Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal ...fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca
is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.
Early and timely detection of surface damages is important for maintaining the functionality, reliability, and safety of concrete bridges. Recent advancement in convolution neural network has enabled ...the development of deep learning‐based visual inspection techniques for detecting multiple structural damages. However, most deep learning‐based techniques are built on two‐stage, proposal‐driven detectors using less complex image data, which could be restricted for practical applications and possible integration within intelligent autonomous inspection systems. In this study, a faster, simpler single‐stage detector is proposed based on a real‐time object detection technique, You Only Look Once (YOLOv3), for detecting multiple concrete bridge damages. A field inspection images dataset labeled with four types of concrete damages (crack, pop‐out, spalling, and exposed rebar) is used for training and testing of YOLOv3. To enhance the detection accuracy, the original YOLOv3 is further improved by introducing a novel transfer learning method with fully pretrained weights from a geometrically similar dataset. Batch renormalization and focal loss are also incorporated to increase the accuracy. Testing results show that the improved YOLOv3 has a detection accuracy of up to 80% and 47% at the Intersection‐over‐Union (IoU) metrics of 0.5 and 0.75, respectively. It outperforms the original YOLOv3 and the two‐stage detector Faster Region‐based Convolutional Neural Network (Faster R‐CNN) with ResNet‐101, especially for the IoU metric of 0.75.
A phototransistor based on a chemical vapor deposited (CVD) MoS2 monolayer exhibits a high photoresponsivity (2200 A W−1) and an excellent photogain (5000). The presence of shallow traps contributes ...to the persistent photoconductivity. Ambient adsorbates act as p‐dopants to MoS2, decreasing the carrier mobility, photoresponsivity, and photogain.
Bicalutamide (Bic) is frequently used in androgen deprivation therapy (ADT) for treating prostate cancer. ADT-induced hypogonadism was reported to have the potential to lead to acute kidney injury ...(AKI). ADT was also shown to induce bladder fibrosis via induction of the transforming growth factor (TGF)-β level. We hypothesized that Bic can likely induce renal fibrosis. To understand this, a cell model was used to explore expressions of relevant profibrotic proteins. Results indicated that Bic initiated multiple apoptotic and fibrotic pathways, including androgen deprivation, downregulation of the androgen receptor → phosphatidylinositol-3-kinase → Akt pathway, upregulation of the extrinsic apoptotic pathway- tumor necrosis factor α → nuclear factor κB → caspase-3, increased expressions of fibrosis-related proteins including platelet-derived growth factor β, fibronectin and collagen IV, and enhanced cell migration. The endoplasmic reticular stress pathway and smooth muscle actin were unaffected by Bic. Co-treatment with testosterone was shown to have an anti-apoptotic effect against Bic, suggesting a better outcome of Bic therapy if administered with an appropriate testosterone intervention. However, since Bic was found to inhibit the membrane transport and consumption rates of testosterone, a slightly larger dose of testosterone is recommended. In conclusion, these pathways can be considered to be pharmaceutically relevant targets for drug development in treating the adverse effects of Bic.
Standard inactivated influenza vaccines are poorly immunogenic in immunologically naive healthy young children, who are particularly vulnerable to complications from influenza. For them, there is an ...unmet need for better influenza vaccines. Oil-in-water emulsion-adjuvanted influenza vaccines are promising candidates, but clinical trials yielded inconsistent results. Here, we meta-analyze randomized controlled trials with efficacy data (3 trials, n = 15,310) and immunogenicity data (17 trials, n = 9062). Compared with non-adjuvanted counterparts, adjuvanted influenza vaccines provide a significantly better protection (weighted estimate for risk ratio of RT-PCR-confirmed influenza: 0.26) and are significantly more immunogenic (weighted estimates for seroprotection rate ratio: 4.6 to 7.9) in healthy immunologically naive young children. Nevertheless, in immunologically non-naive children, adjuvanted and non-adjuvanted vaccines provide similar protection and are similarly immunogenic. These results indicate that oil-in-water emulsion adjuvant improves the efficacy of inactivated influenza vaccines in healthy young children at the first-time seasonal influenza vaccination.
The gut microbiota-derived metabolite, trimethylamine N-oxide (TMAO) plays an important role in cardiovascular disease (CVD). The fasting plasma TMAO was shown as a prognostic indicator of CVD ...incident in patients and raised the interest of intervention targeting gut microbiota. Here we develop a clinically applicable method called oral carnitine challenge test (OCCT) for TMAO-related therapeutic drug efforts assessment and personalising dietary guidance.
A pharmacokinetic study was performed to verify the design of OCCT protocol. The OCCT was conducted in 23 vegetarians and 34 omnivores to validate gut microbiota TMAO production capacity. The OCCT survey was integrated with gut microbiome, host genotypes, dietary records and serum biochemistry. A humanised gnotobiotic mice study was performed for translational validation.
The OCCT showed better efficacy than fasting plasma TMAO to identify TMAO producer phenotype. The omnivores exhibited a 10-fold higher OR to be high TMAO producer than vegetarians. The TMAO-associated taxa found by OCCT in this study were consistent with previous animal studies. The TMAO producer phenotypes were also reproduced in humanised gnotobiotic mice model. Besides, we found the faecal
gene was not associated with TMAO production; therefore, other key relevant microbial genes might be involved. Finally, we demonstrated the urine TMAO exhibited a strong positive correlation with plasma TMAO (r=0.92, p<0.0001) and improved the feasibility of OCCT.
The OCCT can be used to identify TMAO-producer phenotype of gut microbiota and may serve as a personal guidance in CVD prevention and treatment.
NCT02838732; Results.
In first-line treatment of Helicobacter pylori, we have previously shown that the eradication frequency was 83·7% (95% CI 80·4–86·6) for triple therapy for 14 days (T14; lansoprazole 30 mg, ...amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily), 85·9% (82·7–88·6) for concomitant therapy for 10 days (C10; lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily), and 90·4% (87·6–92·6) for bismuth quadruple therapy for 10 days (BQ10; bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). In this follow-up study, we assess short-term and long-term effects of these therapies on the gut microbiota, antibiotic resistance, and metabolic parameters.
This was a multicentre, open-label, randomised trial done at nine medical centres in Taiwan. Adult patients (>20 years) with documented H pylori infection were randomly assigned (1:1:1, with block sizes of six) to receive T14, C10, or BQ10. We assessed long-term outcomes (reinfection frequency, changes in the gut microbiota, antibiotic resistance, and metabolic parameters) in patients with available data, excluding all protocol violators and those with unknown post-treatment H pylori status. Faecal samples were collected before treatment and 2 weeks, 2 months, and at least 1 year after eradication therapy. Amplification of the V3 and V4 hypervariable regions of the 16S rRNA was done followed by high-throughput sequencing. Susceptibility testing for faecal Escherichia coli and Klebsiella pneumoniae was done. This trial is complete and registered with ClinicalTrials.gov, NCT01906879.
Between July 17, 2013, and April 20, 2016, 1620 participants were randomly assigned to the three treatment groups (540 33% per group). 1214 (75%) attended 1-year follow-up and are included in this analysis. Compared with baseline, alpha diversity was significantly reduced 2 weeks after T14 (p=0·0002), C10 (p<0·0001), and BQ10 (p<0·0001) treatment. Beta diversity was also significantly altered 2 weeks after T14 (p=0·0010), C10 (p=0·0001), and BQ10 (p=0·0001). Alpha diversity and beta diversity were restored at week 8 (p=0·14 and p=0·918, respectively) and 1 year (p=0·14 and p=0·918) after T14, but were not fully recovered at week 8 and after 1 year in patients treated with C10 (p=0·0001 and p=0·013 at week 8; p=0·019 and p=0·064 at 1 year) and BQ10 (p<0·0001 and p=0·0002; p=0·001 and p=0·029). A transient increase at week 2 after T14 and C10 of the resistance rates of E coli to ampicillin-sulbactam (12% 15/127 to 66% 38/58 for T14, 7% 10/135 to 64% 28/44 for C10), cefazolin (13% 16/127 to 43% 25/58 for T14, 10% 13/135 to 41% 18/44 for C10), cefmetazole (8% 10/127 to 26% 15/58 for T14, 4% 5/135 to 18% 8/44 for C10), levofloxacin (8% 10/127 to 35% 20/58 for T14, 7% 10/135 to 32% 14/44 for C10), gentamicin (13% 19/146 to 47% 27/58 for T14, 15% 22/149 to 45% 20/44 for C10), and trimethoprim–sulfamethoxazole (33% 48/146 to 86% 50/58 for T14, 28% 42/148 to 86% 38/44 for C10; p<0·05 in paired samples in the above analyses) returned to basal state at week 8 and after 1 year. Although bodyweight and body-mass index slightly increased, there were significant improvements in metabolic parameters, with a decrease in insulin resistance, triglycerides, and LDL and an increase in HDL. Overall, there was no significant change in the prevalence of metabolic syndrome at week 8 and 1 year after T14, C10, and BQ10.
Eradication of H pylori infection has minimal disruption of the microbiota, no effect on antibiotic resistance of E coli, and some positive effects on metabolic parameters. Collectively, these results lend support to the long-term safety of H pylori eradication therapy.
National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.
Sweet potato (
) is one of the most important food crops worldwide and its leaves provide a dietary source of nutrients and various bioactive compounds. These constituents of sweet potato leaves ...(SPL) vary among varieties and play important roles in treating and preventing various diseases. Recently, more attentions in health-promoting benefits have led to several in vitro and in vivo investigations, as well as the identification and quantification of bioactive compounds in SPL. Among them, many new compounds have been reported as the first identified compounds from SPL with their dominant bioactivities. This review summarizes the current knowledge of the bioactive compositions of SPL and their health benefits. Since SPL serve as a potential source of micronutrients and functional compounds, they can be further developed as a sustainable crop for food and medicinal industries.
Extending Sadorsky (2010), this paper focuses on nonlinear effects of financial development and income on energy consumption. Utilizing five alternative measures of financial development, it employs ...a panel threshold regression approach to reexamine the effect of financial development and income on energy consumption. The analysis relies on a sample of 53 countries for the period 1999–2008, showing a single-threshold effect on energy consumption when private credit, domestic credit, value of traded stocks, and stock market turnover are used as financial development indicators. It implies that the sample can be split into two regimes: high income, and non-high income. Energy consumption increases with income in emerging market and developing economies, while in advanced economies energy consumption increases with income beyond a point at which the economy achieves a threshold level of income. In addition, in the non–high income regime, energy consumption increases with financial development when both private and domestic credit are used as financial development indicators. However, when the value of traded stocks and stock market turnover are used as financial development indicators, it slightly declines with financial development in advanced economies, especially in high-income countries, but increases in the higher income countries of emerging market and developing economies.
•Utilizing five alternative measures of financial development.•To split into two regimes: high income, and non-high income.•In non–high income, energy consumption increases with private and domestic credit.•In high income of advanced economies, it declines with stock market development.
Delirium is a critical and highly prevalent problem among critically ill patients. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening ...Checklist (ICDSC) are the most recommended assessment tools for detecting intensive care unit (ICU) delirium.
To synthesize the current evidence and compared the diagnostic accuracy of the two tools in the detection of delirium in adults in ICUs.
Systematic review and meta-analysis.
A comprehensive search of the following electronic databases was performed using PubMed, Embase, CINAHL and ProQuest Dissertations and Theses A&I. The date range searched was from database inception to April 26, 2019.
Two researchers independently identified articles, systematically abstracted data and evaluated the sensitivity and specificity of the CAM-ICU or the ICDSC against standard references. Bivariate diagnostic statistical analysis with a random-effects model was performed to summarize the pooled sensitivity and specificity of the two tools.
In total, 29 CAM-ICU and 12 ICDSC studies were identified. The pooled sensitivity was 0.84 and 0.83 and pooled specificity was 0.95 and 0.87 for the CAM-ICU and the ICDSC, respectively. The CAM-ICU had higher summary specificity than the ICDSC did (p = 0.04). The percentage of hypoactive delirium, ICU type, use of mechanical ventilation, number of participants, and female percentage moderated the accuracy of the tools. Most of the domains of patient selection, index test, reference standards, and flow and timing were rated as having a low or unclear risk of bias.
Although both the CAM-ICU and the ICDSC are accurate assessment tools for screening delirium in critically ill patients, the CAM-ICU is superior in ruling out patients without ICU delirium and detecting delirium in patients in the medical ICU and those receiving mechanical ventilation. Further investigations are warranted to validate our findings. The study protocol is registered at PROSPERO (CRD42020133544).
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