Summary
Chronic kidney disease (CKD)-mineral and bone disorder suggests that fragile bone and vascular disorder might be connected closely in CKD patients. In this study, fracture event was ...significantly associated with myocardial infarction (MI) in end-stage renal disease patients on hemodialysis (HD), especially for vertebral fractures.
Introduction
CKD-mineral and bone disorder is characterized by biochemical abnormalities, bone disorders, and vascular calcification. We aimed to verify the association between fracture and MI in CKD patients.
Methods
Records for incident CKD stage 3 to 5 patients and patients who initiated HD between July 2014 and June 2018 were retrieved from the Korean Health Insurance Review & Assessment Service Database. Fractures were defined using diagnostic codes and were classified into vertebral, femoral, and other site fractures. MI was defined using a combination of MI diagnostic codes and related procedure codes. Multiple logistic regressions and 1:1 propensity score matching analysis were conducted.
Results
A total of 38,935 patients (HD, 11,379; pre-dialysis CKD, 27,556) were included in this study. A total of 5,057 (13.0%) patients experienced fracture, and 1,431 (3.7%) patients had MI. Multiple logistic regression analysis showed that fracture was significantly associated with MI in the HD group (odds ratio (OR) 1.34,
P
= 0.024), but not in the pre-dialysis CKD group (OR 1.04,
P
= 0.701). After propensity score matching for age, gender, and diabetes mellitus between patients with and without fracture, fracture still significantly correlated with MI in HD patients (OR 1.47,
P
= 0.034) but not in patients with pre-dialysis CKD (OR 1.04,
P
= 0.751). Subgroup analysis by fracture site found that vertebral fracture was associated with MI in HD patients (OR 2.11,
P
= 0.024), but femoral or other site fractures were not.
Conclusion
In HD patients, fracture was significantly associated with MI, especially for vertebral fractures patients.
Summary
Background
Asthma in the elderly (aged ≥ 65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late‐onset asthma. Recent studies ...suggest staphylococcal enterotoxin IgE (SE‐IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late‐onset elderly asthma.
Objective
We aimed to examine the associations of SE‐IgE sensitization with late‐onset asthma in the elderly, using a database of elderly asthma cohort study.
Methods
A total of 249 elderly patients with asthma and 98 controls were analysed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE‐IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12‐month follow‐up period.
Results
At baseline, serum SE‐IgE concentrations were significantly higher in patients with asthma than in controls median 0.16 (interquartile range 0.04–0.53) vs. 0.10 (0.01–0.19), P < 0.001. Elderly asthma patients with high SE‐IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE‐IgE levels. In multivariate logistic regression analyses, the associations between serum SE‐IgE concentrations and severe asthma were significant, independently of covariables SE‐IgE‐high (≥ 0.35 kU/L) vs. negative (< 0.10 kU/L) group: odds ratio 7.47, 95% confidence interval 1.86–30.03, P = 0.005. Multiple correspondence analyses also showed that high serum SE‐IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together.
Conclusions and Clinical Relevance
This is the first report on the significant associations of SE‐IgE sensitization with late‐onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma and suggest clues to the pathogenesis of severe late‐onset eosinophilic asthma in the elderly.
Background and Objective
Epitope spreading is one of valid mechanisms operating in immunopathological processes of infection‐induced autoimmune diseases. We hypothesized that the peptide 19 from ...Porphyromonas gingivalis heat shock protein (HSP) 60 (Pep19) may be the dominant epitope from which epitope‐specific immune response to subdominant epitopes may diversify sequentially into autoimmune responses directed at human neoepitopes in P. gingivalis‐induced periodontitis and autoimmune diseases. However, the exact feature and mechanism on how Pep19 may drive epitope spreading into human autoantigens in chronic periodontitis or P. gingivalis‐induced experimental periodontitis has not been clarified. The present study was performed with the following specific aims: (i) to delineate retrospectively the features of epitope spreading by human cross‐sectional analysis; (ii) to demonstrate prospectively the epitope spreading into new antigenic determinants in an ordered, predictable and sequential manner in experimental periodontitis; and (iii) to clarify the mechanism on how immunization with Pep19 may mobilize helper T cells or elicit B‐cell responses to human autoantigens and neoantigen.
Material and Methods
The study was devised for two independent investigations – a cross‐sectional analysis on clinical subjects and a prospective analysis on experimental periodontitis – each being subdivided further into two additional independent observations. Cross‐sectional dot immunoblot pattern against a panel of peptides of P. gingivalis HSP60 and human HSP60 was performed among age‐dependent healthy subjects and between healthy subjects, patients with chronic periodontitis and patients with autoimmune disease, to identify epitope spreading. A peptide‐specific T‐cell line was established for phenotype analysis and for proliferation assay to an array of identical peptides. An identical prospective analysis was performed in P. gingivalis‐induced experimental periodontitis or in Pep19‐immunized mice. Cross‐reactivity of anti‐Pep19 monoclonal antibody was also investigated.
Results
A dominant immune response exclusively to Pep19 prevailed in healthy human subjects (before the age of 40) and mice that persisted in chronic periodontitis and autoimmune diseases without being replaced further by subsequent subdominant epitopes. A sequential epitope spreading provoked by Pep19 to subdominant autoantigen peptide 19 from human HSP60 (Hu19) in most healthy human subjects and mice, and to autoantigen peptide 9 from human HSP60 (Hu9) and neoantigen oxidized low‐density lipoprotein (ox‐LDL) in P. gingivalis‐induced chronic periodontitis and autoimmune diseases could be demonstrated in a reproducible and predictable manner. T‐cell proliferative activity to multiple autoantigens Hu19, Hu9 and ox‐LDL, and cross‐reactivity of anti‐Pep19 monoclonal antibody to these epitopes may be proposed as cellular and molecular mechanisms responsible for the phenomenon. Moreover, the predictive value of Pep19 for Hu9 increased remarkably in the disease group when compared with that of the healthy group.
Conclusion
Taken together, epitope spreading to Hu19, Hu9 and ox‐LDL provoked by Pep19 could be proposed as a solid phenomenon observed in P. gingivalis‐induced chronic periodontitis and infection‐induced autoimmune diseases in a reproducible and predictable manner. T‐cell proliferative activity to these peptides and cross‐reactivity of anti‐Pep19 antibodies to multiple human autoantigens could be proposed as cellular and molecular mechanisms responsible for this phenomenon.
The aim of this study was to explore the phenotypic differences underpinning obesity susceptibility or resistance based on the metabolic and transcriptional profiling of C57BL/6J mice fed a high-fat ...diet (HFD).
The mice were fed either a normal diet or HFD for 12 weeks. After 6 weeks, the mice on HFD were classified as either obesity-prone (OP) or obesity-resistant (OR) depending on the body weight gain.
Lipid profiles from plasma and liver significantly improved in OR mice relative to the OP group. Energy expenditure was greater in OR mice than in OP mice, with a simultaneous decrease in body fat mass. Epididymal white adipose tissue (eWAT) and liver were enlarged in OP mice (with visible immune-cell infiltration), but these effects were attenuated in OR mice compared with OP mice. Overall glucose metabolism was enhanced in OR mice compared with OP mice, including homeostasis model assessment for insulin resistance, plasma glucose and insulin concentrations, glucokinase activity and hepatic glycogen. Plasma adipokines and proinflammatory cytokines were upregulated in OP mice, and these changes were attenuated in OR mice. Transcriptomic profiles of eWAT and liver revealed common and divergent patterns of transcriptional changes in OP and OR mice, and pointed to differential metabolic phenotypes of OP and OR mice. There were substantial differences between OP and OR mice in molecular pathways, including atherosclerosis signaling, sperm motility, cAMP-mediated signaling in eWAT; and fibrosis, agranulocyte adhesion and diapedesis, and atherosclerosis signaling in liver.
Taken altogether, the results provide robust evidence of major divergence in the transcriptomes, phenotypes and metabolic processes between obesity susceptibility and obesity resistance in the HFD-fed C57BL/6J mice.
This study used three-dimensional computed tomography and polysomnography to evaluate the effect of a large mandibular setback on the postoperative pharyngeal airway space and obstructive sleep ...apnoea (OSA). Twelve patients who underwent bimaxillary surgery for a mandibular setback movement of >9mm were included in this study. Changes in the pharyngeal airway space and polysomnography parameters based on the surgical movements were analyzed. The median mandibular setback movement was 11.08mm. The total pharyngeal, oropharyngeal, and hypopharyngeal volumes, and the retroglossal cross-sectional area were significantly decreased postoperatively (P=0.006; P=0.005; P=0.012; P=0.005, respectively). The apnoea–hypopnoea index (AHI) increased significantly after surgery (P=0.021). There were significant positive correlations between the preoperative inferiorly located hyoid bone and both AHI and respiratory disturbance index (RDI) postoperative (P=0.008 and P=0.027) and between the postoperative inferiorly dislocated retropalatal level and both AHI and RDI postoperative (P=0.002 and P=0.014). Four patients (33.3%) developed new onset OSA postoperatively. Large mandibular setback movements significantly reduced the pharyngeal airway space in the setting of bimaxillary surgery (P=0.006).
Anti-atherogenic effect of ferulic acid (0.02%, w/w) was investigated in comparison with the clofibrate (0.02%, w/w) in apolipoprotein E-deficient (apo E
−/−) mice fed Western diet. Concentrations of ...total cholesterol (total-C), apolipoprotein B (apo B) in the plasma and epididymal adipose tissue weight were significantly lower in the ferulic acid and clofibrate supplemented groups compared to the control group. The ratio of apo B to apo A-I was also significantly lower in those groups than in the control group. Activities of hepatic ACAT and HMG-CoA reductase were only significantly lower in the ferulic acid and clofibrate groups, respectively than in the control group. The numbers of mice that exhibited aortic fatty plaque were 8/10 in control groups vs. 0/10 in the ferulic acid or clofibrate group. The activities of anti-oxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and paraoxonase) in the hepatocyte and erythrocyte were significantly higher in the ferulic acid group than in the control group. In contrast, hepatic TBARS level was only markedly lower in the ferulic acid group. These results provide a new insight into the anti-atherogenic property of ferulic acid in the apo E
−/− mice fed a Western diet.
CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. This protein is implicated in motility, invasion, and metastasis of cancer cells, ...but the prevalence of CD151 expression in subtypes of breast cancers and its influence on clinical outcome remains to be evaluated.
The immunohistochemistry-based tissue microarray analysis showed that 127 (14.3%) cases overexpressed CD151 among 886 breast cancer patients. CD151 overexpression was found to be significantly associated with larger tumour size, higher nodal stage, advanced stage, absence of oestrogen receptor and progesterone receptor, and human epidermal growth factor receptor 2 overexpression. CD151 overexpression resulted in poorer overall survival (OS) (P<0.001) and disease-free survival (P=0.02), and stage II and III patients with CD151 overexpression demonstrated substantially poorer OS (P=0.0474 and 0.0169). In the five subtypes analyses, CD151 overexpression retained its adverse impact on OS in the Luminal A (P=0.0105) and quintuple-negative breast cancer (QNBC) subtypes, one subgroup of triple-negative breast cancer (P=0.0170). Multivariate analysis that included stage, subtype, and adjuvant chemotherapy showed that CD151 overexpression was independently associated with poor OS in invasive breast cancer.
CD151 overexpression may be a potential molecular therapeutic target for breast cancer, especially in QNBC subtype and more advanced stages of breast cancer.
Over the past two decades, the age of liver transplantation (LT) recipients has been increasing. We reviewed our experience with LT for patients aged ≥70 years (range: 70–78 years) and investigated ...the feasibility of performing LT, especially living donor LT (LDLT), for older patients. We retrospectively reviewed the medical records of 25 patients (15 LDLT recipients, 10 deceased donor LT recipients) aged ≥70 years who underwent LT from January 2000 to April 2016. Their perioperative morbidity rate was 28.0%, and the in‐hospital mortality rate was 16.0%; these results were comparable to those of matched patients in their 60s (n = 73; morbidity, p = 0.726; mortality, p = 0.816). For patients in their 70s, the 1‐ and 5‐year patient survival rates were 84.0% and 69.8%, and the 1‐ and 5‐year graft survival rates were 83.5% and 75.1%, respectively. Comparisons of patient and graft survival rates between matched patients in their 60s and 70s showed no statistically significant differences (patient survival, p = 0.372; graft survival, p = 0.183). Our experience suggests that patients aged ≥70 years should not be excluded from LT, or even LDLT, based solely on age and implies that careful selection of recipients and donors as well as meticulous surgical technique are necessary for successful results.
Patients aged 70 years or older should not be excluded from undergoing liver transplant or even living donor liver transplant based solely on chronological age.
The information on the frictional resistance of a self-propelled robotic capsule endoscope moving inside the body is very important for the design and the performance enhancement of such parameters ...of the capsule endoscope as power consumption, motion control and positioning accuracy. Based on this motivation, the ultimate goal of this research was to develop an analytical model that can predict the frictional resistance of the capsule endoscope moving inside the living body. In this work, experimental investigations of the fundamental frictional characteristics and the viscoelastic behaviors of the small intestine were performed by using custom-built testers and various capsule dummies. The small intestine of a pig was used for the experiments. Experimental results showed that the average frictional force was 10–50 mN and higher moving speed of the capsule dummy resulted in larger frictional resistance of the capsule. In addition, the friction coefficient did not change significantly with respect to the apparent area of contact between the capsule dummy and the intestine, and also the friction coefficients decreased with an increase in the normal load and varied from 0.08 to 0.2. Such frictional behaviors could be explained by the lubrication characteristics of the intestine surface and typical viscoelastic characteristics of the small intestine material. Also, based on the experimental results, a viscoelasticity model for the stress relaxation of the small intestine could be derived.
It is well known that high-fat diet (HFD) can cause immune system-related pathological alterations after a significant body weight gain. The mechanisms of the delayed pathological alterations during ...the development of diet-induced obesity (DIO) are not fully understood.
To elucidate the mechanisms underlying DIO development, we analyzed time-course microarray data obtained from a previous study. First, differentially expressed genes (DEGs) were identified at each time point by comparing the hepatic transcriptome of mice fed HFD with that of mice fed normal diet. Next, we clustered the union of DEGs and identified annotations related to each cluster. Finally, we constructed an 'integrated obesity-associated gene regulatory network (GRN) in murine liver'. We analyzed the epididymal white adipose tissue (eWAT) transcriptome usig the same procedure.
Based on time-course microarray data, we found that the genes associated with immune responses were upregulated with an oscillating expression pattern between weeks 2 and 8, relatively downregulated between weeks 12 and 16, and eventually upregulated after week 20 in the liver of the mice fed HFD. The genes associated with immune responses were also upregulated at late stage, in the eWAT of the mice fed HFD. These results suggested that a critical transition occurred in the immune system-related transcriptomes of the liver and eWAT around week 16 of the DIO development, and this may be associated with the delayed pathological alterations. The GRN analysis suggested that Maff may be a key transcription factor for the immune system-related critical transition thatoccurred at week 16. We found that transcription factors associated with immune responses were centrally located in the integrated obesity-associated GRN in the liver.
In this study, systems analysis identified regulatory network modules underlying the delayed immune system-related pathological changes during the development of DIO and could suggest possible therapeutic targets.
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