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Purpose: Bardet-Biedl Syndrome (BBS) is an autosomal recessive systemic disorder characterized by retinitis pigmentosa, polydactyly, obesity, intellectual disability, renal impairments, and hypogonadism. The purpose of this study was to determine the ocular characteristics of a boy with BBS caused by a novel homozygous variant in the ARL6 (alternative named BBS3) gene who had been originally diagnosed with retinitis punctata albescens., Methods: This was an observational case study. The patient underwent ophthalmological examinations, electroretinography, and genetic analyses using whole-exome sequencing., Results: A 7-year-old boy was examined in our hospital with complaints of a progressive reduction of his visual acuity and night blindness in both eyes. There was no family history of eye diseases and no consanguineous marriage. Fundus examinations showed numerous white spots in the deep retina and retinal pigment epithelium. Fundus autofluorescence showed hypofluorescence consistent with these spots. Both the scotopic and photopic components of the full-field electroretinographies were non-detectable. Based on these clinical findings, this boy was suspected to have retinitis punctata albescens. Subsequent genetic testing using whole-exome sequencing revealed a novel homozygous variants in the ARL6/BBS3 gene (NM_001278293.3:c.528G>A, (p.Trp176Ter)). A systemic examination by the pediatric department revealed that this boy had a history of a surgical excision of polydactyly on his left foot when he was born, and that he was mildly obese. There were no prominent intellectual or gonadal dysfunctions, no craniofacial or dental abnormalities, no congenital heart disease, and no hearing impairment. He was then clinically and genetically diagnosed with BBS., Conclusion and Importance: In children with night blindness and progressive visual dysfunction, it is important for ophthalmologists to consult clinical geneticists and pediatricians to rule out the possibility of systemic diseases such as BBS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Anti-vascular endothelial growth factor (VEGF) therapy is the first-choice treatment for neovascular age-related macular degeneration (nvAMD); however, patients often are burdened physically, financially, and mentally. We investigated the relationship between mental status and feasibility of an intravitreal ranibizumab treat-and-extend (TAE) regimen for nvAMD., Methods: In this prospective, multicenter study, 75 patients with nvAMD received ranibizumab intravitreally in a TAE regimen. After two monthly injections, the injection intervals were extended step-by-step to 6, 8, 12, and 16 weeks in eyes with dry maculas on optical coherence tomography (OCT) and, if exudation persisted or relapsed, shortened by one step. The best corrected visual acuity (BCVA) measurement and OCT were performed at baseline and on the same days of the scheduled injections. At baseline, all patients completed a survey, the Hospital Anxiety and Depression Scale (HADS), regarding mental burden. At week 52, patients on the TAE regimen for 1 year completed the HADS and a questionnaire designated to assess treatment-associated mental status., Results: Fifty-one patients (68%) completed the 1-year TAE regimen; 24 eyes (32%) discontinued the TAE regimen because of the rescue treatment, difficulty in completing clinical visits, or financial burden. In 51 eyes on the TAE regimen for 1 year, the mean BCVAs improved from 64.3 letters at baseline to 71.6 letters at week 52. The mean anxiety and depression scores on HADS decreased significantly (p < 0.01) after the 1-year treatment. Women tended to have higher anxiety scores, possibly associated with fear of injection and recurrence, while some men had higher depression scores potentially associated with financial burden, difficulty in completing clinical visits, and subsequent interruption of the TAE regimen especially in eyes with low treatment efficacy., Conclusions: A TAE regimen of intravitreal ranibizumab injections preserves vision in eyes with nvAMD and reduces mental burden associated with disease relapse., Trial Registration: This clinical study was registered retrospectively on December 22, 2014 with the ClinicalTrials.gov identifier NCT02321839., (© 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Background: To evaluate the safety and efficacy of a new toric intraocular lens (IOL) with anchor-wing haptics., Methods: The new toric IOL with anchor-wing haptics (NS60YT, NIDEK Co., Ltd.) was implanted in eligible patients with age-related cataracts with preoperative corneal astigmatism of 1.0 D or greater at a university hospital and two private hospitals in Japan. The following IOL cylinder powers were evaluated: 1.50 D (NS60YT3), 2.25 D (NS60YT4), 3.00 D (NS60YT5) and 4.50 D (NS60YT7). All patients were assessed out to 12 months postoperatively. The primary endpoint was visual acuity (VA) with spherical addition at 6 months postoperatively, and the primary analysis calculated the proportion of eyes with VA with spherical addition of 0.1 logMAR or better. The magnitude of rotation was compared to the intended axis of IOL implantation at each postoperative examination. Adverse events were evaluated for the safety analysis., Results: This study enrolled 64 eyes of 53 patients. At 6 months postoperatively, for all IOL powers, VA with spherical addition of 0.1 logMAR or better was achieved in 90% [95% confidence interval (CI): 80-96] of eyes. The mean IOL rotation was 5.3 ± 4.3° at 12 months postoperatively. The mean magnitude of rotation ranged from 1.9° to 2.5° between each postoperative examination from 1 day to 12 months. There were no vision-threatening intraoperative or postoperative complications for the duration of the study., Conclusions: The NS60YT IOL remained stable after implantation and was efficacious for treating 1.00 D or greater astigmatism in patients with senile cataracts., Trial Registration: This study was registered at ClinicalTrials.gov ( NCT03242486 ) on August 8, 2017 - Retrospectively registered., (© 2022. The Author(s).)

Summary: Here, we present Viola, a Python package that provides structural variant (SV; large scale genome DNA variations that can result in disease, e.g. cancer) signature analytical functions and utilities for custom SV classification, merging multi-SV-caller output files and SV annotation. We demonstrate that Viola can extract biologically meaningful SV signatures from publicly available SV data for cancer and we evaluate the computational time necessary for annotation of the data., Availability and Implementation: Viola is available on pip (https://pypi.org/project/Viola-SV/) and the source code is on GitHub (https://github.com/dermasugita/Viola-SV)., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2021. Published by Oxford University Press.)

Background: There is a need for a model of diffuse-type gastric cancer that captures the features of the disease, facilitates the study of its mechanisms, and aids the development of potential therapies. One such model may be Cdh1 and Trp53 double conditional knockout (DCKO) mice, which have histopathological features similar to those of human diffuse-type gastric cancer. However, a genomic profile of this mouse model has yet to be completed., Methods: Whole-genome sequences of tumors from eight DCKO mice were analyzed and their molecular features were compared with those of human gastric adenocarcinoma., Results: DCKO mice gastric cancers harbored single nucleotide variations and indel patterns comparable to those of human genomically stable gastric cancers, whereas their copy number variation fraction and ploidy were more similar to human chromosomal instability gastric cancers (perhaps due to Trp53 knockout). Copy number variations dominated changes in cancer-related genes in DCKO mice, with typical high-level amplifications observed for oncogenic drivers, e.g., Myc, Ccnd1, and Cdks, as well as gastrointestinal transcription factors, e.g., Gata4, Foxa1, and Sox9. Interestingly, frequent alterations in gastrointestinal transcription factors in DCKO mice indicated their potential role in tumorigenesis. Furthermore, mouse gastric cancer had a reproducible but smaller number of mutational signatures than human gastric cancer, including the potentially acid-related signature 17, indicating shared tumorigenic etiologies in humans and mice., Conclusions: Cdh1/Trp53 DCKO mice have similar genomic features to those found in human gastric cancer; hence, this is a suitable model for further studies of diffuse-type gastric cancer mechanisms and therapies., (© 2021. The Author(s).)

We conducted a retrospective study to investigate adverse drug reactions and associated medical costs among elderly individuals that could be avoided if pharmacotherapy was performed in accordance with the Beers Criteria: the Japanese Version (BCJV) and Guidelines for Medical Treatment and Its Safety in the Elderly 2015 (GL2015). Patients aged at least 65 years who were either hospitalized at Gifu Municipal Hospital between October 1 and November 30, 2014 (n = 1236) or had outpatient examinations at Gifu Municipal Hospital on October 1-2, 2014 (n = 980) were included in the study. The outcomes measured were usage rates of drugs listed in the BCJV and GL2015, incidence rates of adverse drug reactions, and additional costs incurred per patient due to adverse reactions. Among the inpatients, usage rates of drugs listed in the BCJV and GL2015 were 24.0 and 72.4%, respectively, and adverse reactions to these drugs occurred at rates of 3.0 and 8.2%, respectively. Among the outpatients, while the usage rates were 26.2% (BCJV) and 59.9% (GL2015), the incidence rates of adverse reactions were 4.7% (BCJV) and 3.9% (GL2015). The additional costs incurred due to adverse drug reactions ranged from 12713-163925 yen per patient. Our results demonstrate that appropriate use of drugs based on the BCJV and GL2015 can help prevent adverse reactions; this would reduce the overall medical costs.

Over-the-counter (OTC) drugs and health foods/supplements are used as means of self-medication with the aim of preventing diseases and maintaining health. No reports have yet addressed the relationship between healthcare systems and self-medication. Here, we carried out a retrospective survey to identify healthcare system factors affecting OTC drug and health food/supplement usage. Patients hospitalized at Gifu Municipal Hospital between October 1, 2014 and March 31, 2015 were given a survey. The items surveyed were age, gender, disease, alcohol intake/smoking status, insurance classification, and medical pharmaceuticals, OTC drugs, and health foods/supplements used immediately before hospitalization. We performed multiple logistic regression analysis using OTC drugs and health foods/supplements as dependent variables with patient attributes, medical insurance, etc. as independent variables. A total of 5,965 patients were analyzed. OTC users comprised 2.6 % (156 people) of the total. The use of OTC drugs was significantly higher for females and alcohol consumers than in other categories. In contrast, the use of OTC drugs was significantly lower for participants in public expense/medical subsidy programs. Health foods/supplements were used by 4.0 % of all subjects (240 people); their use was significantly higher among females and users of medical pharmaceuticals. On the other hand, the use of health foods/supplements was significantly lower for smokers, users of the latter-stage elderly healthcare system, and users of public expense/medical subsidy programs.

Patients on dialysis require caregiving and assistance in their daily lives from family members and/or others for hospital visitation and supervised administration. This places a considerable burden on caregivers, which can in turn influence caregivers' quality of life (QOL). We recruited dialysis patients and their caregivers to elucidate how the QOL of patients relates to that of their caregivers'. Patients completed the EuroQol 5-Dimension scale (EQ-5D) and Kidney Disease Quality of Life-Short Form. Caregivers completed the EQ-5D and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). We calculated utility index values for the EQ-5D, and physical, mental (MCS), and role-social component summary scores for the SF-36. Compared to national norms, the caregivers of dialysis patients tended to have poor physical health-related QOL but normal mental health-related QOL, as also found with patients. The multivariate analysis revealed that ≥ median dialysis period and ≥ average burden of kidney disease were significantly related to caregiver MCS score (odds ratios; 6.79 and 9.89, respectively). Caregivers tended to have lower physical health-related QOL if their patients had high social QOL, and lower mental health-related QOL during the early stage of the patient's dialysis treatment, and when patients experienced low disease-targeted QOL.

Background: Incretin-based drugs are important in the treatment of type 2 diabetes. However, among the incretin-based drugs, glucagon-like peptide-1 receptor agonists (GLP-1-RAs) have been reported to cause gastroesophageal reflux disease (GERD)-like symptoms making it difficult to continue treatment. Therefore, with the aim of clarifying the relationship between incretin-based drugs and GERD-like symptoms, we conducted a pharmacoepidemiological study using the Japanese adverse drug event report database (JADER)., Methods: Dipeptidyl peptidase-4 inhibitors (DPP-4-Is) and GLP-1-RAs were set as the incretin-based target drugs. The reporting odds ratio (ROR) and the information component (IC) was used for the detection of quantitative signals. Furthermore, we also compared the time to onset of GERD-like symptoms by log-rank test., Results: GERD-like symptoms were reported in 36 GLP-1-RAs cases (ROR: 5.61, 95% confidence interval (95% CI): 3.95-7.96 and IC: 2.17, 95% CI: 1.66-2.67) and GLP-1-RAs were detected in the signal. In contrast, DPP-4-Is were not detected in the signal.There was no sex difference with regard to the expression time of GERD-like symptoms by GLP-1-RAs (log-rank test, p  = 0.5381). However, the expression time of GERD-like symptoms from GLP-1-RAs was shorter in patients older than 70 years of age than that in those younger than 70 years of age (log-rank test, p  < 0.0001)., Conclusions: The administration of GLP-1-RA had a higher incidence of GERD-like symptoms earlier than the administration of DPP-4-Is. In this study, although we think that further investigation is necessary, and suggest that patients older than 70 years of age who have been administered GLP-1-RAs need earlier attention to address GERD-like symptoms than younger patients., Competing Interests: Not applicable.Although Laboratory of Community Healthcare Pharmacy, Gifu Pharmaceutical University, is financially supported by donations from WELCIA YAKKYOKU CO., LTD., the authors report no conflicts of interest regarding the content of this article.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Dialysis treatment is known to lead to reduced quality of life (QOL) among patients. This decreased QOL is believed to influence medication compliance, although this effect has not yet been clarified. In this study, we investigated whether decreased QOL due to dialysis treatment does in fact influence medication compliance. Participants were 92 patients who self-managed their medication and were receiving dialysis treatment at Secomedic Hospital or Chiba Central Medical Center. We surveyed their age, sex, dialysis period, and medication management situation, and administered the EQ-5D and Kidney Disease Quality of Life Instrument-Short Form. A multiple logistic regression analysis with medication compliance as the dependent variable and QOL as the independent variable was conducted. The recovery rate and effective response rate were both 100%. The results indicated that patients with good sleep QOL (mean or above) had higher odds of medication compliance (odds ratio, 3.36; 95% confidence interval, 1.26-8.96; P = 0.016). Therefore, improving the quality of sleep of dialysis patients might help to improve their medication compliance.

Background: The contents of the guidelines for the use of non-benzodiazepines (Z-drugs) differ slightly between THE JAPANESE SOCIETY OF SLEEP RESEARCH and THE JAPAN GERIATRIC SOCIETY, and the recommended directions are conflicting. Therefore, we analyzed the use of the Japanese Adverse Drug Event Report database (JADER) for identifying adverse events (AEs) caused by Z-drugs and clarifying their occurrence trend and prognosis., Methods: The signal value for comparison was calculated by using the proportional reporting ratio (PRR) and chi-squared test (χ 2 ) results of data of elderly and non-elderly patients. Among AEs for which signals were detected in the elderly, we determined that those with lower signal values for non-elderly patients that were half the signal value of the elderly should be used with particular caution in the elderly. We also compared the prognoses., Results: The AEs with > 1 risk ratio (RR) in elderly and non-elderly patients were regarded as those that should be noted in the prognosis of AEs in elderly patients. Furthermore, 28 AEs were detected in elderly patients' signals. In this study, in addition to movement disorders such as "falls" and "bone fractures," identified by two academic societies, signal characteristics of the elderly were obtained for psychiatric disorders and eye disorders., Conclusions: There was no difference in prognosis, but these disorders could reduce the quality of life of patients. Therefore, we consider that in prescribing appropriate drug therapy for insomnia, attention should be paid to the occurrence of the AEs caused by the Z-drugs revealed by this study and the guidelines., Competing Interests: Not applicable.Although Laboratory of Community Healthcare Pharmacy, Gifu Pharmaceutical University, is financially supported by donations from WELCIA YAKKYOKU CO., LTD., the authors report no conflicts of interest regarding the content of this article.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Patient background (e.g. age, sex, and primary disease) is an important factor to consider when monitoring adverse drug events (ADEs) for the purpose of pharmacovigilance. However, in disproportionality methods, when additional factors are considered, the number of combinations that have to be computed increases, and it becomes very difficult to explore the whole spontaneous reporting system (SRS). Since the signals need to be detected quickly in pharmacovigilance, a simple exploration method is required. Although association rule mining (AR) is commonly used for the analysis of large data, its application to pharmacovigilance is rare and there are almost no studies comparing AR with conventional signal detection methods., Methods: In this study, in order to establish a simple method to explore ADEs in patients with kidney or liver injury as a background disease, the AR and proportional reporting ratio (PRR) signal detection methods were compared. We used oral medicine SRS data from the Japanese Adverse Drug Event Report database (JADER), and used AR as the proposed search method and PRR as the conventional method for comparison. "Rule count ≥ 3", "min lift value > 1", and "min conviction value > 1" were used as the AR detection criteria, and the PRR detection criteria were "Rule count ≥3", "PRR ≥ 2", and "χ 2 ≥ 4"., Results: In patients with kidney injury, the AR method had a sensitivity of 99.58%, specificity of 94.99%, and Youden's index of 0.946, while in patients with liver injury, the sensitivity, specificity, and Youden's index were 99.57%, 94.87%, and 0.944, respectively. Additionally, the lift value and the strength of the signal were positively correlated., Conclusions: It was suggested that computation using AR might be simple with the detection power equivalent to that of the conventional signal detection method as PRR. In addition, AR can theoretically be applicable to SRS other than JADER. Therefore, complicated conditions (patient's background etc.) that must take factors other than the ADE into consideration can be easily explored by selecting the AR as the first screening for ADE exploration in pharmacovigilance using SRS.

Factors influencing generic drug use must be considered when new drug policies are established and initiatives are implemented to promote generic drug use. This study was conducted to elucidate medical and economic factors that influence generic drug use in the Japanese public health system by evaluating the degree of generic drug use via a multivariate analysis. We conducted a retrospective study of medications administered to inpatients at Gifu Municipal Hospital (Japan) from November 1 to 14, 2014. Details of inpatients (age, sex, and type of medical insurance) and the drugs administered (prescribing institution, dispensing pharmacy, price, and class) were assessed. A total of 1409 drugs (original, 639; generic, 770) were analyzed. Multivariate analysis showed significant differences in out-of-pocket medical fees [odds ratio (OR), 0.595], drugs prescribed at Gifu Municipal Hospital (OR, 1.811), drugs prepared at a health insurance pharmacy (OR, 1.541), drugs containing the same active substances as in the generic drugs used at Gifu Municipal Hospital (OR, 3.712), and drugs costing ≥30 yen and containing the same active substance/having the same specifications (OR, 0.516). Drugs prescribed at a large key hospital in the community with high adoption rates of generic drugs, drugs containing the same active substances as the generic drugs adopted by the hospital, and drugs prepared at health insurance pharmacies contributed to a more frequent use of generic drugs. By contrast, out-of-pocket medical fees and being prescribed expensive drugs contributed to the less frequent use of generic drugs., (Copyright © 2018 John Wiley & Sons, Ltd.)

Introduction: The goal of this study was to assess pharmacy students' satisfaction with long-term practical training programs at hospital and community pharmacies and how these programs benefitted communication skills., Methods: We asked 83 fifth-year pharmacy students to answer anonymous questionnaires assessing their satisfaction and perceived benefits of practical training and to complete Teramachi's Pharmacist Communication Skill Scale (TePSS-31), a measure of pharmacists' communication skills, after undergoing their practical training periods at hospital and community pharmacies in 2014., Results: Over 90% of students who underwent the practical training were satisfied with their experiences. Furthermore, they reported that practical training institution was helpful for improving their communication skills and gave them sufficient opportunity to interact with consulting patients, engage in role play with pharmacists or peers, and observe interactions between pharmacists and patients. Overall, over 80% of students felt that they had shown improvement in communication skills, indicating that the training was effective. We further reconfirmed that the TePSS-31 has good internal consistency. The total scores on the TePSS-31 after the hospital and community pharmacy training programs did not significantly differ, indicating that the place where the training was received did not influence students' acquisition of communication skills., Conclusions: Most students were satisfied with the long-term practical training at hospital and community pharmacies, and the training helped improve their communication skills for dealing with patients and coworkers., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The objective of the current study is to elucidate the effect that the adoption of generic drugs by a large hospital has on the dispensation of generic drugs by community pharmacies. We evaluated the percentage of generic drugs dispensed by pharmacies and the cost of drugs dispensed before and after the adoption of generic drugs by a large hospital., Methods: Participants comprised patients who were admitted to Gifu Municipal Hospital prior to its adoption of generic drugs (November 1, 2013 to November 14, 2013) and after its adoption (November 1, 2014 to November 14, 2014) and who utilized generic drugs dispensed by pharmacies., Results: Results indicated that the pre-adoption dispensation rate of generic drugs by pharmacies was 48.3% (477/926 drugs), while the post-adoption rate was 57.7% (604/1046 drugs), indicating an increase of 9.4 points ( P  < 0.001). Furthermore, an investigation into the price paid for generic drugs as a percentage of the total price paid for all drugs indicated the following: the pre-adoption percentage was 23.5% (9756/41,461 yen), and the post-adoption percentage was 34.1% (19,221/56,438 yen), indicating an increase of 10.6 points ( P  < 0.001)., Conclusions: The results of this study revealed that the adoption of generic drugs by a hospital may promote the use of generic drugs by pharmacies and lead to reduced medical costs as well., Competing Interests: The current study was approved by the Ethical Review Board of Gifu Municipal Hospital (Approval number: 212) and the Bioethics Committee of Gifu Pharmaceutical University (Approval number: 311–2). The study was considered exempt from needing to obtain informed consent in accordance with the domestic ethical guideline; relevant information was open to the public.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Adverse events (AEs) can be caused not only by one drug but also by the interaction between two or more drugs. Therefore, clarifying whether an AE is due to a specific suspect drug or drug-drug interaction (DDI) is useful information for proper use of drugs. Whereas previous reports on the search for drug-induced AEs with signal detection using spontaneous reporting systems (SRSs) are numerous, reports on drug interactions are limited. This is because in methods that use "a safety signal indicator" (signal), which is frequently used in pharmacovigilance, a huge number of combinations must be prepared when signal detection is performed, and each risk index must be calculated, which makes interaction search appear unrealistic. Objective: In this paper, we propose association rule mining (AR) using large dataset analysis as an alternative to the conventional methods (additive interaction model (AI) and multiplicative interaction model (MI)). Methods: The data source used was the Japanese Adverse Drug Event Report database. The combination of drugs for which the risk index is detected by the "combination risk ratio (CR)" as the target was assumed to be true data, and the accuracy of signal detection using the AR methods was evaluated in terms of sensitivity, specificity, Youden's index, F -score. Results: Our experimental results targeting Stevens-Johnson syndrome indicate that AR has a sensitivity of 99.05%, specificity of 92.60%, Youden's index of 0.917, F -score of 0.876, AI has a sensitivity of 95.62%, specificity of 96.92%, Youden's index of 0.925, and F -score of 0.924, and MI has a sensitivity of 65.46%, specificity of 98.78%, Youden's index of 0.642, and F -score of 0.771. This result was about the same level as or higher than the conventional method. Conclusions: If you use similar calculation methods to create combinations from the database, not only for SJS, but for all AEs, the number of combinations would be so enormous that it would be difficult to perform the calculations. However, in the AR method, the "Apriori algorithm" is used to reduce the number of calculations. Thus, the proposed method has the same detection power as the conventional methods, with the significant advantage that its calculation process is simple.

Diabetic nephropathy is one of three major complications of diabetes mellitus, often leading to chronic renal failure requiring dialysis. Recently developed dipeptidyl peptidase-4 (DPP-4) inhibitors may exhibit renoprotective effects in addition to antihyperglycemic effects. In this study, we retrospectively investigated temporal changes in the renal function index of patients with type 2 diabetes mellitus (DM) and examined the influence of DPP-4 inhibitors on renal function. Patients with type 2 DM (>18 years old) prescribed hypoglycemic agents at Gifu Municipal Hospital for ≥3 months between March 2010 and April 2014 were included in the study. Renal function was evaluated as estimated the decline in 12-month glomerular filtration rate from the baseline in patients receiving and not receiving DPP-4 inhibitors. Patient data from the DPP-4 inhibitor-treated (501 patients, 58.6%) and untreated (354, 41.4%) groups were analyzed using multiple logistic regression analysis, as well as Cox proportional-hazards regression analysis (616, 55.6% and 491, 44.4%, for DPP-4 inhibitors-treated and untreated groups). Multiple logistic regression analysis indicated that DPP-4 inhibitors significantly lowered the estimated glomerular filtration rate (eGFR) decline [20% over 12 months; odds ratio (OR), 0.626; 95% confidence interval [CI], 0.409-0.958; P = 0.031]. Similar results were obtained using Cox proportional-hazards regression analysis (hazard ratio [HR], 0.707; 95% CI, 0.572-0.874; P = 0.001). These findings suggest that DPP-4 inhibitors suppress the decrease of estimated glomerular filtration rate in patients with type 2 DM and show a renoprotective effect.

We analyzed impression data and the scale of communication skills of students using text mining method to clarify which area a student was conscious of in communication in practical training. The results revealed that students tended to be conscious of the difference between practical hospital training and practical pharmacy training. In practical hospital training, specific expressions denoting relationships were "patient-visit", "counseling-conduct", "patient-counseling", and "patient-talk". In practical pharmacy training, specific expressions denoting relationships were "patient counseling-conduct", "story-listen", "patient-many", and "patient-visit". In practical hospital training, the word "patient" was connected to many words suggesting that students were conscious of a patient-centered communication. In practical pharmacy training, words such as "patient counseling", "patient", and "explanation" were placed in center and connected with many other words and there was an independent relationship between "communication" and "accept". In conclusion, it was suggested that students attempted active patient-centered communication in practical hospital training, while they were conscious of listening closely in patient counseling in practical pharmacy training.

Objective: This longitudinal pilot study aimed to morphologically and quantitatively investigate the progress of non-carious cervical lesions (NCCLs) by using swept-source optical coherence tomography (SS-OCT)., Methods: The samples examined comprised sets of NCCL epoxy resin replicas obtained from 10 lesions in 6 patients who attended annual dental visits over 4 or 5 years. SS-OCT images of the replicas were analyzed in terms of the maximum depth (D max ) and corresponding vertical width (VW) - using an image analyzer to estimate progression of the NCCLs over time., Results: It was found that differences between wedge- and saucer-shaped lesions were morphologically distinguished well by the OCT images. There were significant differences in dimensions among D max , VW and horizontal width (HW). HW was the largest and D max was the smallest. Although no significant differences in absolute values of annual progression rates were found among D max, VW and HW, the percentage increase in D max was significantly greater compared to VW and HW. The ratios of D max to corresponding VW ranged from 0.49 to 1.01 for the wedge-shaped lesions and from 0.13 to 0.44 for saucer-shaped lesions, respectively., Conclusions: The dimensional analysis demonstrated notable progression with large variations. The wedge-shaped lesions appeared to show greater D max values compared to the saucer-shaped lesions., Clinical Significance: With respect to the depth, the wedge-shaped lesions may progress at a greater rate compared to the saucer-shaped lesions., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Differences in the efficacy of bevacizumab, an antivascular endothelial growth factor (VEGF) agent, against retinopathy with neovascularization when injected into the vitreous cavity of vitrectomized and nonvitrectomized eyes suggests the involvement of hyaluronan, a major component of the vitreous body. This study aimed to compare the affinities of hyaluronan for anti-VEGF agents in vitro., Methods: We examined the affinities of hyaluronan for 3 anti-VEGF agents (bevacizumab, pegaptanib and ranibizumab). Tritium [(3)H]-labeled hyaluronan was incubated separately with each anti-VEGF agent. The ratio of bound and unbound hyaluronan measured using solid and liquid phase methods was calculated., Results: Hyaluronan demonstrated a significantly greater affinity for bevacizumab than for pegaptanib or ranibizumab., Conclusions: The absence or presence of hyaluronan may be associated with the clinical efficacy of bevacizumab injected into the vitreous cavity due to the affinity of hyaluronan for bevacizumab., (Copyright © 2012 S. Karger AG, Basel.)

Purpose: Tumor necrosis factor-alpha (TNF-α) may disrupt the extracellular matrix components comprising the blood-retinal barrier (BRB) in patients with posterior uveitis, such as Behçet's disease. We investigated changes in the mRNA expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human BRB cells in the presence of TNF-α in vitro and examined the effect of infliximab addition., Methods: Cells were cultured in the presence or absence of TNF-α, and TNF-α-exposed cells were treated with or without infliximab. We measured the expression levels of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 mRNA in human retinal microvascular endothelial ACBRI181 cells and retinal pigment epithelial ARPE-19 cells by real-time polymerase chain reaction. The cell-derived proteins degraded by MMP were observed after sodium dodecyl sulfate-polyacrylamide gel electrophoresis., Results: Expression of MMP-3 increased and TIMP-1 decreased in the presence of 10 ng/mL TNF-α in ACBRI181 cells. Expression of MMP-1 increased and TIMP-2 decreased in the presence of 10 ng/mL TNF-α in ARPE-19 cells. These altered levels of expression were reversed by the addition of infliximab. The cell-derived proteins degraded by MMP-1 and -3 were detected in each set of cells., Conclusions: The presence of TNF-α altered expression of MMPs and TIMPs in cells comprising the BRB, and infliximab counteracted this alteration.

Background and Objective: We investigated the levels of matrix metalloproteinase-2 (MMP-2), which has been implicated in various vitreoretinal diseases, in the retina after laser photocoagulation (LPC)., Materials and Methods: The time course of MMP-2 expression in 2-day-old chicken retinas before and 6 hours, 12 hours, 1 day, 2 days, 4 days, 8 days, 16 days, and 32 days after LPC was determined by real-time PCR and gelatin zymography. The basal level of MMP-2 in the retina and vitreous was also measured by gelatin zymography. MMP-2 localization in the retina was examined by immunohistochemistry. The localization of MMP-2 mRNA was determined by fluorescent in situ hybridization. The internal limiting membrane (ILM) was observed by scanning electron microscopy., Results: MMP-2 mRNA expression in the retina peaked at day 4, but gelatin zymography showed that MMP-2 peaked 6 hours after LPC and the significant increase in the level of active MMP-2 lasted for more than 4 days. The concentration of MMP-2 in the vitreous was significantly higher than that in the retina. A distinct MMP-2 signal around the ILM was identified 6 hours after LPC, but MMP-2 mRNA was not detected there. Electron microscopy showed a damaged retinal surface after LPC., Conclusion and Outlook: The significant increase in retinal MMP-2 which lasted for more than 4 days after LPC may be induced by influx from the vitreous into the retina. This MMP-2 dynamics may contribute to pathological processes in the retina after LPC.

In the chicken, two creatine kinase-type B (B-CK) isoproteins, Ba- and Bb-CK, both of which are derived from a single copy gene by alternative splicing, dimerize in neural tissues. The two isoproteins contain distinct N-terminal portions, but their functional difference remains unknown. We investigated the binding affinities of Ba- and Bb-CK to heparin, hyaluronan and chondroitin sulfates, and examined the influence of these glycosaminoglycans on enzyme activity. Chicken retinal samples analyzed by Western blotting and amino acid sequence study after two-dimensional gel electrophoresis showed that heparin binds Bb-CK, but not Ba-CK, while hyaluronan and chondroitin sulfates showed no interaction with either isoprotein. Using fusion proteins covering the distinct N-terminal portions, we also showed that heparin did not react with the N-terminus of Ba-CK, but did react with that of Bb-CK. Site-directed mutagenesis of basic amino acids found in the N-terminal portion of Bb-CK identified three basic amino acids critical for this binding. Furthermore, heparin dose-dependently inhibited the enzymatic activities of Ba-CK; Bb-CK activities were less intensely inhibited. Hyaluronan and chondroitin sulfates had no effects on the activities of these enzymes. Thus, the N-terminal portion of B-CK is critical to mediate its affinity to heparin and control enzyme activity, which may be important for regulating energy metabolism in neural tissues such as brain and retina, unique organs abundant in heparan sulfates.

A tribenzotetraazachlorin (TBTAC)-C(60) conjugate having three 15-crown-5 units as substituents, , has been synthesized, and the electronic and supramolecular structure modulations in the presence of Na(+) or K(+) have been elucidated by means of massmetric and spectroscopic techniques.

The accumulation of DNA damages by environmental stresses is represented by the steady state level of single strand breaks (SSBs) and double strand breaks (DSBs). Terminal deoxynucleotidyl transferase (TdT) mediated end labeling is suitable in detecting DSBs, but is unsuitable for SSBs due to its catalyzing characteristics. However, the sensitivity of TdT to detect SSBs may be significantly improved by first denaturing the double strands and expose all the DNA nicks as potential substrates for TdT. By coupling DNA denaturation to slot blot southern hybridization, the authors demonstrate the sensitive detection of SSBs as well as DSBs in 20 ng DNA samples derived from a retinal pigment epithelial cell line treated with tert-butyl hydroperoxide. The signal intensity of denatured and TdT-treated DNA in slot blot hybridization correlated to the amount of SSBs calculated in an S1 nuclease digestion assay. The signal ratio between denatured and non-denatured DNA likely approximates the SSBs/DSBs ratio in genomic DNA. The combination of DNA denaturing, TdT treatment and slot blot hybridization could be a useful method to assess oxidative stress-induced DNA strand damages.

We report a case of a postoperative brain infarction, in which an asymptomatic preoperative brain infarction was also revealed postoperatively. A 63-year-old man with bladder carcinoma was scheduled for the cystoplasty. The patient had no prominent preoperative abnormality. Anesthesia was maintained with isoflurane in N2O/oxygen combined with a spinal block and a continuous epidural block. Anesthesia lasted uneventfully for 16.5 hours. However, emergence from anesthesia was delayed. On the first postoperative day, motor aphasia and right hemiparalysis was confirmed. The computed tomography (CT) of the brain demonstrated a low density area in the frontoparietal region. The magnetic resonance imaging (MRI) indicated the corresponding lesion as the CT had demonstrated, and an old brain infarction in the parietal region. This meant that the patient had a history of asymptomatic brain infarction (ABI). Patients with ABI are considered to be a high-risk group for a brain infarction. It is important to evaluate the risk factors of brain infarction preoperatively and to minimize those risks during the operation. Maintenance of the cerebral perfusion pressure is imperative.

To assess the incidence of valvular regurgitation, 180 patients more than 40 years of age without cardiac symptoms were studied by pulsed Doppler echocardiography. The 180 patients were categorized by age as group 1, 40 to 49 years; group 2, 50 to 59 years; group 3, 60 to 69 years; group 4, 70 to 79 years; and group 5, more than 80 years of age. The incidence of valvular regurgitant flow signals increased significantly with age. Multivalvular regurgitation were often detected in groups 4 and 5. Furthermore, acoustically silent regurgitation at each valve was frequently noted (71 of 85 cases with valvular regurgitant flow signal: 84%). Mitral valve prolapse was diagnosed by two-dimensional echocardiography in 27 patients, but a mid-systolic click or pansystolic murmur with late-systolic accentuation was not noted. In conclusion, valvular regurgitations were common in the aged who lacked auscultatory findings.

Spontaneous echocardiographic contrast is caused by increased ultrasonic density in the cardiac chambers or great vessels, or both, with the characteristic flow pattern of blood, but in the absence of any intravascular injections. This study demonstrated the clinical features and characteristics of the echocardiographic findings of eight patients with spontaneous contrast echoes. Spontaneous contrast echoes were observed in the right heart in five patients, and in the left heart in two. In one patient spontaneous contrast echoes were observed in the right and left heart. All six patients with spontaneous contrast echoes in the right heart had impaired liver function. In these patients, we observed that spontaneous contrast reaching the heart via the hepatic vein on two-dimensional echocardiography. In one patient with atrial septal defect, these contrast echoes were also recognized in the superior mesenteric vein and portal vein. Since capillary beds normally remove ultrasound contrast, the failure of this function suggests porta-systemic shunting in or around the liver. All three patients with spontaneous contrast echoes in the left heart had prosthetic valve dysfunction including paravalvular or transvalvular regurgitation, and consequent hemolysis. Under these conditions, water-vapor bubbles may be formed because of an exhaust pressure decrease due to the Bernoulli effect, or gases may be released from erythrocytes during hemolysis. These water-vapor bubbles or gases could be the cause of spontaneous contrast echoes in the left heart. In conclusion, spontaneous contrast echoes in the right heart are produced by gas absorbed from the intestine because of porta-systemic shunting. The cause of spontaneous left-sided heart echo contrast may be related to prosthetic valve regurgitation, and consequently to hemolysis.