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The left ventricular (LV) apex is recommended as the first choice for positioning the epicardial pacing. We encountered a patient with congenital heart disease (CHD) showing hypokinesis of the LV apical pacing site after implantation of a pacemaker with epicardial leads. This phenomenon was revealed by the early shortening and systolic rebound stretch of the same lesion on two-dimensional speckle tracking echocardiography, which developed in the intraventricular dyssynchrony between the LV apex and base. Cardiac resynchronization therapy provided an excellent result around the hypokinetic lesion. It is wise to arrange detailed evaluations in each patient with complicated CHD, aiming at a successful treatment to enable ventricular synchronicity.

AIMS /Introduction We aimed to replicate a new diabetes subclassification based on objective clinical information at admission in a diabetes educational inpatient program. We also assessed the educational outcomes for each cluster. METHODS We included diabetic patients who participated in the educational inpatient program during 2009-2020 and had sufficient clinical information for the cluster analysis. We applied a data-driven clustering method proposed in a previous study and further evaluated the clinical characteristics of each cluster. We investigated the association between the clusters and changes in HbA1c level from the start of the education program. We also assessed the risk of re-admission for the educational program. RESULTS We divided a total of 651 patients into five clusters. Their clinical characteristics followed the same pattern as in previous studies. The inter-cluster ranking of the cluster center coordinates showed strong correlation coefficients with those of the previous studies (mean ρ=0.88). Patients classified as severe insulin-resistant diabetes (cluster 3) showed a more pronounced progression of renal dysfunction than patients classified as the other clusters. The patients classified as severe insulin-deficient diabetes (SIDD: cluster2) had the highest rate of reduction in HbA1c level from the start of the program (p

Although the Cre-loxP recombination system has been extensively used to analyze gene function in vivo, spatiotemporal control of Cre activity is a critical limitation for easy and precise recombination. Here, we established photoactivatable-Cre (PA-Cre) knock-in (KI) mice at a safe harbor locus for the spatial and temporal regulation of Cre recombinase activity. The mice showed whole-body Cre recombination activity following light exposure for only 1 h. Almost no leaks of Cre recombination activity were detected in the KI mice under natural light conditions. Spot irradiation could induce locus-specific recombination noninvasively, enabling us to compare phenotypes on the left and right sides in the same mouse. Furthermore, long-term irradiation using an implanted wireless LED substantially improved Cre recombination activity, especially in the brain. These results demonstrate that PA-Cre KI mice can facilitate the spatiotemporal control of genetic engineering and provide a useful resource to elucidate gene function in vivo with Cre-loxP. Photoactivatable-Cre (PA-Cre) knock-in mice was established and characterized for the spatial regulation of Cre recombinase activity with blue light exposure. Spot irradiation or long-term irradiation using a wireless LED could induce locus-specific recombination. The PA-Cre knock-in mice promise a useful resource to elucidate gene function in vivo spatiotemporally.

Inflammation is increasingly understood as playing an important role in type 2 diabetes mellitus (T2D) development. A critical mechanism of the inflammatory cascade in developing T2D is nuclear factor-kappa B (NF-kB) activation. As immunoglobulin free light chains (FLC) could be a biomarker of activation of NF-kB, we measured FLC in patients with T2D. The age range of the 77 patients with T2D and the 75 healthy control participants were 45–87 years (median 60) and 25–72 years (median 51), respectively. Serum FLC kappa and lambda were assayed by a competitive-inhibition multiplex Luminex assay. The concentration of circulating FLC the kappa/lambda ratio was lower in patients with T2D than in healthy volunteers. The area under the receiver operating curve (ROC-AUC) of the FLC kappa/lambda ratio showed the largest ROC-AUC compared with other FLC variables and hemoglobin A1c (HbA1c). The diagnostic performance for distinguishing between T2D and healthy control was a sensitivity of 0.96 and a specificity of 1. The odds ratio was 0.000018. These results suggest that FLC kappa/lambda may be more specific and sensitive for the diagnosis of T2D than HbA1c, and thus represents a potentially promising biomarker of inflammation.

Although the Cre-loxP recombination system has been extensively used to analyze gene function in vivo, spatiotemporal control of Cre activity is a critical limitation for easy and precise recombination. Here, we established photoactivatable-Cre (PA-Cre) knock-in (KI) mice at a safe harbor locus for the spatial and temporal regulation of Cre recombinase activity. The mice showed whole-body Cre recombination activity following light exposure for only 1 h. Almost no leaks of Cre recombination activity were detected in the KI mice under natural light conditions. Spot irradiation could induce locus-specific recombination noninvasively, enabling us to compare phenotypes on the left and right sides in the same mouse. Furthermore, long-term irradiation using an implanted wireless LED substantially improved Cre recombination activity, especially in the brain. These results demonstrate that PA-Cre KI mice can facilitate the spatiotemporal control of genetic engineering and provide a useful resource to elucidate gene function in vivo with Cre-loxP.

Background In this study, we measured immunoglobulin free light chains (FLC), a biomarker of inflammation in the sera of patients with heart failure due to myocarditis. Methods FLC kappa and FLC lambda were assayed in stored serum samples from patients with heart failure with myocarditis from the US myocarditis treatment trial by a competitive-inhibition multiplex Luminex® assay. Results The median concentration of circulating FLC kappa/lambda ratio was significantly lower in the sera from patients with heart failure with myocarditis than in healthy controls, and FLC kappa/lambda ratio had good diagnostic ability for identification of heart failure with myocarditis. Further, FLC kappa/lambda ratio was an independent prognostic factor for overall survival, and allowed creation of three prognostic groups by combining with N-terminal pro-B-type natriuretic peptide. Conclusions This study suggests that FLC kappa/lambda ratio is a promising biomarker of heart failure with myocarditis.

Although the Cre-loxP recombination system has been extensively used to analyze gene function in vivo, spatiotemporal control of Cre activity is a critical limitation for easy and precise recombination. Here, we established photoactivatable-Cre (PA-Cre) knock-in mice at safe harbor locus for the spatial and temporal regulation of Cre recombinase activity. The mice showed Cre recombination activity in a whole-body following light exposure for only 1 h. Almost no leaks of Cre recombination activity were detected in the knock-in mouse under natural light conditions. Spot irradiation could induce locus-specific recombination noninvasively, enabling us to compare phenotypes on the left and right sides in the same mouse. Furthermore, long-term irradiation using an implanted wireless LED substantially improved Cre recombination activity, especially in the brain. These results demonstrated that the PA-Cre knock-in mice can facilitate spatiotemporal control of genetic engineering and promise a useful resource to elucidate gene function in vivo with Cre-loxP.

Alternatives to syringe-based administration are considered for vaccines. Intradermal vaccination with dissolvable microneedle arrays (MNA) appears promising in this respect, as an easy-to-use and painless method. In this work, we have developed an MNA patch (MNAP) made of hydroxyethyl starch (HES) and chondroitin sulphate (CS). In swines, hepatitis B surface antigen (HBsAg) formulated with the saponin QS-21 as adjuvant, both incorporated in HES-based MNAP, demonstrated the same level of immunogenicity as a commercially available aluminum-adjuvanted HBsAg vaccine, after two immunizations 28 days apart. MNAP application was associated with transient skin reactions (erythema, lump, scab), particularly evident when the antigen was delivered with the adjuvant. The thermostability of the adjuvanted antigen when incorporated in the HES-based matrix was also assessed by storing MNAP at 37, 45 or 50 °C for up to 6 months. We could demonstrate that antigenicity was retained at 37 and 45 °C and only a 10% loss was observed after 6 months at 50 °C. Our results are supportive of MNAP as an attractive alternative to classical syringe-based vaccination.

Two-phase (acid-gas) anaerobic digestion can improve process performance relative to conventional, mesophilic, single-phase anaerobic digestion. However, few studies have considered the impact of phase separation on microbial community structure. We compared six full-scale, two-phase digestion (TPD) facilities and four conventional digestion (CD) facilities at municipal wastewater treatment plants by collecting performance data and evaluating microbial community structure via Illumina 16S rRNA gene sequencing. Sequence data indicated that nearly complete phase separation was achieved in all TPDs with few syntrophic bacteria or methanogens detected in acid phase digesters (APDs). Thermophilic methane phase digesters (MPDs) exhibited poor performance relative to mesophilic MPDs consistent with substantially lower relative abundances of syntrophic bacteria and methanogens in thermophilic MPDs. Although known syntrophic acetate oxidizers were only detected at very low levels in MPDs (0.11 ± 0.20%), the low abundance of aceticlastic methanogens observed suggests that syntrophic acetate oxidation plays a prominent role by yet to be described populations in TPD. TPDs exhibited greater microbial diversity than CDs, likely due to APDs supporting more diverse populations of hydrolytic and fermentative bacteria.

Background: Inflammation is increasingly understood as playing an important role in type 2 diabetes mellitus (T2D) development. A critical mechanism of the inflammatory cascade in developing T2D is nuclear factor-kappa B (NF-kB) activation. As immunoglobulin free light chains (FLC) could be a biomarker of activation of NF-kB, we measured FLC in patients with T2D. Methods: The age range of the 77 patients with T2D and the 75 healthy control participants were 45 to 87 years (median 60) and 25 to 72 years (median 51), respectively.Serum FLC kappa and lambda were assayed by a competitive-inhibition multiplex Luminex assay. Findings: The concentration of circulating FLC kappa and the kappa/lambda ratio was lower, while in contrast, FLC lambda was higher, in patients with T2D than in healthy volunteers (p

Aim It is difficult to determine whether or not end-of-life care is necessary for frail older adults complaining of anorexia without underlying disease, such as cancer or organ failure. The main reason for this is the lack of the specification of the anorexia cause and no understanding of the cause-providing factor and the prognostic factor. This study aimed to clarify the cause of anorexia, and the determinant of the cause and recovery from anorexia. Methods Retrospective chart reviews were conducted on patients with anorexia without an underlying disease who were aged ≥65 years and visited the emergency department of a single tertiary care center between 2016 and 2017. Patient characteristics at hospital visit, the cause of anorexia, and diagnostic modalities were summarized. The diagnosis-providing rate, recovery rate, and the association between them were analyzed. Results Eighty-three patients (mean age 82.3 years; 50.6% male) were investigated. In 67 patients (81%), the causes of anorexia were identified, including 18 patients (22%) with infection, 13 (16%) with benign gastrointestinal diseases, and 7 (8%) with cardiovascular diseases. In 16 patients (19%), the causes of anorexia were not identified despite examinations. The modality that most contributed to diagnosis was plain computed tomography followed by blood tests. The value regarding information in history-taking and physical examinations was limited. Sixty-five patients (78%) recovered. Only 73% of patients with a definite cause recovered; all patients with an unknown cause recovered. Conclusions Older adults with anorexia are not always at the end of life, and efforts to identify the cause are crucial. Moreover, it is vital to realize the limitations associated with the treatment of infections and cardiovascular diseases.

118 consecutive patients of suspected acute myocardial infarction with acute chest pain and shortness of breath visiting our emergency room were subjected for this clinical study. Based on final diagnosis of acute myocardial infarction (AMI) comprehensively determined by medical record, physical examination, ECG, echocardiography, cardiac catheterization, etc., except for cardiac biomarkers, the patients were classified into two groups, with AMI group (1) and without AMI group (0) and then ROC curve analysis was performed between without AMI group (1) and with AMI group (0). As a result of ROC curve analysis, AUC, cutoff value, sensitivity, specificity and likelihood ratio (LR) were calculated as shown in Fig. 4 (1-7) and Table 2 (1-7). Based on calculating equation led from Bayesian rules, post-test odds were calculated as product of pre-test odds and LR at the cutoff value in each biomarker such as hsCTnT, hsCTnI, h-FABP CK, CKMB activity and CKMB mass. As a result, post-test probability was improved from predictive pre-test probability 30% to post-test probability 89% and 86% in hsCTnT and hsTnI, respectively but less improved from 30% to 68% in h-FABP and unexpectedly improved from 30% to 82% in CKMB mass compared with hsCTnT and hsTnI. Based on Bayesian rule, it is very valuable to predict post-test probability from predictive pre-test probability 30% by calculation in particular, when post-test probability is over 85-90%. In conclusion, we believe that prediction of post-test probability by Bayesian rule can be surely used to evaluate clinical quality of biomarkers which are not depend on at least, specialty and experience of physicians.