However, the index displayed no correlation with other indicators, including the VF results. Despite the intervention, the index remained unchanged throughout the study., Conclusion: In patients with PD, a decrease in the swallowing sound index suggests a potential association between swallowing disorders and the risk of aspiration pneumonia., Trial Registration Number: jRCTs062220013., Competing Interests: Declaration of Competing Interest HM received honoraria from Eisai, Shionogi, Otsuka Pharmaceutical, Sumitomo Pharma, Country. All other authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Radiocesium dynamics data during food processing are required for the realistic estimation of internal radiation content in food. Radiocesium contamination of leafy vegetables can occur externally due to the adhesion of fallout and/or resuspension from the air, and internally from soil via the root transport. Information regarding the dynamics of both surface and internal radiocesium contamination during food processing is required; however, such information for leafy vegetables is limited compared to other major agricultural products. In this study, the effect of washing on the removal of surface radiocesium contamination by resuspended materials and that of cooking (grilling, boiling, and microwave heating) on internal radiocesium contamination were investigated using komatsuna (Brassica rapa var. perviridis), a leafy vegetable. The surface-contaminated samples were experimentally grown in a difficult-to-return area in Fukushima Prefecture, which has not yet been decontaminated. The internally contaminated komatsuna were obtained after experimental cultivation in a greenhouse with soil containing 137 Cs and no surface contamination. The concentration of 137 Cs in surface-contaminated komatsuna was reduced to approximately half (processing factor: 0.55) after washing with water. However, the annual processing factor ranged from 0.12 to 0.95, suggesting that the growing environment and climatic conditions may affect the removal rate of radiocesium by washing. Internal contamination of 137 Cs was removed by 23% and 14% by boiling and grilling, respectively, but no effect was observed for microwaving. Moreover, the concentration of 137 Cs decreased by 0.66-fold after boiling, while it increased by 1.19- and 1.20-fold after grilling and microwaving, respectively. Therefore, boiling was found to be preferable than grilling or microwaving for radiocesium removal., Competing Interests: Declaration of Competing Interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hideshi FUJIWARA reports financial support was provided by Agriculture Forestry and Fisheries Research Council. Takuro SHINANO reports financial support was provided by Tojuro Iijima Foundation for Food Science and Technology., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Upregulated p38 MAPK signaling is implicated in the accelerated proliferation of pulmonary artery smooth muscle cells (PA-SMCs) and the pathogenesis of pulmonary artery remodeling observed in pulmonary arterial hypertension (PAH). Previously, we reported that after endothelin-1 (ET-1) pretreatment, bone morphogenetic protein 2 (BMP2) activates p38 MAPK signaling and accelerates PA-SMC proliferation. The activity of p38 MAPK signaling is tightly regulated by the inactivation of dual-specificity phosphatase 1 (DUSP1). Activated p38 MAPK induces DUSP1 expression, forming a negative feedback loop. Prostacyclin IP receptor agonists (prostacyclin and selexipag) are used to treat PAH. In this study, we aimed to verify whether IP receptor agonists affect DUSP1 expression and accelerate the proliferation of PA-SMCs., Main Methods: PA-SMCs were treated with BMP2, ET-1, prostacyclin, and MRE-269, an active metabolite of selexipag, either alone or in combination. We quantified mRNA expressions using real-time quantitative polymerase chain reaction. Pulmonary artery specimens and PA-SMCs were obtained during lung transplantation in patients with PAH., Key Findings: Both prostacyclin and MRE-269 increased DUSP1 expression. Combined treatment with BMP2 and ET-1 induced cyclin D1 and DUSP1 expression and increased PA-SMC proliferation. MRE-269 attenuated BMP2/ET-1-induced cell proliferation. ET-1 increased DUSP1 expression in PA-SMCs from control patients but not in PA-SMCs from patients with PAH., Significance: This study showed that the p38 MAPK /DUSP1 negative feedback loop is impaired in PAH, contributing to unregulated p38 MAPK activation and PA-SMC hyperplasia. IP receptor agonist MRE-269 increases DUSP1 expression and inhibit p38 MAPK -mediated PA-SMC proliferation. Future elucidation of the detailed mechanism underlying reduced DUSP1 expression would be informative for PAH treatment., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Strongyloides is a genus of parasitic nematodes of vertebrates comprising approximately 50 documented species, each with various host ranges. Among these, three species (S. stercoralis, S. fuelleborni, and S. cebus) are known to infect primate hosts. S. fuelleborni typically infects non-human primates in the Old World. To complement the existing information on the global genetic structure of this species, we conducted a genotyping study of S. fuelleborni samples collected from rhesus macaques in Myanmar, Japanese macaques in Japan, and some zoo-kept primates. This study identified a novel haplotype group in isolates from the Myanmar rhesus macaques. Subsequently, we obtained the complete or nearly complete mitochondrial genome sequences of S. fuelleborni, S. cebus (Strongyloides of New World monkeys), and S. vituli (Strongyloides of cattle). Phylogenetic analysis based on concatenated mitochondrial protein sequences of various Strongyloides species indicated a close relationship between S. fuelleborni, S. vituli and S. papillosus (Strongyloides in sheep and cattle). S. cebus is quite distantly related to both S. fuelleborni and S. stercoralis, which led to the hypothesis that the three primate Strongyloides species evolved independently as parasites of primates., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Transforming growth factor (TGF)-β/Smad pathway is implicated in the pathogenesis of liver fibrosis, a condition characterized by excessive deposition of extracellular matrix (ECM) proteins such as collagen in response to chronic inflammation. It has been reported that ceramide regulates collagen production through TGF-β/Smad pathway activation. In this study, we examined whether miglustat, an inhibitor of glucosylceramide synthase, can suppress liver fibrosis by reducing TGF-β/Smad pathway activity. Human hepatic stellate cells (HHSteCs) were cultured with TGF-β and multiple miglustat concentrations to examine dose-dependent effects on the expression levels of ECM-related genes and Smad proteins. To evaluate the efficacy of miglustat for fibrosis mitigation, C57BL/6 mice were treated with carbon tetrachloride (CCl 4 ) for 4 weeks to induce liver fibrosis, followed by combined CCl 4 plus miglustat for a further 2 weeks. To examine if miglustat can also prevent fibrosis, mice were treated with CCl 4 for 2 weeks, followed by CCl 4 plus miglustat for 2 weeks. Miglustat dose-dependently downregulated expression of α-smooth muscle actin and ECM components in TGF-β-treated HHSteCs. Both phosphorylation and nuclear translocation of Smad2 and Smad3 were also suppressed by miglustat treatment. Sirius-Red staining and hydroxyproline assays of model mouse liver samples revealed that miglustat reduced fibrosis, an effect accompanied by decreased expression of ECM. Our findings suggest that miglustat can both prevent and reverse liver fibrosis by inhibiting TGF-β/Smad pathway., 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 © 2022 Elsevier Inc. All rights reserved.)

To mitigate radioactive cesium from soil to plant, increasing and maintaining the exchangeable potassium (ExK) level during growth is widely accepted after Tokyo Electric Company's Fukushima Dai-ichi Nuclear Plant accident in Japan. This is because the antagonistic relationship between soil solution K and 134 Cs + 137 Cs (RCs) concentrations changes the transfer factor (TF: designated as the ratio of radioactivity of plant organ to soil) of RCs. As the relationship between ExK and TF depends on the soil types, crop species, and other environmental factors, the required amount of ExK should be set to a safe side. Eleven years after the accident, as the activity of 134 Cs was almost negligible, 137 Cs became the main RCs in most of the agricultural fields in Fukushima Prefecture. We propose a new indicator, the concentration ratio of plant 137 Cs to soil exchangeable 137 Cs (Ex 137 Cs), instead of TF, which showed a better correlation with ExK even among soils with different properties (or mineralogy)., 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 © 2022 Elsevier B.V. All rights reserved.)

Background: Osimertinib has demonstrated impressive efficacy as a first-line treatment for patients with advanced epidermal growth factor receptor (EGFR) mutation-positive (m+) lung cancer. Drug-related pneumonitis (DRP) is a potentially lethal complication of osimertinib treatment, but reliable real-world data currently are lacking., Research Question: What is the prevalence of osimertinib-induced DRP in first-line settings? What are the characteristics, clinical impact, and risk factors of osimertinib-induced DRP?, Study Design and Methods: We conducted a retrospective multicenter cohort study of patients who received osimertinib as a first-line treatment for advanced EGFR m+ non-small cell lung cancer (NSCLC) between August 2018 and December 2019. All chest CT scans and clinical information during osimertinib exposure were collected until June 2020. The primary end point was DRP incidence identified through central review., Results: A total of 452 patients from 18 institutions were evaluated. Eighty patients (18%) had a diagnosis of DRP (all grades), and 21 patients (4.6%) had a diagnosis of grade 3 or more DRP. Among the patients with DRP, 46% were identified as having transient asymptomatic pulmonary opacity (TAPO). Regarding the CT scan patterns, organizing pneumonia, simple pulmonary eosinophilia, hypersensitivity pneumonia, diffuse alveolar damage, and nonspecific interstitial pneumonia were found in 30, 21, 18, 9, and two patients (38%, 26%, 23%, 11%, and 3%), respectively. In multivariate analysis, smoking history was identified as an independent risk factor for DRP (hazard ratio, 1.72; 95% CI, 1.01-2.89; P = .046). In the 3-month landmark analysis, DRP was associated with poor treatment efficacy; however, the presence of TAPO did not affect treatment efficacy negatively., Interpretation: For osimertinib treatment in first-line settings, the frequency of DRP was considerably elevated to 18 %, and half of these patients exhibited TAPO features., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to detect specific motor unit (MU) abnormalities in people with amyotrophic lateral sclerosis (ALS) compared to controls using high-density surface electromyography (HD-SEMG)., Methods: Sixteen people with ALS and 16 control subjects. The participants performed ramp up and sustained contractions at 30% of their maximal voluntary contraction. HD-SEMG signals were recorded in the vastus lateralis muscle and decomposed into individual MU firing behavior using a convolution blind source separation method., Results: In total, 339 MUs were detected (people with ALS; n = 93, control subjects; n = 246). People with ALS showed significantly higher mean firing rate, recruitment threshold, coefficient of variation of the MU firing rate, MU firing rate at recruitment, and motoneurons excitability than those of control subjects (p < 0.001). The number of MU, MU firing rate, recruitment threshold, and MU firing rate at recruitment were significantly correlated with disease severity (p < 0.001). Multivariable analysis revealed that an increased MU firing rate at recruitment was independently associated with ALS., Conclusions: These results suggest increased excitability at recruitment, which is consistent with neurodegeneration results in a compensatory increase in MU activity., Significance: Abnormal MU firing behavior provides an important physiological index for understanding the pathophysiology of ALS., 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 © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Although hypercoagulability using D-dimer levels may be a useful marker for predicting outcomes in ischemic stroke patients with cancer, other biological markers for predicting outcomes are unclear. We aimed to investigate the associations between several biological markers and short-term or long-term outcomes among ischemic stroke patients with cancer., Methods: Consecutive acute ischemic stroke patients with cancer (n = 309) were registered. Biological markers such as hemoglobin, albumin, C-reactive protein and D-dimer levels were assessed. Stroke outcomes, namely, a 3-month modified Rankin Scale score indicating poor functional outcome (mRS score of 3-6) and 1-year survival, were assessed., Results: Of the 277 patients who could be assessed for 3 months outcome, 131 patients (47.3%) had a poor outcome at 3 months. Multivariable analysis revealed that increased D-dimer levels and decreased albumin levels were independently associated with poor stroke outcomes (adjusted odds ratio [aOR]: 1.04, 95% confidence interval [CI]: 1.00-1.08, and aOR: 0.50, 95% CI: 0.31-0.80, respectively). Of 309 patients, 70 patients (22.7%) died during the follow-up period (median, 241 days). Multivariate Cox proportional hazard analyses showed that high D-dimer levels and hypoalbuminemia were independently associated with mortality (adjusted hazard ratio [aHR]: 2.65, 95% CI: 1.37-5.12, and aHR: 2.29, 95% CI: 1.21-4.49, respectively). The effect of each biological marker on mortality was notably observed among patients with active cancer but not among those with nonactive cancer., Conclusion: Low albumin levels were independently associated with short- and long-term outcomes, as were D-dimer levels, in acute ischemic stroke patients with cancer., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To study the longitudinal seizure outcomes of people with epilepsy (PWE) following the acute and chronic phases of the coronavirus disease 2019 (COVID-19) pandemic., Methods: Consecutive PWE who were treated at the epilepsy center of Hiroshima University Hospital between 2018 and 2021 were enrolled. We evaluated the incidence of seizure frequency increase or decrease following the pandemic during observational periods in 2020 and 2021. Data between 2018 and 2019 were used as a control set. The sustainability of the altered seizure frequency condition was evaluated throughout the study period. We analyzed the clinical, psychological, and social factors associated with PWE with seizure exacerbation or amelioration., Results: Among the 223 PWE who were evaluated (mean age 37.8 ± 16.3 years), seizure frequency increased for 40 (16.8%) and decreased for 34 (15.2%) after the pandemic began. While seizure exacerbation tended to be a transient episode during 2020, seizure amelioration was likely to maintain excellent status over the observation periods; the sustainability of the altered seizure frequency condition was more prominent for amelioration than exacerbation (p < 0.001). Seizure exacerbation was significantly associated with "no housemate" (odds ratio [OR] 3.37; p = 0.045) and "comorbidity of insomnia" (OR 5.80; p = 0.004). Conversely, "structural abnormality of MRI" (OR 2.57; p = 0.039) and "two-generation householding" (OR 3.70; p = 0.004) were independently associated with seizure amelioration., Conclusion: This longitudinal observation confirmed that seizure exacerbation and amelioration emerged during the COVID-19 pandemic. The COVID-19 pandemic has shed light on the stark difference that social support systems can make on outcomes for PWE., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Mutations in optineurin (OPTN) have been identified in a small proportion of sporadic and familial amyotrophic lateral sclerosis (ALS) cases. Recent evidences suggest that OPTN would be involved in not only the pathophysiological mechanisms of motor neuron death of ALS but also myofiber degeneration of sporadic inclusion body myositis. However, the detailed role of OPTN in muscle remains unclear. Initially, we showed that OPTN expression levels were significantly increased in the denervated muscles of mice, suggesting that OPTN may be involved in muscle homeostasis. To reveal the molecular role of OPTN in muscle atrophy, we used cultured C2C12 myotubes treated with tumor necrosis factor-like inducer of apoptosis (TWEAK) as an in vitro model of muscle atrophy. Our data showed that OPTN had no effect on the process of muscle atrophy in this model. On the other hand, we found that myogenic differentiation was affected by OPTN. Immunoblotting analysis showed that OPTN protein levels gradually decreased during C2C12 differentiation. Furthermore, OPTN knockdown inhibited C2C12 differentiation, accompanied by reduction of mRNA and protein expression levels of myogenin and MyoD. These findings suggested that OPTN may have a novel function in muscle homeostasis and play a role in the pathogenesis of neuromuscular diseases., (Copyright © 2021 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

Introduction: Although phase 2 and 3 clinical trials in Japan showed that zonisamide improved wearing off in patients with Parkinson's disease (PD), no studies to date have evaluated whether zonisamide improves wearing off in patients with PD without exacerbating dyskinesia. Therefore, we examined this hypothesis in a post hoc analysis of pooled data from the previous phase 2 and 3 trials., Methods: Both trials evaluated zonisamide 25 mg and 50 mg versus placebo during a 12-week treatment period. In our analysis, primary efficacy variables were adjusted mean change in wearing off (evaluated as change in "off" time) and dyskinesia from baseline to 12 weeks. Dyskinesia was evaluated using Unified Parkinson's Disease Rating Scale (UPDRS) part 4 items 32 (4-32; duration of dyskinesia) and 33 (4-33; disability of dyskinesia) score. Criteria outcomes included rates of patients meeting specific criteria based on off time plus UPDRS part 4-32 or 4-33., Results: A total of 212 patients were included in this analysis. Zonisamide 50 mg significantly reduced off time and UPDRS part 4-33 score at week 12 versus placebo without increasing UPDRS part 4-32 score. The proportion of patients receiving zonisamide 50 mg who met the criterion "Off time decreased and UPDRS part 4-33 score did not increase" was significantly higher than that of patients receiving placebo., Conclusion: Zonisamide improves wearing off without exacerbating dyskinesia in Japanese patients with PD. Moreover, zonisamide 50 mg may improve dyskinesia. Further studies are needed to prospectively determine the benefits and clinical relevance of zonisamide on dyskinesia., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Small extracellular vesicles (sEV) facilitate signaling molecule transfer among cells. We examined the therapeutic efficacy of human dental pulp stem cell-derived sEV (hDPSC-sEV) against cellular senescence in an irradiated-submandibular gland mouse model. Seven-week-old mice were exposed to 25 Gy radiation and randomly assigned to control, phosphate-buffered saline (PBS), or hDPSC-sEV groups. At 18 days post-irradiation, saliva production was measured; histological and reverse transcription-quantitative PCR analyses of the submandibular glands were performed. The salivary flow rate did not differ significantly between the PBS and hDPSC-sEV groups. AQP5-expressing acinar cell numbers and AQP5 expression levels in the submandibular glands were higher in the hDPSC-sEV group than in the other groups. Furthermore, compared with non-irradiated mice, mice in the 25 Gy + PBS group showed a high senescence-associated-β-galactosidase-positive cell number and upregulated senescence-related gene (p16 INK4a , p19 Arf , p21) and senescence-associated secretory phenotypic factor (MMP3, IL-6, PAI-1, NF-κB, and TGF-β) expression, all of which were downregulated in the hDPSC-sEV group. Superoxide dismutase levels were lower in the PBS group than in the hDPSC-sEV group. In summary, hDPSC-sEV reduced inflammatory cytokine and senescence-related gene expression and reversed oxidative stress in submandibular cells, thereby preventing irradiation-induced cellular senescence. Based on these results, we hope to contribute to the development of innovative treatment methods for salivary gland dysfunction that develops after radiotherapy for head and neck cancer., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Strongyloides is a genus of parasitic nematodes of vertebrates that contains over 50 species, each with a variable host range. A recent molecular phylogenetic analysis on this genus showed that Strongyloides spp. from various carnivore hosts form a strongly supported clade together with Strongyloides stercoralis, a major pathogen of humans and dogs (named the "stercoralis/procyonis group"). In the present study, we obtained DNA sequencing data of Strongyloides sp. isolated from an imported meerkat (Suricata suricatta). Based on the phylogenetic analysis, we considered this a new member of the stercoralis/procyonis group. This study represents the first isolation and molecular characterization of a Strongyloides species from hosts belonging to the family Herpestidae (mongooses and meerkat). However, whether the meerkat serves as a natural host of this Strongyloides species remains to be investigated., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Although an inverse correlation between smoking and Parkinson's disease (PD) has been reported, research into the effect of smoking on current clinical progression remains limited for PD patients. Elucidation of a specific PD population who would benefit from smoking is challenging., Methods: We evaluated 110 consecutive PD patients (mean age; 71.0 ± 8.0 years) at a single neurology clinic between 2010 and 2018. The association with smoking status was evaluated in sex- and age-matched controls (non-PD). This study assessed the impact of previous smoking exposure on the outcome of current PD-related parameters, along with any confounders, in addition to assessing fluctuation of parkinsonism induced by smoking exposure., Results: The current smoking rate was significantly lower in PD versus non-PD (5.5% vs. 15.5%, P = 0.026), while there were similar rates between former and never smokers. Among the former smokers, most PD patients (97.3%) quit smoking prior to the onset of PD. There were no differences between PD patients with and without a history of smoking for current clinical parameters. Three PD patients with the mean onset age of 51.0 ± 5.3 y reported transient deterioration of their parkinsonism when smoking. Negative mood during cigarette smoke exposure was significantly increased over the entire life in PD patients with a history of smoking than those without (p < 0.001)., Conclusions: Although previous smoking history reportedly had a neuroprotective effect prior to onset, the association between the previous history and current phenotype in PD was not visible in the present study. However, the possibility that current nicotine intake might modify the parkinsonism deterioration will need to be further evaluated, especially in non-elderly patients. Cigarette smoke-related negative mood could be a confounder for quitting smoking in PD patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Schistosomiasis remains a worldwide public health problem, especially in sub-Saharan Africa. The World Health Organization targets the goal for its elimination as a public health problem in the 2030 Neglected Tropical Diseases (NTDs) Roadmap. Concerted action and agile responses to challenges will be necessary to achieve the targets. Better diagnostic tests can accelerate progress towards the elimination by monitoring disease trends and evaluating the effectiveness of interventions; however, current examinations such as Kato-Katz technique are of limited power to detect light-intensity infections. The point-of-care circulating cathodic antigen (POC-CCA) test shows a higher sensitivity compared to the reference standard, Kato-Katz technique, but it still lacks sufficient sensitivity with low infection intensity. In this study, we examined antibody reactions against recombinant protein antigens; Schistosoma mansoni serine protease-inhibitor (SmSerpin) and RP26, by enzyme-linked immunosorbent assay (ELISA) in plasma samples with light-intensity infection. The sensitivity using the cocktail antigen of recombinant SmSerpin and RP26 showed 83.7%. The sensitivity using S. mansoni soluble egg antigen (SmSEA) was 90.8%, but it showed poor specificity (29.7%), while the cocktail antigen presented improved specificity (61.4%). We conclude that antibody detection to the SmSerpin and RP26 protein antigens is effective to detect S. mansoni light-intensity infections. Our study indicates the potential of detecting antibody against recombinant protein antigens to monitor the transmission of schistosomiasis in low endemicity contexts., (Copyright © 2021. Published by Elsevier B.V.)

Treatment of intractable Pneumocystis jirovecii pneumonia (PCP) patients with primaquine (PQ) in combination with clindamycin (CLDM) was conducted by the Research Group on Chemotherapy of Tropical Diseases (RG-CTD), as a kind of compassionate use. Primaquine was not nationally licensed at the time but imported by RG-CTD for the use in a clinical research to investigate safety and efficacy in malaria treatment. Eighteen Japanese adult patients thus treated were analyzed. Prior to the treatment with PQ-CLDM, most of the patients had been treated with trimethoprim-sulfamethoxazole first, all of which being followed by pentamidine and/or atovaquone treatment. This combination regimen of PQ-CLDM was effective in 16 (89%) patients and developed adverse events (AEs) in five (28%) patients. AEs included skin lesions, methemoglobinemia, and hepatic dysfunction, though none of them were serious. As a second-line or salvage treatment for PCP, PQ-CLDM appears to be a better option than pentamidine or atovaquone. Currently in Japan, both PQ and CLDM are licensed drugs but neither of them is approved for treatment of PCP. Considering the potentially fatal nature of PCP, approval of PQ-CLDM for treating this illness should be urged., Competing Interests: Declaration of competing interest All authors have no conflict of interest to declare., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Recombinant Fasciola cathepsin L-1 (rCatL1) was evaluated in enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of human fasciolosis in Japan. Quality characteristics of the test were accessed by receiver operating characteristic (ROC) analysis, with sera from fasciolosis patients (n = 10), patients with no evidence of parasitic infections (n = 29), and patients with other helminth infections (n = 119). Both the sensitivity and specificity of the test achieved 100% with the control samples. To test the performance of the assay in an authentic situation, 311 serum samples, which had been sent to our laboratory for the diagnosis of parasitic infections from January 2018 to February 2019, were re-assessed using the rCatL1 ELISA. In this case, the sensitivity of the rCatL1 ELISA was 100%, giving positive results to all fasciolosis sera (n = 7), and the specificity was 99.0%, in which three of the 304 non-fasciolosis samples were judged positive. Careful re-examination of the laboratory data and medical imaging of these three patients revealed that one of the patients, who had been diagnosed as having larva migrans syndrome, was judged to be infected with Fasciola, in addition to ascarid nematodes. Thus the true specificity of the assay in the authentic reached 99.3% (302/304). As the rCatL1 ELISA exhibited a highly significant positive likelihood ratio (152.0) and negative likelihood ratio (0.0), calculated from the 311 sample data, this rCatL1 ELISA can be used for routine screening and definitive diagnosis test for fasciolosis in reference laboratories., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Lenvatinib is one of the first-line drugs for patients with advanced hepatocellular carcinoma (HCC) and widely used around the world. However, the mechanisms underlying resistance to lenvatinib remain unclear. In this study, we conducted characteristic analyses of lenvatinib-resistant HCC cells. Lenvatinib-resistant HCC cell lines were established by exposure to serially escalated doses of lenvatinib over 2 months. The biological characteristics of these cells were examined by in vitro assays. To investigate the cytokine profile of lenvatinib-resistant HCC cells, the supernatant derived from lenvatinib-resistant Huh7 cells was subjected to nitrocellulose membrane-based sandwich immunoassay. Both activation of the MAPK/MEK/ERK signaling pathway and upregulation of epithelial mesenchymal transition markers were observed in lenvatinib-resistant cells. Concordant with these findings, proliferation and invasion abilities were enhanced in these cells compared with control cells. Screening of a cytokine array spotted with 105 different antibodies to human cytokines enabled us to identify 16 upregulated cytokines in lenvatinib-resistant cells. Among them, 3 angiogenic cytokines: vascular endothelial growth factor (VEGF), platelet-derived growth factor-AA (PDGF-AA), and angiogenin, were increased significantly. Conditioned medium from lenvatinib-resistant cells accelerated tube formation of human umbilical vein cells. In conclusion, lenvatinib-resistant HCC cells were characterized by enhanced proliferation and invasion abilities. These findings might contribute to the establishment of new combination therapies with lenvatinib., 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 © 2021 Elsevier Inc. All rights reserved.)

We encountered an outbreak of paragonimiasis among Cambodian technical intern trainees (TITs) at a food-processing factory in Fukuoka, Japan. The patients were 20-28 years old, seven females and two males, who had been in Japan for one to four years. All of them had consumed raw or undercooked Japanese mitten crab they purchased at a local grocery store near their training place. CT images showed multiple lesions not only in the lungs but in the extrapulmonary organs as well, such as subcutaneous tissues, abdominal muscles, and mesentery, in most of the patients. Their medical records indicated that all of them acquired infection in Japan, not in Cambodia. Diagnosis was made serologically and the patients were treated with praziquantel successfully. Foreign workers and TITs are increasing in Japan so rapidly, that food borne-infections, including paragonimiasis, should be considered in people from developing countries who have exotic dietary habits., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Abstract: Escherichia albertii is an emerging foodborne pathogen. The source of the E. albertii infection in most foodborne outbreaks is unknown because E. albertii is difficult to isolate from suspected food or water. E. albertii has a broad host range among birds and can be isolated from chicken meat. In this study, PCR assay, enrichment, and isolation conditions for detecting E. albertii in chicken meat were evaluated. The growth of 47 E. albertii strains isolated in Japan between 1994 and 2018 and a type strain was evaluated in modified EC broth (mEC) and mEC supplemented with novobiocin (NmEC) and on media containing carbohydrates. The enzyme used for the nested PCR, the enrichment conditions, the most-probable-number (MPN) method, and agar media were also evaluated with chicken meat. To distinguish E. albertii from presumptive non-E. albertii bacteria, desoxycholate hydrogen sulfide lactose agar (DHL), MacConkey agar (MAC), and these agars supplemented with rhamnose and xylose (RX-DHL and RX-MAC, respectively) were used. All E. albertii strains grew in mEC and NmEC at both 36 and 42°C and did not utilize rhamnose, sucrose, or xylose. Both the first and nested PCRs with TaKaRa Ex Taq, which was 10 to 100 times more active than the other enzymes, produced positive results in enrichment culture of 25 g of chicken meat inoculated with >20 CFU of E. albertii and incubated in mEC and NmEC at 42°C for 22 ± 2 h. Thus, the first PCR was sensitive enough to detect E. albertii in chicken meat. The MPN values in mEC and NmEC were 0.5- and 2.3-fold higher than the original inoculated bacterial levels, respectively. E. albertii in chicken meat was more efficiently isolated with enrichment in NmEC (70.1 to 100%) and plating onto RX-DHL (85.4%) and RX-MAC (100%) compared with enrichment in mEC (53.5 to 83.3%) and plating onto DHL (70.1%) and MAC (92.4%). Thus, optimized conditions for the surveillance of E. albertii contamination in food and investigations of E. albertii outbreaks, including the infectious dose, were clarified., (Copyright ©, International Association for Food Protection.)

Purpose: To assess the utility of globotriaosylsphingosine (lyso-Gb 3 ) for clinical monitoring of treatment response in patients with Fabry disease receiving migalastat., Methods: A post hoc analysis evaluated data from 97 treatment-naive and enzyme replacement therapy (ERT)-experienced patients with migalastat-amenable GLA variants from FACETS (NCT00925301) and ATTRACT (NCT01218659) and subsequent open-label extension studies. The relationship between plasma lyso-Gb 3 and measures of Fabry disease progression (left ventricular mass index [LVMi], estimated glomerular filtration rate [eGFR], and pain) and the relationship between lyso-Gb 3 and incidence of Fabry-associated clinical events (FACEs) were assessed in both groups. The relationship between changes in lyso-Gb 3 and kidney interstitial capillary (KIC) globotriaosylceramide (Gb 3 ) inclusions was assessed in treatment-naive patients., Results: No significant correlations were identified between changes in lyso-Gb 3 and changes in LVMi, eGFR, or pain. Neither baseline lyso-Gb 3 levels nor the rate of change in lyso-Gb 3 levels during treatment predicted FACE occurrences in all patients or those receiving migalastat for ≥24 months. Changes in lyso-Gb 3 correlated with changes in KIC Gb 3 inclusions in treatment-naive patients., Conclusions: Although used as a pharmacodynamic biomarker in research and clinical studies, plasma lyso-Gb 3 may not be a suitable biomarker for monitoring treatment response in migalastat-treated patients.

Strongyloides stercoralis is a parasitic nematode and a major pathogen responsible for human strongyloidiasis. The presence of this species in the dog population has led to an interest in studying the phylogenetic relationships among Strongyloides spp. in carnivore hosts. In the present study, Strongyloides spp. from various carnivore hosts (raccoon, Japanese badger, Siberian weasel, raccoon dog, masked palm civet, and domestic cat) were sought. Except for civets, Strongyloides spp. were identified in all host species. Based on 18S rDNA sequences, nine OTUs (operational taxonomy units) were identified. Molecular phylogenetic analyses using 18S28S rDNA and mitochondrial cox1 (cytochrome c oxidase subunit 1) sequences clustered them into two groups. The first group (named the stercoralis/procyonis group) was comprised of six OTUs and occurred in cats, raccoon dogs, raccoons (S. procyonis), Siberian weasels, and Japanese badgers and included S. stercoralis from humans and dogs. The second group (named the planiceps group) was made up of Strongyloides spp. from raccoon dogs (two OTUs) and one OTU from Siberian weasels. Subsequent analysis using almost the full-length nucleotide sequences of protein-coding genes in their mitochondrial genomes placed Strongyloides spp. of cats in a sister taxon position to S. stercoralis, whereas S. procyonis from raccoons was more distantly related to them. The presence of Strongyloides spp. from various carnivore hosts, which are close relatives of S. stercoralis, suggests this group of Strongyloides (the stercoralis/procyonis group) essentially evolved as parasites of carnivores, although more data on Strongyloides spp. from primate hosts are needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: The association of malnutrition on stroke subtypes has not been well established. We investigated the relationship between malnutrition and functional outcome according to stroke subtypes., Methods: Acute consecutive ischemic stroke patients (n = 1915, 73 ± 12 years) were analysed. The nutritional status was evaluated using the Controlling Nutritional Status (CONUT) score, which was calculated from the serum albumin level, lymphocyte count, and total cholesterol level; malnutrition was defined as a CONUT score of 5 to 12. A poor outcome was defined as a modified Rankin Scale score ≥ 3 at 3 months., Results: Of the 1518 patients, 113 (7.4%) had malnutrition, and 533 (33.1%) had a poor outcome. Among the patients with cardioembolic stroke and stroke of other etiologies, those with malnutrition had higher rates of poor outcomes than those without. After adjusting for age, sex, and baseline stroke severity, malnutrition was independently associated with poor outcomes in patients with cardioembolic stroke and other stroke etiologies (odds ratio 3.25, 95% confidence interval 1.02-10.4, p = .044; 6.22, 2.71-14.3, p < .001, respectively)., Conclusions: Considering stroke subtype, malnutrition determined using the CONUT score was independently associated with poor outcomes in the patients with cardioembolic stroke or stroke of other etiologies., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Under the assumption that neurovascular compression can be caused by elongation or kinking of the artery, we measured the length of each section of the vertebrobasilar artery, compared the lengths between various age groups, and evaluated the involvement of the arterial sections in brain stem compression in 1000 cases. The lengths of the posterior inferior cerebellar artery (PICA)-union of both vertebral arteries (union), union-anterior inferior cerebellar artery (AICA), AICA-superior cerebellar artery (SCA), and union- superior cerebellar artery were measured using an arterial length measuring tool applied to three-dimensional images. The presence of arterial compression of the brain stem was also evaluated. The mean age of the participants was 66.8 ± 12.9 years, and 44.8% were men. Intraclass correlation coefficients for both inter-rater reliability and intra-rater reliability were high in all sections. The vessel lengths of left AICA-SCA (P < 0.001), left union-SCA (P < 0.0001), left PICA-union (P = 0.03), right AICA-SCA (P = 0.002), right union-SCA (P < 0.0001), and right PICA-union (P = 0.04) increased with age, but each R 2 was less than 0.05. Brain stem compression by PICA or vertebral artery was identified in 13.8% of cases. The proportion of the presence of brain stem compression was significantly higher in the cases with arterial elongation than in those without (P = 0.01). Vessel length increased with age, but age had a relatively small impact on the elongation of vertebrobasilar arteries. Brain stem compression might be caused by kinking of the artery rather than arterial elongation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Proliferative sparganosis is one of the most bizarre and mysterious parasitic diseases ever described. The causative parasite is Sparganum proliferum, which is a pseudophyllidean cestode distinct from Spirometra tapeworms. Here we overview this rare but fascinating disease with the all original case reports on human patients published in the last 115 years. Proliferative sparganosis is clearly divided into two disease types, cutaneous and internal proliferative sparganosis. Cutaneous type starts with a skin eruption caused by the dermal invasion of a sparganum. Skin lesion progresses to larger areas of the body if left untreated. Various internal organs and body wall can be eventually affected. The clinical symptoms of patients in this group are very similar to each other. Molecular data suggest that cutaneous proliferative sparganosis is caused by S. proliferum of which genetic variation is limited, regardless of the time or localities of the emergence of patients. Internal proliferative sparganosis, on the other hand, is much more heterogeneous. Some cases show aggressive infection in internal organs, while others show only restricted lesions. Some of the cases that had been cited as proliferative sparganosis in the past literature were removed from the list, because they were judged as cyclophyllidean tapeworm infections. DNA sequencing is mandatory for the definite diagnosis of proliferative sparganosis. The Venezuelan strain of S. proliferum is maintained in experimental mice in Japan, which is fully prepared for the experimental study with advanced technologies in modern molecular biology., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)