Using a mouse model, we previously demonstrated that subcutaneous infection with the JaTH160 strain of Japanese encephalitis virus (JEV) causes significantly higher virulence and stronger virus propagation in the brain compared with that of the JaOArS982 strain. We also showed that the JaTH160 strain, but not JaOArS982, expresses the NS1’ protein and that NS1’ enhances JEV production in avian cells and embryonated chicken eggs. In this study, we examined whether NS1’ expression affects virulence in mice infected with the JaOArS982 and JaTH160 strains using the corresponding recombinant viruses S982-IC and JaTH-IC. Expression of the NS1’ protein in S982-IC diminished the mortality in mice, whereas S982-IC viruses without NS1’ caused 40–60% mortality. However, the viral loads in the brains of these mice were not significantly different despite the dvariation in NS1’ expression. JaTH-IC viruses depleted of the NS1’ protein exhibited high mortality levels, similar to those of the virus expressing NS1’. Previous studies showed that the NS1’ protein plays a role in the enhanced virulence of the JEV SA14 strain in mice. However, our current data suggest that NS1’ protein expression in S982-IC reduces, rather than enhances, the mortality in mice. Thus, the effect of NS1’ on pathogenicity in vivo may vary among virus strains. Our data also suggest that the reduced mortality resulting from NS1’ expression in S982-IC is not simply due to viral replication in the brains. Further investigation is needed to uncover the mechanism by which NS1’ affects pathogenicity in JEV-infected animals.

Using a mouse model,we previously demonstrated that subcutaneous infection with the JaTH160 strainof Japaneseencephalitis virus (JEV) causes significantly higher virulence and strongervirus propagation in the brain compared with that of the JaOArS982strain. We also showed that the JaTH160 strain,but not JaOArS982, expresses the NS1’ protein and that NS1’ enhances JEVproduction in avian cells and embryonated chicken eggs. In this study, weexamined whether NS1’ expression affects virulence in mice infected with theJaOArS982 and JaTH160 strains using the corresponding recombinant viruses S982-ICand JaTH-IC.Expression of the NS1’ protein in S982-IC diminishedthe mortality in mice, whereas S982-IC viruses without NS1’ caused 40% mortality.However, the viral loads in the brains of these mice were not significantlydifferent despite the difference in NS1’ expression. JaTH-IC viruses depletedof the NS1’ protein exhibited high mortality levels, similar to those of thevirus expressing NS1’.Previousstudies showed that the NS1’ protein plays a role in the enhanced virulenceof the JEV SA14 strain in mice. However, ourcurrent data suggest that NS1’ protein expression in S982-IC reduces,rather than enhances, the mortality in mice. Thus, the effect of NS1’ on pathogenicity invivo may vary among virus strains. Our data also suggest that the reducedmortality resulting from NS1’ expression in S982-IC is not simply due to viralreplication in the brains. Furtherinvestigation is needed to uncover the mechanism by which NS1’ affectspathogenicity in JEV-infected animals.

In 2012, the external prescription rate was 66.1% of the national average. A dispensing doctor is recognized by the escape clauses of Article 22 of the Medical Law, Article 21 of the Dentist Medical Law, and Article 19 of the Pharmacists Act. In this study, the medicine inventories of dispensing doctors and pharmacies were compared. The medicine supplies of 7 dispensing doctors and 11 pharmacies in Saitama were classified according to the medicinal effects. We also investigated the conditions in which high-risk medicines, poisons, or drugs were stored. The average number of medicines in the medicine inventory of a dispensing doctor was 262.3 (range : 99, 439), whereas the average number of medicines in the medicine inventory of a pharmacy was 1179.7 (minimum, 275 ; maximum, 1980). Further, among these medicines, there were an average of 41.0 high-risk medicines (minimum, 18 ; maximum, 76) in the inventory of a dispensing doctor and an average of 176.7 high-risk medicines (minimum, 5 ; maximum, 299) in the inventory of a pharmacy. In addition, poisons (average, 0.3) and narcotics (average, 0.9) were found to be stored by dispensing doctors. The study results revealed that pharmacies as well as dispensing doctors stored high-risk medicines. The dispensing doctor may be indirectly associated with critical medical accidents to need cross-check by pharmacist exceedingly high-risk medicine. Thus, for patients to use medicines appropriately and for them to be reassured of the safety of medicines, only professionals such as pharmacists, rather than doctors, should dispense medicines.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease endemic in East Asia. Transmitted to other organisms by infected ticks, the SFTS virus (SFTSV) and is endemic to Nagasaki in western Japan. However, epidemiological information regarding SFTSV in Nagasaki ticks has not been available to date. In this study, we began by examining the sensitivities of SFTSV gene detection by real-time RT-PCR and virus isolation in cultured cells and mice. These methods could detect SFTSV in the samples containing more than 4 × 10⁰ ffu. Next, we attempted to isolate SFTSV and to detect viral gene in 2,222 nymph and adult ticks collected from May to August 2013 among seven regions of Nagasaki. However, neither virus isolation nor viral gene detection were confirmed in the tick pools. SFTSV positivity rates are considered to be very low in ticks, and viral loads are also very limited. Further investigations increasing the number of ticks and including larval samples as well as improved detection methods, may be required to find SFTSV-positive ticks in this region.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease that is endemic in East Asia. The SFTS virus (SFTSV) is transmitted to other organisms by infected ticks and is endemic to Nagasaki in western Japan. However, epidemiological information regarding SFTSV in Nagasaki ticks has not been elucidated. In this study, we first examined the sensitivities of SFTSV gene detection by real-time RT-PCR and virus isolation in cultured cells and mice. These methods could detect SFTSV in the samples containing more than 4 × 10⁰ ffu. Next, we attempted to isolate SFTSV and to detect viral gene in 2,222 nymph and adult ticks collected from May to August 2013 among seven regions of Nagasaki. However, neither virus isolation nor viral gene detection were confirmed in those tick pools. SFTSV positivity rates are considered very low in ticks and viral loads in ticks are also very limited. Further investigation by increasing the number of ticks and including larval samples in the investigation, as well as improved detection methods, may be required to find SFTSV-positive ticks in this region.

Background/Aims: Application of polyglycolic acid (PGA) sheets using fibrin glue in post-endoscopic submucosal dissection (ESD) ulcers to prevent bleeding has been reported to be difficult with the conventional delivery method because of gravity. This study assessed the usefulness of the envelope-based delivery system with and against gravity in living pigs. Methods: PGA sheets were applied on post-ESD ulcers with and against gravity six times each using the conventional and envelope methods, respectively. The PGA sheet delivery time and the endoscopic and histological findings of the treated ulcer floors were compared. Results: With gravity, the median PGA sheet application time was 1.00 (0.68–1.30) min/cm2 and 0.32 (0.18–0.52) min/cm2 with the conventional and envelope techniques (p=0.002), respectively, and against gravity, it was 1.20 (1.13–1.63) min/cm2 and 0.50 (0.39–0.58) min/cm2 (p=0.002), respectively. Against gravity, the endoscopic and histological findings revealed that the conventional group had insufficient fixation of the PGA sheets, but the envelope groups had sufficient fixation. The results with gravity were similar between the groups. Conclusions The envelope method makes it possible to deliver PGA sheets to the stomach quickly and cover ulcers appropriately both with and against gravity in living pigs.

Objective: To investigate the effect on early mobilization in patients undergoing extra-corporeal membrane oxygenation (ECMO) and acute blood purification therapy in the intensive care unit (ICU). Methods: We conducted this multicenter retrospective cohort study by collecting data from six ICUs in Japan. Consecutive patients who were admitted to the ICU, aged ≥18 years, and received mechanical ventilation for >48 hours were eligible. The analyzed were divided into two groups: ECMO/blood purification or control group. Clinical outcomes; time to first mobilization, number of total ICU rehabilitations, mean and highest ICU mobility scale (IMS); and daily barrier changes were also investigated. Results: A total of 204 patients were included in the analysis, 43 in the ECMO/blood purification group and 161 in the control group. In comparison of clinical outcome, the ECMO/blood purification group had a significantly longer time to first mobilization: ECMO/blood purification group 6 vs. control group 4 (p=0.003), higher number of total ICU rehabilitations: 6 vs. 5 (p=0.042), lower mean: 0 vs. 1 (p=0.043) and highest IMS: 2 vs. 3 (p=0.039) during ICU stay. Circulatory factor were most frequently described as barriers to early mobilization on days 1 (51%), 2 (47%), and 3 (26%). On days 4 to 7, the most frequently described barrier was consciousness factors (21%, 16%, 19%, and 21%, respectively) Conclusion The results of this study comparing the ECMO/blood purification group and the untreated group in the ICU showed that the ECMO/blood purification group had significantly longer days to mobilization and significantly lower mean and highest IMS.

A 61 year old woman who had been receiving treatment for ulcerative colitis for 14 years complained of respiratory discomfort on exertion and was diagnosed with severe mitral regurgitation due to mitral valve prolapse. Minimally invasive mitral valvuloplasty with right mini-thoracotomy was performed in our facility. Laboratory findings showed elevated levels of serum creatine kinase (CK) and CK-MB immediately after surgery. In addition to elevated levels of myocardial enzymes, ST depression was seen in an electrocardiogram on postoperative day 2 ; therefore, we suspected myocardial ischemia during the surgery. Despite the persistently elevated levels of myocardial enzymes, coronary angiography showed no significant abnormalities. Because of the possibility of false CK elevation, we performed CK electrophoresis, which revealed the presence of macro-CK type 1. CK-MB activity is often falsely elevated when determined by immune-inhibition in macro-CK patients, and that leads to the suspicion of myocardial ischemia. We considered that it may be highly difficult to identify macro-CK in a patient after cardiovascular surgery owing to elevated levels of myocardial enzymes in most such patients.

Objective: Our previous study reported many technical alarms in the dispensing inspection support system due to setting or operation errors, but not due to dispensing errors, and that countermeasures reduce technical alarms. In this study, we investigated the long-term effects of the countermeasures.Methods: The log data of the inspection results were extracted from the dispensing inspection support system and divided into image inspection and weight inspection data. The details and frequency of technical alarms before (April-June 2019), after (April-June 2020), and one year after (April-June 2021) the countermeasures were compared by chi-square test.Results: The frequency of technical alarms in image inspection was 13.7, 11.3, and 9.1% in 2019, 2020, and 2021, respectively (p< 0.01). However, the frequency of technical alarms in weight inspection was 3.0, 3.0, and 1.6% in 2019, 2020, and 2021,respectively (p< 0.01). The ratio of technical alarms to all alarms was 98.2% for image inspections and 91.2% for weight inspections in 2021.Conclusion: The frequency of technical alarms was reduced by the countermeasures. However, the ratio of technical alarms to all alarms is still high, and further improvements are needed to prevent the loss of reliability due to technical alarms.

Context: Delirium in cancer is often difficult to control and refractory when haloperidol is invalid which is considered standard therapy. We need second and subsequent-line therapy to reduce hyperactivity and not to over-sedation for refractory delirium. Objectives: To investigate the efficacy and safety of continuous subcutaneous infusion chlorpromazine on delirium refractory to first-line antipsychiatric medications in advanced cancer palliative care setting. Method: The study population consisted of patients who received continuous subcutaneous infusion chlorpromazine for delirium at two certified PCU. Primary endpoint was the proportion of patients who showed improvements in delirium severity by Delirium Rating Scale Revised 98 score of less than 13 or decrease from baseline and maintained the ability to communicate coherently by Communication Capacity Scale Item-4 score of 2 or less. Secondary outcome were the Nursing Delirium Screening Scale subscale score, and injection site reactions evaluated according to the Common Terminology Criteria for Adverse Events. These outcome measures were assessed at baseline, 48 hours and 7 days after the start of the study. Result: Among eighty-four patients, sixty were positive responders (71.4%, 95% CI [61–80]). The mean CCS Item-4 scores significantly decreased from the baseline value of 1.48 (range 0–3) to 1.03 (range 0–3) at post-treatment (p<0.001). Grade 2 or higher injection site reactions were observed in 1 patient (1.2%, 95% CI [0–7]). Conclusion: Our study suggested that continuous subcutaneous infusion chlorpromazine could improve refractory delirium symptoms and patients’ communication capabilities. Although most of the skin disorders observed in association with chlorpromazine were mild, their incidence rates were relatively high, suggesting the need for careful monitoring.