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Key Clinical Message: Most drugs that cause adverse events are difficult to identify in critically ill patients undergoing polypharmacy. We share our experience in identifying the causative drug among four suspect drugs administered during emergency treatment. We present the case of a 93‐year‐old man who was admitted for the treatment of cerebrovascular events. The patient was initially prescribed dual antiplatelet therapy with aspirin and clopidogrel along with lansoprazole, Hange‐koboku‐toh, and elobixibat. On day 36 after admission, the patient was found to have developed agranulocytosis. To improve his cerebrovascular prognosis, we first discontinued medications other than the anticoagulant medicines and initiated filgrastim. We discontinued clopidogrel 9 days after the discontinuation of the other medicines considering his low white blood cell count. One day after the discontinuation of clopidogrel, the agranulocytosis was alleviated. Considering the time course, clopidogrel, lansoprazole, Hange‐koboku‐toh, and elobixibat were suspected as the culprit medicines. This case highlights the considerable challenges encountered in clinical practice when attempting to identify the drugs responsible for agranulocytosis, particularly in patients on intensive medication therapy. [ABSTRACT FROM AUTHOR]

Vaccine development for herpes simplex virus 2 (HSV‐2) has been attempted, but no vaccines are yet available. A plasmid‐based reverse genetics system for Rotavirus (RV), which can cause gastroenteritis, allows the generation of recombinant RV containing foreign genes. In this study, we sought to develop simian RV (SA11) as a vector to express HSV‐2 glycoprotein D (gD2) and evaluated its immunogenicity in mice. We generated the recombinant SA11‐gD2 virus (rSA11‐gD2) and confirmed its ability to express gD2 in vitro. The virus was orally inoculated into suckling BALB/c mice and into 8‐week‐old mice. Serum IgG and IgA titers against RV and gD2 were measured by ELISA. In the 8‐week‐old mice inoculated with rSA11‐gD2, significant increases in not only antibodies against RV but also IgG against gD2 were demonstrated. In the suckling mice, antibodies against RV were induced, but gD2 antibody was not detected. Diarrhea observed after the first inoculation of rSA11‐gD2 in suckling mice was similar to that induced by the parent virus. A gD2 expressing simian RV recombinant, which was orally inoculated, induced IgG against gD2. This strategy holds possibility for genital herpes vaccine development. [ABSTRACT FROM AUTHOR]

A reverse genetics technology is an incredibly useful technique both for a proper understanding of different aspects of virus biology and for the generation of complementary DNA (cDNA)‐derived infectious viruses, which can act as safe and effective vaccines and viral vectors. Rotaviruses (RVAs), especially human RVAs (HuRVAs), had been very refractory to this technology until very recently. Here, we describe the historical background of the development of a long‐awaited HuRVA reverse genetics system, culminating in the generation of replicative HuRVAs entirely from cloned cDNAs. [ABSTRACT FROM AUTHOR]

Group A rotavirus (RVA) is a major cause of acute gastroenteritis in infants and young children worldwide. This study aims to clarify the distribution of G/P types and genetic characteristics of RVAs circulating in Thailand. Between January 2014 and September 2016, 1867 stool specimens were collected from children and adults with acute gastroenteritis in six provinces in Thailand. RVAs were detected in 514/1867 (27.5%) stool specimens. G1P[8] (44.7%) was the most predominant genotype, followed by G3P[8] (33.7%), G2P[4] (11.5%), G8P[8] (7.0%), and G9P[8] (1.3%). Unusual G3P[9] (0.8%), G3P[10] (0.4%), G4P[6] (0.4%), and G10P[14] (0.2%) were also detected at low frequencies. The predominant genotype, G1P[8] (64.4%), in 2014 decreased to 6.1% in 2016. In contrast, the frequency of G3P[8] markedly increased from 5.5% in 2014 to 65.3% in 2015 and 89.8% in 2016. On polyacrylamide gel electrophoresis, most (135/140; 96.4%) of the G3P[8] strains exhibited a short RNA profile. Successful determination of the nucleotide sequences of the VP7 genes of 98 G3P[8] strains with a short RNA profile showed that they are all equine‐like G3P[8] strains. On phylogenetic analysis of genome segments of two representative Thai equine‐like G3P[8] strains, it was noteworthy that they possessed distinct NSP4 genes, one bovine‐like and the other human‐like. Thus, we found that characteristic equine‐like G3P[8] strains with a short RNA electropherotype are becoming highly prevalent in children and adults in Thailand. Highlight: The frequency of G3P[8] markedly increased in Thailand.The emerged strains were identified as equine‐like G3P[8] strains.Equine‐like G3P[8] strains are becoming highly prevalent in Thailand. [ABSTRACT FROM AUTHOR]

The emergence and rapid spread of novel DS‐1‐like intergenogroup reassortant rotaviruses having the equine‐like G3 genotype (DS‐1‐like G3P[8] strains) have been recently reported from several countries. During rotavirus surveillance in Japan in 2015–2016, three DS‐1‐like G3P[8] strains were identified from children with severe diarrhea. In the present study, we sequenced and characterized the full genomes of these three strains. On full‐genomic analysis, all three strains showed a unique genotype constellation including both genogroup 1 and 2 genes: G3‐P[8]‐I2‐R2‐C2‐M2‐A2‐N2‐T2‐E2‐H2. Phylogenetic analysis revealed that each of the 11 genes of the three strains was closely related to that of Japanese DS‐1‐like G1P[8] and/or Japanese equine‐like G3P[4] human strains. Thus, the three study strains were suggested to be reassortants that acquired the G3‐VP7 gene from equine G3 rotaviruses on the genetic background of DS‐1‐like G1P[8] strains. Our observations will provide important insights into the evolutionary dynamics of emerging DS‐1‐like G3P[8] strains. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most common and feared cancers faced by women. The prognosis of patients with advanced or recurrent breast cancer remains poor despite refinements in multimodality therapies involving chemotherapeutic and hormonal agents. Multimodal therapy with more specific and effective strategy is urgently needed. The oncolytic herpes simplex virus (HSV) has potential to become a new effective treatment option because of its broad host range and tumor selective viral distribution. Bevacizumab is a monoclonal antibody against VEGFA, which inhibits angiogenesis and therefore tumor growth. Our approach to enhance the antitumor effect of the oncolytic HSV is to combine oncolytic HSV HF10 and bevacizumab in the treatment of breast cancer. Our results showed that bevacizumab enhanced viral distribution as well as tumor hypoxia and expanded the population of apoptotic cells and therefore induced a synergistic antitumor effect. HF10 is expected to be a promising agent in combination with bevacizumab in the anticancer treatment. [ABSTRACT FROM AUTHOR]