Two hidden taxa in the Japanese encephalitis vector mosquito, Culex tritaeniorhynchus, and the potential for long-distance migration from overseas to Japan.

The Culex vishnui subgroups, particularly Culex tritaeniorhynchus, are considered the primary vectors of the Japanese encephalitis virus (JEV) in Asia. Recent molecular phylogenetic analyses of JEV isolates from Asian countries have shown that JEVs with diverse genetic variants are present in Asia. Furthermore, some JEV strains have been found to have crossed the East China Sea and been introduced into Japan. In this study, the possibility of overseas migration of the JE vector mosquito, Cx. tritaeniorhynchus was examined from the genetic, physical, and meteorological perspectives. Molecular phylogenetic analysis was performed based on both whole coding sequences and on the barcoding region of the mitochondrial cytochrome c oxidase subunit I (COI) gene of Cx. vishnui subgroups collected from Asian countries. Culex tritaeniorhymchus was classified into two genetically independent taxa by COI sequences: the Japanese type (Ct-J), which inhabits Japan except for the Amami Islands of southern Japan, and the continental type (Ct-C), which inhabits the Asian region except for Japan. It was confirmed that approximately 10% of Cx. tritaeniorhynchus trapped during the summer in western Kyushu were Ct-C, and that they could fly for up to 38 h continuously. The meteorological analysis also confirmed that the atmospheric flow occurring over the continent coincided with the date of Ct-C capture. This is the first report showing the existence of two taxa in Cx. tritaeniorhynchus. Their physical and physiological characteristics suggest the possibility of long-distance migration from overseas regions to Japan across the East China Sea. Future efforts are expected to provide evidence to support the occurrence of long-distance migration of Cx. tritaeniorhynchus with JEV.

Post COVID-19 condition of the Omicron variant of SARS-CoV-2

BackgroundNo epidemiological data on post coronavirus disease (COVID-19) condition due to Omicron variant has been reported yet. MethodsThis was as a single-center, cross-sectional study, that interviewed via telephone the patients who recovered from Omicron COVID-19 infection (Omicron group), and surveyed via self-reporting questionnaire those patients infected with other strains (control group). Data on patients characteristics, information regarding the acute-phase COVID-19, as well as presence and duration of COVID-19-related symptoms were obtained. Post COVID-19 condition in this study was defined as a symptom that lasted at least 2 months within 3 months since the onset of COVID-19. We investigated and compared the prevalence of post COVID-19 condition in both groups after performing propensity score matching. ResultsWe conducted interviews for 53 out of 128 patients with Omicron, and obtained 502 responses in the control group. After matching, 18 patients each in Omicron and control group had improved covariate balance of the older adult, female sex, obese patients, and vaccination status. There were no significant differences in the prevalence of each post-acute COVID-19 symptoms between the two groups. The numbers of patients with at least one post-acute COVID-19 symptom in the Omicron and the control group were 1 (5.6%) and 10 (55.6%) (p=0.003), respectively. ConclusionThe prevalence of post Omicron COVID-19 conditions was less than that of the other strains. Further research with more participants is needed to investigate the precise epidemiology of post COVID-19 condition of Omicron, and its impact on health-related quality of life and social productivity.

Risk factors associated with development and persistence of long COVID

BackgroundLong COVID has been a social concern. Though patient characteristics associated with developing long COVID are partially known, those associated with persisting it have not been identified. MethodsWe conducted a cross-sectional questionnaire survey of patients after COVID-19 recovery who visited the National Center for Global Health and Medicine between February 2020 and March 2021. Demographic and clinical data, and the presence and duration of long COVID were obtained. We identified factors associated with development and persistence of long COVID using multivariate logistic and linear regression analysis, respectively. ResultsWe analyzed 457 of 526 responses (response rate, 86.9%). The median age was 47 years, and 378 patients (84.4%) had mild disease in acute phase. The number of patients with any symptoms after 6 and 12 months after onset or diagnosis were 120 (26.3%) and 40 (8.8%), respectively. Women were at risk for development of fatigue (OR 2.03, 95% CI 1.31-3.14), dysosmia (OR 1.91, 95% CI 1.24-2.93), dysgeusia (OR 1.56, 95% CI 1.02-2.39), and hair loss (OR 3.00, 95% CI 1.77-5.09), and were at risk for persistence of any symptoms (coefficient 38.0, 95% CI 13.3-62.8). Younger age and low body mass index were risk factors for developing dysosmia (OR 0.96, 95% CI 0.94-0.98, and OR 0.94, 95% CI 0.89-0.99, respectively) and dysgeusia (OR 0.98, 95% CI 0.96-1.00, and OR 0.93, 95% CI 0.88-0.98, respectively). ConclusionWe identified risk factors for the persistence as well as development of long COVID. Many patients suffer from long-term residual symptoms, even in mild cases. SummaryOur cross-sectional questionnaire survey of patients recovering from COVID-19 revealed that women, young age, and low body mass index were risk factors for the development of multiple symptoms, and that even mild cases of COVID-19 suffered from long-term residual symptoms.

Education and household income and carotid intima-media thickness in Japan: baseline data from the Aidai Cohort Study in Yawatahama, Uchiko, Seiyo, and Ainan

BACKGROUND@#Epidemiological evidence for the relationship between education and income and carotid intima-media thickness (CIMT) has been limited and inconsistent. The present cross-sectional study investigated this issue using baseline data from the Aidai Cohort Study.@*METHODS@#Study subjects were 2012 Japanese men and women aged 34-88 years. Right and left CIMT were measured at the common carotid artery using an automated carotid ultrasonography device. Maximum CIMT was defined as the largest CIMT value in either the left or right common carotid artery. Carotid wall thickening was defined as a maximum CIMT value > 1.0 mm.@*RESULTS@#The prevalence of carotid wall thickening was 13.0%. In participants under 60 years of age (n = 703) and in those aged 60 to 69 years (n = 837), neither education nor household income was associated with carotid wall thickening or with maximum CIMT. Among those aged 70 years or older (n = 472), however, higher educational level, but not household income, was independently related to a lower prevalence of carotid wall thickening: the multivariate-adjusted odds ratio for high vs. low educational level was 0.43 (95% confidence interval 0.21-0.83, p for trend = 0.01). A significant inverse association was observed between education, but not household income, and maximum CIMT (p for trend = 0.006).@*CONCLUSIONS@#Higher educational level may be associated with a lower prevalence of carotid wall thickening and a decrease in maximum CIMT only in participants aged 70 years or older.

Palliative Radiotherapy for Primary and Metastatic Liver Tumors

Although there have been studies reporting the efficacy of palliative radiation in treating liver tumors, there are very few reports in Japan. Therefore, this study aimed to evaluate the effect of palliative radiation on pain in patients with liver tumors. Between December 2014 and November 2016, 15 patients received palliative radiotherapy of 8 Gy in a single fraction for primary or metastatic liver tumors. Among them, 12 patients were assessed for pain before and after the radiation therapy using the Numeric Rating Scale (NRS). A decrease in the NRS score post radiation therapy was reported in all cases. No grade 3 or higher acute phase adverse events were observed. In conclusion, palliative irradiation managing pain due to liver tumors is possibly effective in relieving pain and well tolerated.

Epidemiology of vaccine-preventable diseases in Japan: considerations for pre-travel advice for the 2019 Rugby World Cup and 2020 Summer Olympic and Paralympic Games

Introduction@#In 2019 and 2020, Japan will host two international sporting events estimated to draw a combined 22 million visitors. Mass gatherings like these ones increase the risk of spread of infectious disease outbreaks and international transmission. Pre-travel advice reduces that risk. @*Methods@#To assist ministries of health and related organizations in developing pre-travel advice, we summarized national surveillance data in Japan (2000–2016, to the extent available) for rubella, invasive pneumococcal disease, measles, non-A and non-E viral hepatitis, hepatitis A, invasive Haemophilus influenzae disease, tetanus, typhoid fever, invasive meningococcal disease, Japanese encephalitis, influenza, varicella, mumps and pertussis by calculating descriptive statistics of reported cases and reviewing trends. (See Annex A for details of reviewed diseases.)@*Results@#Our findings showed notable incidences of rubella (1.78 per 100 000 person-years), influenza (243.5 cases per sentinel site), and mumps (40.1 per sentinel site); seasonal increases for influenza (November–May) and Japanese encephalitis (August–November); and a geographical concentration of Japanese encephalitis in western Japan. Measles cases decreased from 11 013 in 2008 to 35 in 2015, but outbreaks (n = 165 cases) associated with importation occurred in 2016. Though invasive meningococcal disease incidence was only 0.03 per 100 000, international transmission occurred at a mass gathering in Japan in 2015.@*Discussion@#Ministries of health and related organizations should use these findings to develop targeted pre-travel advice for travellers to the 2019 Rugby World Cup and the 2020 Summer Olympic and Paralympic Games, especially for mumps, measles, rubella, influenza, and meningitis. Travellers with increased exposure risk should also be advised about hepatitis A and Japanese encephalitis.

Nationwide Survey on Complementary and Alternative Medicine (CAM) in Cancer Patients Who Died at Palliative Care Units in Japan: Prevalence of CAM and Family Experience

<p>The aim of this study was to understand the use of complementary and alternative medicine (CAM) in cancer patients in Japan. This study was part of the Japan Hospice and Palliative care Evaluation 2016 (J-HOPE2016) Study. A multicenter questionnaire survey was conducted on a sample of bereaved family members of cancer patients who died at palliative care units. Data suggest that 54% of cancer patients use CAM. In comparison with a previous study in 2005 in Japan, categories of CAM vary widely; CAM previously included supplements mostly, but now exercise and mind and body therapy are also used. Most cancer patients use CAM without any harmful influence on their household economy and cancer treatment; however, in some patients, CAM incurs a large expense and a delay in starting cancer treatment. Therefore, it is important for medical staff and patients to have an opportunity to discuss CAM use. Multiple logistic regression analysis shows that CAM use is significantly associated with younger patients and highly educated families; moreover, there is a possibility that family members who use CAM have a high level of psychological distress. We must pay attention to the physical and the psychological aspects of cancer patients who use CAM and their families. Further studies are needed to investigate the use of each category of CAM, and to understand patients who use CAM and who die at home or in hospitals other than palliative care units.</p>

Ongoing increase in measles cases following importations, Japan, March 2014: times of challenge and opportunity

Since late 2013 through March 2014, Japan experienced a rapid rise in measles cases. Here, we briefly report on the ongoing situation and share preliminarily findings, concerns and challenges and the public health actions needed over the coming months and years. Measles is a notifiable disease in Japan based on nationwide case-based surveillance legally requiring physicians to report all clinically diagnosed and laboratory-confirmed cases within seven days, but preferably within 24 hours. After a large outbreak in 2007–2008 (more than 11 000 cases reported in 2008 alone) and a goal of elimination by April 2015, a catch-up programme using the bivalent measles-rubella (MR) vaccine was offered for grades seven and 12 (ages 12–13 and 17–18 years) from April 2008 through March 2013. During this period, there was an estimated 97% decline in measles notifications, and the cumulative number of reported cases has been steadily declining over the last five years (732 cases in 2009, 447 cases in 2010, 439 cases in 2011, 293 cases in 2012 and 232 cases in 2013). However, since late 2013 through March 2014, the country experienced a resurgence only a year after a large rubella outbreak.

Four cases in which octreotide treatment relieved symptoms of gastrointestinal bleeding in end―stage cancer patients

<b>Background：</b>Although octreotide is effective in the relief of symptoms of gastrointestinal obstruction, it is also effective for gastrointestinal bleeding. It has been reported that octreotide reduced the splanchnic blood flow, and reduced the bleeding from esophageal varices, peptic ulcer and the tumor of gastrointestinal tract. We experienced four cases of end―stage cancer patients admitted to a palliative care unit whose symptoms of gastrointestinal bleeding were alleviated by octreotide（300μg／day）. <b>Case：</b>Case 1；A 75―year―old woman with gastric cancer developed melena and received octreotide. After octreotide was discontinued, melena and hematemesis recurred. Octreotide was restarted subsequently, and hematemesis resolved. Case 2；An 87―year―old woman with gastric cancer received octreotide for increase of bloody drainage from a stomach tube. She had epigastric pain and emotional distress from the blood. These symptoms were alleviated following the administration of octreotide. Cases 3 and 4；A 76―year―old man with gastric cancer and a 62―year―old man with bile duct cancer received octreotide for massive vomiting of blood. After the administration of octreotide, there was no reoccurrence of hematemesis in both patients. <b>Conclusion：</b>Octreotide may alleviate symptoms of gastrointestinal bleeding in end―stage cancer patients.

Morbidity and mortality conference established on the basis of residents’ autonomous needs / 医学教育

  Since 2010 we have held morbidity and mortality conferences established on the basis of the needs of residents in the postgraduate training program of Nagano Red Cross Hospital. In addition to teaching about patient safety, we consider the palliating “second victim” effect. Senior residents act as moderators and will gain valuable experience as conference facilitators. Here, we report on the conference because we believe its background is unique. For further improvement, the educational effects of the conference should be analyzed.

Study on Anti-Proliferative Activities of Cultured <i>Cordyceps Militaris </i>on Cancer Cells / 日本補完代替医療学会誌

<i>Cordyceps militaris</i> has been known to produce an anticancer agent, cordycepin. Investigation on optimum culture condition for <i>C. militaris</i> had been performed. In the research program for discovering a novel function in the culture of <i>C. militaris</i>, the culture media was applied to a proliferation assays using various cell lines. The media showed significant anti-proliferative activities against al cell lines, especially to human leukemia cell line HL-60. The activity-guided purification of active ingredient was performed to obtain uracil. To the best of our knowledge, uracil has not been reported to possess anti-proliferative activity. However, the uracil obtained from the culture media was subjected to ICP-MS analysis to reveal that sodium, potassium and magnesium were found to co-exist with uracil, which might show anti-proliferative activity. Further study on the mechanism of the expression of the activity is now underway.<br>

A case in which sodium valproate through a percutaneous endoscopic gastrostomy tube was effective for delirium in a terminal cancer patient

<b>Purpose</b>: We report a case in which oral sodium valproate through a percutaneous endoscopic gastrostomy (PEG) tube for palliative decompression drainage in inoperable ileus achieved an effective drug concentration and ameliorated delirium and extrapyramidal side effects. <b>Case Report</b>: The patient was a male in his seventies who suffered from bladder cancer. He underwent PEG because of paralytic ileus with cancerous peritonitis. He had been receiving continuous intravenous infusion of haloperidol for the management of delirium, but needed to discontinue treatment with this agent due to tremor, an extrapyramidal side effect of haloperidol. Oral sodium valproate was therefore administered through the PEG tube for palliative decompression drainage. Plasma valproate concentrations showed effective levels, and his irritability was relieved. A good combination of sodium valproate and quetiapine fumarate allowed successful reduction of and eventual withdrawal from haloperidol, and tremor then improved. <b>Conclusion</b>: We often encounter difficulty with symptom control for patients who cannot use oral medications. When medication by other routes is difficult, this case suggests that sodium valproate through a PEG tube for palliative decompression drainage may be useful as a last resort for improving delirium.

[A high school measles outbreak--control measures and vaccine efficacy].

Epidemiological investigation of a March 2007 detected measles outbreak of 28 cases in a 792-student high school in Tokyo. Students with a vaccination history had significantly milder symptoms than those without, and no cases occurred among students having two of measles vaccine in two doses of measles vaccine in their childhood. Vaccine efficacy (VE) calculated in our investigation was 93.9% (95% CI:87-97), and no significant difference was observed in vaccine type or manufacturer product. Students and parents were extremely difficult to persuade to cooperate in control measures such as emergency vaccination and home isolation through notification letters even during outbreaks. Schools should thus develop measles outbreak preparedness and response plans and identify potentially susceptible students in advance through documented proof of case histories and MCV vaccination. Outbreaks should promote early detection of patients and emergency vaccination targetting potentially susceptible students backed through close cooperation with medical facilities, education institutions, and the public health sector, together with school closures as appropriate.

Study of the Suitability and Reliability of Evaluations of Initial Objective Structured Clinical Examinations at the Niigata University School of Medicine / 医学教育

At the Niigata University School of Medicine, objective structured clinical examinations (OSCEs) were performed for the first time in 2001 for 92 fourth-year medical students. The average evaluation scores students received from instructors were summarized, and the differences between scores given by different instructors were examined. We found that practice methods for the medical interview and physical examination before OSCE and the question topics and evaluation methods of OSCE were appropriate, but scores on some items were extremely low. The standardization and objectivity of the evaluation were satisfactory, perhaps because one explanatory conference and two training conferences were held for instructors before OSCE. However, some questions tended to produce differences between instructors, as did some topics, especially in the medical interview. The scores with standardized patients and those by teachers were strongly correlated, but those with the former were lower than those by the latter.

Mechanism of Cytotoxicity of Paraquat

Acute paraquat poisoning seems to be very complex because many possible mechanisms of paraquat cytotoxicity have been reported. Some may not be the cause of paraquat poisoning but the result or an accompanying phenomenon of paraquat action. The mechanism critical for cell damage is still unknown. Paraquat poisoning is probably a combination of several paraquat actions. Arguing which mechanism is more critical may not be important, and these clarified mechanisms should be connected and utilized in the development of treatment for paraquat poisoning. Many people still die of pulmonary fibrosis after paraquat exposure. The next target of study will be to verify the mechanism of pulmonary fibrosis by paraquat on the basis of the outcome of studies such as this review.

Mechanism of cytotoxicity of paraquat

Acute paraquat poisoning seems to be very complex because many possible mechanisms of paraquat cytotoxicity have been reported. Some may not be the cause of paraquat poisoning but the result or an accompanying phenomenon of paraquat action. The mechanism critical for cell damage is still unknown. Paraquat poisoning is probably a combination of several paraquat actions. Arguing which mechanism is more critical may not be important, and these clarified mechanisms should be connected and utilized in the development of treatment for paraquat poisoning. Many people still die of pulmonary fibrosis after paraquat exposure. The next target of study will be to verify the mechanism of pulmonary fibrosis by paraquat on the basis of the outcome of studies such as this review.