Introduction: Tissue characterization using cardiac magnetic resonance (CMR) is helpful for risk stratification in non-ischemic dilated cardiomyopathy (NIDCM). Hypothesis: This study aimed to investigate the predictive role of tissue characterization identified by CMR on cardiac resynchronization therapy (CRT) response. Methods: We retrospectively reviewed the patients who underwent CMR within 1 year before CRT implantation in NIDCM patients at a single tertiary center from January 2018 to September 2022. Late gadolinium enhancement (LGE), native T1, T2 and extracellular volume (ECV) were analyzed. CRT response was defined as a decrease in left ventricular end-systolic volume (LVESV) > 15% or an increase in left ventricular ejection fraction > 5% on TTE after at least 3 months after CRT implantation. Results: Among a total of 101 patients (mean age 66 years, 52.5% of male), 76 (75.2%) patients were defined as CRT responders. CRT responders had more LBBB (96.1% vs. 60.0%, p<0.001) and longer QRS duration (156.0±178.5 vs. 167.0±176.5ms, p=0.005) compared with CRT non-responders. However, LGE burden (34.3 vs. 13.3%, p<0.001), native T1 (1371.6 vs. 1336.8ms, p=0.033), T2 (45.9 vs. 42.1ms, p<0.001), and extracellular volume (ECV, 36.8 vs. 31.0%, p<0.001) were significantly higher in CRT non-responders. The area under the curve (AUC) to predict CRT response is the highest in LGE burden (0.817, 95% confidence interval [CI]: 0.710-0.925), followed by ECV (0.808, 95% CI: 0.711-0.905), T2 (0.779, 95% CI: 0.663-0.895), and native T1 (0.643, 95% CI: 0.520-0.766). After adjustment, LGE burden>20% (odds ratio [OR]: 0.15, 95% CI: 0.02-0.71, p=0.024) and ECV > 34% (OR: 0.13, 95% CI: 0.01-0.78, p=0.037) were independently poor CRT response predictors. Conclusions: The tissue characterization by using CMR is helpful to predict CRT response and clinical outcomes in patients with NIDCM, independently of conventional CRT response predictors.
Additional file 1: Figure S1. Flow chart describing CD progressors demographics and sample size. Figure S2. Violin plot representation of most enriched genus/species in CD progressors compared to healthy controls. A. Fold change in ASVs at age 2.5 CD progressors (left panel, n=15) and healthy controls (right panel, n=16). B. Fold change in ASVs at age 5 in CD progressors (left panel, n=10) and healthy controls (right panel, n=13). Figure S3. Gating strategy for IgA sequencing and analysis. A. Schematic overview of IgA-based fecal bacteria separation combined with 16S rRNA gene sequencing (IgA-seq) for stool samples from CD progressors and healthy controls. MACS: Magnetic-activated cell separation. B. Gating strategy for the isolation of IgA-/+ bacteria from the CD progressors and healthy controls’ fecal samples. C. Empirical Bayes quasi-likelihood F-tests analysis for comparing IgA-coated and non-coated gut microbiota ASVs in healthy controls (upper row) and CD progressors (lower row) at ages 2.5, and 5. Frequency: number of ASVs. FDR: False Discovery Rate. D. Empirical Bayes quasi-likelihood F-tests analysis for the comparisons of IgA-coated or non-coated gut microbiota ASVs between CD progressors and healthy controls (upper row: age 2.5 years old; lower row: age 5 years old). F. Box plots showing representative ASVs in which abundances were similar in the gut microbiota (presorting samples) but differently targeted by IgA at age 2.5. E. Violin plots showing representative ASVs in which abundances were similar in the gut microbiota (presorting samples) but differently targeted by IgA at age 5. Figure S4. Heat Map showing IgA target in CD progressors and healthy subjects. A. Heat map showing the relative abundance of the top ASVs significantly different between IgA+ and IgA- samples of CD progressors and healthy controls (ASVs=51, selected based on p-value) at age 2.5 B. at age 5. Each column represents an individual participant and each row represents an ASV. Figure S5. The cytokine and plasma metabolome profiles of CD progressors and CD patients. A. Comparison of all 48 cytokines analyzed in plasma samples obtained from CD progressors (n=10) and healthy controls (n=10) at age 5. Data were expressed as means ±SEM. *p<0.05, **p<0.01, ***p<0.001. Statistical analysis was performed by a two-tailed, unpaired student’s t-test. B. Violin plots showing the representative Clostridium XIVa bacteria abundance between CD progressors and healthy controls (Left: before separation by IgA coating, Right: in IgA+ bacteria). Figure S6. Gating Strategy for the Flow cytometry analysis. Strategy 1- Gating strategy for NK1.1 and Qa-1 expression in TCRβ+ cells. Strategy 2- Gating strategy for CD8, CD4, NKG2D, CD103, and NKp46. Figure S7. TDCA diet induces changes in T-cell composition in different cell subsets. A. H&E images of ileum tissue sections of control and TDCA treated female mice. Full image (upper panel) and image at high magnification (lower panel). Scale =20μm. B. Villi/ Crypt ratio in ileum tissue sections of control and the TDCA treated female mice. C. Number of plasma cells in the lamina propria of the ileum section of female mice. D. TCRβ+ cells as % of total CD45+ cells. E. NKG2D+ cells as % of total TCRβ+ CD45+ cells. F. CD103+ cells as % of total CD4+ cells. G. Qa-1+ cells as % of total CD4+ cells in the IELs, PP, LP, and spleen of female (left panel) and male (right panel) mice. H Relative gene expression of Qa-1 and IL-10 in the ileum tissue analyzed using qPCR. Female (left panel) and male (right panel) mice after 10 weeks of TDCA treatment compared to controls. Data were expressed as mean ± SEM. *p<0.05, **p <0.01, ***p<0.001. Statistical analysis was performed by a two-tailed unpaired student’s t-test.
Stent thrombosis is a very serious problem after drug-eluting stent (DES) implantation even though its incidence is about or less than 1%. As the clopidogrel resistance is expected to play an important role in the occurrence of stent thrombosis, new anti-platelet agents overcoming this issue can give us another choice. We experienced a case of a 58-year-old male with successful prasugrel rescue therapy in a patient with clopidogrel resistance who had recurrent stent thrombosis following DES implantation.
While the association between the gut microbiome and the immune system has been studied in autoimmune disorders, little is known about ocular disease. Previously we reported that IRT5, a mixture of five probiotic strains, could suppress autoimmune dry eye. In this study, we investigated the mechanism by which IRT5 performs its immunomodulatory function in a mouse model of autoimmune dry eye.NOD.B10.H2b mice were used as an autoimmune dry eye model. Either IRT5 or PBS was gavaged orally for 3 weeks, with or without 5 days of antibiotic pretreatment. The effects on clinical features, extraorbital lacrimal gland and spleen proteins, and fecal microbiota were analyzed.The ocular staining score was lower, and tear secretion was higher, in the IRT5-treated groups than in the PBS-treated groups. After IRT5 treatment, the downregulated lacrimal gland proteins were enriched in the biological processes of defense response and immune system process. The relative abundances of 33 operational taxonomic units were higher, and 53 were lower, in the feces of the IRT5-treated groups than in those of the PBS-treated groups. IRT5 administration without antibiotic pretreatment also showed immunomodulatory functions with increases in the Lactobacillus helveticus group and Lactobacillus hamsteri. Additional proteomic assays revealed a decrease of proteins related to antigen-presenting processes in the CD11b+ and CD11c+ cells of spleen in the IRT5-treated groups.Changes in the gut microbiome after IRT5 treatment improved clinical manifestations in the autoimmune dry eye model via the downregulation of antigen-presenting processes in immune networks.
Background: Suicide is one of the most important causes of deaths in the United Kingdom, and the numbers are currently increasing. Aim: There are numerous identified determinants of suicidality, and physical multimorbidity is potentially important but is currently understudied. Thus, this study aims to investigate the association of physical multimorbidity with suicidality. Methods: Cross-sectional data from the Adult Psychiatric Morbidity Survey 2007, which was conducted in England between October 2006 and December 2007 by the National Center for Social Research and Leicester University were analyzed. Respondents were asked about 20 physical health conditions, and suicidal ideation and suicide attempts were assessed. Results: Out of 7,403 individuals aged 16 years or over, the prevalence of physical multimorbidity, suicidal ideation, and suicide attempts were 35.1%, 4.3%, and 0.7%, respectively. After adjustment for potential confounders, compared to no physical conditions, 1, 2, 3, and ⩾4 conditions were associated with significant 1.79 (95% CI [1.25, 2.57]), 2.39 (95% CI [1.63, 3.51]), 2.88 (95% CI [1.83, 4.55]), and 6.29 (95% CI [4.12, 9.61]) times higher odds for suicidal ideation. Mediation analysis showed that cognitive problems (mediated percentage 39.2%) and disability (37.5%) explained the largest proportion between multimorbidity and suicidal ideation. Pain (38.0%) and cognitive problems (30.7%) explained the largest proportion between multimorbidity and suicide attempts. Conclusion: In this large sample of UK adults, physical multimorbidity was associated with significantly higher odds for suicidal ideation and suicide attempts. Moreover, several potential mediators were identified, and these may serve as future targets for interventions that aim to prevent suicidality among people with physical multimorbidity.
Objective: In the elderly, the effect of blood pressure on brain structure or cognitive function has not been clear. However, there are limitations in that most of studies was done using serial change in clinic blood pressure. We sought to determine the association of the ambulatory blood pressure over time with the brain structural alterations and cognitive function Design and method: In this study, we sought to examine the association between blood pressure and brain structure/cognitive function in the elderly over the age of 60 by using the 24-hour ambulatory blood pressure information at 2 different visits (mean time interval is 3.4 years). From October 2018, we included participants performed Korean Mini Mental State Exam; older than 60 years old among the participants in Cardiovascular and Metabolic Disease Etiology Research Center-High Risk Cohort. Results: When we divided the 170 participants into two groups according to the control of cumulative average daytime blood pressure, the cortical thickness of frontal lobe was thinner and the average hippocampal volume was smaller in the uncontrolled group (P = 0.002, P = 0.01 respectively). In multivariate linear analysis, the uncontrolled group for cumulative average daytime blood pressure was associated with thinner cortical thickness of frontal lobe and smaller average hippocampal volume (P = 0.007, P = 0.024 respectively). However, the baseline daytime blood pressure had no associations with brain structure or cognitive function. Conclusions: Our observations suggest that serial measurements of 24-hour ambulatory blood pressure may be important to assess the cumulative pressure load and the association with structural changes of the brain.
Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) with clinical phenotypes that vary across regions and genotypes. We sought to characterize the clinical characteristics of ATTR-CM in Asia. Data from a nationwide cohort of patients with ATTR-CM from six major tertiary centres in South Korea were analysed between 2010 and 2021. All patients underwent clinical evaluation, biochemical laboratory tests, echocardiography, and transthyretin (TTR) genotyping at the time of diagnosis. The study population comprised 105 Asian ATTR-CM patients (mean age: 69 years; male: 65.7%, wild-type ATTR-CM: 41.9%). Among our cohort, 18% of the patients had a mean left ventricular (LV) wall thickness < 12 mm. The diagnosis of ATTR-CM increased notably during the study period (8 [7.6%] during 2010-2013 vs. 22 [21.0%] during 2014-2017 vs. 75 [71.4%] during 2018-2021). Although the duration between symptom onset and diagnosis did not differ, the proportion of patients with HF presenting mild symptoms increased during the study period (25% NYHA class I/II between 2010-2013 to 77% between 2018-2021). In contrast to other international registry data, male predominance was less prominent in wild-type ATTR-CM (68.2%). The distribution of TTR variants was also different from Western countries and from Japan. Asp38Ala was the most common mutation. A nationwide cohort of ATTR-CM exhibited less male predominance, a proportion of patients without increased LV wall thickness, and distinct characteristics of genetic mutations, compared to cohorts in other parts of the world. Our results highlight the ethnic variation in ATTR-CM and may contribute to improving the screening process for ATTR-CM in the Asian population.
Cytosine bases can be deaminated spontaneously to uracil, causing DNA damage. Uracil-DNA glycosylase (UDG), a ubiquitous uracil-excising enzyme found in bacteria and eukaryotes, is one of the enzymes that repair this kind of DNA damage. To date, no UDG-coding gene has been identified in Methanococcus jannaschii, although its entire genome was deciphered. Here, we have identified and characterized a novel UDG from M.jannaschii designated as MjUDG. It efficiently removed uracil from both single- and double-stranded DNA. MjUDG also catalyzes the excision of 8-oxoguanine from DNA. MjUDG has a helix-hairpin-helix motif and a [4Fe-4S]-binding cluster that is considered to be important for the DNA binding and catalytic activity. Although MjUDG shares these features with other structural families such as endonuclease III and mismatch-specific DNA glycosylase (MIG), unique conserved amino acids and substrate specificity distinguish MjUDG from other families. Also, a homologous member of MjUDG was identified in Aquifex aeolicus. We report that MjUDG belongs to a novel UDG family that has not been described to date.
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