Mathematical model estimation of dengue fever transmission risk from Southeast and South Asia into Japan between 2016 and 2018.

BACKGROUND: Dengue fever is a viral infection transmitted to humans through the bite of a mosquito infected with the dengue virus. Dengue is one of the most common infectious diseases in the world, and its incidence is rapidly increasing. We estimated the risk of dengue importation from endemic countries to Japan and the transmission risk within Japan using data collected between 2016 and 2018. METHODS: We conducted simulations that included the number of reported dengue infections and travelers per month in ten countries in Southeast and South Asia. RESULTS: The estimated importation risks for Japanese returnees and international travelers from each of the ten endemic countries was approximately 1.0 every month from 2016 to 2018. The autochthonous transmission risk in Japan from any target country was 1.0 from June to September yearly. The estimated number of Japanese dengue cases returning to Japan is approximately 25 times higher than that of imported cases reported in Japan. CONCLUSIONS: The risk of dengue importation into Japan can be sufficiently high. Attention should be paid to autochthonous transmission spread between June and September when mosquitoes are active in Japan. Estimates of seasonal risk variation from each dengue virus-endemic country can be used to inform preventive and control measures for dengue in Japan.

Rate of diagnosed seasonal influenza in children with influenza-like illness: A cross-sectional study.

INTRODUCTION: Although influenza surveillance systems have been used to monitor influenza epidemics, these systems generally evaluate diagnostic information obtained from medical institutions and they do not include patients who have not been examined. In contrast, community based epidemiological studies target people with influenza-like illness (ILI) that self-reported influenza-like symptoms whether they have medical examinations or not. Because the criteria for influenza surveillance systems and ILI differ, there is a gap between them. The purpose of this study was to clarify this gap using school-based survey data. METHODS: Questionnaires about both ILI and the influenza diagnosis history during the 2018/19 season were administered to the guardians of 11,684 elementary schoolchildren in a single city in Japan. Based on their responses, a Bayesian model was constructed to estimate the probability of infection, ILI onset, and diagnosis at medical institutions. RESULTS: Responses were obtained from guardians of 10,309 children (88.2%). Of these, 3,380 children (32.8%) had experienced ILI, with 2,380 (23.1%) diagnosed as influenza at a medical institution. Bayesian estimation showed that the probability of influenza cases being diagnosed among ILI symptomatic children was 70% (95% credible interval, 69-71%). Of the infected children, 5% were without ILI symptoms, with 11% of these patients diagnosed with influenza. CONCLUSIONS: This epidemiological study clarified the proportion gap between ILI and influenza diagnosis among schoolchildren. These results may help to establish epidemic control measures and secure sufficient medical resources.

The association between the dynamics of COVID-19, related measures, and daytime population in Tokyo.

In Japan, a novel coronavirus has been prevalent since January 2020. The Japanese and local governments have implemented various measures, including declaring a state of emergency, according to the epidemic situation in each region. This study estimated the effective reproduction number (Rt) using the number of confirmed positive cases and positivity rates in Tokyo and examined the association between Rt and the rate of increase/decrease in the number of people across 12 sites. In Tokyo, there were five waves in which Rt was persistently estimated as approximately 1.0. The fourth and fifth waves started under the declaration of the state of emergency and coincided with an increase in the number of people. However, the contribution of the number of people to Rt was inconsistent, even when the number of people was of the same magnitude. A possible reason for this is difference in the countermeasures content, as the impact of vaccination was considered to be minor at the time. Where vaccination is insufficient, the wave is terminated by controlling the number of people leaving their homes. It is suggested that infection could be controlled more efficiently, depending on the content of the countermeasures.

Optimal Breast Density Characterization Using a Three-Dimensional Automated Breast Densitometry System.

Dense breasts are a risk factor for breast cancer. Assessment of breast density is important and radiologist-dependent. We objectively measured mammographic density using the three-dimensional automatic mammographic density measurement device Volpara™ and examined the criteria for combined use of ultrasonography (US). Of 1227 patients who underwent primary breast cancer surgery between January 2019 and April 2021 at our hospital, 441 were included. A case series study was conducted based on patient age, diagnostic accuracy, effects of mammography (MMG) combined with US, size of invasion, and calcifications. The mean density of both breasts according to the Volpara Density Grade (VDG) was 0-3.4% in 2 patients, 3.5-7.4% in 55 patients, 7.5-15.4% in 173 patients, and ≥15.5% in 211 patients. Breast density tended to be higher in younger patients. Diagnostic accuracy of MMG tended to decrease with increasing breast density. US detection rates were not associated with VDG on MMG and were favorable at all densities. The risk of a non-detected result was high in patients without malignant suspicious calcifications. Supplementary use of US for patients without suspicious calcifications on MMG and high breast density, particularly ≥25.5%, could improve the breast cancer detection rate.

Quantification of bromide ion in biological samples using headspace gas chromatography-mass spectrometry.

OBJECTIVES: In this study, we aimed to establish a method for quantifying bromide ions (Br- ) in blood and urine using gas chromatograph-mass spectrometer (GC-MS) equipped with a headspace sampler, for biological monitoring of workers exposed to methyl bromide. METHODS: Samples were mixed with dimethyl sulfate, and Br- ions were detected using GC-MS with a headspace sampler. The validity of the proposed method was evaluated based on most of the US FDA guidance. The values obtained were compared with reference values by analysis using SeronormTM Trace Elements Whole Blood L-1 RUO. RESULTS: The calibration curve showed good linearity in the Br- concentration range of 0.1-20.0 mg/L, and the coefficient of determination R2 value was >.999. Intraday and interday accuracy values were 99.3%-103.1% and 97.4%-101.8%, respectively. The measured and reference values of Seronorm were concordant. Herein, eight urine and serum samples of workers were analyzed; the samples' Br- concentrations were known. The correlation coefficients of urine and serum samples were 0.97 and 0.96, respectively, and results were consistent. CONCLUSIONS: This study established a simple and rapid method for the determination of Br- concentration in biological samples using GC-MS with a headspace sampler. Moreover, it can be used for biological monitoring of occupational exposure to methyl bromide and for the determination of Br- concentration in a wide range of biological samples.

Zinc-containing Mohs' paste affects blood flow and angiogenesis suppression.

PURPOSE: Mohs' paste, which is composed of zinc chloride and zinc oxide starch, is used for hemostasis of superficial malignancy in the clinical setting. We investigated the concentration of intramuscular zinc in mice after Mohs' paste application and evaluated its relationship with angiogenesis from the perspective of blood flow levels within 24 h. METHODS: Male C57BL/6JJmsSlc mice were administered single dose of Mohs' paste at 25%, 50%, and 75% after unilateral hind limb surgery, and glycerin, a viscosity modifier, was administered to the control group (0%). Hind limb blood flow levels were measured with a laser Doppler perfusion imaging system (n = 6). The amounts of intramuscular zinc and vascular endothelial growth factor-A (VEGF-A) expression were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) and western blotting, respectively (n = 5 or 3). RESULTS: Blood flow levels were significantly decreased in the 50% group after 8 h, and significantly decreased in the 25% and 50% groups after 24 h. Intramuscular zinc was significantly increased in the 50% and 75% groups after 8 h. Western blotting showed that VEGF-A levels were significantly increased in the 25% and 50% groups after 8 h. Based on analytical experiments and biological investigation, we predicated the pharmacological effect of Mohs' paste and found over 50% of it is critical in the blood flow and angiogenesis suppression after more than 8 h of its application. CONCLUSIONS: The results suggest that the mechanism of blood flow suppression is independent of VEGF-A levels and might suppress future angiogenesis. Our findings support that of previous studies, in which Mohs' paste was expected to induce hemostasis and suppress angiogenesis. It is an excellent ointment that facilitates hemostasis by suppressing blood flow regardless of angiogenesis, and may be apt for situations where hemostasis is required in the clinical setting.

The Prognostic Value of Left Atrial Reservoir Functional Indices Measured by Three-Dimensional Speckle-Tracking Echocardiography for Major Cardiovascular Events.

BACKGROUND: Left atrial (LA) volume and left ventricular longitudinal strain (LVLS) have significant prognostic values for major cardiovascular events (MACEs). Prognostic values of LA reservoir functional indices measured by 3-dimensional (3D) speckle-tracking echocardiography (STE) were evaluated.Methods and Results:A total of 264 patients, who underwent 2-dimensional (2D) echocardiography and 3DSTE for various underlying heart diseases, were followed up to record MACE. After a mean follow up of 547±435 days, 30 patients developed MACE: 7 cardiac deaths, 6 strokes, 1 non-fatal myocardial infarction, and 22 admissions for heart failure (5 of these had cardiac death after discharge, whereas 1 sustained stroke after discharge). Receiver operating characteristic curve analysis was performed to determine the optimal cut-off levels of 4 LA functional indices: LA emptying fraction (LAEmpF), LA longitudinal strain (LALS), LA circumferential strain (LACS), and LA area change ratio (LAAC), using 3DSTE. Among these factors, 2DLVLS, 3DLAEmpF, and 3DLALS demonstrated a higher hazard ratio (>5.0) than other variables. The 3DLAEmpF and 3DLALS had a higher average treatment effect (ATE) and ATE on the treated (ATT), respectively, than the other indices after propensity score matching. Addition of 3DLAEmpF to the base model using clinical variables and LV ejection fraction or 2DLVLS demonstrated higher prognostic power. CONCLUSIONS: LAEmpF calculated using 3DSTE possessed additive prognostic values for the prediction of MACE.

Effects of live yeast supplementation on serum oxidative stress biomarkers and lactation performance in dairy cows during summer.

This study aimed to evaluate the effects of live yeast (Saccharomyces cerevisiae) (LY) supplementation on serum oxidative stress biomarkers, antioxidant vitamin levels, and lactation performance in dairy cows during summer. A total of 16 lactating cows weighing 707.5 ± 13.1 kg (mean ± standard error) were enrolled and randomly assigned to either supplemented (n=8) or control group (n=8). In the supplemented group, the cows were administered with LY product at 10 g/day per cow from mid-July to mid-September for 8 weeks. The serum levels of derivatives of reactive oxygen metabolites in the supplemented group were lower (P<0.05) at week 6. The serum retinol and blood glucose concentrations in the supplemented group were higher (P<0.01) at week 8. LY supplementation did not affect physiological responses, such as rectal temperature, respiratory rate, protein and cholesterol metabolism, and lactation performance. During the study period, daily average milk yield decreased in both groups. The reduction rates of milk yield in the supplemented and control groups were 17.6 and 20.0%, respectively. These results suggest that LY supplementation may reduce oxidative stress and improve carbohydrate metabolism in lactating dairy cows during summer.

Metabolism of 3-[5'-deoxy-5'-(dimethylarsinoyl)-ß-ribofuranosyloxy]-2-hydroxypropylene glycol in an artificial digestive system.

Seaweeds contain large amounts of organoarsenic compounds, mostly arsenosugars (AsSug) and arsenolipids (AsLipid). AsSug is mainly metabolized into dimethylarsinic acid (DMA V ) in humans. However, this metabolic process is not well understood. We investigated the metabolism of an AsSug, 3-[5'-deoxy-5'-(dimethylarsinoyl)-ß-ribofuranosyloxy]-2-hydroxypropylene glycol (AsSug328), in the gastrointestinal tract using an in vitro artificial gastrointestinal digestion system. AsSug328 was incubated with gastric juice for 4 h, with bile-pancreatic juice for 0.5 h, and finally with enteric bacteria solution for 24 h. The conversion of arsenic compounds after artificial digestion was analyzed by HPLC-ICP-MS and HPLC-ESI-Q-TOF-MS. Our results show that artificial gastrointestinal digestion converted AsSug328 into thio-AsSug328. However, no formation of DMA V was detected. Under the artificial digestion system, the 5-deoxyribofuranose structure of AsSug was maintained. Therefore, AsSug should be absorbed in the intestinal tract after its sugar moiety is partially decomposed. They are then possibly metabolized to DMA V in the liver and subsequently excreted through urine.

Prognostic Value of Left Atrial Size and Functional Indices Measured by 3-Dimensional Speckle-Tracking Analysis.

BACKGROUND: The prognostic value of indices for left atrial volumes (LAV) and reservoir function measured by 3D speckle-tracking analysis (3DSTA) has not been determined. Methods and Results: LA maximal and minimal volume indices (LAVImax, LAVImin), and LA emptying fraction (LAEmpF) were measured via 2D echocardiography (2DE) and 3DSTA in 514 patients (62% male, mean age: 66±15 years) with various cardiovascular diseases. Two cutoff values using normal±2SD (cutoff criterion 1) and receiver-operating characteristic analysis (cutoff criterion 2) were evaluated. During a mean follow-up of 720±383 days, MACE (cardiac death, nonfatal myocardial infarction, stroke and admission for heart failure) occurred in 98 patients. Kaplan-Meier survival analysis showed both cutoff criteria measured by 2DE and 3DSTA had significant predictive power for MACE (P<0.001). For cutoff criterion 1, 3DSTA measurements yielded higher hazard ratios than 2DE by Cox proportional hazard model. Cutoff criterion 2 using 3DSTA had higher average treatment effect values than 2DE by matching propensity scores on the outcome. Further, a regression model that included clinical variables, left ventricular ejection fraction and cutoff criterion 2 using 3DSTA-derived LAEmpF had significantly higher prognostic power than 2DE. CONCLUSIONS: LA indices measured by 3DSTA had greater prognostic power for future MACE than 2DE. In particular, 3DSTA-derived LAEmpF has the potential to be a valuable prognostic tool in clinical settings.

Estimation of the effective reproduction number of influenza based on weekly reports in Miyazaki Prefecture.

In Japan, as part of surveillance for seasonal influenza, the number of patients per influenza sentinel site is counted on a weekly basis. Currently, reference values are set for the weekly reported number of influenza cases per sentinel, and pre-epidemic and epidemic warnings are issued based on these values. In this study, we examined the association between these reference values and the effective reproduction number (Rt) using surveillance data for Miyazaki Prefecture collected from 2010 to 2011. There are nine public health centre jurisdictions in this prefecture, and Rt exceeded 1.0 at the time when pre-epidemic warnings were issued in almost all the jurisdictions. Thus, it was indicated that the validity of the reference value was also high for influenza transmission. However, our results indicated the presence of secondary epidemic caused by infections originating both from other jurisdictions and inner jurisdictions, and it is occasionally not possible to evaluate the end of an epidemic in a jurisdiction using only the reference value of termination. It is necessary to establish new methods after considering the situation in the surrounding jurisdictions for more detailed epidemic predictions.

Assessing the chronic respiratory health risk associated with inhalation exposure to powdered toner for printing in actual working conditions: a cohort study on occupationally exposed workers over 10 years.

BACKGROUND: Little epidemiological evidence exists regarding the chronic respiratory effects of inhaled powdered toner exposure in humans, although several case reports have suggested the existence of lung disorders that might be related to exposure to toner dust. OBJECTIVE: We aimed to estimate the chronic health risk to humans associated with routine toner dust exposure in copier industry workers under current actual work conditions. DESIGN: A prospective observational cohort study of occupational population. METHODS: Changes in chest radiogram, spirometry measurements and serum and urine biomarkers of biomedical responses to extrinsic stress, as well as subjective symptoms were longitudinally observed for up to 10 years in Japanese copier industry workers responsible for the manufacturing, maintenance or recycling of powdered toner or toner-using machines. A total of 694 subjects who did not change their work category during the follow-up and were free from chronic respiratory diseases at the baseline survey provided reliable results on at least three survey occasions during 3 years or more of follow-up. RESULTS: Typical fibrosis findings associated with pneumoconiosis was not observed on chest radiograms. No significant differences associated with toner exposure were noted in the frequency of new incidence of either non-specific findings on chest radiogram or serum fibrosis biomarkers (sialylated carbohydrate antigen KL-6 and surfactant protein D). However, the exposed subjects tended to show increases in the frequency of respiratory symptoms and reduced spirometry results during the follow-up compared with the control group, although significant differences were only seen in chronic cough. CONCLUSIONS: Under the current reasonably controlled work environmental conditions, lung fibrotic changes caused by inhaled dust exposure, including powdered toner, appear to be relatively uncommon; however, non-specific temporal irritation causing subjective symptoms and inflammatory responses might exist.

Seasonal changes in serum oxidative stress biomarkers in dairy and beef cows in a daytime grazing system.

This study aims to evaluate the oxidative stress during hot summer season using serum oxidative stress biomarkers and elucidate the effects of serum antioxidant vitamin levels in dairy and beef cows in a daytime grazing system. Blood samples were collected once a month from eight Holstein Friesian (HF) and 10 Japanese Black (JB) cows from November 2013 to October 2014. Serum values of derivatives of reactive oxygen metabolites (d-ROMs) tended to be higher in March in both breeds and those in HF cows were kept at higher (P<0.001) levels than those in JB cows during the study period. Serum levels of biological antioxidant potential (BAP) in both breeds were maintained at almost the same values during study period. The OSI [(d-ROMs/BAP) × 100] values in both breeds showed similar seasonal changes, i. e. increase from December to March and decrease from March to August or September. In addition, the OSI values in HF cows were kept at higher (P<0.01) levels than those in JB cows during the study period. Serum concentrations of α-tocopherol, ß-carotene, blood urea nitrogen and total cholesterol showed similar seasonal changes in both breeds, low in the winter and high from spring to summer, which may be attributed to the pasture grass intake. Opposite changes in OSI values and serum concentrations of α-tocopherol and ß-carotene indicated that antioxidant vitamin levels could affect oxidative stress status.

Histopathological changes in the pancreas of cattle with abdominal fat necrosis.

The association between pancreatic disorder and abdominal fat necrosis in cattle remains unclear. The pancreases of 29 slaughtered cattle with or without fat necrosis were collected to investigate pathological changes. Japanese Black (JB) cattle were classified into the FN group (with abdominal fat necrosis; n=9) and N group (without fat necrosis; n=5). The pancreases were also collected from 15 Holstein Friesian (HF) cows. All JB cattle showed high body condition scores. Regarding the pathological findings, fatty pancreas which involves adipocyte infiltration into the pancreas and fat necrosis (saponification) were observed in 25 and 27 cases, respectively. Immunohistochemical staining with anti-Iba-1 antibody showed large numbers of macrophages surrounding the saponified fat in the pancreas. CD3-positive T cells were significantly more common in the pancreas of both the FN and N groups compared with the HF group (P<0.05). Furthermore, fibrosis in the pancreas exhibited a correlative tendency with the formation of necrotic fat mass in the peritoneal cavity (P<0.1). These results indicate that obesity leads to increased severity of pancreatic disorder, including fatty pancreas and pancreatitis. The pathological lesions in the pancreas may play a key role in abdominal fat necrosis through the inflammatory process.

Clinical impact of undersized- versus oversized-stenting approaches in ST-elevation myocardial infarction.

BACKGROUND: Primary percutaneous coronary intervention (PCI) is the standard treatment in patients with ST-elevation myocardial infarction (STEMI). However, some patients still develop ST re-elevation during PCI, resulting in further myocardial damage and a poor outcome. An undersized-stenting approach may prevent ST re-elevation. We aimed to determine the association between final stent area and ST re-elevation during primary PCI for STEMI. METHODS: Overall, 102 consecutive STEMI patients who underwent primary PCI under integrated backscatter intravascular ultrasound guidance were enrolled. The stent-reference (SR) ratio was defined as the stent cross-sectional area (CSA) divided by the average CSA of the 5-mm proximal and distal reference lumens. The patients were divided into two groups according to the SR ratio: undersize group (SR<1.0, n=62) and oversize group (SR≥1.0, n=40). The incidences of ST re-elevation and total ST resolution (STR) were compared. RESULTS: The oversize group showed a higher incidence of ST re-elevation (32.5 vs. 9.7%, p=0.004) and a lower total STR (22.4±62.7 vs. 43.4±38.6%, p=0.04). After adjustment, the oversized-stenting approach was independently associated with ST re-elevation [odds ratio: 3.74, 95% confidence interval (CI) 1.27-12.1, p=0.02]. The peak creatine kinase-MB level was higher in the oversize group (341±259 vs. 242±208IU/l, p=0.04). The incidences of stent thrombosis and restenosis were similar between the two groups. CONCLUSIONS: An oversized-stenting approach in patients with STEMI was associated with a higher incidence of ST re-elevation and a lower total STR, resulting in increased myocardial damage.

Quantitative effects of a declaration of a state of emergency on foot-and-mouth disease.

OBJECTIVES: The law in Japan requires the declaration of a state of emergency and implementation of countermeasures for an epidemic of a new infectious disease. However, because a state of emergency has never been declared in Japan, its effects remain unknown. The required countermeasures are similar to those implemented in the foot-and-mouth disease epidemic in Miyazaki in 2010. This study aimed to quantitatively estimate the effect of the declaration in 2010 and investigate the nature of the epidemic based on the day on which the declaration took effect. METHODS: Only publicly available data were used. Data for farms in the most affected town were analyzed. A modified susceptible-infected-recovered model was used to estimate the effect and for the simulation. Another model was used to estimate the effective reproduction number. RESULTS: After the declaration, the intra-bovine transmission rate decreased by 18.1 %, and there were few days when the effective reproduction number was >1.0. A few weeks delay in the declaration significantly increased the possibility of epidemic, number of farms at peak, and final infection scale. CONCLUSIONS: Based on the substantial decrease in the transmission rate after the declaration of a state of emergency in 2010, a future declaration will have a similar effect for a new infectious disease even though a direct extrapolation is not valid. Although a declaration should be carefully considered owing to the potential socioeconomic effects, it is essential to prepare for the implementation given that a delay of only a few weeks should be acceptable.

Possible production of arsenic hemoglobin adducts via exposure to arsine.

OBJECTIVES: Arsine is an arsenic compound generated as a by-product in metal refineries. Accidental poisoning occurs sporadically; however, the administrative level for workers has not been established. Thus, it is essential to identify a highly specific biomarker for risk management in the workplace. The aim of this study was to identify an arsenic adduct, a potential biomarker, in the plasma. METHODS: Preserved mouse blood was exposed to arsine in vitro, and the plasma was separated. The residual clot of the control sample was hemolyzed using ultrapure water, and the supernatant was collected. Plasma from mice exposed to arsine in vivo was also separated from blood. Immunoprecipitation assays were conducted using all samples after ultrafiltration, and three fractions were collected. The total arsenic concentration in each fraction was quantified using inductively coupled plasma mass spectrometry (ICP-MS). The three in vitro samples and the eluate fraction from immunoprecipitation were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). RESULTS: In the exposed samples, the arsenic concentration in the fraction containing immunocomplexes was higher when immunoprecipitation was conducted with an anti-globin antibody. Three peaks were specifically observed in arsine-exposed samples after MALDI-TOF-MS analysis. Two of them were around m/z 15,000, and the other was m/z 15,700. The latter peak was confirmed even after immunoprecipitation. CONCLUSIONS: Globin forms an adduct with arsenic after both in vitro and in vivo exposure to arsine. This adduct together with hemoglobinuria could be a candidate biomarker of acute arsine poisoning in plasma.