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Neutrophil extracellular traps (NETs) play important roles in sepsis and deep-seated infections, but whether NET formation correlates with clinical outcomes of patients with streptococcal bloodstream infections (BSIs) is unclear.We analyzed serum levels of complexes of myeloperoxidase and DNA (MPO-DNA) in patients with streptococcal-BSIs. In vitro assay of NET induction by serum from BSI patients was performed.MPO-DNA values for the Streptococci-BSI group (n = 59) were significantly higher than those for healthy controls (p 0.00001) and matched control groups (n = 59, p = 0.004). The rate of higher MPO-DNA levels (1.87 μg/mL) were higher in abscess-prone streptococcal groups (streptococcus milleri group) (72.2% vs. 52.5%, p = 0.02). For patients with BSIs due to highly infective endocarditis (IE)-prone pathogens, the values of serum MPO-DNA were also higher in patients diagnosed of IE compared to their counterparts (p = 0.009). Notably, serum from patients with leukopenia could induce higher amounts of in vitro NET formation, despite having low MPO-DNA levels, suggesting that NET formation could be influenced by WBC counts. Therefore, we combined WBC counts with MPO-DNA to predict all-cause 30-day mortality in patients with commensal streptococcal-BSIs. The mortality risk was lowest among patients who had neither high MPO-DNA levels nor abnormal WBC counts (p = 0.058). Furthermore, this group of patients also had a favorable composite outcome consisting of major adverse cardiovascular events (MACE) and all-cause mortality (p = 0.026).Together, these study data suggested that serum MPO-DNA can be a biomarker for predicting a composite outcome consisting of MACE and all-cause mortality in patients with commensal streptococcal-BSIs.

Background Hepatitis C increases the mortality and morbidity of patients after heart transplant. Direct-acting antivirals (DAAs) are the primary drugs for hepatitis C treatment. However, such drugs are expensive and frequently unaffordable for patients. In DAA treatment, the assessment of drug interaction is crucial. Methods We investigated a retrospective case series study from January 2017 to December 2019. Sustained virologic response 12 (SVR12) was used to assess the effectiveness of DAA treatment. Data on patients’ demographic information, timing of hepatitis C virus (HCV) infection (before or after heart transplant), HCV genotypes and viral loads, DAAs used (branded drugs or generic drugs), and drug interaction assessments were collected. Results Fifteen heart transplant patients received hepatitis C treatments during the study period, 11 of whom were infected because their donors had hepatitis C. After DAA treatment, HCV was undetectable in all patients, and 93.3% of them achieved SVR12. Nine patients used the generic sofosbuvir/velpatasvir, and 88.9% of them achieved SVR12. A total of 256 drugs were used with DAAs; 51 records of drug interactions were noted, 3 of which were contraindications, and the remaining records were potential interactions. Patients who used sofosbuvir or elbasvir/grazoprevir experienced fewer drug interactions. Conclusions DAA treatment is effective for hepatitis C treatment in patients after heart transplant. Patients who cannot afford branded drugs because of their prices can use generic drugs as an alternative. Drug interactions must be surveyed during DAA treatment.

Blue carbon ecosystems (BCEs) are a promising resource for the mitigation of global warming; however, climate spectrums and anthropogenic activities could influence the fragile balance of BCEs as carbon sinks or sources. We assess how oyster farming affects dissolved inorganic carbon (DIC) and total alkalinity (TA) on CO

Computed tomography (CT)-determined skeletal muscle measures have been used for predicting postoperative outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). We investigated the impact of CT-determined muscle quantity (measured as psoas muscle area [PMA] and psoas muscle index [PMI]) and quality (measured as psoas muscle density [PMD]) on hospital length of stay (LOS) after TAVI.We retrospectively identified 182 consecutive patients who underwent TAVI between March 2013 and August 2017 with adequate preprocedural CT imaging. Baseline demographic and clinical data, the Society of Thoracic Surgeons score, the essential frailty toolset (EFT) frailty rating, and precontrast PMD, PMA, and PMI were obtained in all study patients. The primary outcome was prolonged postoperative LOS defined as greater than 14 days.Patients with prolonged LOS had a significantly higher Society of Thoracic Surgeons score (p0.001) and significantly lower PMD (p0.001) than those with LOS ≤14 days. More patients with prolonged LOS had concomitant peripheral vascular disease (p = 0.001), had undergone percutaneous coronary interventions (p = 0.022), and had an EFT score ≥4 (p0.001) compared to those without prolonged LOS. Neither PMA (p = 0.123) nor PMI (p = 0.271) were associated with prolonged LOS. Multivariate analysis identified EFT score ≥4, the presence of peripheral vascular disease, and PMD as independent predictors of prolonged LOS.The precontrast CT-determined muscle quality measurement PMD is a simple and objective predictor of prolonged LOS after TAVI.

Background Systemic lupus erythematosus (SLE) is associated with a higher risk of cardiovascular disease. However, it is not clear whether or not SLE is associated with poor outcomes after acute myocardial infarction (AMI). Methods and results Using the Taiwan National Health Insurance Database, we identified the SLE group as patients with AMI who have a concurrent discharge diagnosis of SLE. We also selected an age-, sex-, hospital level-, and admission calendar year-matched non-SLE group at a ratio of 1:3 from the total non-SLE group. One hundred fifty-one patients with SLE, 113,791 patients without SLE, and 453 matched patients without SLE were admitted with a diagnosis of AMI. Patients with SLE were significantly younger, predominantly female, and more likely to have chronic kidney disease than those without SLE. The in-hospital mortality rates were 12.6%, 9.0%, and 4.2% in the SLE, total non-SLE, and matched non-SLE groups, respectively. The in-hospital mortality was significantly higher in the SLE group than in the total non-SLE group (OR = 1.98; 95% CI = 1.2–3.26) and the matched non-SLE group (mortality OR = 2.20; 95% CI = 1.06–4.58). In addition, the SLE group was associated with a borderline significant risk of prolonged hospitalization when compared with the non-SLE group. Conclusion SLE is associated with a higher risk of in-hospital mortality and a borderline significantly higher risk of prolonged hospitalization after AMI.

Zika virus (ZIKV) is an emerging vector-borne virus that is associated with severe congenital cerebral anomalies in fetuses and paralytic Guillain-Barre syndrome in adults. In the current global health crisis, there are no vaccines or therapeutics available for the treatment of ZIKV infection. In the present study, we evaluated the efficacy of the protoberberine alkaloid, palmatine, in inhibiting ZIKV and Japanese encephalitis virus (JEV). Palmatine was shown to bind to restricted viruses, inhibit ZIKV infection, and resist ZIKV-induced cytopathic effects. Palmatine was also shown to inhibit JEV infection in multiple cell lines. Overall, the effects of palmatine in disrupting ZIKV binding, entry, and stability indicate that this small molecule would be a good starting point for the development of treatments aimed at inhibiting ZIKV infection.

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive deterioration of articular cartilage. There have been reports that small molecule inhibitors have anti-osteoarthritis effects; however, the effects of 3-(4-chloro-2-fluorophenyl)-6-(2,4-difluorophenyl)-2H-benzo[e] [1,3]oxazine-2,4(3H)-dione (Cm-02) and 6-(2,4-difluorophenyl)-3-(3,4-difluorophenyl)-2H-benzo[e] [1,3]oxazine-2,4(3H)-dione (Ck-02), small molecule inhibitors which share many structural similarities with quercetin (a potent anti-inflammatory flavonoid), remain unclear. In this study, TNF-α-stimulated porcine and human chondrocyte models were used to investigate the inhibitory effects of Cm-02 and Ck-02 on the molecular mechanisms underlying the anti-OA effects. TNF-α was used to stimulate porcine and human chondrocytes to mimic immunomodulatory potency in-vitro. Anti-osteoarthritic effects were characterized in terms of protein and mRNA levels associated with the pathogenesis of OA. We also examined (1) the inducible nitric oxide synthase (iNOS)-nitric oxide (NO) system in cultured chondrocytes, (2) matrix metalloproteinases (MMPs) in cultured chondrocytes, and (3) aggrecan degradation in cartilage explants. Finally, we tested the activation of nuclear factor-kappaB (NF-κB), interferon regulatory factor-1 (IRF-1), and activate the protein-1 (AP-1), and we tested the signal transduction and activation of transcription-3 (STAT-3). Our results indicate that, in chondrocytes, Cm-02 and Ck-02 inhibit TNF-α induced NO production, iNOS, MMP, the expression of disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), and the enzyme activity of MMP-13. Furthermore, both Cm-02 and Ck-02 were found to stimulate TNF-α, which has been shown to suppress the activation of several transcription factors, including NF-κB, STAT-3, and IRF-1 in porcine and human chondrocytes. Cm-02 and Ck-02 were also found to help prevent the release of proteoglycans from cartilage explants. Our findings demonstrate that both Cm-02 and Ck-02 have potent anti-inflammatory activities and the ability to protect cartilage in an OA cell model. These findings indicate that Cm-02 and Ck-02 have the potential to be further developed for the therapeutic treatment of OA.

The identification of prognostic markers for colorectal cancer (CRC) has important clinical implications. However, the association between meningioma 1 (MN1) expression and clinical outcomes of CRC has not been fully investigated. The aim of this study was to investigate the expression of MN1 in the clinical context of CRC. We first used immunohistochemistry (IHC) staining to examine and compare MN1 expression between multiple human cancer tissues and normal tissues. Initial screening revealed that the expression of MN1 proteins was significantly higher in tumor tissues of the breast, colon, and liver than in normal tissues. In further testing conducted on 59 paired CRC samples, we observed that the expression of MN1 in CRC tissue samples was significantly higher than in adjacent normal tissues. Moreover, high MN1 expression was not significantly associated with clinicopathological characteristics. Kaplan-Meier survival analysis revealed that high expression of MN1 mRNA or MN1 protein was significantly associated with poor CRC prognosis. Furthermore, univariate Cox analysis revealed that a high MN1 score was significantly associated with prognostic factors. Multivariate Cox analysis further indicated that gender, histologic grade, tumor-node-metastasis (TNM) stage, and a high MN1 score were independent factors of overall CRC survival rates. Finally, MN1 and PCNA protein levels were positively correlated, which suggests that MN1 may be involved in the cell proliferation process during CRC formation. Our results, which confirm those of other studies, indicate that (1) high levels of MN1 expression contribute to poor CRC prognosis and (2) MN1 can serve as a novel potential biomarker in predicting the prognosis of CRC patients.