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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.

We established a multi-institution model (big model) of knowledge-based treatment planning with over 500 treatment plans from five institutions in volumetric modulated arc therapy (VMAT) for prostate cancer. This study aimed to clarify the efficacy of using a large number of registered treatment plans for sharing the big model. The big model was created with 561 clinically approved VMAT plans for prostate cancer from five institutions (A: 150, B: 153, C: 49, D: 60, and E: 149) with different planning strategies. The dosimetric parameters of planning target volume (PTV), rectum, and bladder for two validation VMAT plans generated with the big model were compared with those from each institutional model (single-institution model). The goodness-of-fit of regression lines (R2 and χ2 values) and ratios of the outliers of Cook’s distance (CD) > 4.0, modified Z-score (mZ) > 3.5, studentized residual (SR) > 3.0, and areal difference of estimate (dA) > 3.0 for regression scatter plots in the big model and single-institution model were also evaluated. The mean ± standard deviation (SD) of dosimetric parameters were as follows (big model vs. single-institution model): 79.0 ± 1.6 vs. 78.7 ± 0.5 (D50) and 0.13 ± 0.06 vs. 0.13 ± 0.07 (Homogeneity Index) for the PTV; 6.6 ± 4.0 vs. 8.4 ± 3.6 (V90) and 32.4 ± 3.8 vs. 46.6 ± 15.4 (V50) for the rectum; and 13.8 ± 1.8 vs. 13.3 ± 4.3 (V90) and 39.9 ± 2.0 vs. 38.4 ± 5.2 (V50) for the bladder. The R2 values in the big model were 0.251 and 0.755 for rectum and bladder, respectively, which were comparable to those from each institution model. The respective χ2 values in the big model were 1.009 and 1.002, which were closer to 1.0 than those from each institution model. The ratios of the outliers in the big model were also comparable to those from each institution model. The big model could generate a comparable VMAT plan quality compared with each single-institution model and therefore could possibly be shared with other institutions.

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.

Ocular cytomegalovirus (CMV) infections in immunocompetent individuals are rare, but its activation can cause chronic and relapsing inflammation in anterior segment of the eye resulting in loss of corneal clarity and glaucoma. Fifty five patients with anterior segment CMV infection were assessed for their clinical characteristics, and CMV corneal endotheliitis was found to cause significant loss of corneal endothelial cells. The disease duration with recurrences was significantly correlated with the maximum intraocular level of CMV DNA. To examine why CMV is activated in healthy immunocompetent individuals and causing corneal endothelial cell damage, assays of cytotoxic T cells (CTLs) which directly target infected corneal endothelial cells were performed for 9 HLA-matched CMV corneal endotheliitis patients (HLA-A*2402). When the cell loss was analyzed for associations with CTL responses, CMV-induced endothelial cell damage was mitigated by pp65-specific CTL induction. The recurrence-free time was also prolonged by pp65-specific CTL induction (hazard ratio (HR): 0.93, P = 0.01). In contrast, IE1-specific CTL was associated with endothelial cell damage and reduced the time for corneal transplantation (HR: 1.6, P = 0.003) and glaucoma surgery (HR: 1.5, P = 0.001). Collectively, induction of pp65-specific CTL was associated with improved visual prognosis. However, IE1-specific CTL without proper induction of pp65-specific CTL can cause pathological damage leading to the need of surgical interventions.

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.

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.

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.

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.

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.

Viral infections of the cornea including herpes simplex virus 1 (HSV-1) cause visual morbidity, and the corneal endothelial cell damage leads to significant visual impairment. Interferon regulatory factor 7 (IRF7) has been identified as a significant regulator in corneal endothelial cells after an HSV-1 infection. To examine the role played by IRF7, the DNA binding domain (DBD) of IRF7 of human corneal endothelial cells (HCEn) was disrupted. An RNAi inhibition of IRF7 and IRF7 DBD disruption (IRF7 ∆DBD) led to an impairment of IFN-β production. Impaired IFN-β production by IRF7 ∆DBD was regained by IRF7 DNA transfection. Transcriptional network analysis indicated that IRF7 plays a role in antigen presentation function of corneal endothelial cells. When the antigen presentation activity of HCEn cells were examined for priming of memory CD8 T cells, IRF7 disruption abolished the anti-viral cytotoxic T lymphocyte (CTL) response which was dependent on the major histocompatibility complex (MHC) class I. To further examine the roles played by IRF7 in CTL induction as acquired immunity, the contribution of IRF7 to MHC class I-mediated antigen presentation was assessed. Analysis of IRF7 ∆DBD cells indicated that IRF7 played an unrecognized role in MHC class I induction, and the viral infection induced-MHC class I induction was abolished by IRF7 disruption. Collectively, the IRF7 in corneal endothelial cells not only contributed to type I IFN response, but also to the mediation of viral infection-induced MHC class I upregulation and priming of CD8 arm of acquired immunity.

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.

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.

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.

Pupose: To determine the efficacy of real-time PCR for the diagnosis and prognosis of varicella-zoster virus (VZV) keratitis. Study design: Retrospective case series. Methods: Patients: 545 consecutive patients with keratitis were examined to quantify copy numbers of VZV DNA by real-time PCR. Association of copy numbers of DNA of VZV to clinical signs and disease course was assessed using logistic regression analysis and Cox proportional hazard model. Results: Of the 545 eyes, 38 eyes (6.9%) were diagnosed as VZV keratitis. The copy numbers of the DNA of VZV (median: 104.19 copy) was significantly associated with diagnosis of VZV keratitis with the highest odds ratio (OR) of 3390 (for median copy) compared to clinical signs. Diagnostic accuracy of the VZV DNA copy indicated good diagnostic value of area under the curve (0.92) by receiver operating characteristic analysis, and detection of unrelated VZV DNA from the cornea was very rare (0.2%). When the VZV DNA copy and clinical signs were assessed for association with the disease course after herpes zoster ophthalmicus, the disease duration was significantly prolonged in VZV keratitis cases with higher numbers of VZV DNA copies, iritis, and history of recurrences. The amount of VZV DNA led to a continuous risk to prolong disease duration until the ocular inflammation subsides (hazard ratio (HR) 0.17, 95%CI: 0.07 - 0.42, for median copies). Conclusions: Higher VZV DNA copy numbers are associated with the refractoriness of VZV keratitis, and its evaluation may be a clinically useful way to diagnose and manage VZV keratitis.

Infection of the corneal endothelial cells by human cytomegalovirus (CMV) is an important cause of corneal endotheliitis. CMV endotheliitis is difficult to completely cure and relapses are frequent. This can cause blinding corneal bullous keratopathy. However, the pathogenesis of CMV endotheliitis remains undetermined. To understand the immunopathology of endotheliitis, we examined how corneal endothelial cells prime the anti-viral immunity after CMV infection based on global transcriptional responses. To accomplish this, human corneal endothelial (HCEn) cells were infected with CMV, and the global transcriptional responses were determined by microarray analyses for primary anti-viral responses using network analysis. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and protein array analyses were used to examine whether anti-viral cytokines were induced, i.e., to determine whether innate immune responses were activated. To examine whether priming of acquired immune response was activated, CMV-infected HCEn cells were co-cultured with allogeneic CD8+ T cells from CMV seropositive donors and tested for priming activity for the CD8+ effector T cells by measuring interferon-γ secretion. The CMV-induced responses of HCEn cells were characterized by type I interferon and pattern recognition receptor pathways which represent innate immune priming. The global transcriptional activation was specifically associated with antigen presentation with the antimicrobial response functions. Protein array analyses indicated a significant increase in the secretion of anti-viral inflammatory cytokines including CXCL10 as innate immune responses. When HCEn cells were examined to determine whether CMV infection activated anti-viral acquired immunity, CMV-infected HCEn cells directly stimulated the proliferation of CD8+ T cells from CMV-seropositive donors, and pp65 viral epitope induced interferon-γ secretion from the CD8+ T cells. We conclude that CMV-infected HCEn cells induce innate immune priming along with provisions of acquired immune priming of CD8+ effector T cells. This information should help in the development of useful diagnostic procedures and efficacious therapeutic strategy to treat refractory corneal endotheliitis.

Prophylactic intracameral injection of antibiotics is commonly used to prevent endophthalmitis after cataract surgery. However, devastating visual complications have been reported including hemorrhagic occlusive retinal vasculitis (HORV).To determine the toxic and inflammatory effects of moxifloxacin, cefuroxime, and vancomycin on human retinal vascular cells, human retinal vascular endothelial cells (RVEC) and pericytes were exposed to three antibiotics, and the adverse effects were assessed by membrane damage, loss of intrinsic esterase activity, kinetic cell viability, and inflammatory cytokine secretion. Their retinal toxicity was examined by live/dead assays after an intravitreal injection of the three antibiotics into mice eyes. In vascular cells in culture, membrane damage and loss of esterase activity were induced after exposure to the three antibiotics. The toxic effects were most obvious after moxifloxacin (RVEC, ≥125 μg/mL; pericytes, ≥1000 μg/mL) at 24 h. Cefuroxime also reduced esterase activity and the membrane integrity of vascular cells but were less toxic than moxifloxacin. Kinetic cell viability testing showed that 500 μg/mL of moxifloxacin exposure induced significant decrease (29%) in the viability as early as 1 h. When the inflammatory effects of the antibiotics were examined, a significant induction of IL-8 was observed especially by RVECs after exposure to cefuroxime or vancomycin which was exacerbated by L-alanyl-γ-D-glutamyl-meso-diaminopimelic acid (Tri-DAP), a NOD1 ligand. Intravitreal injections in mice showed that cefuroxime and vancomycin caused retinal and vascular toxicity extending to the inner nuclear layers. Collectively, moxifloxacin causes immediate damage to retinal vascular cells in vitro, while cefuroxime and vancomycin induced significant inflammatory effects on vascular endothelial cells and caused retinal toxicity. Surgeons need to be cautious of the toxicity when antibiotics are used prophylactically especially by intravitreal administration.

Purpose: Human cytomegalovirus (HCMV) infections can cause endotheliitis which is associated with an elevation of the intraocular pressure (IOP). However, the mechanism of the IOP elevation has not been determined. The purpose of this study was to determine whether HCMV strains which are capable of infecting corneal endothelial cells can also replicate, induce anti-viral responses, and can reorganize the actin cytoskeleton in trabecular meshwork cells. Study design: Experimental study design Methods: Cultured primary human trabecular meshwork cells (HTMCs) were infected with the Towne or TB40/E strains of HCMV. TB40/E is trophic for vascular endothelial and corneal endothelial cells. Real-time PCR, western blot, and fluorescent immunostaining have been used to determine whether HCMV-infected HTMCs will support the expression of viral mRNA and protein, allow viral replication, and elicit anti-viral host responses. We also determined whether lytic replication was present after an HCMV infection. Results: HCMV infection led to the expression of viral mRNA and proteins of IE1, glycoprotein B(gB), and pp65. TB40/E infection induced interferon-β, a sign of host anti-viral immune response and MCP-1. Together with the induction of the regulators of actin cytoskeleton, myosin phosphatase Rho interacting protein (MPRIP) and monocyte chemotactic protein-1 (MCP-1), TB40/E induced a high level of expression of viral proteins, including IE1, gB, and pp65 as well as actin stress fiber formation, and achieved pathogenically high viral titers. Conclusions: Human trabecular meshwork cells support the replication of endotheliotropic TB40/E strain of HCMV which indicates that this strain may have high virulence for trabecular meshwork.

The present study examined the performance level and its related factors on the process of case management for disabled patients on hemodialysis. Case management performance was evaluated at three stages: patient assessment, making a care plan, and monitoring/evaluation. Candidates for targeting the factors relating to performance included four dimensions: nursing care level, physical malfunction, cognitive malfunction, and barriers to service were used as patient factors; the period of case management for the patient and the knowledge of dialysis emerged as case manager factors; work load was included as an organizational factor; and community resources for these services and communication with surrounding persons were included as system factors. Self-administrated questionnaires were collected from 391 case managers of patients with hemodialysis certified long-term insurance. These were introduced by the dialysis facilities that a member of the Japanese Association of Dialysis Physicians belonged to. Case managers were asked questions about their management of each individual case. The results indicate, for example, that poor knowledge of dialysis is significantly related to poor patient assessment, inadequate development of a care plan, and lower levels of monitoring/evaluation. In addition, work overload and diabetic nephropathy as the primary kidney disease were also found to be significantly related to poor patient assessment. Increasing the opportunity for case managers to learn about dialysis may be needed for better case management performance in respect of the hemodialysis of disabled patients.

The purpose of this study was to explore the factors related to earthquake preparedness in Japanese hemodialysis patients. We focused on three aspects of the related factors: health condition factors, social factors, and the experience of disasters. A mail survey of all the members of the Japan Association of Kidney Disease Patients in three Japanese prefectures (N = 4085) was conducted in March, 2013. We obtained 1841 valid responses for analysis. The health factors covered were: activities of daily living (ADL), mental distress, primary renal diseases, and the duration of dialysis. The social factors were: socioeconomic status, family structure, informational social support, and the provision of information regarding earthquake preparedness from dialysis facilities. The results show that the average percentage of participants that had met each criterion of earthquake preparedness in 2013 was 53%. Hemodialysis patients without disabled ADL, without mental distress, and requiring longer periods of dialysis, were likely to meet more of the earthquake preparedness criteria. Hemodialysis patients who had received informational social support from family or friends, had lived with spouse and children in comparison to living alone, and had obtained information regarding earthquake preparedness from dialysis facilities, were also likely to meet more of the earthquake preparedness criteria.

The effects of a comprehensive intervention program for community-dwelling elderly on frailty and dietary habits were examined.We conducted randomized control trials to examine the efficacy of the intervention. To examine lasting changes, we made paired comparisons between pre- and post- intervention and at a three-month follow-up. The subjects were recruited in Hatoyama town, Saitama prefecture. The program was composed of exercise, nutritional education, and social participation and was held from October to December 2011. The exercise program aimed at fall prevention and took place twice per week for 60 min. The nutritional education aimed at prevention of malnutrition, and the social participation program aimed at prevention of "homeboundness"; both were held once per week for 30 min. Questionnaires inquired about frailty and dietary variety. A blood test was conducted to ascertain nutritional state, and a brief self-administered diet history questionnaire was used to estimate food and nutrient intake. To examine the efficacy of the intervention, 22 control subjects (CR) and 21 subjects in the intervention group (IV) were analyzed with intention to treat. To examine lasting changes, 16 subjects in IV who correctly completed surveys at each of the three time points were analyzed, using repeated ANOVA and a multiple comparison procedure.1. Men comprised 70-80% of subjects, and the average age was 75.7±5.4 and 74.7±5.4 years in IV and CR, respectively. 2. There was no significant difference in pre- and post-intervention changes between IV and CR in frailty, which was the main outcome of the study. 3. A significant difference in pre- and post-intervention values was noted in ① "homeboundness", one of the components of frailty (median [25-75%tile]): IV 0 [0-0] and CR 0 [0-1] (P=0.023); ② nutrient intake (mean±standard deviation [SD], energy ratio [%E]): protein, IV 2.3±0.7 and CR -0.3±2.0 (P=0.002); animal protein, IV 2.4±1.5 and CR -0.5±1.5 (P=0.002); and ③ food intake (mean±SD, g/1000 kcal): fish, IV 18.1±25.1 and CR -4.1±21.9 (P=0.004); egg, IV 5.0±11.2 and CR -2.1±11.3 (P=0.046). All variables improved in IV. 4. Lasting improvement was observed in "homeboundness" and protein intake [%E].Although the intervention did not improve frailty, it may improve frailty and dietary habits by improving homeboundness and increasing protein intake.

A frailty index for Japanese older people is not yet available. This study examined the validity of "Kaigo-Yobo Check-List" (CL) as a frailty index.The study site was Kusatsu town, Gunma prefecture. Out of 612 older persons aged 65 years and over who undertook a comprehensive geriatric assessment in 2007, results from 526 who had no missing data were used to examine the cross-sectional relationship between frailty as defined by Fried's criteria (= external criteria) and CL scores in order to evaluate concurrent and construct validity. Further, 916 older individuals aged 70 years and over who responded to the baseline survey in 2001 were followed for the subsequent 4 years and 4 months regarding the onset of ADL disability, service use under the Long Term Care Insurance program, and mortality. We examined the predictive validity of the CL for such adverse outcomes after adjustment for gender, age, and comorbidity.The CL (cut-off point = 3/4) discriminated frailty from non-frailty at the sensitivity of 70.0% and specificity of 89.3%. The higher the CL score, the higher the prevalence of frailty; the trend was highly significant (P0.001). The Multitrail Multimethod Model showed that there were significant associations among three components of CL (homeboundness, falling, and lower nutrition) and four out of five components of Fried's frailty criteria (shrinking, exhaustion, low activity, and slowness), whereas those components of the CL did not have an association with the weakness component of Fried's frailty criteria. As compared with older persons who had CL scores of 3 points or below, those who had CL scores of 4 or more points had a significantly higher risk for developing adverse outcomes. Multivariate-adjusted odds ratios for ADL disability at 2 and 4 years after baseline were 5.25 (95% confidence interval, 2.79-9.89) and 3.42 (1.79-6.54), respectively. Likewise, multivariate-adjusted hazard ratios for the onset of service use under the Long Term Care Insurance program and mortality during the follow-up period of 4 years and 4 months were 3.50 (2.41-5.07) and 2.43 (1.70-3.47), respectively. Although the construct validity remained inconclusive, the "Kaigo-Yobo Check-List" showedgood concurrent and predictive validity as a frailty index. Since it comprises 15 easy-to-answer questions, it could be widely used for research on frailty and its preventive intervention.

Mitochondrial targeting sequence (MTS) has a common property to form an amphiphilic helical structure which is essential for its effective transport of mitochondrial protein. Natural polymorphism in human MTS which affects its mitochondrial transport ability has not been reported. Furthermore, no structural polymorphism for manganese superoxide dismutase (MnSOD) gene has been studied in human population. We here identify diallelic polymorphism (Ala-9Val) in the MTS of human MnSOD in a Japanese population. Calculation of a helix forming potential predicted the typical amphiphilic helical structure in -9Ala allele and its disruption in -9Val allele. We here suggest that this mutation may reflect functional polymorphism of mitochondrial transport of human MnSOD. An association study using this polymorphism showed significant allelic deviation for -9Ala allele (12.1% vs. 19.3%) in Parkinson's disease.