Effectiveness of catch-up and routine program of the 9-valent vaccine on cervical cancer risk reduction in Japan

Yagi A., Nakagawa S., Ueda Y., et al. Effectiveness of catch-up and routine program of the 9-valent vaccine on cervical cancer risk reduction in Japan. Cancer Science 115, 916 (2024); https://doi.org/10.1111/cas.16055.In 2013, the national human papillomavirus (HPV) immunization program began. However, in June 2013, Japan's Ministry of Health, Labor and Welfare (MHLW) announced a “temporary” suspension of its recommendation for the human papillomavirus vaccine. Finally, in November 2021, the MHLW ended its suspension of the recommendation of the HPV vaccine. To address the 9-year gap in HPV vaccinations the suspension had caused, the MHLW conducted a program of catch-up vaccinations from April 2022 to March 2025. Finally, in April 2023, the 9-valent HPV vaccine was approved for both the routine and catch-up vaccination programs in Japan. In this study, we investigated the potential effects of the introduction of the 9-valent vaccine on the increased risk of cervical cancer in females born after fiscal year (FY) 2000. We estimated the lifetime relative risk of cervical cancer incidence and death using the improved routine and catch-up vaccination rates after the recent resumption of the governmental recommendation for women and girls to have the HPV vaccination. These relative risks were calculated using a lifetime risk of 1.000 for cervical cancer incidence and death for females born in FY 1993. We predicted that even if a 90% vaccination rate were to be achieved by FY 2024 with the 9-valent vaccine among women born between FY 2000 and FY 2005, the risk would remain higher than for the vaccination generation. Therefore, for women born between FY 2000 and FY 2005, it will be necessary to significantly improve the cervical cancer screening rate to compensate for this increased risk

The activation mechanism of the aryl hydrocarbon receptor (AhR) by molecular chaperone HSP90

The aryl hydrocarbon receptor is a member of the nuclear receptor superfamily that associates with the molecular chaperone HSP90 in the cytoplasm. The activation mechanism of the AhR is not yet fully understood. It has been proposed that after binding of ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3methylcholanthrene (3-MC), or β-naphthoflavone (β-NF), the AhR dissociates from HSP90 and translocates to the nucleus. It has also been hypothesized that the AhR translocates to the nucleus and forms a complex with HSP90 and other co-chaperones. There are a few reports about the direct association or dissociation of AhR and HSP90 due to difficulties in purifying AhR. We constructed and purified the PAS domain from AhR. Binding of the AhR-PAS domain to β-NF affinity resin suggested that it possesses ligand-binding affinity. We demonstrated that the AhR-PAS domain binds to HSP90 and the association is not affected by ligand binding. The ligand 17-DMAG inhibited binding of HSP90 to GST-PAS. In an immunoprecipitation assay, HSP90 was co-immunoprecipitated with AhR both in the presence or absence of ligand. Endogenous AhR decreased in the cytoplasm and increased in the nucleus of HeLa cells 15. min after treatment with ligand. These results suggested that the ligand-bound AhR is translocated to nucleus while in complex with HSP90.We used an in situ proximity ligation assay to confirm whether AhR was translocated to the nucleus alone or together with HSP90. HSP90 was co-localized with AhR after the nuclear translocation. It has been suggested that the ligand-bound AhR was translocated to the nucleus with HSP90. Activated AhR acts as a transcription factor, as shown by the transcription induction of the gene CYP1A1 8. h after treatment with β-NF

AUTS2 Governs Cerebellar Development, Purkinje Cell Maturation, Motor Function and Social Communication

Autism susceptibility candidate 2 (AUTS2), a risk gene for autism spectrum disorders (ASDs), is implicated in telencephalon development. Because AUTS2 is also expressed in the cerebellum where defects have been linked to ASDs, we investigated AUTS2 functions in the cerebellum. AUTS2 is specifically localized in Purkinje cells (PCs) and Golgi cells during postnatal development. Auts2 conditional knockout (cKO) mice exhibited smaller and deformed cerebella containing immature-shaped PCs with reduced expression of Cacna1a. Auts2 cKO and knock-down experiments implicated AUTS2 participation in elimination and translocation of climbing fiber synapses and restriction of parallel fiber synapse numbers. Auts2 cKO mice exhibited behavioral impairments in motor learning and vocal communications. Because Cacna1a is known to regulate synapse development in PCs, it suggests that AUTS2 is required for PC maturation to elicit normal development of PC synapses and thus the impairment of AUTS2 may cause cerebellar dysfunction related to psychiatric illnesses such as ASDs

Indo-Pacific Warm Pool convection and ENSO since 1867 derived from Cambodian pine tree cellulose oxygen isotopes

The Indo-Pacific Warm Pool (IPWP) is a major source of heat and moisture to the atmosphere and thus strongly influences the global climate. In this study, we investigate how moisture fluxes from the IPWP influence the stable isotope signature of precipitation over Southeast Asia by analyzing the oxygen isotopic composition (δ^18O) of tree cellulose from southern Cambodia. The cellulose δ^18O record, spanning AD 1867-2006, documents a regular seasonal cycle with an average amplitude of ~4‰ that is primarily controlled by seasonal differences in the isotopic composition of precipitation. Using the outputs from an isotope-enabled atmospheric model, we illustrate how the δ^18O of precipitation at our site is predominantly controlled by the amount of rainout that occurs over the moisture source region, the IPWP. This is verified by strong correlations of our cellulose δ^18O record with instrumental measurements of precipitation and outgoing longwave radiation over the IPWP, suggesting that the cellulose δ^18O could be used to reconstruct the convection intensity over the IPWP. Spectral analysis of the cellulose δ^18O reveals significant peaks at 2-7 years corresponding to ENSO frequencies. The variability of the cellulose δ^18O record on the ENSO band exhibits characteristics that match existing coral δ^18O records from the tropical Pacific, with reduced amplitude of variability in the 1920s through the 1960s, a period of weak ENSO activity

COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study).

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron

Involvement of SPI-2-encoded SpiC in flagellum synthesis in <it>Salmonella enterica </it>serovar Typhimurium

<p>Abstract</p> <p>Background</p> <p>SpiC encoded within <it>Salmonella </it>pathogenicity island 2 on the <it>Salmonella enterica </it>serovar Typhimurium chromosome is required for survival within macrophages and systemic infection in mice. Additionally, SpiC contributes to <it>Salmonella</it>-induced activation of the signal transduction pathways in macrophages by affecting the expression of FliC, a component of flagella filaments. Here, we show the contribution of SpiC in flagellum synthesis.</p> <p>Results</p> <p>Quantitative RT-PCR shows that the expression levels of the class 3 <it>fliD </it>and <it>motA </it>genes that encode for the flagella cap and motor torque proteins, respectively, were lower for a <it>spiC </it>mutant strain than for the wild-type <it>Salmonella</it>. Further, this mutant had lower expression levels of the class 2 genes including the <it>fliA </it>gene encoding the flagellar-specific alternative sigma factor. We also found differences in flagella assembly between the wild-type strain and the <it>spiC </it>mutant. Many flagella filaments were observed on the bacterial surface of the wild-type strain, whereas the <it>spiC </it>mutant had only few flagella. The absence of <it>spiC </it>led to reduced expression of the FlhD protein, which functions as the master regulator in flagella gene expression, although no significant difference at the transcription level of the <it>flhDC </it>operon was observed between the wild-type strain and the <it>spiC </it>mutant.</p> <p>Conclusion</p> <p>The data show that SpiC is involved in flagella assembly by affecting the post-transcription expression of <it>flhDC</it>.</p

Impact of the Threat of COVID-19 Infections on the Perceived Risk to HPV Vaccination

Vaccination rates for human papillomavirus (HPV) in Japan are significantly lower than other countries, and Japanese people are reluctant to be vaccinated. Repeated daily reports of COVID-19 infections and restrictions have made people more health conscious and aware of the danger of infectious diseases. In this study, we used the health belief model (HBM) to examine perceived threats of cancer and infectious diseases and to ascertain whether the new COVID-19 vaccination in addition to these perceived threats would increase vaccination intention against cervical cancer. We conducted a cluster analysis to classify the segmentation regarding the perceived threat, and a logistic regression analysis to predict factors influencing people accepting vaccination. We received 1257 completed surveys during our research. We classified the participants into six clusters, and the logistic regression analysis indicated eight factors significantly associated with the willingness to get the HPV vaccine: reliable information sources such as doctors and social networking sites (SNS), the recognition of COVID-19 symptoms, the awareness of COVID-19 vaccination, the importance of HPV prevention through vaccination, one’s own intention of COVID-19 vaccination, their intention of COVID-19 vaccination toward children, and benefits of HPV vaccination. Further research on HPV and COVID-19 vaccination is encouraged

Association between chronological depressive changes and physical symptoms in postoperative pancreatic cancer patients

Abstract Background Pancreatic cancer (PC) has poorer prognosis and higher surgical invasiveness than many other cancers, with associated psychiatric symptoms including depression and anxiety. Perioperative depression has not been investigated in PC patients regarding surgical stress and relevant interventions. Methods We evaluated chronological depressive changes and subjective physical symptoms in surgically treated PC patients preoperatively and at 3 and 6 months postoperatively. Enrolled patients undergoing pancreatic tumor surgery completed questionnaires based on the Self-Rating Depression Scale (SDS) and Functional Assessment of Cancer Therapy for Patients with Hepatobiliary Cancer (FACT-Hep) preoperatively, and at 3 and 6 months postoperatively. Responses were analyzed with JMP® Pro using one-way and two-way ANOVA, Spearman’s rank correlation coefficient, and multiple regression analysis. Results Malignancy was diagnosed in 73 of 101 patients postoperatively; SDS score was significantly higher in these patients than in those with benign tumors at all timepoints: malignant/benign, 41.8/37.9 preoperatively (p = 0.004); 43.5/37.8 3 months postoperatively (p = 0.006); and 42.9/37.7 6 months postoperatively (p = 0.020). SDS scores were significantly higher in patients < 65 years old with malignancy at 3 months than at 6 months postoperatively (44.6/42.5, p = 0.046) and in patients with malignancy who underwent pancreaticoduodenectomy at 3 months postoperatively than preoperatively (43.4/41.1; p = 0.028). SDS scores moderately correlated with 8 physical symptom-related FACT-Hep items 3 months postoperatively (p < 0.05), showing low-to-moderate correlation with 16 physical symptom-related FACT-Hep items at 6 months postoperatively (p < 0.05). Multiple regression analysis of FACT-Hep symptoms significantly correlated with SDS scores revealed the following significant variables: “lack of energy” (p < 0.000) and “pain” (p = 0.018) preoperatively (R2 = 0.43); “able to perform usual activities” (p = 0.031) and “lack of energy” (p < 0.000) at 3 months postoperatively (R2 = 0.51); and “stomach swelling or cramps” (p = 0.034) and “bowel control” (p = 0.049) at 6 months postoperatively (R2 = 0.52). Conclusions PC patients experience persistently high levels of depression preoperatively through 6 months postoperatively, with associated subjective symptoms including pain and gastrointestinal symptoms. Trial registration UMIN Clinical Trials Registry 000009592, Registered 20 December 2012