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The number of dengue cases has increased dramatically in recent years. In Latin America, the number of cases and deaths in 2023 was the highest ever recorded. We report on a patient who had been infected with dengue virus during his stay in Costa Rica in September 2023, and developed the disease after returning to Japan. Plasma obtained from the patient was used for diagnosis and dengue virus serotyping by real-time PCR. The nucleotide sequence of the envelope region of dengue virus was then determined by the direct sequencing method, and this sequence was used for phylogenetic analyses. The patient was found to be infected with dengue virus type 3 genotype III. The sequence from the present case was more homologous with sequences registered in Florida, USA, associated with travel to Cuba in 2022 than with sequences registered in Costa Rica 10 years ago. The Pan American Health Organization reported that only dengue virus type 1 and 2 cases were reported in Costa Rica in 2019–2021, whereas dengue virus type 3 and 4 cases started being reported in 2022. In 2023, the reported numbers of cases with dengue virus types 3 and 4 exceeded those of dengue virus types 1 and 2. In addition, regional differences in endemic strains have been observed in Costa Rica. Our findings suggest that the dengue virus type 3 that infected the patient was more likely an influx of a strain that had been circulating in Caribbean countries such as Cuba in recent years, rather than a re-emergence of an indigenous virus in Costa Rica. The serotypes of dengue virus prevalent in Costa Rica have been changing since 2022. All four serotypes were prevalent in 2023, with a particularly sharp increase in the number of cases of dengue virus types 3 and 4. Future monitoring and surveillance are essential because changes in endemic serotypes can cause antibody-dependent enhancement, which can lead to severe dengue disease presentations.

The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the resulting Omicron subvariants display further immune evasion and antibody escape. An engineered angiotensin-converting enzyme 2 (ACE2) decoy composed of high-affinity ACE2 and an IgG1 Fc domain could offer an alternative modality to neutralize SARS-CoV-2. We previously reported its broad spectrum and therapeutic potential in rodent models. Here, we demonstrate that the engineered ACE2 decoy retains neutralization activity against Omicron subvariants, including the currently emerging XBB and BQ.1 strains, which completely evade antibodies currently in clinical use. SARS-CoV-2, under the suboptimal concentration of neutralizing drugs, generated SARS-CoV-2 mutants escaping wild-type ACE2 decoy and monoclonal antibodies, whereas no escape mutant emerged against the engineered ACE2 decoy. Furthermore, inhalation of aerosolized decoys improved the outcomes of rodents infected with SARS-CoV-2 at a 20-fold lower dose than that of intravenous administration. Last, the engineered ACE2 decoy exhibited therapeutic efficacy for cynomolgus macaques infected with SARS-CoV-2. These results indicate that this engineered ACE2 decoy represents a promising therapeutic strategy to overcome immune-evading SARS-CoV-2 variants and that liquid aerosol inhalation could be considered as a noninvasive approach to enhance the efficacy of COVID-19 treatments.

ABSTRACTChikungunya fever is a mosquito-borne disease of key public health importance in tropical and subtropical countries. Although severe joint pain is the most distinguishing feature of chikungunya fever, diagnosis remains difficult because the symptoms of chikungunya fever are shared by many pathogens, including dengue fever. The present study aimed to develop a new immunochromatographic diagnosis test for the detection of chikungunya virus antigen in serum. Mice were immunized with isolates from patients with Thai chikungunya fever, East/Central/South African genotype, to produce mouse monoclonal antibodies against chikungunya virus. Using these monoclonal antibodies, a new diagnostic test was developed and evaluated for the detection of chikungunya virus. The newly developed diagnostic test reacted with not only the East/Central/South African genotype but also with the Asian and West African genotypes of chikungunya virus. Testing of sera from patients suspected to have chikungunya fever in Thailand (n= 50), Laos (n= 54), Indonesia (n= 2), and Senegal (n= 6) revealed sensitivity, specificity, and real-time PCR (RT-PCR) agreement values of 89.4%, 94.4%, and 91.1%, respectively. In our study using serial samples, a new diagnostic test showed high agreement with the RT-PCR within the first 5 days after onset. A rapid diagnostic test was developed using mouse monoclonal antibodies that react with chikungunya virus envelope proteins. The diagnostic accuracy of our test is clinically acceptable for chikungunya fever in the acute phase.

ABSTRACTSince its emergence in April 2009, pandemic influenza A virus H1N1 (H1N1 pdm), a new type of influenza A virus with a triple-reassortant genome, has spread throughout the world. Initial attempts to diagnose the infection in patients using immunochromatography (IC) relied on test kits developed for seasonal influenza A and B viruses, many of which proved significantly less sensitive to H1N1 pdm. Here, we prepared monoclonal antibodies that react with H1N1 pdm but not seasonal influenza A (H1N1 and H3N2) or B viruses. Using two of these antibodies, one recognizing viral hemagglutinin (HA) and the other recognizing nucleoprotein (NP), we developed kits for the specific detection of H1N1 pdm and tested them using clinical specimens of nasal wash fluid or nasopharyngeal fluid from patients with influenza-like illnesses. The specificities of both IC test kits were very high (93% for the HA kit, 100% for the NP kit). The test sensitivities for detection of H1N1 pdm were 85.5% with the anti-NP antibody, 49.4% with the anti-HA antibody, and 79.5% with a commercially available influenza A virus detection assay. Use of the anti-NP antibody could allow the rapid and accurate diagnosis of H1N1 pdm infections.

Anomalously large substrate current has been observed in a metal--oxide--semiconductor field-effect transistor (MOSFET) with a large channel width of 1600 \mbox{$\mu$m}. The magnitude of the substrate current per unit channel width is approximately 2 orders larger than that of a MOSFET with a channel width of 100 \mbox{$\mu$m} when they are compared at the maxima. Furthermore, the substrate current measured as a function of gate voltage could not be fit to a typical simulation model based on the conventional theory of impact ionization. In addition to the substrate current, anomalies were also observed in the drain current and the gate leakage current measured simultaneously with the substrate current. To explain the interrelation of the anomalous phenomena, we have introduced a hypothesis in which two modes of impact ionization are excited in the respective voltage regions generating electron--hole pairs in specific directions.

A new micelle capillary electrophoresis based on cyclodextrin micellar electrokinetic chromatography (MEKC) for the determination of bisphenol A and 10 alkylphenols in rat serum is reported. Several surfactants and dextrins were studied. Bisphenol A and alkylphenols were separated using a 50 µm × 50 cm capillary with 20 mMborate phosphate buffer (pH 8.0) containing 20 mMsodium dodecylsulfate and 5 mMγ‐cyclodextrin as carrier. The method could determine 0.6–2000 µg/mL of phenols in 100 µL serum by photometric detection at 214 nm. Using 2.0 mL serum, 1.0 ng/mL of phenols could be determined. The relative standards deviations were 6.3–7.7% at 10 µg/mL in serum. The recoveries were 91.8–93.0% with 10 µg/mL serum samples. Copyright © 2001 John Wiley & Sons, Ltd.

A new micelle capillary electrophoresis based on cyclodextrin micellar electrokinetic chromatography (MEKC) for the determination of bisphenol A and 10 alkylphenols in rat serum is reported. Several surfactants and dextrins were studied. Bisphenol A and alkylphenols were separated using a 50 µm × 50 cm capillary with 20 mM borate phosphate buffer (pH 8.0) containing 20 mM sodium dodecylsulfate and 5 mM γ-cyclodextrin as carrier. The method could determine 0.6–2000 µg/mL of phenols in 100 µL serum by photometric detection at 214 nm. Using 2.0 mL serum, 1.0 ng/mL of phenols could be determined. The relative standards deviations were 6.3–7.7% at 10 µg/mL in serum. The recoveries were 91.8–93.0% with 10 µg/mL serum samples. Copyright © 2001 John Wiley & Sons, Ltd.

A new and sensitive high-performance chromatographic method for the determination of bisphenol A and 8 alkylphenols with fluorescence detection is reported. Each phenol was derivatized by reaction with 2-(4-carboxyphenyl)-5,6-dimethylbenzimidazole at 40°C for 60 min. The fluorescence derivatives were separated on a Wakosil 5C18 column (4.0 i.d. × 300 mm, 5 µm) with methanol:water (10:90) as mobile phase (detection wavelength: λex 336 nm, λem 440 nm). The detection limits were in the range of 0.1–10.0 pg/mL in serum. The calibration graphs were linear to 1.0 µg/mL. The relative standard deviations were 7.2–8.9%, respectively. The proposed method was applied to the determination of bisphenol A in mother and infant rat serum. Copyright © 2001 John Wiley & Sons, Ltd. Abbreviations used: CDB 2-(4-carboxyphenyl)-5,6-dimethylbenzimidazole ED endocrine discriptor IDC 1-isopropyl-3-(3-dimethylaminopropyl) carbodiimide perchlorate.

A new and sensitive high‐performance chromatographic method for the determination of bisphenol A and 8 alkylphenols with fluorescence detection is reported. Each phenol was derivatized by reaction with 2‐(4‐carboxyphenyl)‐5,6‐dimethylbenzimidazole at 40°C for 60 min. The fluorescence derivatives were separated on a Wakosil 5C18 column (4.0 i.d. × 300 mm, 5 µm) with methanol:water (10:90) as mobile phase (detection wavelength: λex336 nm, λem440 nm). The detection limits were in the range of 0.1–10.0 pg/mL in serum. The calibration graphs were linear to 1.0 µg/mL. The relative standard deviations were 7.2–8.9%, respectively. The proposed method was applied to the determination of bisphenol A in mother and infant rat serum. Copyright © 2001 John Wiley & Sons, Ltd.

Five new yohimbine-type indole alkaloids were isolated from the leaves of Tabernaemontana corymbosa. Their structures were determined on the basis of the NMR and Circular Dichroism (CD) spectroscopy.

A statistical approach has been exploratively applied to extract an influential factor of anomalous decreases in drain current observed in metal--oxide--semiconductor field-effect transistors with large channel widths. Since negative slopes were detected in drain current vs drain voltage ($I_{\text{d}}$--$V_{\text{ds}}$) curves even with negligible heat quantity or density, the self-heating effect was excluded as the primary factor. In contrast, the aspect ratio of the device areas showed a significant influence. These results support the validity of a hypothesis, namely, that acoustic standing waves are excited and thereby the probabilities of impact ionizations are synchronously magnified in the devices.