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Although rubella is an infectious disease that can be prevented by vaccination, there have been periodic epidemics in Japan, mainly among adult males. One of the reasons for this is the lack of interest in vaccination among the target adult male population. To clarify the reality of the discussion about rubella and provide basic resource for enlightening activities for rubella prevention, we collected and analyzed Twitter posts about rubella in Japanese between January 2010 and May 2022. We examined time series, number of tweets per account, tweeted contents, and retweet network. We found that the weekly number of rubella reports and the number of Twitter posts fluctuate simultaneously. During the 2018 rubella epidemic, the number of tweets increased due to the start of the rubella routine vaccination program and the use of cartoons to raise awareness. While 80% of the accounts posted three times or fewer during the period, some accounts posted multiple times per day for more than 12 years. Medical terms such as vaccines and antibodies were frequently used in the tweet contexts. In the retweet activity, a variety of actors, including mass media, medical professionals, and even rubella sufferers, contributed to disseminate rubella-related information.

Background Empyema is a life-threatening infection often caused by oral microbiota. To the best of our knowledge, no reports have investigated the association between the objective assessment of oral health and prognosis in patients with empyema. Materials and methods A total of 63 patients with empyema who required hospitalization at a single institution were included in this retrospective study. We compared non-survivors and survivors to assess risk factors for death at three months, including the Renal, age, pus, infection, diet (RAPID) score, and Oral Health Assessment Tool (OHAT) score. Furthermore, to minimize the background bias of the OHAT high-score and low-score groups determined based on the cut-off value, we also analyzed the association between the OHAT score and death at 3 months using the propensity score matching method. Results The 3-month mortality rate was 20.6% (13 patients). Multivariate analysis showed that a RAPID score ≥5 points (odds ratio (OR) 8.74) and an OHAT score ≥7 points (OR 13.91) were significantly associated with death at 3 months. In the propensity score analysis, a significant association was found between a high OHAT score (≥7 points) and death at 3 months (P = 0.019). Conclusion Our results indicated that oral health assessed using the OHAT score may be a potential independent prognostic factor in patients with empyema. Similar to the RAPID score, the OHAT score may become an important indicator for the treatment of empyema.

Background Endoscopic transpapillary gallbladder drainage (ETGBD) has been reported as an alternative procedure for acute cholecystitis but remains a challenging procedure. Aims To elucidate the efficacy of a strategic approach for ETGBD that utilizes a four-step classification system and the optional use of ‘Three-pillar’ assistance with the following devices: cholangioscopy (SpyGlass DS, SG), a flex-type guidewire (Flex-GW), and a 3-Fr microcatheter (3-Fr Micro). Methods A total of 115 patients undergoing ETGBD were studied retrospectively. Characteristics and technical outcomes were compared between conventional ETGBD technique (Classical ETGBD, N = 50) and strategic ETGBD with optional Three-pillar assistance (Strategic ETGBD, N = 65). Results SG-assistance (15/65, 23.1%) was as an excellent troubleshooter in Category 1 (failure to identify the cystic duct [CD] orifice) and Category 2 (failure to advance the GW across the CD takeoff due to unfavorable angle). Flex-GW (19/65, 29.2%) worked for Category 3b (failure of GW access to the GB due to multiple tortuosities). 3-Fr Micro (11/65, 16.9%) was effective for Category 3a (failure of GW access to the GB due to CD obstruction) and Category 4 (failure of drainage stent insertion to the GB). The overall technical success rate was significantly higher for Strategic ETGBD (63/65, 96.9%) compared with Classical ETGBD (36/50, 72.0%) (p = 0.0001). Conclusions Strategic ETGBD, which includes the Three-pillar assistance options of SG in the initial steps, Flex-GW for tortuous CD, and 3-Fr Micro for stenotic CD, achieved a significantly higher success rate than for Classical ETGBD.

Tramadol is a useful analgesic which acts as a serotonin and noradrenaline reuptake inhibitor in addition to μ-opioid receptor agonist. Cytoplasmic serotonin modulates the small GTPase activity through serotonylation, which is closely related to the human platelet activation. We recently reported that the combination of subthreshold collagen and CXCL12 synergistically activates human platelets. We herein investigated the effect and the mechanism of tramadol on the synergistic effect. Tramadol attenuated the synergistically stimulated platelet aggregation (300 μM of tramadol, 64.3% decrease, p

Background The features of hepatitis C virus patients with a sustained virologic response (SVR) who developed hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) therapy are unclear. Methods The study population included 1494 DAA-SVR patients without a history of HCC. The cumulative carcinogenesis rate after the end of treatment (EOT) and factors related to HCC were analyzed. Results Sixty (4.0%) patients developed HCC during a median observation period of 47.6 months. At four years, the cumulative carcinogenesis rate was 4.7%. A Cox proportional hazards analysis showed that age ≥73 years (hazard ratio [HR]: 2.148), male sex (HR: 3.060), hyaluronic acid (HA) ≥75 ng/mL (HR: 3.996), alpha-fetoprotein at EOT (EOT-AFP) ≥5.3 ng/mL (HR: 4.773), and albumin at EOT (EOT-Alb) Conclusions EOT-AFP ≥5.3 ng/mL is useful for predicting HCC development after an SVR. However, AFP does not increase in patients with EOT-AFP

Early detection and management of adverse drug reactions (ADRs) is crucial for improving patients’ quality of life. Hand-foot syndrome (HFS) is one of the most problematic ADRs for cancer patients. Recently, an increasing number of patients post their daily experiences to internet community, for example in blogs, where potential ADR signals not captured through routine clinic visits can be described. Therefore, this study aimed to identify patients with potential ADRs, focusing on HFS, from internet blogs by using natural language processing (NLP) deep-learning methods. From 10,646 blog posts, written in Japanese by cancer patients, 149 HFS-positive sentences were extracted after pre-processing, annotation and scrutiny by a certified oncology pharmacist. The HFS-positive sentences described not only HFS typical expressions like “pain" or “spoon nail”, but also patient-derived unique expressions like onomatopoeic ones. The dataset was divided at a 4 to 1 ratio and used to train and evaluate three NLP deep-learning models: long short-term memory (LSTM), bidirectional LSTM and bidirectional encoder representations from transformers (BERT). The BERT model gave the best performance with precision 0.63, recall 0.82 and f1 score 0.71 in the HFS user identification task. Our results demonstrate that this NLP deep-learning model can successfully identify patients with potential HFS from blog posts, where patients’ real wordings on symptoms or impacts on their daily lives are described. Thus, it should be feasible to utilize patient-generated text data to improve ADR management for individual patients.

Background Previous studies have attempted to characterize depression using electroencephalography (EEG), but results have been inconsistent. New noise reduction technology allows EEG acquisition during conversation. Methods We recorded EEG from 40 patients with depression as they engaged in conversation using a single-channel EEG device while conducting real-time noise reduction and compared them to those of 40 healthy subjects. Differences in EEG between patients and controls, as well as differences in patients’ depression severity, were examined using the ratio of the power spectrum at each frequency. In addition, the effects of medications were examined in a similar way. Results In comparing healthy controls and depression patients, significant power spectrum differences were observed at 3 Hz, 4 Hz, and 10 Hz and higher frequencies. In the patient group, differences in the power spectrum were observed between asymptomatic patients and healthy individuals, and between patients of each respective severity level and healthy individuals. In addition, significant differences were observed at multiple frequencies when comparing patients who did and did not take antidepressants, antipsychotics, and/or benzodiazepines. However, the power spectra still remained significantly different between non-medicated patients and healthy individuals. Limitations The small sample size may have caused Type II error. Patients’ demographic characteristics varied. Moreover, most patients were taking various medications, and cannot be compared to the non-medicated control group. Conclusion A study with a larger sample size should be conducted to gauge reproducibility, but the methods used in this study could be useful in clinical practice as a biomarker of depression.

Background Decision-making in healthcare policy involves assessing both costs and benefits. In determining the cost-effectiveness (CE) threshold, willingness to pay (WTP) per quality-adjusted life year (QALY), GDP per capita, and other factors are important. However, the relationship between WTP/QALY or GDP per capita and the CE threshold is unclear. It is important to clarify the relationship between WTP/QALY and GDP to provide a clear basis for setting the CE threshold. Objective The purpose of this study was to compare WTP/QALY and GDP per capita, and to develop a new CE threshold range based on WTP using GDP per capita. The relationship between WTP/QALY and healthy life expectancy (HALE) was also investigated. Methods We searched MEDLINE, EMBASE and Web of Science from 1980/01/01 to 2020/12/31 using the following selection criteria (latest search: Dec 2021):1, studies that estimated WTP/QALY; 2, the general population was surveyed; 3, the article was in English. From the collected articles, we obtained average values of WTP/QALY for various countries and compared WTP/QALY with GDP per capita. The correlation between WTP/QALY and HALE was also examined. Results We identified 20 papers from 17 countries. Comparison of mean WTP/QALY values with GDP per capita showed that most WTP/QALY values were in the range of 0.5–1.5 times GDP per capita, though the median values were less than 0.5 times. Comparison of WTP/QALY with HALE showed a statistically significant positive correlation when Taiwan was excluded as an outlier. Conclusions Our results suggest a CE threshold range of 0.5–1.5 times GDP per capita is appropriate but lower than the WHO-recommended range of 1–3 times. The correlation between WTP/QALY and HALE suggests that investment in healthcare is reflected in an increased healthy life expectancy. Since WTP is based on consumer preferences, this range could be used to set a generally acceptable criterion.

Purpose To retrospectively assess the repeatability of physiological F-18 labeled fluorodeoxyglucose (FDG) uptake in the skin on positron emission tomography/magnetic resonance imaging (PET/MRI) and explore its regional distribution and relationship with sex and age. Methods Out of 562 examinations with normal FDG distribution on whole-body PET/MRI, 74 repeated examinations were evaluated to assess the repeatability and regional distribution of physiological skin uptake. Furthermore, 224 examinations were evaluated to compare differences in the uptake due to sex and age. Skin segmentation on PET was performed as body-surface contouring on an MR-based attenuation correction map using an off-line reconstruction software. Bland–Altman plots were created for the repeatability assessment. Kruskal–Wallis test was performed to compare the maximum standardized uptake value (SUVmax) with regional distribution, age, and sex. Results The limits of agreement for the difference in SUVmean and SUVmax of the skin were less than 30%. The highest SUVmax was observed in the face (3.09±1.04), followed by the scalp (2.07±0.53). The SUVmax in the face of boys aged 0–9 years and 10–20 years (1.33±0.64 and 2.05±1.00, respectively) and girls aged 0–9 years (0.98±0.38) was significantly lower than that of men aged ≥20 years and girls aged ≥10 years (p Conclusion PET/MRI enabled the quantitative analysis of skin FDG uptake with repeatability. The degree of physiological FDG uptake in the skin was the highest in the face and varied between sexes. Although attention to differences in body habitus between age groups is needed, skin FDG uptake also depended on age.

Background Lower blood pressure (BP) levels are linked to a slower decline of kidney function in patients with chronic kidney disease (CKD) without kidney replacement therapy. However, there are limited data on this relation in peritoneal dialysis (PD) patients. Here we evaluated the association of BP levels with the decline of residual kidney function (RKF) in a retrospective cohort study. Methods We enrolled 228 patients whose PD was initiated between 1998 and 2014. RKF was measured as the average of creatinine and urea clearance in 24-hr urine collections. We calculated the annual decline rate of RKF by determining the regression line for individual patients. RKF is thought to decline exponentially, and thus we also calculated the annual decline rate of logarithmic scale of RKF (log RKF). We categorized the patients’ BP levels at 3 months after PD initiation (BP3M) into four groups (Optimal, Normal & High normal, Grade 1 hypertension, Grade 2 & 3 hypertension) according to the 2018 European Society of Cardiology and European Society of Hypertension Guidelines for the management of arterial hypertension. Results The unadjusted, age- and sex-adjusted, and multivariable-adjusted decline rate of RKF and log RKF decreased significantly with higher BP3M levels (P for trend Conclusions Higher BP levels after PD initiation are associated with a faster decline in RKF among PD patients.

During pregnancy in placental mammals, small numbers of maternal cells (maternal microchimeric cells, or MMc cells) migrate into the fetus and persist decades, or perhaps for the rest of their lives, and higher frequencies of MMc cells are reported to correlate with variety of phenomena, such as immune tolerance, tissue repair, and autoimmune diseases. While detection of these MMc cells is considered in all pregnancies, their frequency differs largely according to tissue type and disease cases, and it remains unclear whether the number of MMc cells differs significantly among embryos in normal pregnancies. Here, for the first time, we developed a whole embryonic detection method for MMc cells using transgenic mice and counted live MMc cells in each individual embryo. Using this technique, we found that the number of MMc cells was comparable in most of the analyzed embryos; however, around 500 times higher number of MMc cells was detected in one embryo at the latest stage. This result suggests that the number of MMc cells could largely differ in rare cases with unknown underlying mechanisms. Our methodology provides a basis for testing differences in the numbers of MMc cells among individual embryos and for analyzing differences in MMc cell type repertoires in future studies. These data could provide a hint toward understanding the mechanisms underlying the variety of apparently inconsistent MMc-related phenomena.

Background Coronavirus disease (COVID-19) is associated with a high mortality rate in older adults; therefore, it is important for medical institutions to take measures to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. This study aimed to assess the risk of SARS-CoV-2 infection among healthcare workers (HCWs) and the effectiveness of infection control measures. Methods This study had a cross-sectional component and a prospective cohort component. The cross-sectional component comprised an anti-SARS-CoV-2 antibody survey among HCWs at a medical center in Saitama City, Japan. In the prospective cohort component, HCWs at the same medical center were tested for anti-SARS-CoV-2 antibodies monthly over a 3-month period (May to July 2020) to assess the effectiveness of infection prevention measures, including personal protective equipment use. All participants in the cohort study also participated in the antibody survey. The primary outcome was anti-SARS-CoV-2 antibody (measured using Elecsys® Anti-SARS-CoV-2) positivity based on whether participants were engaged in COVID-19-related medical care. Other risk factors considered included occupational category, age, and sex. Results In total, 607 HCWs participated in the antibody survey and 116 doctors and nurses participated in the cohort study. Only one of the 607 participants in the survey tested positive for anti-SARS-CoV-2 antibodies. All participants in the cohort study were anti-SARS-CoV-2 antibody negative at baseline and remained antibody negative. Engaging in the care of COVID-19 patients did not increase the risk of antibody positivity. During the study period, a total of 30 COVID-19 in-patients were treated in the hospital. Conclusions The infection control measures in the hospital protected HCWs from nosocomially acquired SARS-CoV-2 infection; thus, HCWs should engage in COVID-19-related medical care with confidence provided that they adhere to infectious disease precautions.

Introduction Bone mineral density (BMD) measured with dual-energy X-ray absorptiometry (DXA) can be used to predict fractures, but its clinical utility has not been fully established in chronic kidney disease (CKD) patients. Magnesium is an essential trace element. Although magnesium is associated with the risk of fractures in non-CKD populations, the relationship is unknown in CKD patients. Methods BMD and serum magnesium levels were measured in 358 stable outpatients undergoing maintenance hemodialysis therapy. The primary outcome was fragility fracture. Patients were divided into groups according to the median level of magnesium and the normal threshold value of lumbar spine BMD. Results During the median follow-up period of 36 months, 36 (10.0%) fractures occurred. The cumulative incidence rates of fractures were 17.6% and 5.2% [adjusted hazard ratio (aHR) 2.31, 95% confidence interval (CI) 1.03–5.17, P = 0.030] in the lower ( Discussion/Conclusions The combination of serum magnesium and lumbar spine BMD can be used for fracture risk stratification and synergistically improves the prediction of fractures in CKD patients.

Winter activities on ice are culturally important for many countries, yet they constitute a high safety risk depending upon the stability of the ice. Because consistently cold periods are required to form stable and thick ice, warmer winters could degrade ice conditions and increase the likelihood of falling through the ice. This study provides the first large-scale assessment of winter drowning from 10 Northern Hemisphere countries. We documented over 4000 winter drowning events. Winter drownings increased exponentially in regions with warmer winters when air temperatures neared 0 ̊C. The largest number of drownings occurred when winter air temperatures were between -5 ̊C and 0 ̊C, when ice is less stable, and also in regions where indigenous traditions and livelihood require extended time on ice. Rates of drowning were greatest late in the winter season when ice stability declines. Children and adults up to the age of 39 were at the highest risk of winter drownings. Beyond temperature, differences in cultures, regulations, and human behaviours can be important additional risk factors. Our findings indicate the potential for increased human mortality with warmer winter air temperatures. Incorporating drowning prevention plans would improve adaptation strategies to a changing climate. Funding was provided to SS by the Ontario Ministry of Research, Innovation and Science Early Researcher Award and York University Research Chair programme. Funding support for BAD was provided by Kempestiftelserna. AL was supported by Estonian Research Council Grant PSG 32. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding was provided to SS by the Ontario Ministry of Research, Innovation and Science Early Researcher Award and York University Research Chair programme. Funding support for BAD was provided by Kempestiftelserna. AL was supported by Estonian Research Council Grant PSG 32. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Selective estrogen receptor modulator (SERM) interacts with estrogen receptors and acts as both an agonist or an antagonist, depending on the target tissue. SERM is widely used as a safer hormone replacement therapeutic medicine for postmenopausal osteoporosis. Regarding hepatocellular carcinoma (HCC), accumulating evidence indicates gender differences in the development, and that men are at higher morbidity risk than premenopausal women, suggesting that estrogen protects against HCC. However, it remains unclear whether SERM affects the HCC progression. Previously, we have shown that transforming growth factor (TGF)-α promotes the migration of HCC cells via p38 mitogen-activated protein kinases (MAPK), c-Jun N-terminal kinase and AKT. In the present study, we investigated whether SERM such as tamoxifen, raloxifene and bazedoxifene, affects the HCC cell migration using human HCC-derived HuH7 cells. Raloxifene and bazedoxifene but not tamoxifen, significantly suppressed the TGF-α-induced HuH7 cell migration. ERB041 and DPN, estrogen receptor (ER) β agonists, inhibited the TGF-α-induced cell migration whereas PPT, an ERα agonist, did not show the suppressive effect on the cell migration. ERB041 attenuated the TGF-α-induced phosphorylation of AKT without affecting the phosphorylation of p38 MAPK and c-Jun N-terminal kinase. Raloxifene and bazedoxifene also inhibited the phosphorylation of AKT by TGF-α. Furthermore, PHTPP, an ERβ antagonist, significantly reversed the suppression by both raloxifene and bazedoxifene of the TGF-α-induced cell migration. Taken together, our results strongly indicate that raloxifene and bazedoxifene, SERMs, suppress the TGF-α-induced migration of HCC cells through ERβ-mediated inhibition of the AKT signaling pathway.