Explore the vast range of titles available.

The quadrivalent (q) human papillomavirus (HPV) vaccine protects against infection and disease related to HPV types 6, 11, 16, and 18. We report efficacy, immunogenicity, and safety of qHPV vaccine in a Phase 3 study in Japanese men. In this randomized, double-blind trial (NCT01862874), Japanese men (aged 16–26 years) were randomized in a 1:1 ratio to receive three doses of qHPV vaccine or placebo (Day 1, Month 2, Month 6). The primary efficacy endpoint was the combined incidence of HPV6/11/16/18-related persistent anogenital infection (detected at ≥2 consecutive visits ≥6 months apart), assessed in the per-protocol population of men who received all three vaccinations, and were seronegative at Day 1 and PCR negative from Day 1 to Month 7 to the relevant HPV type. Results are from the interim and final analyses. In total, 1124 participants were randomized. The vaccine demonstrated 83.3% (95% confidence interval: 24.9, 98.2; p = 0.007) and 85.9% (95% confidence interval: 52.7, 97.3; p < 0.001) efficacy against HPV6/11/16/18-related persistent infection in the interim and final analyses, respectively. Two cases of HPV6/11/16/18-related external genital lesions (condyloma and PIN 1) were observed in the placebo group and none in the qHPV vaccine group at study end. At Month 7, >97% of participants who received qHPV vaccine seroconverted to each of the vaccine HPV types. Most participants remained seropositive at Month 36, although the seropositivity rate declined between Months 7 and 36. Vaccination-related adverse events were reported in 60.8% and 56.5% of participants in the qHPV vaccine and placebo groups, respectively; most commonly mild to moderate injection-site pain, erythema, and swelling. Injection-site pain and swelling were more common with qHPV vaccine than placebo (each p < 0.05). Results suggest qHPV vaccine is efficacious against HPV6/11/16/18-related persistent infections, immunogenic, and well-tolerated in Japanese men. Clinical trial registration identifier: NCT01862874.

Cytomegalovirus (CMV) infection can cause newborn morbidity and mortality; no pharmacological method of reducing CMV infection during pregnancy is currently available. In a phase 1 study in the United States, V160, a conditionally replication-defective CMV vaccine, was immunogenic and well tolerated. This placebo-controlled study (NCT03840174) investigated the safety and immunogenicity of a three-dose V160 vaccine administered over six months. A total of 18 healthy adult Japanese males (9 seronegative and 9 seropositive) were enrolled at a single center and randomized 2:1 to intramuscular V160 or placebo. In vitro, V160 induced high CMV-specific neutralizing antibody (NAb) titers (50% neutralization titer [NT50], 3651; 95% confidence interval [CI], 1688–7895) in the CMV-seronegative per-protocol immunogenicity (PPI) population one month after the third vaccine dose was administered compared with no change in the placebo arm (NT50, <94; 95% CI <94–115). The geometric mean titer ratio in the seronegative population versus baseline was 77.7 (95% CI, 23.9–252.4). CMV NAb titers in the CMV-seropositive PPI population were similar to baseline NAb titers observed in the CMV-seropositive population. V160 was well tolerated, and no vaccine viral DNA shedding was observed. In conclusion, the immunogenicity and safety profile of V160 in Japanese participants was consistent with other populations.

Surgical decannulation for venoarterial extracorporeal membrane oxygenation (VA-ECMO) is recommended as a standard weaning strategy considering large-sized cannulas (14-22 French) are inserted in VA-ECMO. However, we should be aware of complications such as bleeding and infection when removing an arterial cannula, especially in facilities without on-site cardiac surgical backup. Percutaneous closure devices for femoral arterial access sites are currently approved for the decannulation of a 10-French or smaller sheath. We reported a case of successful weaning off from ECMO using a combination method of a balloon catheter and a Perclose ProGlide closure device. We successfully removed the arterial cannula using this technique for four ECMO-treated patients without vascular complications or blood transfusion. Percutaneous decannulation by this method could reduce the procedural time and adverse events and be safely performed even in facilities without on-site cardiac surgical backup.

The purpose is to evaluate quantified kidney echogenicity as a biomarker for the early diagnosis of acute kidney injury (AKI) and predicting progression to chronic kidney disease (CKD) in a mouse model of ischemia–reperfusion injury (IRI). Two separate protocols of murine models of IRI were used: (1) 10, 30, and 40 min of bilateral ischemia duration and (2) 45 and 60 min of unilateral ischemia duration. Renal echogenicity was measured with ultrasound and compared with serum creatinine or urine neutrophil gelatinase-associated lipocalin (NGAL) at various timepoints after IRI. In mice subjected to 10, 30, and 40 min of bilateral ischemia, renal echogenicity increased about 2 h after IRI for all ischemia times, earlier than serum creatinine or urine NGAL. In those subjected to 45 and 60 min of unilateral ischemia, 60 min of unilateral ischemia, which represents atrophic changes 28 days after IRI, resulted in a sustained high level of echogenicity and was significantly different 24 h after IRI, while 45 min of unilateral ischemia resulted in trivial levels of histological damage 28 days after IRI. Renal echogenicity might have the potential to be a biomarker for the early diagnosis of AKI and the prognosis of CKD.

  The Society for the Promotion of Japanese Literature has made special efforts for the commemorative event, but observers say the authority the semi-annual prizes carry sometimes makes it difficult for society to explore new horizons. To name a few, Keita Genji (1912-1985) blossomed as a writer who depicted the lives of salaried workers, while Toyoko Yamazaki served as a leading figure in the genre of fiction that revealed the roots of social problems until her death last year.

The life span of intestinal epithelial cells (IECs) is short (3-5 days), and its regulation is thought to be important for homeostasis of the intestinal epithelium. We have now investigated the role of commensal bacteria in regulation of IEC turnover in the small intestine. The proliferative activity of IECs in intestinal crypts as well as the migration of these cells along the crypt-villus axis were markedly attenuated both in germ-free mice and in specific pathogen-free (SPF) mice treated with a mixture of antibiotics, with antibiotics selective for Gram-positive bacteria being most effective in this regard. Oral administration of chloroform-treated feces of SPF mice to germ-free mice resulted in a marked increase in IEC turnover, suggesting that spore-forming Gram-positive bacteria contribute to this effect. Oral administration of short-chain fatty acids (SCFAs) as bacterial fermentation products also restored the turnover of IECs in antibiotic-treated SPF mice as well as promoted the development of intestinal organoids in vitro. Antibiotic treatment reduced the phosphorylation levels of ERK, ribosomal protein S6, and STAT3 in IECs of SPF mice. Our results thus suggest that Gram-positive commensal bacteria are a major determinant of IEC turnover, and that their stimulatory effect is mediated by SCFAs.

5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid (5,6-DiHETE) is an eicosapentaenoic acid-derived newly discovered bioactive anti-inflammatory lipid mediator having diverse functions. Here, we assessed the potential of orally administered 5,6-DiHETE in promoting healing of dextran sulfate sodium (DSS)-induced colitis in mice. We measured the plasma concentrations of 5,6-DiHETE in untreated mice before and 0.5, 1, 3, and 6 h after its oral administration (150 or 600 μg/kg) in mice. Mice developed colitis by DSS (2% in drinking water for 4 days), and 5,6-DiHETE (150 or 600 μg/kg/day) was orally administered from day 9 to 14. Next, the faecal hardness and bleeding were assessed, and the dissected colons on day 14 via H&E staining. The plasma concentration of 5,6-DiHETE reached 25.05 or 44.79 ng/mL 0.5 h after the administration of 150 or 600 μg/kg, respectively, followed by a gradual decrease. The half-life of 5,6-DiHETE was estimated to be 1.25–1.63 h. Diarrhoea deteriorated after day 3 and peaked on day 5, followed by a gradual recovery. Histological assessment on day 14 showed DSS-mediated granulocyte infiltration, mucosal erosion, submucosal edema, and cryptal abscesses in mice. Oral administration of 150 or 600 μg/kg/day of 5,6-DiHETE accelerated the recovery from the DSS-induced diarrhoea and significantly ameliorated colon inflammation. The therapeutic effect of 600 μg/kg/day 5,6-DiHETE was slightly stronger than that by 150 μg/kg/day. Our study reveals attenuation of DSS-induced colitis in mice by the oral administration of 5,6-DiHETE dose-dependently, thereby suggesting a therapeutic potential of 5,6-DiHETE for inflammatory bowel disease.

Genome editing can introduce designed mutations into a target genomic site. Recent research has revealed that it can also induce various unintended events such as structural variations, small indels, and substitutions at, and in some cases, away from the target site. These rearrangements may result in confounding phenotypes in biomedical research samples and cause a concern in clinical or agricultural applications. However, current genotyping methods do not allow a comprehensive analysis of diverse mutations for phasing and mosaic variant detection. Here, we developed a genotyping method with an on-target site analysis software named Determine Allele mutations and Judge Intended genotype by Nanopore sequencer (DAJIN) that can automatically identify and classify both intended and unintended diverse mutations, including point mutations, deletions, inversions, and cis double knock-in at single-nucleotide resolution. Our approach with DAJIN can handle approximately 100 samples under different editing conditions in a single run. With its high versatility, scalability, and convenience, DAJIN-assisted multiplex genotyping may become a new standard for validating genome editing outcomes.