We investigated a case of hepatitis E acquired after persons ate wild boar meat. Genotype 3 hepatitis E virus (HEV) RNA was detected in both patient serum and wild boar meat. These findings provided direct evidence of zoonotic foodborne transmission of HEV from a wild boar to a human.
University of Hawai'i at M a anoaThe present study investigated the effects of intensive recasting on second language learners' use of the Japanese aspectual form -te i-(ru) using a time-series design. Four college classroom learners participated in 8 conversational sessions, with the researcher providing recasts during the middle 4 sessions, and 2 of the learners also participated in a delayed-posttest session after 7 weeks. Overall accuracy increased significantly in correlation with the number of recasts provided during the treatment period, and the accuracy rate was retained. However, in contrast to the prediction based on the aspect hypothesis, the progressive use of -te i-(ru) was less
Objective To evaluate the efficacy and safety of two dosing regimens of fremanezumab in Japanese and Korean patients with episodic migraine. Background Episodic migraine, which accounts for more than 90% of migraine cases, is inadequately addressed by widely available preventive therapies. Fremanezumab, a monoclonal antibody that selectively targets the trigeminal sensory neuropeptide calcitonin gene‐related peptide involved in migraine pathogenesis, has demonstrated efficacy in international Phase 3 trials of patients with both chronic and episodic migraine. Methods This Phase 3 randomized, placebo‐controlled trial randomly assigned patients with episodic migraine to receive subcutaneous fremanezumab monthly (225 mg at baseline, week 4, and week 8), fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), or matching placebo. The primary endpoint was the mean change from baseline in the monthly average number of migraine days during the 12‐week treatment period after the first dose. Results Of 357 patients enrolled (safety set, n = 356; full analysis set, n = 354), the least‐squares mean (±standard error) reductions in the average number of migraine days per month during 12 weeks were significantly greater with fremanezumab monthly (−4.0 ± 0.4, n = 121) and fremanezumab quarterly (−4.0 ± 0.4, n = 117) than with placebo (−1.0 ± 0.4, n = 116; p < 0.0001 for both comparisons). The proportion of patients reaching at least a 50% reduction in the monthly average number of migraine days during the 12‐week period after initial administration was also significantly improved with fremanezumab (fremanezumab monthly, 41.3%; fremanezumab quarterly, 45.3%; placebo, 11.2%; p < 0.0001 for both comparisons) as were other secondary endpoints (p < 0.001 for all comparisons between fremanezumab and placebo). Injection‐site reactions were more common in fremanezumab‐treated patients (fremanezumab monthly, 25.6%; fremanezumab quarterly, 29.7%; placebo, 21.4%). Conclusion Fremanezumab prevents episodic migraine in Japanese and Korean patients to a similar extent than in previously reported populations with no new safety concerns.
Several mutations in the surfactant protein C (SP-C) gene (SFTPC) have been reported as causing familial pulmonary fibrosis (FPF). However, the genetic background and clinical features of FPF are still not fully understood.We identified one Japanese kindred, in which at least six individuals over three generations were diagnosed with pulmonary fibrosis. We examined the patients radiologically and histopathologically and sequenced their SFTPC and ABCA3 genes. We also established a cell line stably expressing the mutant gene.All the patients had similar radiological and histopathological characteristics. Their histopathological pattern was that of usual interstitial pneumonia, showing numerous fibroblastic foci even in areas without abnormal radiological findings on chest high-resolution computed tomography. No child had respiratory symptoms in the kindred. Sequencing of SFTPC showed a novel heterozygous mutation, c.298G.A (G100S), in the BRICHOS domain of proSP-C, which co-segregated with the disease. However, in the ABCA3 gene, no mutation was found. In vitro expression of the mutant gene revealed that several endoplasmic reticulum stress-related proteins were strongly expressed.The mutation increases endoplasmic reticulum stress and induces apoptotic cell death compared with wild-type SP-C in alveolar type II cells, supporting the significance of this mutation in the pathogenesis of pulmonary fibrosis.
Objective To determine the efficacy and safety of fremanezumab administration in Japanese and Korean patients with chronic migraine (CM). Background Available preventive treatments for CM are limited by various efficacy and safety issues. Fremanezumab, a monoclonal antibody that targets the calcitonin gene‐related peptide pathway involved in migraine pathogenesis, has been shown to be effective and well tolerated in large‐scale, international Phase 3 trials. Methods Randomized, placebo‐controlled trial of patients with CM who received subcutaneous fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), or matching placebo. Primary endpoint was the mean change from baseline in the monthly (28‐day) average number of headache days of at least moderate severity during the 12 weeks after the first dose. Results Among 571 patients randomized (safety set, n = 569; full analysis set, n = 566), the least‐squares mean (±standard error [SE]) reduction in the average number of headache days of at least moderate severity per month during 12 weeks was significantly greater with fremanezumab monthly (–4.1 ± 0.4) and fremanezumab quarterly (–4.1 ± 0.4) than with placebo (–2.4 ± 0.4). The difference from the placebo group in the mean change (95% confidence interval [CI]) was −1.7 days (−2.54, −0.80) for the fremanezumab monthly group and −1.7 days (−2.55, −0.82) for the fremanezumab quarterly group (p < 0.001 vs. placebo for both fremanezumab groups). The percentage of patients with a ≥50% reduction in the average number of headache days of at least moderate severity per month (response rate) was higher with fremanezumab monthly (29.0%) and fremanezumab quarterly (29.1%) than with placebo (13.2%) in addition to other improvements in secondary endpoints, including reduction of acute medication use (mean change from baseline during 12‐week period ± SE: fremanezumab monthly, –3.7 ± 0.4; fremanezumab quarterly, –3.9 ± 0.4; placebo, –2.4 ± 0.4) and improvements in disability scores (mean change from baseline in six‐item Headache Impact Test score at 4 weeks after third injection ± SE: fremanezumab monthly, –8.1 ± 0.7; fremanezumab quarterly, –8.0 ± 0.7; placebo, –6.5 ± 0.7). Fremanezumab was well tolerated with a similar incidence of adverse events including injection‐site reactions as placebo (patients with at least one treatment‐emergent adverse event: fremanezumab total, n = 232 [61.4%]; placebo, n = 118 [61.8%]). Conclusion Fremanezumab effectively prevents CM in Japanese and Korean patients and was well tolerated. No safety signal was detected.
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