ABSTRACT
Protein growth differentiation factor 11 (GDF11) plays crucial roles in cellular processes, including differentiation and development; however, its clinical relevance in breast cancer patients is poorly understood. We enrolled 68 breast cancer patients who underwent surgery at our hospital and assessed the expression of GDF11 in tumorous, ductal carcinoma in situ (DCIS), and non-tumorous tissues using immunohistochemical staining, with interpretation based on histochemical scoring (H-score). Our results indicated higher GDF11 expressions in DCIS and normal tissues compared to tumorous tissues. In addition, the GDF11 H-score was lower in the patients with a tumor size ≥ 2 cm, pathologic T3 + T4 stages, AJCC III-IV stages, Ki67 ≥ 14% status, HER2-negative, and specific molecular tumor subtypes. Notably, the patients with triple-negative breast cancer exhibited a loss of GDF11 expression. Spearman correlation analysis revealed associations between GDF11 expression and various clinicopathological characteristics, including tumor size, stage, Ki67, and molecular subtypes. Furthermore, GDF11 expression was positively correlated with mean corpuscular hemoglobin concentration and negatively correlated with neutrophil count, as well as standard deviation and coefficient of variation of red cell distribution width. These findings suggest that a decreased GDF11 expression may play a role in breast cancer pathogenesis.
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BACKGROUND: In Indonesia, the number of Type 2 diabetes cases is increasing rapidly, making it the third leading cause of death and among the leading noncommunicable disease healthcare expenditures in the country. Thus, there is a critical need for Indonesians with Type 2 diabetes to perform better self-care to optimize their health and prevent the onset of comorbidities. PURPOSE: This study was designed to investigate the influence of knowledge, depression, and perceived barriers on Type 2 diabetes self-care performance in Indonesia. METHODS: A cross-sectional study was conducted on 185 patients with Type 2 diabetes, with demographic, diabetes history, obesity status, diabetes knowledge, depression, perceived barriers, and self-care performance data collected. The Indonesian version of the Revised Diabetes Knowledge Test, Depression Anxiety Stress Scale, Perceived Barrier Questionnaire and Self-Care Inventory-Revised were used. Descriptive, bivariate, and multiple linear regression analyses were performed. RESULTS: Study participants were found to have moderate diabetes self-care performance scores. Annual eye checks, blood glucose self-monitoring, healthy diet selection, and regular exercise were the least common self-management techniques performed and were consistent with the perceived difficulties of the participants. Being illiterate or having an elementary school education (ß = 4.59, p = .002), having a junior or senior high school education (ß = 3.01, p = .006), having moderate depression (ß = -0.92, p = .04), diabetes knowledge (ß = 0.09, p = .006), and perceived barriers (ß = 0.31, p < .001) were found to explain 40% of the variance in self-care performance. Educational level, depression, and perceived barriers were the strongest factors that impacted Type 2 diabetes self-care performance in this study. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Nurses should not only provide diabetes education but also identify barriers to diabetes self-care early, screen for the signs and symptoms of depression, and target patients with lower levels of education.
Subject(s)
Diabetes Mellitus, Type 2 , Southeast Asian People , Humans , Diabetes Mellitus, Type 2/complications , Cross-Sectional Studies , Self Care , ObesityABSTRACT
Objective: Breast cancer is the second most common malignancy globally and a leading cause of cancer death in women. Analysis of factors related to disease-free survival (DFS) has improved understanding of the disease and characteristics related to recurrence. The aim of this study was to investigate the predictors of DFS in patients with breast cancer to enable the identification of patients at high risk who may benefit from prevention interventions. Methods: We retrospectively analyzed 559 women with breast cancer who underwent treatment between 2004 and 2022. The study endpoint was DFS. Recurrence was defined as local recurrence, regional recurrence, distant metastases, contralateral breast cancer, other second primary cancer, and death. Baseline tumor-related characteristics, treatment-related characteristics, sociodemographic and biochemical data were analyzed using Cox proportional hazards analysis. Results: The median DFS was 45 months (range, 2 to 225 months). Breast cancer recurred in 86 patients (15.4%), of whom 10 had local recurrence, 10 had regional recurrence, 17 had contralateral breast cancer, 29 had distant metastases, 10 had second primary cancer, and 10 patients died. Multivariate forward stepwise Cox regression analysis showed that AJCC stage III, Ki67 ≥14%, albumin, platelet, and red cell distribution width-standard deviation (RDW-SD) were predictors of worse DFS. In addition, the effects of albumin, platelet, and RDW-SD on disease recurrence were confirmed by structural equation model (SEM) analysis. Conclusion: In addition to the traditional predictors of worse DFS such as AJCC stage III and Ki67 ≥14%, lower pretreatment circulating albumin, higher pretreatment circulating platelet count and RDW-SD could significantly predict worse DFS in this study, and SEM delineated possible causal pathways and inter-relationships of albumin, platelet, and RDW-SD contributing to the disease recurrence among Chinese women with breast cancer.
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Background: Transcription factor 21 (TCF21, epicardin, capsuling, pod-1) is expressed in the epicardium and is involved in the regulation of cell fate and differentiation via epithelial-mesenchymal transformation during development of the heart. In addition, TCF21 can suppress the differentiation of epicardial cells into vascular smooth muscle cells and promote cardiac fibroblast development. This study aimed to explore whether TCF21 gene (12190287G/C) variants affect coronary artery disease risk. Methods: We enrolled 381 patients who had stable angina, 138 with ST elevation myocardial infarction (STEMI), and 276 healthy subjects. Genotyping of rs12190287 of the TCF21 gene was performed. Results: Higher frequencies of the CC genotype were found in the patients with stable angina/STEMI than in the healthy controls. After adjusting for diabetes mellitus, hypertension, age, sex, smoking, body mass index and hyperlipidemia, the patients with the CC genotype of the TCF21 gene were associated with 2.49- and 9.19-fold increased risks of stable angina and STEMI, respectively, compared to the patients with the GG genotype. Furthermore, TCF21 CC genotypes showed positive correlations with both stable angina and STEMI, whereas TCF21 GG genotypes exhibited a negative correlation with STEMI. Moreover, the stable angina and STEMI patients with the CC genotype had significantly elevated high-sensitivity C-reactive protein levels than those with the GG genotype. In addition, significant associations were found between type 2 diabetes mellitus, hypertension, and hyperlipidemia with TCF21 gene polymorphisms (p for trend < 0.05). Conclusion: TCF21 gene polymorphisms may increase susceptibility to stable angina and STEMI.
Subject(s)
Angina, Stable , Diabetes Mellitus, Type 2 , Hyperlipidemias , Hypertension , ST Elevation Myocardial Infarction , Humans , Angina, Stable/genetics , ST Elevation Myocardial Infarction/genetics , China , Basic Helix-Loop-Helix Transcription Factors/geneticsABSTRACT
BACKGROUND: Mannose-binding lectin (MBL) has been associated with cardiovascular disease and its complications, the progression of diabetic nephropathy, and complement-mediated renal interstitial injury. However, the relationship between plasma MBL concentration with both heart failure and renal function is unclear. In this study, we examined associations of plasma MBL with both renal function and heart failure in patients with stable coronary artery disease (CAD). METHODS: We enrolled 348 consecutive stable CAD patients and used ELISA to evaluate plasma concentrations of MBL. Renal function was classified into KDIGO G1, G2 and G3a-G4 groups according to the eGFR of ≥ 90, 60-89 and 15-59, ml/min/1.73 m2, respectively. Patients with a left ventricular ejection fraction (LVEF) ≤ 40 % were classified to have heart failure. RESULTS: A significant positive association was found between MBL with diabetes mellitus, current smoker, blood urea nitrogen, creatinine, and brain natriuretic peptide, and a significant negative association was found between MBL with eGFR and LVEF. KDIGO stage G3a-G4 and heart failure increased along with tertiles of MBL (p for trend < 0.05). Multivariate analysis showed that compared to the patients with a low MBL concentration, the odds ratios of having KDIGO stage G3a-G4 were 1.89 (1.01-3.55) times and 2.37 (1.25-4.59) times higher for those with medium and high MBL concentrations. Furthermore, compared to the patients with a low MBL concentration, the OR of having heart failure were 1.97 (1.01-3.93) times higher for those with high MBL concentrations. Moreover, multivariate analysis showed an independent association between plasma MBL concentration with both KDIGO stage G3a-G4 and heart failure (LVEF < 40 %). In addition, the effect of MBL on both LVEF and eGFR was confirmed by structural equation model analysis. CONCLUSION: There are associations between circulating MBL concentration with both heart failure and renal function in stable CAD patients, suggesting that increased plasma MBL may contribute to the pathogenesis of both chronic kidney disease and heart failure.
Subject(s)
Cardiovascular Diseases , Coronary Artery Disease , Heart Failure , Humans , Coronary Artery Disease/complications , Stroke Volume , Ventricular Function, Left , Heart Failure/complicationsABSTRACT
Patients with coronavirus disease 2019 (COVID-19) has been isolated in hospital-managed isolation hotels under a policy of the Taiwan government. Centrally isolation patients are more likely to experience psychological symptoms. The purpose of the study was to investigate emotional disturbance during their isolation period and then pinpoint the factors during their isolation period associated with the emotional disturbance. We retrospectively analysed the medical charts of the patients confined to a Banqiao isolation hotel between May 28 and July 3, 2021. The 5-item brief symptom rating scale (BSRS-5) was used to evaluate emotional disturbance levels. Descriptive and logistic regression was used for the data analysis. In total, 197 complete medical records were reviewed, and of these 84 (42.6%) showed emotional disturbance. The majority of them reported only minor disturbance (n = 49, 58.3%). After controlling for confounding factors, being satisfied about medical information was the only protective factor associated with emotional disturbance (OR = 0.2, P = 0.018). Being a male patient (OR = 3.0, P = 0.005), worrying about stigmatization (OR = 2.2, P = 0.041) and being unable to contact family members (OR = 2.9, P = 0.018) increased the risk of experiencing emotional disturbance. Patients with clinical symptoms, namely sore throat (OR = 3.4, P = 0.013) and muscle aches (OR = 6.3, P = 0.005), were also found to be more likely to report emotional disturbance. Mental disturbance commonly occurs among patient with COVID-19 who are isolated in a hospital-managed hotel. Being a male patient, having symptoms, namely a sore throat and muscle pain, being unable to contact family and/or a failure to receive sufficient medical information were found to be associated with emotional disturbance. In order to help isolated patients, government officials should provide a clear rationale for isolation and recognize the patients' efforts to follow the government's policy, which will help to minimize social stigma.
Subject(s)
COVID-19 , Humans , Male , SARS-CoV-2 , Affective Symptoms , Retrospective Studies , Risk FactorsABSTRACT
Introduction: Of all psychiatric disorders, schizophrenia is associated with the highest risk of all-cause mortality. This study aimed to investigate independent risk factors for all-cause mortality in patients with chronic schizophrenia. In addition, the possible causal inter-relationships among these independent risk factors and all-cause mortality were also explored. Methods: We conducted an analysis of 1,126 patients with chronic schizophrenia from our psychiatric department from April 2003 to August 2022, and retrospectively reviewed their medical records. The study endpoint was all-cause mortality. Baseline clinical characteristics including sociodemographic data, biochemical data, lifestyle factors, comorbidities and antipsychotic treatment were examined with Cox proportional hazards analysis. Results: The all-cause mortality rate was 3.9% (44 patients). Multivariate Cox regression analysis revealed that several factors were independently associated with all-cause mortality, including diabetes mellitus (DM), hypertension, heart failure, gastroesophageal reflux disease (GERD), peptic ulcer disease, ileus, underweight, fasting glucose, triglycerides, albumin, and hemoglobin. Structural equation modeling (SEM) analysis revealed that several factors had statistically significant direct effects on all-cause mortality. Heart failure, hypertension, underweight, age at onset, and ileus showed positive direct effects, while albumin and hemoglobin demonstrated negative direct effects. In addition, several factors had indirect effects on all-cause mortality. GERD indirectly affected all-cause mortality through ileus, and peptic ulcer disease had indirect effects through albumin and ileus. Ileus, underweight, DM, and hypertension also exhibited indirect effects through various pathways involving albumin, hemoglobin, and heart failure. Overall, the final model, which included these factors, explained 13% of the variability in all-cause mortality. Discussion: These results collectively suggest that the presence of DM, hypertension, heart failure, GERD, peptic ulcer disease, ileus, and underweight, along with lower levels of albumin or hemoglobin, were independently associated with all-cause mortality. The SEM analysis further revealed potential causal pathways and inter-relationships among these risk factors contributing to all-cause mortality in patients with chronic schizophrenia.
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Natural leaf senescence is an acclimation strategy that enables plants to reallocate nutrients. In the present study, interestingly, we found that the basal mature leaves of grapevine primary shoots (P) exhibited the earliest senescence, followed by the apical young leaves of secondary shoots (ST), and then the basal mature leaves of secondary shoots (S). The Chl level decreased with the extent of leaf senescence. According to the genome-wide identification and expression analysis, sixteen senescence-associated genes (SAGs) involved in Chl breakdown were identified in the grapevine genome. Their expression patterns showed that the transcript changes in VvSGR, VvPPH2, and VvFtsH6-2 corresponded to the changes in Chl content among P, S, and ST. The changes in the transcription of VvNYC1, VvSGR, VvPAO1, VvPAO2, VvPAO4, VvPPH1, VvPPH3, and VvFtsH6-1 only contributed to low Chl levels in P. The cis-element analysis indicated that these SAGs possessed several light- and hormone-responsive elements in their promoters. Among them, ABA-responsive elements were found in twelve of the sixteen promoters of SAGs. Correspondingly, ABA-signaling components presented various changes in transcription among P, S, and ST. The transcription changes in VvbZIP45 and VvSnRK2.1 were similar to those in VvSGR, VvPPH2, and VvFtsH6-2. The other nine ABA-signaling components, which included VvRCAR2, VvRCAR4, VvRCAR6, VvRCAR7, VvRCAR2, VvPP2C4, VvPP2C9, VvbZIP25, and VvSnRK2.3, were highly expressed in P but there was no difference between S and ST, with similar expression patterns for VvNYC1, VvSGR, VvPAO1, VvPAO2, VvPAO4, VvPPH1, VvPPH3, and VvFtsH6-1. These results suggested that the senescence of P and ST could be regulated by different members of Chl breakdown-related SAGs and ABA-signaling components. These findings provide us with important candidate genes to further study the regulation mechanism of leaf senescence order in grapevine.
Subject(s)
Vitis , Vitis/metabolism , Abscisic Acid/metabolism , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Senescence , Plant Leaves/metabolismABSTRACT
Background: Obesity and cognitive function decline are independent risk factors for chronic kidney disease (CKD). However, few studies have examined the combined effects of obesity status and cognitive function on change in CKD risk. We aimed to evaluate the association between obesity status, cognitive function and CKD risk change in patients with type 2 diabetes mellitus (T2DM). Methods: Data on 3399 T2DM patients were extracted from a diabetes disease management program between 2006 and 2018. Univariate and multivariate analyses were used to assess the association between obesity, cognitive decline, and CKD risk change. Three indexes, including the relative excess risk of interaction (RERI), attributable proportion of interaction (API), and synergy index (SI), were used to analyze interactions. CKD risk was classified according to the KDIGO 2012 CKD definition. Results: In multivariate analysis, the hazard ratio (HR, 95%Cis) for CKD risk progression was 1.34 (1.12-1.61) times higher in the moderate and severely obese patients compared with the normal weight patients, and 1.34 (1.06-1.67) times higher in the patients with a Mini-Mental State Examination (MMSE) score ≤18 compared to those with an MMSE score ≥24. There was a synergistic interaction between moderate and severe obesity and MMSE score ≤18 on CKD risk progression (SI=4.461; 95% CI: 1.998-9.962), and the proportion of CKD risk progression caused by this interaction was 52.7% (API=0.527; 95% CI: 0.295-0.759). However, normal weight and MMSE score ≥24 were not beneficial on CKD risk improvement in the patients with a moderate risk and very high-risk stage of CKD. Conclusion: There may be a synergistic interaction between obesity and cognitive function decline, and the synergistic interaction may increase the risk of CKD progression.
Subject(s)
Cognitive Dysfunction , Diabetes Mellitus, Type 2 , Renal Insufficiency, Chronic , Cognition , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/etiology , Cohort Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Disease Progression , Glomerular Filtration Rate , Humans , Obesity/complications , Obesity/epidemiology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Risk FactorsABSTRACT
BACKGROUND: Growth differentiation factor 1 (GDF1) is a member of the transforming growth factor-ß (TGF-ß) superfamily and a protective mediator against the development of post-infarction cardiac remodeling by negatively regulating MEK-ERK1/2 and Smad signaling pathways in the heart. The TGF-ß/SMAD pathway has been shown to play a key role in the development of hepatic fibrosis. In addition, fatty liver disease has been associated with reduced MEK/ERK1/2 signaling. However, no previous study has investigated the association between GDF1 and liver fibrosis. Therefore, the aim of this study was to investigate the association between plasma GDF1 and liver fibrosis in patients with stable angina. METHODS: We included 327 consecutive patients with stable angina. ELISA was used to measure circulating levels of GDF1, and the fibrosis-4 index was used to assess liver fibrosis. RESULTS: The advanced liver fibrosis group had lower median plasma GDF1 levels than those with minimal liver fibrosis. There was a significant negative association between GDF1 plasma level and fibrosis-4 index (r = -0.135, p = 0.019). A lower concentration of GDF1 was significantly and independently associated with an increased risk of liver fibrosis when concentration was analyzed as a continuous variable and by tertile. In addition, fibrosis-4 index, aspartate aminotransferase (AST)-to-platelet ratio index, and AST/alanine aminotransferase ratio were significantly associated with GDF1 concentration. CONCLUSIONS: Our results indicated an association between low plasma GDF1 and liver fibrosis in the enrolled patients. Further investigations into the role of plasma GDF1 in the pathogenesis of liver fibrosis are warranted.
Subject(s)
Angina, Stable , Growth Differentiation Factor 1 , Liver Cirrhosis , Humans , Growth Differentiation Factor 1/blood , Liver/metabolism , Liver Cirrhosis/complications , Liver Cirrhosis/pathology , Mitogen-Activated Protein Kinase Kinases/metabolism , Smad Proteins/metabolism , Transforming Growth Factor beta/metabolismABSTRACT
BACKGROUND: Fibroblast growth factor 21 (FGF21) is produced by cardiac cells, may acts in an autocrine manner, and was suggested to has a cardioprotective role in atherosclerosis. Wide QRS complex and heart rate-corrected QT interval (QTc interval) prolongation are associated to dangerous ventricular arrhythmias and cardiovascular disease mortality. Yet, the role of FGF21 in cardiac arrhythmia has never been studied. The aim of the study was to investigate the relationship between plasma FGF21 and the QRS duration and QTc interval in patients with stable angina. METHODS: Three hundred twenty-one consecutive stable angina patients were investigated. Plasma FGF21 was measured through ELISA, and each subject underwent 12-lead electrocardiography. RESULTS: FGF21 plasma levels were positively associated with the QRS duration (ß = 0.190, P = 0.001) and QTc interval (ß = 0.277, P < 0.0001). With increasing FGF21 tertiles, the patients had higher frequencies of wide QRS complex and prolonged QTc interval. After adjusting for patients' anthropometric parameters, the corresponding odd ratios (ORs) for wide QRS complex of the medium and high of FGF21 versus the low of FGF21 were 1.39 (95% CI 0.51-3.90) and 4.41 (95% CI 1.84-11.59), respectively, and p for trend was 0.001. Furthermore, multiple logistic regression analysis also showed the corresponding odd ratios (ORs) for prolonged QTc interval of the medium and high of FGF21 versus the low of FGF21 were 1.02 (95% CI 0.53-1.78) and 1.93 (95% CI 1.04-3.60) respectively with the p for trend of 0.037. In addition, age- and sex-adjusted FGF21 levels were positively associated with fasting glucose, HbA1c, creatinine, and adiponectin, but negatively associated with albumin, and the estimated glomerular filtration rate. CONCLUSIONS: This study indicates that plasma FGF21 is associated with wide QRS complex and prolonged corrected QT interval in stable angina patients, further study is required to investigate the role of plasma FGF21 for the underlying pathogenesis.
Subject(s)
Angina, Stable , Fibroblast Growth Factors , Long QT Syndrome , Humans , Adiponectin , Albumins , Arrhythmias, Cardiac , Creatinine , Electrocardiography , Electrolytes , Fibroblast Growth Factors/metabolism , Glucose , Glycated HemoglobinABSTRACT
BACKGROUND & AIMS: Aging is a pathophysiological process driven by a diverse set of complex biological processes, and environmental pollution plays an important role in this process. This study aimed to explore the association between serum α-Klotho levels and urinary perchlorate, nitrate, and thiocyanate levels. METHODS: This secondary dataset analysis included 4875 participants (mean age, 57.69 year; male, 49.58%; non-Hispanic White, 47.67%) from the US National Health and Nutrition Examination Survey (2007-2014). Enzyme-linked immunosorbent assay was used to quantify α-Klotho levels, and ion chromatography coupled with electrospray tandem mass spectrometry was used to quantify thiocyanate, nitrate, and perchlorate levels. Multivariate linear regression models were applied to estimate the association between perchlorate, nitrate, and thiocyanate levels and serum α-Klotho levels. RESULTS: Urinary thiocyanate levels were negatively associated with α-Klotho levels (ß = - 0.006; 95% confidence interval, - 0.010 to - 0.003; P = 0.0004) after adjusting for age, sex, body mass index, race, alcohol consumption, estimated glomerular filtration rate, underlying disease, physical activity, smoking status, usual energy intake, and urinary creatinine and serum cotinine levels and mutual adjustment of urinary perchlorate, urinary nitrate, and urinary thiocyanate levels. The α-Klotho level in participants in the highest quartile was higher by 50.567 ng/mL (ß = 50.567; 95% confidence interval, 14.407 to 86.726; P = 0.009) than that in participants in the lowest quartile of urinary perchlorate. A linear relationship was observed between urinary thiocyanate and α-Klotho levels. CONCLUSIONS: Urinary thiocyanate levels were negatively associated with serum α-Klotho levels. Urinary thiocyanate should be further investigated as a potential mediator of aging and age-related diseases.
Subject(s)
Perchlorates , Thiocyanates , Environmental Exposure/adverse effects , Humans , Male , Nitrates/urine , Nutrition Surveys , Perchlorates/urine , Thiocyanates/urineABSTRACT
A urine albumin/creatinine ratio (UACR) <30 mg/g is considered to be normal, while increased risk of incident hypertension and cardiovascular disease mortality in subjects with high normal UACR level had been observed. However, a mild elevated but normal UACR level was associated with the risk of initiating chronic kidney disease (CKD) is uncertain. We investigated whether higher normal UACR is associated with the risk of developing CKD. A total of 4821 subjects with type 2 diabetes mellitus (T2DM), an estimated glomerular filtration rate >60 ml/min/1.73 m2 and UACR <30 mg/g enrolled in a diabetes disease management program between 2006 and 2020 were studied. The optimal cutoff point for baseline UACR as a predictor for progression to CKD according to the 2012 KDIGO definition was calculated using receiving operating characteristic curve analysis. After a mean of 4.9 years follow-up, the CKD risk progression increased in parallel with the quartiles of baseline UACR <30 mg/g (p for trend <0.0001). UACR cutoff points of 8.44 mg/g overall, 10.59 mg/g in males and 8.15 mg/g in females were associated with the risk of CKD progression. In multivariate Cox regression analysis, the hazard ratios for the association between UACR (>8.44 mg/g, >10.9 mg/g, >8.15 mg/g in overall, male, and female patients, respectively) and the risk of CKD progression were significant. This study demonstrated that a cutoff UACR value of >10 mg/g could significantly predict the cumulative incidence and progression of CKD in patients with T2DM.
Subject(s)
Diabetes Mellitus, Type 2 , Renal Insufficiency, Chronic , Albumins , Albuminuria/complications , Albuminuria/epidemiology , Creatinine , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Female , Humans , Male , Renal Insufficiency, Chronic/complicationsABSTRACT
The ω-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to attenuate inflammation processes, whereas the molecular mechanisms remain unclear. This study was aimed at figuring out the differential effects of EPA and DHA on fatal arrhythmias and whether the signaling pathway could be a target after myocardial infarction, an inflammatory status. Male Wistar rats after ligating coronary artery were randomized to either vehicle, EPA, or DHA for 4 weeks. Postinfarction was associated with increased myocardial norepinephrine levels and sympathetic innervation. Furthermore, infarction was associated with the activation of NLRP3 inflammasomes and increased the protein and expression of IL-1ß and nerve growth factor (NGF). These changes were blunted after adding either EPA or DHA with a greater extent of EPA than DHA. Immunoblotting and immunohistochemical analysis showed that EPA had significantly lower phosphorylation of PPARγ at Ser 112 compared with DHA. Arrhythmic severity during programmed stimulation in the infarcted rats treated with EPA was significantly lower than those treated with DHA. Specific inhibition of GPR120 by AH-7614 and PPARγ by T0070907 reduced the EPA-or DHA-related attenuation of IL-1ß and NGF release. Besides, AH-7614 treatment partially reduced the PPARγ levels, whereas T0070907 administration did not affect the GPR120 levels. These results suggest that EPA was more effective than DHA in prevention of fatal arrhythmias by inhibiting NLRP3 inflammasome and sympathetic innervation through activation of PPARγ-mediated GPR120-dependent and -independent signaling pathways in infarcted hearts.
Subject(s)
Eicosapentaenoic Acid , Myocardial Infarction , Animals , Docosahexaenoic Acids/metabolism , Docosahexaenoic Acids/pharmacology , Eicosapentaenoic Acid/metabolism , Eicosapentaenoic Acid/pharmacology , Inflammasomes/metabolism , Male , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Nerve Growth Factor , PPAR gamma/metabolism , Rats , Rats, WistarABSTRACT
BACKGROUND: In intensive care units, patient death can have a negative psychological influence on the patient's nurse. However, how the frequency of events and factors contributed to acute stress among nurses remains unknown. OBJECTIVE: The objective of this study was to explore the prevalence of and the factors affecting acute stress disorder among intensive care unit nurses after their patient death. METHODS: Nurses from five adult intensive care units whose patient had died during the nurses' working shift were recruited from July 2018 to April 2019. Bryant's Acute Stress Disorder Scale, the Beck Anxiety Inventory, and the Beck Depression Inventory-II were used to measure acute stress, depression, and anxiety. Descriptive statistics, chi-square tests, independent sample t-tests, and stepwise logistic regression were used for data analysis. RESULTS: In total, 119 nurses were enrolled. Nearly one in three nurses (29.4%) had suffered from acute stress disorder after their patient had died. Nurses experienced a higher risk of acute stress disorder when their patients underwent cardiopulmonary resuscitation before death (odds ratio [OR] = 13.75, 95% confidence interval [CI]: 2.59-72.95), when their patients died unexpectedly (OR = 4.88, 95% CI: 1.16-20.56), and when they experienced verbal abuse from the patient family at the patient death (OR = 4.61, 95% CI: 1.18-18.05) compared with their counterparts. CONCLUSION: Intensive care unit nurses often experience acute stress disorder after their patient death. The nurses of patients who underwent cardiopulmonary resuscitation before death and/or who died unexpectedly and/or nurses who were subjected to verbal abuse by the patient's family were at higher risk of acute stress disorder. A comprehensive program aimed at improving the knowledge, skills, and resilience of nurses is needed.
Subject(s)
Critical Care Nursing , Nurses , Stress Disorders, Traumatic, Acute , Adult , Critical Care , Humans , Intensive Care UnitsABSTRACT
BACKGROUND: High electromechanical activation time (EMAT) is associated with paroxysmal atrial fibrillation and heart failure. Little is known about the association between EMAT and metabolic syndrome (MetS), a precursor of cardiovascular disease. OBJECTIVES: To explore the association between EMAT and MetS. METHODS: A total of 429 male volunteers were divided into MetS (n = 135, age 60.3 ± 3.7 years) and non-MetS (n = 294, age 58.1 ± 26.6 years) groups in this cross-sectional study. A complete medical history, fasting blood analysis and phonoelectrocardiographic parameters were recorded. EMAT was defined as the time from the onset of Q- wave to the peak first heart sound (Q-S1 interval), and this interval divided by the R-R interval for heart rate correction was calculated as normalized EMAT (nEMAT). RESULTS: The subjects with MetS had a significantly higher rate of positive nEMAT (nEMAT ≥ 15%: 6.7% vs. 2%, p = 0.015), higher heart rate (HR, 71.9 ± 12.0 vs. 69.2 ± 11.1 bpm, p = 0.022) but shorter left ventricular ejection time (LVST = 312.4 ± 33.5 vs. 319.8 ± 31.8 msec, p = 0.029). However, the normalized LVST (nLVST) was not significantly different after adjusting for HR. In multivariate analysis, nEMAT was significantly associated with MetS (odds ratio = 3.43, 95% confidence interval = 1.195-9.837, p = 0.022). CONCLUSIONS: Positive nEMAT, a prolonged early phase of contraction, was significantly associated with MetS in males. High nEMAT may be an earlier sign of cardiac function abnormality in MetS.
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Background: Higher concentrations of plasma fatty acid-binding protein 3 (FABP3) play a role in the development of cardiovascular events, cerebrovascular deaths, and acute heart failure. However, little is known about the relationship between plasma FABP3 level and prolonged QT interval and reduced ejection fraction (EF). This study aimed to investigate the relationship between plasma FABP3 level and prolonged corrected QT (QTc) interval and reduced EF in patients with stable angina. Inflammatory cytokine and adipocytokine levels were also measured to investigate their associations with plasma FABP3. Methods: We evaluated 249 consecutive patients with stable angina. Circulating levels of FABP3 were measured by ELISA. In addition, 12-lead ECG and echocardiography recordings were obtained from each patient. Results: Multiple regression analysis showed that high-density lipoprotein cholesterol, high sensitivity C-reactive protein (hs-CRP), white blood cell (WBC) count, visfatin, adiponectin, FABP4, heart rate, QTc interval, left atrial diameter, left ventricular mass index, end-systolic volume, end-systolic volume index, fractional shortening, and EF were independently associated with FABP3 (all p<0.05). Patients with an abnormal QTc interval had a higher median plasma FABP3 level than those with a borderline and normal QTc interval. With increasing FABP3 tertiles, the patients had higher frequencies of abnormal QTc interval, left ventricular systolic dysfunction, and all-cause mortality, incrementally lower EF, higher WBC count, and higher levels of hs-CRP, visfatin, adiponectin, and FABP4. Conclusion: This study indicates that plasma FABP3 may act as a surrogate parameter of prolonged QTc interval and reduced EF in patients with stable angina, partially through the effects of inflammation or cardiomyocyte injury. Further studies are required to elucidate whether plasma FABP3 plays a role in the pathogenesis of QTc prolongation and reduced EF.
Subject(s)
Angina, Stable/complications , Fatty Acid Binding Protein 3/blood , Long QT Syndrome/diagnosis , Ventricular Dysfunction, Left/diagnosis , Aged , Aged, 80 and over , Angina, Stable/blood , Angina, Stable/physiopathology , Angina, Stable/surgery , Biomarkers/blood , Echocardiography , Electrocardiography , Female , Follow-Up Studies , Humans , Long QT Syndrome/blood , Long QT Syndrome/etiology , Long QT Syndrome/physiopathology , Male , Middle Aged , Percutaneous Coronary Intervention , Prospective Studies , Stroke Volume/physiology , Ventricular Dysfunction, Left/blood , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathologyABSTRACT
Background: Chronic kidney disease (CKD) is a major risk factor for coronary artery disease and it is often associated with hepatic steatosis. Hepassocin (also known as hepatocyte-derived fibrinogen related protein or fibrinogen-like 1) is a novel hepatokine that causes hepatic steatosis and induces insulin resistance. However, the role of hepassocin in renal function status remains unclear. Our objective was to investigate the association of plasma hepassocin level with fatty liver and renal function status in patients with stable angina. Methods: Plasma hepassocin levels were determined by enzyme-linked immunosorbent assays in 395 consecutive patients with stable angina. Renal function was defined as an estimated glomerular filtration rate (eGFR). Fatty liver was defined by ultrasonography and fibrosis-4 (FIB-4) index. Results: With increasing hepassocin tertiles, patients had higher prevalence of fatty live, an increased waist-to-hip ratio, and neutrophil count, monocyte count, and FIB-4 index, higher levels of uric acid, blood urine nitrogen and higher sensitivity C-reactive protein. They also had incrementally lower eGFR, serum hemoglobin and albumin levels. In multiple linear stepwise regression analysis, only eGFR was significantly independent negatively associated with plasma hepassocin levels. Conclusion: Our results indicate that circulating hepassocin in patients with stable angina is associated with fatty liver and renal function, which suggests that increased plasma hepassocin may be involved in the pathogenesis of fatty liver and CKD.
Subject(s)
Angina, Stable/etiology , Fibrinogen/analysis , Non-alcoholic Fatty Liver Disease/blood , Renal Insufficiency, Chronic/blood , Aged , Aged, 80 and over , Angina, Stable/blood , Biomarkers/blood , Female , Glomerular Filtration Rate/physiology , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnosis , Prospective Studies , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/physiopathology , Risk FactorsABSTRACT
BACKGROUND: Total p-cresylsulfate (PCS), indoxyl sulfate (IS) and hippuric acid (HA) are harmful uremic toxins known to be elevated in patients with uremia. Serum total PCS, IS and HA levels have been associated with coronary atherosclerosis, left ventricular hypertrophy, metabolic acidosis, neurological symptoms, and accelerated renal damage associated with chronic kidney disease; however, no study has examined the effect of total PCS, IS and HA on hemodialysis (HD) quality indicators. The aim of this study was to examine associations among total PCS, IS and HA with HD quality indicators in patients undergoing HD treatment. METHODS: This study included 264 consecutive patients at a single HD center who assessed using previously demonstrated HD quality indicators including anemia, bone-mineral metabolism, dialysis dose, cardiovascular risk, and middle molecule removal area. Serum HA was measured using a capillary electrophoresis method. Serum total PCS and IS concentrations were measured using an Ultra Performance LC System. RESULTS: Multiple regression analysis showed that sex, potassium, systolic blood pressure (SBP), average BP, ß2-microglobulin, and creatinine were independently positively associated with IS level, and that age, total cholesterol, and estimated glomerular filtration rate (eGFR) was independently negatively associated with IS level. In addition, ß2-microglobulin was independently positively associated with total PCS. Moreover, potassium, diastolic blood pressure, average BP, ß2-microglobulin, dialysis vintage, and albumin were independently positively associated with HA level, and age, transferrin saturation, fasting glucose, and eGFR were independently negatively associated with HA level. When the patients were stratified by age and sex, serum IS and HA levels were still independently associated with some hemodialysis quality indicators. In addition, canonical correlation analysis also confirmed the relationship between uremic toxins (IS and HA) and HD quality indicators (potassium, ß2-microglobulin, average BP, creatinine, and eGFR). CONCLUSION: This study demonstrated that uremic toxins (IS and HA) and HD quality indicators (potassium, ß2-microglobulin, average BP, creatinine, and eGFR) constructs were correlated with each other, and that there were sex and age differences in these associations among maintenance HD patients.
Subject(s)
Indican , Uremia , Cresols , Hippurates , Humans , Quality Indicators, Health Care , Renal Dialysis , Sulfuric Acid EstersABSTRACT
Background: Diabetes mellitus is the leading cause of diabetic nephropathy and a major public health issue worldwide. Approximately 20-30% of patients with type 2 diabetes mellitus (T2DM) have renal impairment. Fatty acid-binding protein 1 (FABP1) is expressed in renal proximal tubule cells and released into urine in response to hypoxia caused by decreased peritubular capillary blood flow, and FABP2 is responsible for the transport of free fatty acids in the intestinal endothelium cells. There is increasing evidence that FABP1 and FABP 2 play a role in the development and progression of chronic kidney disease. The aim of this study was to investigate the relation of circulating FABP1 and FABP2 levels to nephropathy in patients with T2DM. Methods: For this study, 268 subjects with T2DM who were enrolled in a disease management program were stratified according to urinary microalbumin and serum creatinine measurements. The plasma FABP1 and FABP2 concentrations were examined by enzyme-linked immunosorbent assay. Demographic and potential metabolic confounding factors were analyzed with logistic regression to calculate the effects of FABP1 and FABP2 levels on diabetic nephropathy. Results: The FABP1 and FABP2 levels increased in parallel with the advancement of diabetic nephropathy. Increasing concentrations of FABP1 and FABP2 were independently and significantly associated with diabetic nephropathy. Multiple logistic regression analysis revealed FABP1 and FABP2 as an independent association factor for diabetic nephropathy, even after full adjustment of known biomarkers. Furthermore, receiver operating characteristic curve analysis showed that a FABP1 level of >33.8 ng/mL and a FABP2 level of >2.8 ng/mL were associated with diabetic nephropathy. Conclusion: Our results suggest that FABP1 and FABP2 may be novel biomarkers of diabetic nephropathy.