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Purpose: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, crucial in infectious and inflammatory diseases by regulating IL-1ß, presents a target for disease management. Neisseria gonorrhoeae causes gonorrhea in over 87 million people annually, with previous research revealing NLRP3 inflammasome activation in infected macrophages. No natural products have been reported to counteract this activation. Exploring honokiol, a phenolic compound from Chinese herbal medicine, we investigated its impact on NLRP3 inflammasome activation in N. gonorrhoeae-infected macrophages. Methods: Honokiol's impact on the protein expression of pro-inflammatory mediators was analyzed using ELISA and Western blotting. The generation of intracellular H2O2 and mitochondrial reactive oxygen species (ROS) was detected through specific fluorescent probes (CM-H2DCFDA and MitoSOX, respectively) and analyzed by flow cytometry. Mitochondrial membrane integrity was assessed using specific fluorescent probes (MitoTracker and DiOC2(3)) and analyzed by flow cytometry. Additionally, the effect of honokiol on the viability of N. gonorrhoeae was examined through an in vitro colony-forming units assay. Results: Honokiol effectively inhibits caspase-1, caspase-11 and GSDMD activation and reduces the extracellular release of IL-1ß, NLRP3, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in N. gonorrhoeae-infected macrophages. Detailed investigations have demonstrated that honokiol lowers the production of H2O2 and the phosphorylation of ERK1/2 in N. gonorrhoeae-infected macrophages. Importantly, the phosphorylation of JNK1/2 and p38 and the activation of NF-κB remain unaffected. Moreover, honokiol reduces the N. gonorrhoeae-mediated generation of reactive oxygen species within the mitochondria, preserving their integrity. Additionally, honokiol suppresses the expression of the pro-inflammatory mediator IL-6 and inducible nitric oxide synthase induced by N. gonorrhoeae independently of NLRP3. Impressively, honokiol exhibits in vitro anti-gonococcal activity against N. gonorrhoeae. Conclusion: Honokiol inhibits the NLRP3 inflammasome in N. gonorrhoeae-infected macrophages and holds great promise for further development as an active ingredient in the prevention and treatment of symptoms associated with gonorrhea.
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BACKGROUND: Worldwide, more than 125 million people are infected with Shigella each year and develop shigellosis. In our previous study, we provided evidence that Shigella sonnei infection triggers activation of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome in macrophages. NLRP3 inflammasome is responsible for regulating the release of the proinflammatory cytokines interleukin (IL)-1ß and IL-18 through the protease caspase-1. Researchers and biotech companies have shown great interest in developing inhibitors of the NLRP3 inflammasome, recognizing it as a promising therapeutic target for several diseases. The leaves of Cinnamomum osmophloeum kaneh, an indigenous tree species in Taiwan, are rich in cinnamaldehyde (CA), a compound present in significant amounts. Our aim is to investigate how CA affects the activation of the NLRP3 inflammasome in S. sonnei-infected macrophages. METHODS: Macrophages were infected with S. sonnei, with or without CA. ELISA and Western blotting were employed to detect protein expression or phosphorylation levels. Flow cytometry was utilized to assess H2O2 production and mitochondrial damage. Fluorescent microscopy was used to detect cathepsin B activity and mitochondrial ROS production. Additionally, colony-forming units were employed to measure macrophage phagocytosis and bactericidal activity. RESULTS: CA inhibited the NLRP3 inflammasome in S. sonnei-infected macrophages by suppressing caspase-1 activation and reducing IL-1ß and IL-18 expression. CA also inhibited pyroptosis by decreasing caspase-11 and Gasdermin D activation. Mechanistically, CA reduced lysosomal damage and enhanced autophagy, while leaving mitochondrial damage, mitogen-activated protein kinase phosphorylation, and NF-κB activation unaffected. Furthermore, CA significantly boosted phagocytosis and the bactericidal activity of macrophages against S. sonnei, while reducing secretion of IL-6 and tumour necrosis factor following infection. CONCLUSION: CA shows promise as a nutraceutical for mitigating S. sonnei infection by diminishing inflammation and enhancing phagocytosis and the bactericidal activity of macrophages against S. sonnei.
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Police officers often face emotionally challenging interpersonal situations and numerous studies have demonstrated that policing is a stressful occupation. A study revealed a significant positive correlation between emotional demands among police officers and emotional dissonance, as well as burnout. Health-promoting behaviors can contribute to better overall health outcomes and reduce the risk of developing health problems, but there is limited research evaluating the association of job strain and health behaviors with mental health outcomes in police officers. The objective of this study was to assess the job strain associated with mental health mediated by health behaviors in Taiwanese police officers. This was a cross-sectional quantitative study conducted in Oct 2016. A total of 41,871 police officers (response rate was 79.7%) participated questionnaire that consisted of demographic information, job characteristics, health behaviors, and mental component summary (MCS) scores of the Short-Form Health Survey. Independent t-tests and one-way analysis of variance (One-way ANOVA) were conducted to assess the differences in mean MCS scores across various demographics, health behavior, and job characteristics. Multivariate regression analyses were used to assess the relationship between job strain and health behaviors with mental health outcomes. MCS scores were associated with job characteristics and health behaviors among police officers except for gender. After adjusting for covariates, multivariate analysis indicated that police officers with high job demands and high job strain index exhibited poor MCS scores. Job strain was significantly associated with MCS mediated by health behaviors (consumption of fruits and vegetables, and physical activity) in Taiwanese police officers. Since regular physical activity and increased vegetable and fruit consumption might alleviate the effects of job strain on mental health status, it is recommended that institutional policies be established to promote health-enhancing behaviors among police officers.
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Comportamentos Relacionados com a Saúde , Saúde Mental , Estresse Ocupacional , Polícia , Humanos , Polícia/psicologia , Masculino , Feminino , Adulto , Taiwan/epidemiologia , Estresse Ocupacional/epidemiologia , Estresse Ocupacional/psicologia , Estudos Transversais , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Background: Serum D-dimer level has been associated with worsening outcomes in patients with acute myocardial infarction. This study aimed to explore the association between serum D-dimer level and clinical outcomes in Taiwanese patients with acute myocardial infarction. Methods: We analyzed Tri-Service General Hospital-Coronary Heart Disease registry data related to patients with acute myocardial infarction who were admitted between January 2014 and December 2018. A total of 748 patients were enrolled and categorized into high (≥ 495 ng/ml) and low (< 495 ng/ml) D-dimer groups. The primary endpoint was in-hospital mortality, and secondary endpoints were post-discharge mortality and post-discharge major adverse cardiovascular events. Results: Overall, 139 patients died, with 77 from cardiovascular causes and 62 from non-cardiovascular causes. In-hospital mortality was higher in the high D-dimer group than in the low D-dimer group. Among the patients alive at discharge, those with a high D-dimer level had higher cardiovascular mortality and future major adverse cardiovascular events than those with a low D-dimer level. Multivariate Cox regression analysis revealed that higher serum D-dimer levels were significantly associated with higher risks of in-hospital mortality [hazard ratio (HR) = 1.11; 95% confidence interval (CI), 1.06-1.16, p < 0.001], subsequent cardiovascular mortality after discharge (HR = 1.15; 95% CI, 1.08-1.22, p < 0.001), and major adverse cardiovascular events (HR = 1.10; 95% CI, 1.04-1.16, p < 0.001). Conclusions: This is the first study in Taiwan to demonstrate that a higher baseline serum D-dimer level was independently associated with higher risks of in-hospital mortality, post-discharge mortality, and major adverse cardiovascular events in patients with acute myocardial infarction.
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BACKGROUND: Medical students need to build a solid foundation of knowledge to become physicians. Clerkship is often considered the first transition point, and clerkship performance is essential for their development. We hope to identify subjects that could predict the clerkship performance, thus helping medical students learn more efficiently to achieve high clerkship performance. METHODS: This cohort study collected background and academic data from medical students who graduated between 2011 and 2019. Prediction models were developed by machine learning techniques to identify the affecting features in predicting the pre-clerkship performance and clerkship performance. Following serial processes of data collection, data preprocessing before machine learning, and techniques and performance of machine learning, different machine learning models were trained and validated using the 10-fold cross-validation method. RESULTS: Thirteen subjects from the pre-med stage and 10 subjects from the basic medical science stage with an area under the ROC curve (AUC) >0.7 for either pre-clerkship performance or clerkship performance were found. In each subject category, medical humanities and sociology in social science, chemistry, and physician scientist-related training in basic science, and pharmacology, immunology-microbiology, and histology in basic medical science have predictive abilities for clerkship performance above the top tertile. Using a machine learning technique based on random forest, the prediction model predicted clerkship performance with 95% accuracy and 88% AUC. CONCLUSION: Clerkship performance was predicted by selected subjects or combination of different subject categories in the pre-med and basic medical science stages. The demonstrated predictive ability of subjects or categories in the medical program may facilitate students' understanding of how these subjects or categories of the medical program relate to their performance in the clerkship to enhance their preparedness for the clerkship.
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Estágio Clínico , Aprendizado de Máquina , Humanos , Estudos de Coortes , Estudantes de Medicina , Masculino , FemininoRESUMO
BACKGROUND/OBJECTIVE: Limited evidence exists regarding the socioeconomic inequalities in cerebrovascular disease (CBD) mortality at different urbanization levels. Therefore, this study was conducted to assess the socioeconomic inequalities and urbanization levels in township-based CBD mortality in Taiwan. METHODS: Socioeconomic variables, including the percentages of low-income households, individuals with a university education and above, and tax payments, were measured at the township level from 2011 to 2020. Urbanization was also determined by the national survey and divided into seven levels. Age-standardized mortality rate (ASMR) of CBD was calculated using a Geographic Information System (GIS) in 358 townships. The effects of socioeconomic variables and urbanization levels on relative and absolute inequalities in township-based CBD mortality rates were examined. RESULTS: Significant differences in ASMR of CBD were observed across all socioeconomic status indicators over the years. Higher proportions of low-income households were associated with higher ASMR of CBD. Conversely, there were negative correlations between higher proportions of individuals with a university education and above and tax payments with ASMR of CBD. The regression analysis indicated significant impacts of relative and absolute socioeconomic inequalities on ASMR of CBD. Additionally, a moderation effect of socioeconomic variables and urbanization on CBD mortality rates was observed, with rural areas showing sensitivity to these factors. CONCLUSION: Although ASMR of CBD showed significant decreases over time, socioeconomic inequalities in CBD mortality rates persist. Interventions targeting socioeconomic inequalities in health outcomes, especially in rural areas, are needed to address this issue.
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Transtornos Cerebrovasculares , Disparidades nos Níveis de Saúde , Classe Social , Urbanização , Humanos , Taiwan/epidemiologia , Transtornos Cerebrovasculares/mortalidade , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Fatores SocioeconômicosRESUMO
The intracellular sensor protein complex known as the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome plays a crucial role in regulating inflammatory diseases by overseeing the production of interleukin (IL)-1ß and IL-18. Targeting its abnormal activation with drugs holds significant promise for inflammation treatment. This study highlights LCZ696, an angiotensin receptor-neprilysin inhibitor, as an effective suppressor of NLRP3 inflammasome activation in macrophages stimulated by ATP, nigericin, and monosodium urate. LCZ696 also reduces caspase-11 and GSDMD activation, lactate dehydrogenase release, propidium iodide uptake, and the extracellular release of NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in ATP-activated macrophages, suggesting a potential mitigation of pyroptosis. Mechanistically, LCZ696 lowers mitochondrial reactive oxygen species and preserves mitochondrial integrity. Importantly, it does not significantly impact NLRP3, proIL-1ß, inducible nitric oxide synthase, cyclooxygenase-2 expression, or NF-κB activation in lipopolysaccharide-activated macrophages. LCZ696 partially inhibits the NLRP3 inflammasome through the induction of autophagy. In an in vivo context, LCZ696 alleviates NLRP3-associated colitis in a mouse model by reducing colonic expression of IL-1ß and tumor necrosis factor-α. Collectively, these findings suggest that LCZ696 holds significant promise as a therapeutic agent for ameliorating NLRP3 inflammasome activation in various inflammatory diseases, extending beyond its established use in hypertension and heart failure treatment.
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Aminobutiratos , Compostos de Bifenilo , Colite , Sulfato de Dextrana , Modelos Animais de Doenças , Inflamassomos , Macrófagos , Mitocôndrias , Proteína 3 que Contém Domínio de Pirina da Família NLR , Valsartana , Animais , Camundongos , Aminobutiratos/farmacologia , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo/farmacologia , Colite/tratamento farmacológico , Colite/induzido quimicamente , Colite/metabolismo , Sulfato de Dextrana/toxicidade , Combinação de Medicamentos , Inflamassomos/metabolismo , Inflamassomos/antagonistas & inibidores , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neprilisina/antagonistas & inibidores , Neprilisina/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Valsartana/farmacologia , MasculinoRESUMO
ABSTRACT: Wound soaking is a physical debridement method that helps reduce bacterial colonization and consequently promotes wound healing. Although soaking in povidone-iodine solution was ineffective in reducing bacterial colonization in acute trauma wounds, there is still a lack of evidence supporting the efficacy of this method in treating severe soft tissue infection. This study aimed to explore the effects of wound soaking in 1% dilute povidone-iodine solution on necrotizing fasciitis caused by diabetic foot ulcers. We retrospectively reviewed and finally included 153 patients who were admitted because of diabetic foot ulcers after undergoing fasciotomy for necrotizing infection from January 2018 to December 2021. Results showed no statistical difference in the outcomes between patients in the soaking and nonsoaking groups. End-stage renal disease (P = 0.029) and high serum C-reactive protein level (P = 0.007) were the only independent factors for below-knee amputation in the univariate and multivariate logistic regression analyses. Therefore, soaking diabetic wounds with severe infection in 1% dilute povidone-iodine solution may not reduce the hospital length of stay, risk of below-knee amputation, and readmission rate.
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Diabetes Mellitus , Pé Diabético , Fasciite Necrosante , Humanos , Povidona-Iodo/uso terapêutico , Pé Diabético/cirurgia , Fasciite Necrosante/cirurgia , Estudos Retrospectivos , CicatrizaçãoRESUMO
BACKGROUND: In the real-world setting, data regarding renal decline following sacubitril/valsartan treatment are lacking. This study aimed to develop a scoring system to predict renal outcome in sacubitril/valsartan-treated patients. METHODS: Between 2017 and 2018, a total of 1505 heart failure patients with reduced ejection fraction (HFrEF) undergoing sacubitril/valsartan treatment were consecutively enrolled from 10 hospitals to serve as the derivation cohort. Another 1620 HFrEF patients receiving sacubitril/valsartan were included as the validation cohort. Worsening renal function (WRF) was defined as a serum creatinine increase of >0.3â¯mg/dL and/or >25â¯% at 8â¯months of sacubitril/valsartan treatment. The derivation cohort was used to identify independent predictive factors for WRF through multivariate analysis, which were then used to develop the risk score system. RESULTS: Among the 3125 HFrEF patients, 689 (22.0â¯%) patients had WRF at 8â¯months following sacubitril/valsartan treatment. In the derivation cohort, six prognostic factors (age, functional class, history of peripheral arterial disease, diabetes mellitus, gout or hyperuricemia, and serum albumin level) were independently associated with WRF, and were combined into a risk predicting score. This score showed accurate discrimination in the derivation and validation cohorts (Harrell's concordance indexes 0.74 and 0.71, 95â¯% confidence intervals 0.71-0.78 and 0.69-0.74, respectively). Patients with a higher risk score experienced a more rapid decline in renal function, poorer clinical outcomes, and a higher rate of discontinuation of sacubitril/valsartan treatment. CONCLUSIONS: This study developed a score for WRF after sacubitril/valsartan treatment, which may assist clinicians with risk stratification and therapeutic decision-making.
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Insuficiência Cardíaca , Humanos , Volume Sistólico , Tetrazóis/efeitos adversos , Resultado do Tratamento , Valsartana/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Rim/fisiologia , Medição de Risco , Antagonistas de Receptores de Angiotensina/uso terapêuticoRESUMO
Gut microbiota play a key role in health maintenance and disease pathogenesis in animals. Dietary phytochemicals are crucial factors shaping gut bacteria. Here, we investigated the function and mechanism of a phytogenic formulation, EUBIO-BPSG (BP), in laying hens. We found that BP dose-dependently improved health and egg production in 54-week-old hens. Furthermore, BP was correlated with increased fecal Lactobacillus, decreased Escherichia coli and Salmonella enterica, and reduced antibiotic resistance (AR) and antibiotic resistance genes (ARG) in chicken stools. The 16S rDNA data showed that BP increased seven genera of probiotics and reduced 13 genera of pathogens in chicken feces. In vitro co-culture experiments showed that BP at 4 µg/mL and above promoted growth of L. reuteri while large 100- and 200-fold higher doses suppressed growth of E. coli and S. enterica, respectively. Mechanistic studies indicated that L. reuteri and its supernatants antagonized growth of E. coli and S. enterica but not vice-versa. Five short-chain fatty acids and derivatives (SCFA) produced from L. reuteri directly killed both pathogens via membrane destruction. Furthermore, BP inhibited conjugation and recombination of ARG via interference with conjugation machinery and integrase activity in E. coli. Collectively, this work suggests that BP promotes host health and reproductive performance in laying hens through regulation of gut microbiota through increasing probiotics and decreasing pathogens and spreading ARG.
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BACKGROUND: TGF-ß superfamily signaling is indispensable for bone homeostasis. However, the global expression profiles of all the genes that make up this signaling module in bone and bone-related diseases have not yet been well characterized. METHODS: Transcriptomic datasets from human bone marrows, bone marrow-derived mesenchymal stem cells (MSCs) and MSCs of primary osteoporotic patients were used for expression profile analyses. Protein treatments, gene quantification, reporter assay and signaling dissection in MSC lines were used to clarify the interactive regulations and feedback mechanisms between TGF-ß superfamily ligands and antagonists. Ingenuity Pathway Analysis was used for network construction. RESULTS: We identified TGFB1 in the ligand group that carries out SMAD2/3 signaling and BMP8A, BMP8B and BMP2 in the ligand group that conducts SMAD1/5/8 signaling have relatively high expression levels in normal bone marrows and MSCs. Among 16 antagonist genes, the dominantly expressed TGF-ß superfamily ligands induced only NOG, GREM1 and GREM2 via different SMAD pathways in MSCs. These induced antagonist proteins further showed distinct antagonisms to the treated ligands and thus would make up complicated negative feedback networks in bone. We further identified TGF-ß superfamily signaling is enriched in MSCs of primary osteoporosis. Enhanced expression of the genes mediating TGF-ß-mediated SMAD3 signaling and the genes encoding TGF-ß superfamily antagonists served as significant features to osteoporosis. CONCLUSION: Our data for the first time unveiled the transcription landscape of all the genes that make up TGF-ß superfamily signaling module in bone. The feedback mechanisms and regulatory network prediction of antagonists provided novel hints to treat osteoporosis. Video Abstract.
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Osteoporose , Transcriptoma , Humanos , Retroalimentação , Ligantes , Osteoporose/genética , Osso e Ossos , Fator de Crescimento Transformador betaRESUMO
Objective: The aim of this study was to investigate the application of sacubitril/valsartan in clinical practice and the utility of PREDICT-HF score for outcome prediction in Asian heart failure patients with difference risk profiles. Methods: The TAROT-HF study was a multicenter, single-arm, observational study. Totally 1,187 outpatients with HFrEF treated with sacubitril/valsartan were enrolled and categorized by: (1) high-risk group with ≥1 of the following three risk factors: old age (≥80 years), low baseline systolic blood pressure (<100 mmHg), and renal impairment (eGFR <30 ml/min/1.73 m2), and (2) standard-risk group, those who did not have any risk factors. Clinical outcomes were assessed using the PREDICT-HF risk model. Results: A total of 305 (25.7%) patients matched the criteria for the high-risk group. The event rates of cardiovascular death or first unplanned heart failure hospitalization (HFH) among the overall population, high-risk, and standard-risk groups were 13.7, 24.9, and 10.8 events per 100 patient-years, respectively. The C statistics for the PREDICT-HF model in the overall cohort and high-risk group for cardiovascular death or first unplanned HFH at 2 years were 0.73 (95% CI 0.70-0.76) and 0.71 (95% CI 0.65-0.76), respectively. The permanent discontinuation rate among the high-risk patients was significantly higher than that among the standard-risk patients (8.3 vs. 2.5 per 100 patient-years, p < 0.001). Conclusions: Real-world outcomes of the TAROT-HF study demonstrated that the PREDICT-HF model performed well in Asian HFrEF patients. Three easily detected clinical profiles of age, renal function, and systolic BP could help to identify patients at risk before initiating sacubitril/valsartan.
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BACKGROUND: Since the policy of "keeping trash off of the ground" in Taiwan, long-term exposure to repetitive motion in waste collection process results in high risk of upper extremity musculoskeletal disorders (UEMDs). Thus, we assessed the moderation and mediation effects of job-related stress and job support on work-related UEMDs among municipal waste collectors. METHODS: A cross-sectional study was conducted in two cities located at northern Taiwan during 2018-2019. 626 municipal waste collectors voluntarily participated and anonymously filled out a structured questionnaire. The moderation and mediation effects of effort-reward imbalance (ERI) and social support on UEMDs were analyzed by Haye's Process Macro Model. RESULTS: Prevalence of UEMDs in municipal waste collectors were 43.4% for neck, 56.0% for shoulder, 24.1% for upper back, and 33.1% for hand/wrist. There was high prevalence of shoulder (72.2%), neck (48%), and upper back (30%) in female workers compared to male, most significantly in shoulders. In univariate and multivariate analysis, high ERI and low job support were significantly associated with ORs of 3.11 (95% CI:1.58-6.13) for elbow, 2.79 (95% CI:1.39-5.56) for shoulder, 3.39 (95% CI:1.64-7.00) for upper back and 3.83 (95% CI:1.98-7.41) for hand/wrist. Prevalent UEMDs were positively associated with high ERI in municipal waste collectors but negatively with job support. The moderation effects of ERI and job support on UEMDs, of which the measured synergy index exceeded one, were 18.24 for shoulder, 3.32 for elbow, and 2.45 for hand/wrist, but mediation effects were not significant. CONCLUSIONS: This study found municipal waste collectors with work-related upper extremity disorders were significantly associated with work-related psychological risk factors. Therefore, waste collection cannot only to be improved by semi-automatic and automatic processes but immediate intervention programs for the reduction of psychological risk factors is needed promptly.
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Doenças Musculoesqueléticas , Doenças Profissionais , Estresse Ocupacional , Estudos Transversais , Feminino , Humanos , Masculino , Doenças Musculoesqueléticas/complicações , Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/epidemiologia , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Inquéritos e Questionários , Extremidade SuperiorRESUMO
AIMS: Sacubitril/valsartan (SAC/VAL) has been used in patients with heart failure and reduced ejection fraction (HFrEF), and cardiac resynchronization therapy (CRT) could benefit the HFrEF patients with wide QRS durations. This study aimed to evaluate the clinical impacts of SAC/VAL on reverse cardiac remodelling in CRT-eligible and CRT-ineligible HFrEF patients with different QRS durations. METHODS AND RESULTS: The TAROT-HF study was a multicentre, observational study enrolling patients who initiated SAC/VAL from 10 hospitals since 2017. Patients with baseline left ventricular ejection fraction (LVEF) ≤ 35% were classified into two groups: (i) Group 1: CRT-eligible group, patients with left bundle branch block (LBBB) morphology plus QRS duration ≥130 ms or non-LBBB morphology plus QRS duration ≥150 ms; and (ii) Group 2: CRT-ineligible group. Propensity score matching was performed to adjust for confounders, and 1168 patients were analysed. Baseline characteristics were comparable between the two groups. The improvements in LVEF and left ventricular end-systolic volume index (LVESVi) were more significant in Group 2 than in Group 1 after 1 year SAC/VAL treatment (LVEF: 8.4% ± 11.3% vs. 4.5% ± 8.1%, P < 0.001; change percentages in LVESVi: -14.4% ± 25.9% vs. -9.6% ± 23.1%, P = 0.004). LVEF improving to ≥50% in Groups 1 and 2 constituted 5.2% and 20.2% after 1 year SAC/VAL treatment (P < 0.001). Multivariate analyses showed that wide QRS durations were negatively associated with the reverse cardiac remodelling in these HFrEF patients with SAC/VAL treatment. CONCLUSION: Despite SAC/VAL treatment, wide QRS durations are associated with lower degrees of left ventricular improvement than narrow ones in the HFrEF patients. Optimal intervention timing for the CRT-eligible patients requires further investigation.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Terapia de Ressincronização Cardíaca/métodos , Volume Sistólico , Função Ventricular Esquerda , Remodelação Ventricular , Eletrocardiografia , Resultado do Tratamento , Bloqueio de Ramo , Arritmias Cardíacas/complicações , ValsartanaRESUMO
OBJECTIVES: Work-related stress (WRS) is significantly associated with health-related quality of life (HRQoL), but the amounts of evidence on differences of effort-reward imbalance (ERI) and job strain index (JSI) remain sparse and have limited generalizability. Therefore, we aimed to assess the association between ERI and JSI with HRQoL and assess the mediation effect of social support (JS) and over-commitment (OC) on this association in Taiwan's civil servants. MATERIAL AND METHODS: A cross-sectional national survey was given to registered civil servants in Taiwan - 20 046 civil servants from 647 institutions were enrolled using multistage stratified random cluster sampling. A web-questionnaire collected demographic information, job characteristics, and different indexes of ERI and job-control-demand-support (JCDS) models. Structural equation model (SEM) was used to examine the association between ERI and JSI with HRQoL, and the mediation effect of JS and OC on the associations. RESULTS: In the ERI model, ERI and OC were consistently negatively associated with the mental component score (MCS) (r = -0.46 and r = -0.37) and physical component score (PCS) (r = -0.45 and r = -0.34), which were higher than job demand (r = -0.28 and r = -0.22) and JSI (r = -0.38 and r = -0.29). Using hierarchical multiple regression analyses, ERI was significantly correlated with MCS and PCS, which was consistently higher than JSI. The ERI and JSI were significantly correlated with MCS (ß = -0.170 and ß = -0.140) and PCS (ß = -0.150 and ß = -0.082) using SEM analysis, whereas ERI was considerably higher than in JSI. In addition, OC and JS mediated the association between The ERI and JSI with HRQoL. CONCLUSIONS: We found the ERI index is significantly correlated with HRQoL superior to JSI, in particular among Taiwan civil servants. Further longitudinal studies are needed to determine the causality and spatiotemporal relation of these differences. Int J Occup Med Environ Health. 2022;35(4):425-36.
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Estresse Ocupacional , Qualidade de Vida , Estudos Transversais , Humanos , Satisfação no Emprego , Estresse Ocupacional/epidemiologia , Recompensa , Estresse Psicológico/epidemiologia , Inquéritos e QuestionáriosRESUMO
Aberrant activation of the NLRP3 inflammasome promotes the pathogenesis of many inflammatory diseases. The development of the NLRP3 inflammasome inhibitors from existing drugs for new therapeutic purposes is becoming more important. Candesartan is an angiotensin II receptor antagonist widely used as a blood pressure-lowering drug; however, the inhibitory potential of candesartan on the NLRP3 inflammasome has not yet been investigated. We demonstrated that candesartan significantly inhibited the NLRP3 inflammasome and pyroptosis in macrophages. Mechanistic analysis revealed that candesartan inhibited the expression of NLRP3 and proIL-1ß by suppressing NF-κB activation and reducing the phosphorylation of ERK1/2 and JNK1/2. Candesartan reduced mitochondrial damage and inhibited the NLRP3 inflammasome assembly by suppressing NLRP3 binding to PKR, NEK7 and ASC. In addition, candesartan inhibited IL-1ß secretion partially through autophagy induction. Furthermore, oral administration of candesartan reduced peritoneal neutrophil influx, NLRP3 and ASC expression in peritoneal cells, and lavage fluid concentrations of active caspase-1, IL-1ß, IL-6 and MCP-1 in uric acid crystal-injected mice. These results indicated that candesartan has board anti-inflammatory effects and has the potential to be repositioned to ameliorate inflammatory diseases or NLRP3-associated complications.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Antagonistas de Receptores de Angiotensina , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Benzimidazóis , Compostos de Bifenilo , Reposicionamento de Medicamentos , Inflamassomos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , TetrazóisRESUMO
Trichloroethylene (TCE) is commonly used in various industries. If wastewater in factories is not effectively treated, the inflow into and subsequent contamination of underground water is likely. Our study assessed the association of exposure to TCE in underground water with oxidative stress and renal tubule damage. We selected 579 residents from areas with underground water contaminated with TCE. Each participant was interviewed via a questionnaire. We also assessed their urinary trichloroacetic acid (TCA) levels by gas chromatography (GC)-FID. Urinary malondialdehyde (MDA) and N-acetyl-ß-D-glucosaminidase (NAG) were taken as indicators of oxidative stress and renal tubule damage. We found about 73% of the residents to have consumed underground water. The average duration of consumption was 26 years, with an average of 1.6 L per day. Currently, only 1.5% of the residents still continuously consume underground water. The consumption of underground water positively correlated with heightened urinary TCA levels (r = 0.554). Heightened urinary TCA levels, in turn, were positively associated with NAG levels (r = 0.180) but negatively associated with MDA levels (r = -0.193). The results held even after we had segmented urinary TCA levels into three groups of different levels. The elimination of the source of heightened TCE levels from various industrial effluents is essential. Residents exposed to TCE-laden underground water should periodically undergo health inspections.
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ABSTRACT: Ectopic pregnancy is the most common cause of maternal mortality in the first trimester of pregnancy. The aim of this study was to find risk factors and clinical characteristics associated with ruptured ectopic pregnancies at a medical center in eastern Taiwan in a 19-year period. This was a retrospective observational study that included patients diagnosed with ectopic pregnancy between August 1999 and December 2018. Data about the demographic variables, initial presentation, pre-treatment beta-human chorionic gonadotropin levels, treatment routes (laparoscopy or laparotomy), surgical methods (salpingostomy or salpingectomy), operation time, blood loss amount, the status of ectopic pregnancy (ruptured or unruptured), the requirement for transfusion, and duration of hospital stay were collected. The categorical and continuous variables were analyzed using the correlation coefficients. This study included 225 women who were diagnosed as having an ectopic pregnancy. There were 49 and 176 women with unruptured and ruptured ectopic pregnancies, respectively. The beta-human chorionic gonadotropin levels, history of previous ectopic pregnancy, pelvic inflammatory disease, tubal surgery, abdominal history, and vaginal bleeding were not significantly different between the 2 groups. The ratio of women with abdominal pain was significantly higher in the ruptured ectopic pregnancy group than in the unruptured group (89.1% vs. 63.8%, respectively, Pâ<â.001). Preoperative hemoglobin was lower in the ruptured group compared with the unruptured group (Pâ<â.001). Blood loss, postoperative hemoglobin, and blood transfusion were significantly higher in the ruptured group than in the unruptured group (Pâ=â.000 and Pâ=â.001 for blood loss and blood transfusion, respectively). Multiple logistic regression analysis revealed that abdominal pain and blood loss were associated with ruptured tubal pregnancies (adjusted odds ratio [95% confidence intervals]: 3.42 {1.40, 8.40}; 1.01 {1.005, 1.014}, respectively). In conclusion, early pregnancy with abdominal pain, more parity, and lower preoperative hemoglobin should be aware of the possibility of ruptured ectopic pregnancy. More blood loss, transfusion and lower postoperative hemoglobin were also noted with ruptured ectopic pregnancy.
Assuntos
Gravidez Ectópica , Gravidez Tubária , Dor Abdominal/epidemiologia , Dor Abdominal/etiologia , Gonadotropina Coriônica Humana Subunidade beta , Feminino , Humanos , Gravidez , Gravidez Ectópica/diagnóstico , Gravidez Ectópica/epidemiologia , Gravidez Ectópica/cirurgia , Gravidez Tubária/epidemiologia , Gravidez Tubária/cirurgia , Fatores de Risco , Ruptura/complicaçõesRESUMO
Objective: Evidence indicated that shift work is a contributing factor to risk of obesity and leads to cardiovascular diseases (CVDs), but few researches have examined the moderating effects of job demand and contingent work schedule on overweight and obesity. Thus, we assessed the modification effect of contingent work schedules and job demand on overweight and obesity among Taiwan's civil servants. Methods: Multistage stratified random cluster sampling was used based on a proportional probabilistic sampling (PPS) in a national survey for civil servants. A total of 20,046 participants from 647 registered governmental institutions were enrolled and anonymously and voluntarily filled out web-based questionnaires. Results: Compared to fixed work schedule, odd ratios (ORs) of obesity and overweight were 1.63 and 1.78 times in contingent work schedule, respectively. In addition, the modification effects of contingent work schedule and high job demand on overweight and obesity with Rothman's synergy index were 2.43 and 2.56, respectively. Using a hierarchical regression model adjusted for covariates, both high job demand and contingent work schedule were interactively associated with overweight and obesity compared to low job demand and fixed work schedule. Conclusion: Since precarious schedules affect employee's obesity through work-related stress and unhealthy behaviors, further research is needed to determine whether interventions aimed at modification of work schedule may be useful in combating obesity.