Three-year questionnaire study on human papillomavirus vaccination targeting new female college school students: Follow-up to a 2021 report to reveal the impact of a policy change in Japan.

AIM: The purpose of this study was to examine the trend in human papillomavirus (HPV) vaccination rates in Japan before and after a policy change in 2022, involving resumption of active recommendation and start of catch-up vaccination. METHODS: From 2021 to 2023, a web-based questionnaire survey was administered to newly enrolled female college students in Yokohama, Japan. The questionnaire included items such as age, HPV vaccination status, HPV vaccine awareness, and awareness of catch-up vaccination. We compared knowledge about the HPV vaccine and cervical cancer in 2021 and 2023, before and after resumption of the national vaccination program. RESULTS: The HPV vaccination rates were 5.4% in 2021, 7.5% in 2022, and 35.3% in 2023, with a significant upward trend (p < 0.001). A similar upward trend was observed for HPV vaccine awareness (p < 0.001). Comparing 2022 and 2023 after the start of catch-up vaccination, there was no significant difference in awareness of catch-up vaccination (p = 0.669), but there was a significant increase in awareness of free vaccination tickets (p < 0.001). After resumption of the national vaccination program with adoption of the catch-up vaccination program, there was no difference in knowledge of cervical cancer, but there was a difference in knowledge of the HPV vaccine. CONCLUSIONS: Although the HPV vaccination rate has increased after the policy change, it has not recovered to the level before the suspension of active recommendation. It is important for healthcare providers and school educators to actively communicate the safety and effectiveness of the HPV vaccine.

Mouse Scarb2 Modulates EV-A71 Pathogenicity in Neonatal Mice.

Enterovirus A71 (EV-A71) is a human pathogen that causes hand, foot, and mouth disease, which can progress to severe neurological disease. EV-A71 infects humans via the human scavenger receptor B2 (hSCARB2). It can also infect neonatal mice experimentally. Wild-type (WT) EV-A71 strains replicate primarily in the muscle of neonatal mice; however, susceptibility lasts only for a week after birth. Mouse-adapted (MA) strains, which can be obtained by serial passages in neonatal mice, are capable of infecting both muscle and neurons of the central nervous system. It is not clear how the host range and tropism of EV-A71 are regulated and why neonatal mice lose their susceptibility during development. We hypothesized that EV-A71 infection in neonatal mice is mediated by mouse Scarb2 (mScarb2) protein. Rhabdomyosarcoma (RD) cells expressing mScarb2 were prepared. Both WT and MA strains infected mScarb2-expressing cells, but the infection efficiency of the WT strain was much lower than that of the MA strain. Infection by WT and MA strains in vivo was abolished completely in Scarb2-/- mice. Scarb2+/- mice, in which Scarb2 expression was approximately half of that in Scarb2+/+ mice, showed a milder pathology than Scarb2+/+ mice after infection with the WT strain. The Scarb2 expression level in muscle decreased with aging, which was consistent with the reduced susceptibility of aged mice to infection. These results indicated that EV-A71 infection is mediated by mScarb2 and that the severity of the disease, the spread of virus, and the susceptibility period are modulated by mScarb2 expression. IMPORTANCE EV-A71 infects humans naturally but can also infect neonatal mice. The tissue tropism and severity of EV-A71 disease are determined by several factors, among which the virus receptor is thought to be important. We show that EV-A71 can infect neonatal mice using mScarb2. However, the infection efficiency of WT strains via mScarb2 is so low that an elevated virus-receptor interaction associated with mouse adaptation mutation and decrease in mScarb2 expression level during development modulate the severity of the disease, the spread of virus, and the susceptibility period in the artificial neonatal mice model.

Naldemedine-induced Opioid Withdrawal Syndrome in a Patient with Breast Cancer without Brain Metastasis.

Opioid-induced-constipation (OIC) can be treated by naldemedine and other peripherally acting mu-opioid receptor antagonists (PAMORA) via a novel mechanism. We describe the case of a 52-year-old female outpatient who developed OIC while receiving oxycodone for pain due to cancer with multiple bone metastases. Although she did not have brain metastasis, opioid withdrawal syndrome (OWS) developed after taking naldemedine orally. Her Clinical Opiate-Withdrawal Score (COWS) was 19 (moderate symptoms). However, she recovered from OWS on intravenous fentanyl and a continuous infusion of oxycodone. She did not develop OWS thereafter and was discharged two days after recovery.

The parathyroid hormone regulates skin tumour susceptibility in mice.

Using a forward genetics approach to map loci in a mouse skin cancer model, we previously identified a genetic locus, Skin tumour modifier of MSM 1 (Stmm1) on chromosome 7, conferring strong tumour resistance. Sub-congenic mapping localized Parathyroid hormone (Pth) in Stmm1b. Here, we report that serum intact-PTH (iPTH) and a genetic polymorphism in Pth are important for skin tumour resistance. We identified higher iPTH levels in sera from cancer-resistant MSM/Ms mice compared with susceptible FVB/NJ mice. Therefore, we performed skin carcinogenesis experiments with MSM-BAC transgenic mice (Pth MSM-Tg) and Pth knockout heterozygous mice (Pth +/-). As a result, the higher amounts of iPTH in sera conferred stronger resistance to skin tumours. Furthermore, we found that the coding SNP (rs51104087, Val28Met) localizes in the mouse Pro-PTH encoding region, which is linked to processing efficacy and increased PTH secretion. Finally, we report that PTH increases intracellular calcium in keratinocytes and promotes their terminal differentiation. Taken together, our data suggest that Pth is one of the genes responsible for Stmm1, and serum iPTH could serve as a prevention marker of skin cancer and a target for new therapies.

A Gastrointestinal Calpain Complex, G-calpain, Is a Heterodimer of CAPN8 and CAPN9 Calpain Isoforms, Which Play Catalytic and Regulatory Roles, Respectively.

Calpains (CAPN) are a family of Ca2+-dependent cysteine proteases that regulate various cellular functions by cleaving diverse substrates. Of the 15 mammalian calpains, CAPN8 and CAPN9 are two that are expressed predominantly in the gastrointestinal tract, where they interact to form a protease complex, termed G-calpain. However, because native G-calpain exhibits a highly restricted expression pattern, it has never been purified, and the interactions between CAPN8 and CAPN9 have not been characterized. Here, we clarified the molecular nature of G-calpain by using recombinant proteins and transgenic mice expressing FLAG-tagged CAPN8 (CAPN8-FLAG). Recombinant mouse CAPN8 and CAPN9 co-expressed in eukaryotic expression systems exhibited the same mobility as native mouse G-calpain in Blue Native-PAGE gels, and CAPN8-FLAG immunoprecipitation from stomach homogenates of the transgenic mice showed that CAPN9 was the only protein that associated with CAPN8-FLAG. These results indicated that G-calpain is a heterodimer of CAPN8 and CAPN9. In addition, active recombinant G-calpain was expressed and purified using an in vitro translation system, and the purified protease exhibited enzymatic properties that were comparable with that of calpain-2. We found that an active-site mutant of CAPN8, but not CAPN9, compromised G-calpain's substrate cleavage activity, and that the N-terminal helix region of CAPN8 and the C-terminal EF-hands of CAPN8 and CAPN9 were involved in CAPN8/9 dimerization. Furthermore, CAPN8 protein in Capn9-/- mice was almost completely lost, whereas CAPN9 was only partially lost in Capn8-/- mice. Collectively, these results demonstrated that CAPN8 and CAPN9 function as catalytic and chaperone-like subunits, respectively, in G-calpain.

[Reversal of rocuronium-induced neuromuscular blockade with sugammadex in patients for cesarean delivery treated with magnesium sulfate].

BACKGROUND: We investigated whether sugammadex could reverse neuromuscular blockade induced by rocuronium in patients for cesarean delivery treated with magnesium sulfate preoperatively. METHODS: Twenty-three pregnant women received general anesthesia induced with thiopental and rocuronium. They were maintained by nitrous oxide, oxygen and sevoflurane (GOS) before delivery and after delivery by GOS, midazolam, and propofol. After the surgery, the patients with two or more counts of train-of-four (TOF), the moderate block group were classified into Mg (-) M and Mg (+) M, depending whether magnesium sulfate had been injected or not, and sugammadex 2 mg x kg(-1) was administered to both groups. Patients with PTC 2 or more, the profound block group, were classified into Mg (-) P or Mg (+) P and sugammadex 4 mg x kg(-1) was administered to both groups. Recovery time was defined as the time required to reach TOFR 0.9 or more after the injection of sugammadex. RESULTS: Median recovery times of the Mg (-) M, the Mg (-) P, the Mg (+) M and the Mg (+) P were 63 seconds (range: 26-130, N = 7), 127 seconds (range: 63-228, N = 7), 104 seconds (range: 67-133, N = 5), and 142 seconds (range: 57-209, N = 4), respectively. CONCLUSIONS: Sugammadex could reverse rocuronium-induced neuromuscular blockade in a dose-response manner even in the patients treated with magnesium sulfate.

Application of the COOP/WONCA charts to aged patients with chronic obstructive pulmonary disease: a comparison between Japanese and Chinese populations.

BACKGROUND: The prevalence of chronic obstructive pulmonary disease (COPD) is similar in Japan and China and is increasing due to high rates of smoking in these countries. Reducing COPD is an important public health issue. The goals of this study were to verify the reliability and validity of the Japanese version of the COOP/WONCA charts, a tool for measuring health status, and to examine the qualitative differences in health status between Japanese and Chinese patients with COPD and between these patients and healthy subjects. METHODS: From 2008 to 2011, we examined the factors affecting the health status of Japanese and Chinese populations living in six cities. Participants were patients with COPD staged according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (140 Japanese, 201 Chinese) and healthy subjects (243 Japanese, 199 Chinese), all 50 to 79 years old. Health status was measured by using the COOP/WONCA charts, and basic information such as smoking status and medical history was reported by the participants. RESULTS: The Japanese and Chinese versions of the COOP/WONCA charts were shown to be reliable and valid by test-retest, comparison with the SF-36 and respiratory symptoms, and correlation of results obtained from patients and their physicians. Stepwise multiple regression analyses demonstrated that "Physical fitness", "Daily activities", and "Social activities" were predicted by COPD status and/or respiratory symptoms; "Feelings" by nationality and respiratory symptoms; "Pain" by sex and respiratory symptoms; and "Overall health" by nationality. When the COOP/WONCA scores were stratified by nationality, age, sex, and COPD status, the difference of each score between the patients and healthy subjects was larger for the Chinese subjects than for the Japanese. The physical, psychosocial activities, and pain scores increased significantly as COPD status worsened in Chinese subjects, whereas these scores were not affected by sex, age, or COPD status for Japanese subjects. Brinkman index and use of smoky fuel indoors affected the COOP/WONCA scores in Chinese patients but not in Japanese patients. CONCLUSIONS: The Japanese COOP/WONCA charts are reliable and valid. COPD more severely affected the health status of Chinese participants than of Japanese participants. These results suggest that countermeasures against insufficient health care and smoky environments may improve the health status of Chinese patients with COPD.

The reliability and validity of the Japanese version of the Diabetes Family Behavior Checklist (DFBC) for assessing the relationship between type 2 diabetes mellitus patients and their families with respect to adherence to treatment regimen.

AIMS: An appropriate questionnaire for assessing family support of self-management behavior of Japanese Type 2 diabetes patients has yet to be developed. We produced a Japanese version of the Diabetes Family Behavior Checklist (DFBC) and tested its reliability and validity. METHODS: The study enrolled Japanese patients with Type 2 diabetes mellitus who were living with their families: 158 patients in the Insulin Group and 169 in the Oral Hypoglycemic Agents Group. The external validity of the DFBC was tested with questionnaires of self-managed dietary and exercise behaviors, the Appraisal of Diabetes Scale (ADS), and HbA1c. RESULTS: The DFBC comprised two components: "Negative" and "Positive" feedbacks. Cronbach's alpha in the subcategories was ≥0.93, and the test-retest showed an intraclass correlation coefficient of 0.89. "Positive" and "Negative" scores correlated with self-managed dietary and/or exercise behaviors, the ADS scores in the both Groups. For patients having HbA1c levels of ≤6.8% there was a correlation between their "Positive" and "Negative" scores and the scores of their families in both Groups. CONCLUSION: The DFBC showed evidence of validity and reliability and may be a useful tool for quick assessment of self-managed treatment behavior of Japanese Type 2 diabetes patients and support received from their family.

[Safe practice of oral rehydration therapy by oral rehydration solution and carbohydrate loading--evaluation by non-invasive gastric echo examination].

Many anesthesiologists are reluctant to depart from their traditional long fasting periods, even though many guidelines recommend that oral intake of clear fluids administered up to 2-3 hours prior to general anesthesia does not adversely affect the gastric contents. It also indicates that the application of these guidelines does not affect the incidence of pulmonary aspiration. One of the reasons why they have not changed their practices is that they wonder whether it is safe to administer clear fluids as recommended in the guidelines. In this review, we emphasize that oral rehydration therapy using clear fluids (such as OS-1, water and carbohydrate-rich beverage) is safe based on the non-invasive gastric echo examinations as many guidelines have already indicated. Oral rehydration therapy should be considered not only as an alternative to intravenous therapy for preoperative fluid and electrolyte management but also as one of the important modalities which can enhance the recovery of surgical patients.

[Safety of preoperative oral rehydration therapy].

BACKGROUND: OS-1 is an oral rehydration solution that conforms with the principles of oral rehydration therapy. It may be useful for preoperative fluid management of surgical patients. While intake of clear fluids 2 hours before surgery is considered safe, it is not known if the same applies to OS-1. We therefore investigated the safety of OS-1 for preoperative patients as compared with clear fluids. METHODS: First, eight healthy adult volunteers were studied in a crossover manner. Volunteers ingested 500 ml of OS-1 or water (clear fluid). Gastric emptying time was measured using gastric ultrasonography. Gastric antral area as measured by ultrasonography correlates well with gastric volume in a close-to-linear manner. Next, we measured gastric volume of elective surgical patients who had drunk OS-1 until two hours before the induction of anesthesia. RESULTS: Gastric emptying time did not differ between OS-1 and water. The stomach was emptied 30 minutes after ingestion of both OS-1 and water. The fasting stomach was identified in all patients who had drunk OS-1 before surgery. CONCLUSIONS: We concluded that allowing elective surgical patients to drink OS-1 until two hours before anesthesia did not affect the volume of gastric contents.