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This study examined the discordance between hemodialysis patients' reports and their physicians' estimates of dietary restriction adherence and related factors in Japan.In a cross-sectional survey of 6644 outpatients, physicians who estimated higher and lower adherence than their patients' self-reported were categorized as overestimation and underestimation in terms of discordance, respectively. Possible factors included clinical indicators, patient characteristics related to negative stereotypes, and health beliefs related to statistical discrimination.The concordance rate was 0.069 based on the weighted kappa coefficient. The coefficients of acceptable serum potassium, prevalence of diabetes, and self-efficacy on overestimates were 0.663, -0.126, and -0.132, respectively. The coefficients of these factors on underestimates were -0.589, 0.338, and 0.145, respectively. All these coefficients were significant.The discordance may be high and is related to physicians' clinical data reliance, negative stereotypes about patient characteristics, and a lack of understanding of patients' health beliefs.

Purpose: To evaluate whether knowledge-based volumetric modulated arc therapy plans with from a multi-institution model (broad model) are clinically useful and effective as a standardization method. Methods: A knowledge-based planning (KBP) model was trained with 561 prostate VMAT plans from five institutions with different contouring and planning policies. Five clinical plans at each institution were reoptimized with the broad and single institution model, and the dosimetric parameters and relationship between Dmean and the overlapping volume (rectum or bladder and target) were compared. Results: The differences between the broad and single institution models in the dosimetric parameters for V50, V80, V90, and Dmean were: rectum; 9.5% ± 10.3%, 3.3% ± 1.5%, 1.7% ± 1.6%, and 3.6% ± 3.6%, (p < 0.001), bladder; 8.7% ± 12.8%, 1.5% ± 2.6%, 0.7% ± 2.4%, and 2.7% ± 4.6% (p < 0.02), respectively. The differences between the broad model and clinical plans were: rectum; 2.4% ± 4.6%, 1.7% ± 1.7%, 0.7% ± 2.4%, and 1.5% ± 2.0%, (p = 0.004, 0.015, 0.112, and 0.009) bladder; 2.9% ± 5.8%, 1.6% ± 1.9%, 0.9% ± 1.7%, and 1.1% ± 4.8%, (p < 0.018), respectively. Strong correlations were observed (p < 0.001) in the relationship between Dmean and the rectal and bladder volume overlapping with the target in the broad model (R = 0.815 and 0.891, respectively). The broad model had the smallest R2 of the three plans. Conclusions: KBP with the broad model is clinically effective and applicable as a standardization method at multiple institutions.

Background Animal movement is considered the most significant factor in the transmission of infectious diseases in livestock. A better understanding of its effects would help provide a more reliable estimation of the disease spread and help develop effective control measures. If the movement pattern is heterogeneous, its characteristics should be considered in epidemiological analyses, such as when using simulation models to obtain reliable outputs. In Japan, following the bovine spongiform encephalopathy epidemic, a traceability system for cattle was established in 2003, and the registration of all cattle movements in the national database began. This study is the first to analyze cattle movements in Japan. We examined regional and seasonal heterogeneity in dairy cow movements, which accounted for most Japanese breeding cattle. Results In the 14 years from April 2005 to March 2018, 4,577,709 between-farm movements of dairy cows were recorded, and the number of movements was counted by month and age for both inter- and intra-regional movements. As a result, two characteristic round-trip movements were observed: one was non-seasonal and inter-regional movements related to cattle-breeding ranches in Hokkaido (the northern region of Japan), which consists of the movement of cows around ages 6 to 8 and 21 to 23 months old. In addition, the seasonal movement of heifers for summer grazing within Hokkaido occurred in May and October at the peak ages of 13 to 14 and 19 to 20 months old, respectively. The observed heterogeneity seemed to reflect the suitability of raising the Holstein breed in Hokkaido and the shortage of supply of replacement heifers and available farming areas outside Hokkaido. Conclusions Understanding the patterns of dairy cow movements will help develop reliable infectious disease models and be beneficial for developing effective control measures against these diseases.

Classical swine fever (CSF) is a worldwide devastating disease of the pig industry caused by classical swine fever virus (CSFV). In September 2018, an outbreak of CSF occurred in Japan where the disease had been eradicated and was officially designated a CSF-free country since 2015. Following the detection of the first 2018 case on a farm in Gifu Prefecture, the disease spread among both farm pigs and wild boars and still continues. Epigenome analysis using whole-genome information is helpful in identifying the infection route, but the current approaches provide an insufficient resolution. In this study, a novel method of using single-nucleotide variants (SNVs) was employed to identify the associations among 158 isolates (65 from farms and 93 from wild boars). The identified groups of CSFV strains were plotted in different colours on a map, identifying the location where each strain was collected. The lack of an SNV set shared between the index case and the other strains suggested the first infection in Japan during the outbreak occurred in wild boars, not at the index farm. For the Atsumi Peninsula outbreaks, where nine farms were found infected within a 10-km radius area, the farm strains were assembled into three groups, suggesting these outbreaks resulted from at least three different infection events in this area. For the infections in the area around Saitama Prefecture, an area remote from the epicentre, strains from both the farms and wild boars were identified as being in the same group, suggesting they resulted from one viral introduction. Likewise, seven infected farms in Okinawa Prefecture, almost 1,500 km from Gifu Prefecture, were identified as being in a common, but separate group. By demonstrating the variety of transmission routes and possibility of long-distance infection, these results will help improve disease control measures.

Purpose To analyze the epidemiologic characteristics of an outbreak of human adenovirus type 54 (HAdV-54) on Oki Island, Shimane Prefecture, Japan, in 2017 and to assess the effectiveness of a compartmentalization method in controlling the incidence and spread. Study design Retrospective cohort study. Methods The infection was diagnosed in 136 individuals, and typing was confirmed by PCR and direct sequencing. The epidemiologic characteristics of the disease including the infection rate, incubation period, and basic reproductive number (R0), ie, number of cases directly infected by an infectious patient during the course of the disease, were investigated. The effectiveness of compartmentalization for infection control was determined by simulating the outbreak using the Susceptible-Exposed-Infectious-Recovered (SEIR) model. Results The majority of the HAdV-54-infected individuals were the children of 3 nursery schools (A, B, and C) and their parents on Oki Island. The infection rates in the 3 schools were 13.2%, 16.9%, and 17.2%, respectively. The one class of school B without the index case was initially compartmentalized, and the infection rate in this compartment was 0%. The incubation period was calculated to be 9.3 ± 3.5 days, and the disease duration, 13.0 ± 5.4 days. The R0 was 1.43. Using these parameters, a SEIR model was constructed. The SEIR model well predicted the daily incidence of infection and indicated that the compartmentalization method provides effective reduction in the incidence of the infection, with much earlier control. Conclusions The compartmentalization method is effective to control HAdV-54 outbreaks. Supplementary Information The online version contains supplementary material available at 10.1007/s10384-021-00826-8.

The increase in some wildlife species is of global concern. The utilization of wildlife meat as food and feed represents a potential source of food-borne pathogens; this is particularly a potential concern for the use of wild board as a food source in Japan. Regarding food safety and an animal infectious disease control, however, little is known about the infection level of zoonotic pathogens including Toxoplasma gondii (T. gondii) in wild boar populations in their natural habitats in Japan. A total of 1279 blood samples from 41 prefectures were collected from apparently healthy wild boars during the three hunting periods (September to February) of 2014-2015, 2015-2016, and 2017-2018. Out of these sera, 461 samples tested positive by a commercial indirect ELISA for T. gondii, and the total apparent and adjusted true seroprevalence were estimated to 36.0% (95% confidence interval [CI], 33.4-38.7) and 31.3% (95% CI, 33.1-38.9), respectively. The seroprevalence was significantly higher in yearlings and adults than in piglets (P < 0.05); however, no significant difference according to gender was noted. These results indicate the importance of adequate heating of wild boar meat before consumption to prevent transmission of T. gondii to humans. Furthermore, freezing meat for several days before cooking is recommended to reduce the risk of infection. In addition, although the incidence of toxoplasmosis in pig farms is relatively low in Japan, biosecurity measures against the felids and the varied intermediate hosts should be strengthened, especially, at the farms located in the wild boar habitats to prevent livestock infection.

Acanthamoeba can cause visually destructive Acanthamoeba keratitis (AK) in contact lens (CL) users. The purpose of this study was to determine whether Acanthamoeba was present in the CL cases of CL wearers and to develop techniques to prevent the contaminations. To accomplish this, 512 CL case samples were collected from 305 healthy CL wearers. Using real-time PCR, Acanthamoeba DNA was detected in 19.1% of CL cases, however their presence was not directly associated with poor CL case care. Instead, the presence of Acanthamoeba DNA was associated with significant levels of many different bacterial species. When the CL cases underwent metagenomic analysis, the most abundant bacterial orders were Enterobacteriales followed by Burkholderiales, Pseudomonadales, and Flavobacteriales. The presence of Acanthamoeba was characterized by Propionibacterium acnes and Rothia aeria and was also associated with an increase in the α diversity. Collectively, Acanthamoeba contamination occurs when a diversified bacterial flora is present in CL cases. This can effectively be prevented by careful and thorough CL case care.

Hidehiro Sugisawa,1 Yumiko Shimizu,2 Tamaki Kumagai,3 Kanji Shishido,4 Toshio Shinoda5 1International Graduate School for Advanced Studies, J. F. Oberlin University, Machida-city, Tokyo, Japan; 2The Jikei University School of Nursing, Chofu-city, Tokyo, Japan; 3Graduate School of Health Sciences at Odawara, International University of Health and Welfare, Odawara-city, Kanagawa, Japan; 4Kawasaki Clinic, Kawasaki-city, Kanagawa, Japan; 5Faculty of Medical and Health Sciences, Tsukuba International University, Tsuchiura-city, Ibaraki, JapanCorrespondence: Hidehiro Sugisawa, International Graduate School for Advanced Studies, J. F. Oberlin University, 3758, Machida-city, Tokyo, 194-0294, Japan, Tel/Fax +81(0)02-797-9847, Email sugisawa@obirin.ac.jpPurpose: This study analyzed the influence of financial strains over the life course before initiating hemodialysis on the health outcomes of older Japanese patients. This study was limited to financial strains over the life course before initiating hemodialysis to eliminate the influence of financial strains resulting from resignation from paid jobs. We examined which of the four life course models—pathway, latent, social mobility, and accumulation—were appropriate to describe the influences of financial strains over the life course on older patients’ health.Patients and Methods: Data were obtained from a cross-sectional survey of 6,644 outpatients in dialysis facilities across Japan. We selected participants aged 60 years and older at the time of the survey. Numbers of dialysis complications, activities of daily living (ADL) disability, and depressive symptoms were selected as health outcomes. Benchmark periods over the life course were constructed in three parts: less than 18 years (childhood), 18– 35 years (young adults), and 35– 50 years (middle-aged). We retrospectively measured financial strains over the life course.Results: Pathway models best described the influence of financial strains over the life course on the three types of health outcomes. Experiences of financial strains as young adults had a direct influence on ADL disability of older patients. This result supports latent models. Social mobility models (upward and downward mobility) and accumulation models explained the number of dialysis complications, ADL disability, and depressive symptoms in older patients.Conclusion: These results suggest that socioeconomic disadvantages over the life course before initiating hemodialysis were significantly associated with health outcomes in older patients.Keywords: socioeconomic status over the life course, latent models, social mobility models, accumulation models, pathway models

This study examined differences in caregiving appraisal between primary family caregivers of disabled older adults receiving hemodialysis (PFCGs-wHD) and disabled older adults not receiving dialysis (PFCGs-woD). A total of 242 PFCGs-wHD and 335 PFCGs-woD were included in the analyses. We used adjustment by propensity score to control for bias by confounding factors. Caregiving appraisal was measured in terms of role strain, emotional exhaustion, and caregiving satisfaction. On the first task, PFCGs-wHD demonstrated significantly worse levels on all three appraisal indicators than did PFCGs-woD. On the second task, only higher emotional exhaustion was significantly mediated by higher role strain in PFCGs-wHD. Further, PFCGs-wHD status directly influenced lower caregiving satisfaction without mediation by higher role strain. Caregiving for disabled older adults receiving HD may be associated with significant challenges for caregivers.

Ambient air pollution is a well-recognized risk for various diseases including asthma and heart diseases. However, it remains unclear whether air pollution may also be a risk of ocular allergic diseases. Using a web-based, nation-wide, cross-sectional study design, we examined whether the level of ambient air pollution is significantly associated with the prevalence of ocular allergic diseases. A web-based questionnaire was posted to invite the participants who are members of the Japan Ophthalmologist Association and their family members. The answers from 3004 respondents were used to determine whether there were significant associations between the level of the pollutants and the prevalence of ocular allergic diseases. The study period was between March to May 2017. The data of the air pollutants during 2012 to 2016 were obtained from the National Institute for Environmental Studies. The prevalence of allergic diseases was calculated by post stratification and examined for significant associations with the level of pollutants using multiple logistic regression analyses. The prevalence of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, atopic keratoconjunctivitis (AKC), and vernal keratoconjunctivitis (VKC) in Japan was 45.4%, 14.0%, 5.3%, and 1.2%, respectively. The high prevalence of the severe forms of allergic conjunctivitis, including AKC and VKC, were significantly associated with the levels of the air pollutants. The prevalence of AKC was significantly associated with the levels of NO2 with an odds ratio (OR) of 1.23 (per quintile). The prevalence of VKC was significantly associated with the levels of NOx and PM10 with ORs of 1.72 and 1.54 respectively. The significant associations between the prevalence of AKC and VKC and the levels of air pollutants indicate that clinicians need to be aware that air pollutants may pose serious risks of vision threatening severe ocular allergy.

Background Nursery farms that accept nursing and growing pre-weaned heifer calves from private dairy farms must work to prevent bovine respiratory disease (BRD). Knowledge of the BRD-associated risk factors related to calf management and calves’ condition will help to develop appropriate neonatal management practices at original farms and to identify calves at higher risk for BRD at nursery farms. In this study, the relationship between BRD and calf management practices (colostrum feeding, dam parity, serum total protein concentration at introduction (TP), body weight at introduction, introduction season, and daily average growth) was investigated using observational data from pre-weaned dairy calves introduced into a nursery farm in Hokkaido, Japan between 2014 and 2018 (n = 3185). Using additive Bayesian network (ABN) analysis, which is a multivariate statistical modelling approach, the direct and indirect associations between these factors were assessed. Results Colostrum feeding contributed to an increase in TP (correlation 1.02 [95 % CI, 0.94;1.10]), which was negatively associated with BRD directly (log odds ratio − 0.38 [− 0.46;−0.31]) and indirectly through increasing daily growth (correlation 0.12 [0.09;0.16]). Calves of multiparous dams had higher body weight at introduction (correlation 0.82 [0.74;0.89]), which indirectly reduced BRD risk through the increasing daily growth (correlation 0.17 [0.14;0.21]). Calves introduced during winter had the highest risk for BRD (log odds ratio 0.29 [0.15;0.44]), while those introduced in summer had the lowest risk (log odds ratio − 0.91 [− 1.06;−0.75]). The introduction season was also associated with BRD indirectly through dam parity, body weight at introduction, and daily growth. Conclusions The following calf management practices are recommended for preventing BRD in pre-weaned calves at nursery farms: (1) encouraging colostrum feeding to neonatal calves at their original farms; and (2) identifying calves with higher BRD risk, i.e., those without feeding colostrum, born to primiparous cattle, with low body weight at introduction, and/or introduced in winter, and paying intensive attention to the calves for rapid detection of BRD. ABN analysis applied enabled us to understand the complex inter-relationships between BRD incidence and the risk factors, which will help to reduce BRD incidence and to rear healthy calves at nursery farms.

Corneal opacities are an important cause of blindness, and its major etiology is infectious keratitis. Slit-lamp examinations are commonly used to determine the causative pathogen; however, their diagnostic accuracy is low even for experienced ophthalmologists. To characterize the “face” of an infected cornea, we have adapted a deep learning architecture used for facial recognition and applied it to determine a probability score for a specific pathogen causing keratitis. To record the diverse features and mitigate the uncertainty, batches of probability scores of 4 serial images taken from many angles or fluorescence staining were learned for score and decision level fusion using a gradient boosting decision tree. A total of 4306 slit-lamp images and 312 images obtained by internet publications on keratitis by bacteria, fungi, acanthamoeba, and herpes simplex virus (HSV) were studied. The created algorithm had a high overall accuracy of diagnosis, e.g., the accuracy/area under the curve (AUC) for acanthamoeba was 97.9%/0.995, bacteria was 90.7%/0.963, fungi was 95.0%/0.975, and HSV was 92.3%/0.946, by group K-fold validation, and it was robust to even the low resolution web images. We suggest that our hybrid deep learning-based algorithm be used as a simple and accurate method for computer-assisted diagnosis of infectious keratitis.

To verify the possibility that preoperative topical antibiotics are not essential as long as iodine disinfection is performed during surgery. Crossover equivalence trial. In 204 eyes of 102 patients who underwent routine bilateral cataract surgery, 1 eye was treated with intraoperative iodine, and the other, with preoperative topical antibiotics. For the intraoperative iodine eyes, 5 mL of 0.25% povidone-iodine was applied at 2 stages: (1) just after the placement of the speculum and (2) before intraocular lens (IOL) insertion. For the contralateral eyes, preoperative topical antibiotics were administered 3 days before surgery without intraoperative iodine. Conjunctival samples for culture were obtained at 3 time points: (a) presurgery, (b) beginning of surgery, and (c) postsurgery. Real-time polymerase chain reaction (PCR) samples were obtained at the beginning of surgery and before IOL insertion. Intracameral moxifloxacin was applied in all the cases. The respective positive bacterial culture rates for intraoperative iodine eyes and preoperative topical antibiotics eyes were 95.1% and 98.0% at (a), 7.8% and 5.9% at (b), and 60.8% and 62.7% at (c). A significant difference in the positive bacterial culture rate was not found at any time point. For the intraoperative iodine eyes, the bacterial DNA copy number at (b) was significantly lower than that for the preoperative topical antibiotics eyes. The cleanliness of the operative field without using topical antibiotics was revealed to be equivalent to that of the conventional method (using preoperative antibiotics without intraoperative iodine) as long as intraoperative iodine was used.

We control the formation of Bi-induced nanostructures on the growth of GaAs/GaAsBi core-shell nanowires (NWs). Bi serves as not only a constituent but also a surfactant and nanowire growth catalyst. Thus, we paved a way to achieve unexplored III-V nanostructures employing the characteristic supersaturation of catalyst droplets, structural modifications induced by strain, and incorporation into the host GaAs matrix correlated with crystalline defects and orientations. When Ga is deficient during growth, Bi accumulates on the vertex of core GaAs NWs and serves as a nanowire growth catalyst for the branched structures to azimuthal112. We find a strong correlation between Bi accumulation and stacking faults. Furthermore, Bi is preferentially incorporated on the GaAs (112)B surface, leading to spatially selective Bi incorporation into a confined area that has a Bi concentration of over 7%. The obtained GaAs/GaAsBi/GaAs heterostructure with an interface defined by the crystalline twin defects in a zinc-blende structure can be potentially applied to a quantum confined structure. Our finding provides a rational design concept for the creation of GaAsBi based nanostructures and the control of Bi incorporation beyond the fundamental limit.

To evaluate the efficacy of real-time PCR for 16S ribosomal DNA (16S r-DNA) and sequencing for diagnosing microbial keratitis. We studied 272 eyes of 272 patients with keratitis. Eyes with keratitis were classified as “definite” (N = 118), “likely” (N = 71), or “non-bacterial” (N = 83) to have bacterial keratitis. The diagnostic efficacy of real-time PCR and conventional testing was determined by receiver operating characteristic analysis. The copy numbers of bacterial DNA and clinical characteristics were retrospectively analyzed for association with concordant culture results in the “definite” cases. The level of bacterial DNA was significantly associated with the diagnostic probability of the three diagnostic categories. The level of bacterial DNA had comparable diagnostic efficacy with the area under the curve (AUC) at 0.67, by culture at 0.65, and by smear testing at 0.73. The efficacy was significantly improved by combining the DNA level with the conventional culture testing with an AUC of 0.81. Analysis of the “definite” cases showed culture positivity in 51.8% (58 eyes), and of these, 41 eyes (70.7%) were higher than the cutoff PCR values and 40 eyes were identified by 16S r-DNA sequencing. In the culture-negative eyes, the level of bacterial DNA was significantly lower (P = 0.0008). Eyes with higher bacterial DNA levels had significantly concordant outcomes with sequencing and culture results (P = 0.006). Previous antibiotic treatments decreased the bacterial DNA amount by 0.09-fold, and it was a significant factor for discordance (P = 0.006). Quantification of the bacterial DNA level and conventional testing improves the diagnostic efficacy of infectious bacterial keratitis.

Purpose The aim of this study was to investigate whether additional manual objectives are necessary for the RapidPlan (RP) with a single optimization. We conducted multi-institutional comparisons of plan quality for head and neck cancer (HNC) using the models created at each institute. Methods The ability of RP to produce acceptable plans for dose requirements was evaluated in two types of oropharynx cancers at five institutes in Japan. Volumetric modulated arc therapy plans created without (RP plan) and with additional manual objectives (M-RP plan) were compared in terms of planning target volume (PTV), brainstem, spinal cord and parotid glands in dosimetric parameters. Results There were no major dosimetric PTV differences between RP and M-RP plans. For the brainstem and spinal cord in the RP plans, only 40% and 30% of the plans achieved the dose requirements, while the M-RP plans with upper objective added to volume 0% at all institutes achieved them for 90% of the plans. For the L-parotid gland, there was no difference in the RP and M-RP plans (both were 40%) in achieving the acceptable criteria. For the R-parotid gland, 60% and 80% of the RP and M-RP plans achieved the constraint criteria, and in terms of the achievement rate, the RP plans were relatively high. Conclusions M-RP plans did not require reoptimization; only an upper objective was needed for the brainstem and spinal cord, while the parotid gland dose was reduced in both RP plans with the auto generated line objectives alone.

Research aimed at understanding transmission networks, representing a network of "who infected whom" for an infectious disease outbreak, have been actively conducted in recent years. Transmission network models incorporating epidemiological and genetic data are valuable for elucidating disease transmission pathways. In this study, we reconstructed the transmission network of the foot-and-mouth disease (FMD) epidemic in Japan in 2010, and explored farm-level risk factors associated with increased risk of secondary transmission. A published, systematic Bayesian transmission network model was applied to epidemiological data of 292 infected farms and whole genome sequence data of 104 of the infected farms. This model can make inferences for known infected farms even lacking genetic data. After estimating the consensus network, the accuracy of the network was examined by comparison with epidemiological data. Then, risk factors inferred to have been sources of secondary transmission were explored using zero-inflated Poisson regression model. As far as we are aware, this study represents the largest FMD outbreak transmission network to be published by such means combining epidemiological and genetic data. The consensus network reasonably generated the epidemiological links, which were estimated from the actual epidemiological investigation. Among 292 farms, 101 farms (35%) were inferred to have been the sources of secondary transmission, and amongst these farms, the median number of secondary cases was 2 (min:1-max:18) farms. The farm-type (small and large -sized pig farms), the number of days from onset to notification, and the number of susceptible farms within a 1-km radius were significantly associated with secondary transmission. Transmission network modelling enabled inference of the connections between infected farms during the FMD epidemic and identified important factors for controlling the risk of secondary transmission. This study demonstrated that the predominant susceptible species held on a farm, farm size, and animal density were associated with increased onwards transmission.

Senescence, sterile inflammation, and infection cause dysfunction of corneal endothelial cells, leading to visual morbidity that may require corneal transplantation. With increasing age, the extracellular matrix is modified by non-enzymatic glycation forming advanced glycation end products (AGEs). The modifications are primarily sensed by the receptors for the AGEs (RAGE) and are manifested as a type I interferon response. Interestingly, in our study, human corneal endothelial cells (HCEn) cells did not respond to the typical RAGE ligands, including the AGEs, high mobility group box 1 (HMGB1), and serum amyloid-A (SAA). Instead, HCEn cells responded exclusively to the CpG DNA, which is possessed by typical corneal pathogen, herpes simplex virus-1 (HSV-1). Upon HSV-1 infection, the surface expression of RAGE was increased, and endocytosed HSV-1 was associated with RAGE and CpG DNA receptor, TLR9. RAGE DNA transfection markedly increased interferon-β secretion by CpG DNA or HSV-1 infection. HSV-1 infection-induced interferon-β secretion was abolished by TLR9 inhibition and partially by RAGE inhibition. Global transcriptional response analysis confirmed that RAGE and TLR9 were both significantly involved in type I interferon responses. We conclude that RAGE is a sensor of HSV-1 infection and provokes a type I interferon response.

To understand the clinical course of human adenoviral (HAdV) conjunctivitis for establishing a better treatment regimen, thirty-eight eyes of 19 patients with HAdV-54 conjunctivitis for less than one week from onset were evaluated for clinical signs and symptoms and DNA copy numbers. It is observed that a viral load of 104-105 is required to develop symptoms of HAdV conjunctivitis, as symptoms were present in all the eyes whose viral load was ≥104 at least once during the course. Next, it is observed that asymptomatic infections in contralateral eyes are common as the virus was detected in most eyes that did not develop conjunctivitis. Furthermore, there was no rapid decrease of the viral load in healed eyes, on the contrary, the viral load in healed eyes on day 15 was significantly higher than in unhealed eyes. This was likely due to corticosteroid instillation that rapidly alleviated symptoms but prolonged the duration of viral shedding. Recently, combination treatment with iodine and corticosteroids has been recommended for HAdV conjunctivitis. Assessing changes in viral load as well as clinical symptoms would be helpful to better understand the clinical course of this disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

III-V semiconductor nanowires (NWs), such as those based on GaAs, are attractive for advanced optoelectronic and nanophotonic applications. The addition of Bi into GaAs offers a new avenue to enhance the near-infrared device performance and to add new functionalities, by utilizing the remarkable valence band structure and the giant bowing in the bandgap energy. Here, we report that alloying with Bi also induces the formation of optically-active self-assembled nanodisks caused by Bi segregation. They are located in the vicinity to the (112) corners of the GaAsBi shell and are restricted to twin planes. Furthermore, the Bi composition in the disks is found to correlate with their lateral thickness. The higher Bi composition in the disks with respect to the surrounding matrix provides a strong confinement for excitons along the NW axis, giving rise to narrow emission lines (Funding Agencies|Swedish Research CouncilSwedish Research Council [2019-04312]; Swedish Foundation for International Cooperation in Research and Higher Education (STINT) [JA2014-5698]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009 00971]; KAKENHI from Japan Society of Promotion of Science [19H00855, 16H05970]

This study describes the epidemiological characteristics of classical swine fever (CSF) outbreaks in Japan. The first case was confirmed in September 2018, 26 years after the last known case. Outbreaks occurred on 39 farms, 34 commercial farms, and 5 non-commercial farms, between September 2018 and August 2019. In this study, a descriptive analysis was conducted of the epidemiological data on the characteristics of the affected farms, clinical manifestations, intra-farm transmission, association with infected wild boars, and control measures implemented on the farms. Twenty-eight of the 34 affected commercial farms were farrow-to-finish farms. It was assumed that the major risk factors were frequent human-pig interactions and the movement of pigs between farms. Fever and leukopenia were commonly observed in infected pigs. In 12 out of 18 farms where clinical manifestations among fattening pigs was the reason for notification, death was the most frequent clinical manifestation, but the proportion of dead animals did not exceed 0.5% of the total number of animals at most of the affected farms. Therefore, the clinical form of CSF in Japan was considered to be sub-acute. Twenty-three of the 29 farms (79%) with pigs at multiple stages (i.e., piglets, fattening pigs, and sows), had infection across the multiple stages. Many of these farms were within 5 km of the site where the first infected wild boars had been discovered, suggesting that infected wild boars were the source of infection. Infections still occurred at farms that had implemented measures at their farm boundaries to prevent the introduction of the virus into their farms, such as disinfection of vehicles and people, changing boots of the workers, and installation of perimeter fences. It is necessary to continue to strengthen biosecurity measures for farms located in areas with infected wild boars and to continue monitoring the distribution of infected wild boars so that any abnormalities can be reported and inspected at an early stage.

The prevalence of ocular allergies has been increasing worldwide for the past several decades. The geographical distribution and hot spots of rhinoconjunctivitis have been documented in a global survey by the International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC indicated that Africa, Latin America, and Japan were notable for their high prevalence of rhinoconjunctivitis. The outcomes of follow-up studies of regional differences and the characteristics of allergic conjunctivitis are summarized in this review. Currently, comorbid diseases and socioeconomic and environmental factors, including climate and air pollution, are proposed to contribute to the regional differences in the prevalence of allergic conjunctivitis. Of them, rhinitis has been shown repeatedly to be significantly associated with allergic conjunctivitis. Their mechanistic aspects on association with the prevalence of systemic allergic diseases have been reviewed by examining the birth cohort or in vitro analyses. A vision threatening form of ocular allergy, vernal keratoconjunctivitis, is prevalent in the African countries and Japan. Of the proposed associated factors, air pollution was shown to contribute not only to aggravating the symptoms but also to the increase in the incidence of its severe forms. Its mechanistic aspects are discussed in this review in the context of comorbid diseases.

The aim of this study was to compare the efficacy of the topical regimens of iodine/steroids vs. antibiotics/steroids in acute to subacute adenoviral keratoconjunctivitis. A prospective open-label study. Nineteen patients diagnosed with unilateral or bilateral adenoviral conjunctivitis at less than 1 week from onset were enrolled in this study. Patients were divided randomly into two groups; group 1 was treated with 1.5% levofloxacin with 0.1% fluorometholone administered four times a day and group 2 was treated with a sixfold dilution of polyvinyl alcohol iodine (PAI) solution with 0.1% fluorometholone four times a day. Conjunctival samples from all affected eyes were obtained for real-time PCR. The total scores of acute signs (i.e., eyelid edema, conjunctival injecton, conjunctival discharge, follicules, pseudomembranes, subconjunctival hemorrhage) and symptoms, HAdV DNA copy number, and the presence of multiple subepithelial corneal infiltrates (MSI) were evaluated every 5 visits up to Day 30 after diagnosis. Comparing the total scores of acute signs and symptoms and viral load, we observed no significant differences between the two groups. At day 15 after diagnosis the proportion of patients with MSI in group 2 (35.7%) was significantly lower than in group 1 (0%). The impact of topical iodine/steroid therapy on acute signs and symptoms associated with adenoviral conjunctivitis is limited and not substantially different in the responses to antibiotics/steroids. However, this regimen results in a significant decrease in the incidence of MSI during the subacute phase of infection.

Age-associated sterile inflammation can cause dysregulated choroidal neovascularization (CNV) as age-related macular degeneration (AMD). Intraocular fluid screening of 234 AMD patients identified high levels of IL-4. The purpose of this study was to determine the functional role of IL-4 in CNV formation using murine CNV model. Our results indicate that the IL-4/IL-4 receptors (IL4Rs) controlled tube formation and global proangiogenic responses of bone marrow cells. CCR2+ bone marrow cells were recruited to form very early CNV lesions. IL-4 rapidly induces CCL2, which enhances recruitment of CCR2+ bone marrow cells. This in vivo communication, like quorum-sensing, was followed by the induction of IL-4 by the bone marrow cells during the formation of mature CNVs. For CNV development, IL-4 in bone marrow cells are critically required, and IL-4 directly promotes CNV formation mainly by IL-4R. The IL-4/IL-4Rα axis contributes to pathological angiogenesis through communications with bone marrow cells leading to retinal degeneration.

Background: The aim of this study was to investigate the performance of the RapidPlan knowledge-based treatment planning system using models including registered pseudo-structures, and to determine how many structures are required for automatic optimization of volumetric modulated arc therapy (VMAT) for postoperative uterine cervical cancer. Methods: Pseudo-structures were retrospectively contoured for patients who had completed treatment at one of five institutions. For 22 patients, RPs were generated with a single optimization for models with two (RP_2), four (RP_4), or five (RP_5) registered structures, and the dosimetric parameters of these models were compared with a clinical plan with several optimizations. The total times for pseudo-structure creation and optimization were also measured.Results: Most dosimetric parameters showed no major differences between each RP. In particular, the rectum Dmax, V50Gy, and V40Gy with RP_2, RP_4, and RP_5 were not significantly different, and were lower than those of the clinical plan. In addition, the average proportions of plans achieving acceptable criteria for all dosimetric parameters were 98%, 99%, 98%, and 98% for the clinical plan, RP_2, RP_4, and RP_5, respectively. The average times for the creation and optimization of pseudo-structures were 105, 17, 21, and 29 minutes, for the clinical plan, RP_2, RP_4, and RP_5, respectively. Conclusions: The RapidPlan model with two registered pseudo-structures could generate clinically acceptable plans while saving time. This modeling approach using pseudo-structures could possibility be used for the VMAT planning process.

In 2018, classical swine fever (CSF) re-emerged in the Gifu Prefecture, central Japan, causing an on-going outbreak among wild boars and domestic pigs in the country. Consequently, oral vaccination for wild boar and compulsory vaccination for pig farms started in 2019. We have previously shown that, before vaccination in the Gifu Prefecture, the presence of CSF-infected wild boar near pig farms increased the risk of CSF transmission. This study aimed to re-evaluate the transmission risk from wild boars to pig farms under a vaccination program. The effectiveness of vaccination was evaluated by comparing the transmission risk estimated before and after the implementation of vaccinations. In this study, we focused on two affected areas, the Kanto (eastern Japan) and Kinki (west-central Japan) regions, in which eight of 11 infected farms were detected between the start of pig farm vaccinations and April 2021. Wild boar surveillance data from an area within a 50-km radius from the infected farms were used for analysis, consisting of 18,870 1-km grid cells (207 infected cells) in the Kanto region, and 15,677 cells (417 infected cells) in the Kinki region. The transmission rates in the post-vaccination period in the Kanto and Kinki regions were much lower than that in the pre-vaccination period in the Gifu Prefecture. The values of transmission kernels (h

Glaucoma is a leading cause of blindness worldwide. Purpose of this study was to identify molecular markers that were significantly correlated with presence of glaucoma and outcome of glaucoma surgery. To accomplish this, we determined the profiles of pro-inflammatory cytokines in the aqueous humor of 101 glaucoma patients; 31 primary open angle glaucoma (POAG), 38 pseudoexfoliation glaucoma (PEG), and 32 neovascular glaucoma (NVG). We also studied 100 normal subjects as controls. In eyes with POAG or PEG, the level of interleukin (IL)-1α, IL-2, IL-4, IL-8, IL-23, and CCL2 were significantly elevated. In the NVG eyes, many inflammatory cytokines were also highly elevated. IL-8 had the highest odds ratio, and levels of IL-8 and CCL2 were significantly correlated with preoperative IOP or visual field defects in PEG eyes. Principal component analysis showed that IL-8 had the highest association to the IOP-cytokine component, and Cox proportional hazard model indicated that an elevation of IL-8 was a significant risk of filtering surgery failure. Together with modeling of their interactions and prognosis, IL-8 elevation is a significant risk factor both for detecting and managing glaucoma and may serve as a therapeutic target candidate to improve the prognosis of glaucoma surgery.

Purpose The aim of this study is to determine the efficacy of quantitative real-time PCR (qPCR) and clinical characteristics to diagnose ocular cytomegalovirus (CMV) infections. Methods The technical factors were assessed by the outcomes of the qPCR assay at five institutions in Japan using the WHO International Standard of cytomegalovirus. The clinical factors were assessed by examining the aqueous humor samples of 197 eyes of 197 consecutive patients suspected of CMV using the receiver operating characteristics (ROCs). Results All of the institutions had excellent detection efficacy, although the copy number ranged from 0.82 to 4.66 copies/IU. In the clinical samples, CMV was detected in 51 eyes, and the amount of CMV DNA was significantly higher for CMV retinitis. In corneal diseases, the amount of CMV DNA was significantly associated with frequency of recurrences and IOP elevations. The sensitivity and specificity of qPCR for the diagnosis was 90.0 and 98.7%, respectively. For the corneal and anterior uveitis types of CMV diseases, the area under the curve (AUC) of qPCR was 0.95 and 0.96, followed by frequency of recurrences with AUC of 0.89 and 0.82, and IOP elevations with AUC of 0.78 and 0.76. Unclassified cytomegalovirus detection, which did not meet diagnostic criteria of CMV corneal endotheliitis, anterior uveitis, or retinitis, was 4.6%, and it was significantly associated with corneal diseases and history of corneal transplantation. Conclusions qPCR with standardization is specific and accurate; however, the inclusion and knowledge of the clinical characteristics improve the diagnostic efficacy.