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Aims: Limited evidence exists regarding the association of selenium with risk of death in individuals with nonalcoholic fatty liver disease (NAFLD). This study was designed to investigate the relationship between dietary selenium intake with mortality in a nationally representative sample of United States adults with NAFLD. Methods: Dietary selenium intake was assessed in 2274 NAFLD adults younger than 60 years of age from the National Health and Nutrition Examination Survey (NHANES) III through a 24-hour dietary recall. NAFLD was diagnosed by liver ultrasound after excluding liver disease due to other causes. Cox proportional hazards models were utilized to assess the effect of dietary selenium intake on all-cause and cardiovascular mortality among individuals with NAFLD. Results: At a median follow-up of 27.4 years, 577 deaths occurred in individuals with NAFLD, including 152 cardiovascular deaths. The U-shaped associations were discovered between selenium intake with all-cause (Pnolinear = 0.008) and cardiovascular mortality (Pnolinear < 0.001) in adults with NAFLD after multivariate adjustment, with the lowest risk around selenium intake of 121.7 or 125.9 μg/day, respectively. Selenium intake in the range of 104.1–142.4 μg/day was associated with a reduced risk of all-cause mortality and, otherwise, an increased risk. Selenium intake in the range of 104.1–150.6 μg/day was associated with a reduced risk of cardiovascular death and, otherwise, an increased risk. Conclusions: Both high and low selenium intake increased the risk of all-cause and cardiovascular death in adults younger than 60 years of age with NAFLD, which may help guide dietary adjustments and improve outcomes in adults with NAFLD. [ABSTRACT FROM AUTHOR]

Current evidences show that regional anesthesia is associated with decreased risk of complications after major surgery. However, the effects of combined regional-general anesthesia remain controversial. The purpose of our study was to analyze the impact of anesthesia (combined epidural-general anesthesia vs. general anesthesia) on the risk of postoperative complications in patients undergoing open surgery for pheochromocytoma.This was a retrospective cohort study. 146 patients who underwent open surgery for pheochromocytoma (100 received combined epidural-general anesthesia and 46 received general anesthesia) in Peking University First Hospital from January 1, 2002 to December 31, 2015 were enrolled. The primary outcome was the occurrence of postoperative complications during hospital stay after surgery. Multivariate Logistic regression models were used to analyze the association between the choice of anesthetic method and the risk of postoperative complications.17 (11.6%) patients developed complications during postoperative hospital stay. The incidence of postoperative complications was lower in patients with combined epidural-general anesthesia than in those with general anesthesia (6% [6/100] vs. 23.9% [11/46], P = 0.006). Multivariate Logistic regression analysis showed that use of combined epidural-general anesthesia (OR 0.219, 95% CI 0.065-0.741; P = 0.015) was associated with lower risk, whereas male gender (OR 5.213, 95% CI 1.283-21.177; P = 0.021) and perioperative blood transfusion (OR 25.879; 95% CI 3.130-213.961; P = 0.003) were associated with higher risk of postoperative complications.For patients undergoing open surgery for pheochromocytoma, use of combined epidural-general anesthesia may decrease the occurrence of postoperative complications.

BACKGROUND:Dexmedetomidine in combination with opioids has been used for postoperative analgesia. The purpose of this study was to investigate the impacts of dexmedetomidine supplemented intravenous analgesia on morphine consumption and subjective sleep quality in elderly patients after open abdominal surgery. METHODS:This was a pilot randomized controlled trial. 58 elderly patients (age ≥ 60 years) who underwent open abdominal surgery were randomized to receive either dexmedetomidine supplemented morphine analgesia (0.5 mg/ml morphine plus 2 μg/ml dexmedetomidine in 100 ml normal saline, DEX group) or morphine analgesia (0.5 mg/ml morphine in 100 ml normal saline, CTRL group) for 72 hours after surgery. Patient-controlled analgesia pump was programmed to deliver a 2ml bolus with a lockout interval of 8 minutes and a background infusion at a rate of 1 ml/h. The primary endpoint was 72-hour morphine consumption. Secondary endpoints included pain intensity, subjective sleep quality, and 30-day complications and mortality after surgery. RESULTS:The 72-hour morphine consumption was lower in the DEX group than in the CTRL group (median 39.0 mg [interquartile range 37.3, 41.0] in the DEX group vs. 49.0 mg [45.5, 50.0] in the CTRL group; median difference -9.0 mg [95% CI -10.0, -6.0], P < 0.001). The intensity of pain within 48 hours was lower (P

Amyloid-β (Aβ), the major component of neuritic plaques in Alzheimer's disease (AD), is derived from sequential proteolytic cleavage of amyloid protein precursor (APP) by secretases. In this study, we found that cystatin C (CysC), a natural cysteine protease inhibitor, is able to reduce Aβ40 secretion in human brain microvascular endothelial cells (HBMEC). The CysC-induced Aβ40 reduction was caused by degradation of β-secretase BACE1 through the ubiquitin/proteasome pathway. In contrast, we found that CysC promoted secretion of soluble APPα indicating the activated non-amyloidogenic processing of APP in HBMEC. Further results revealed that α-secretase ADAM10, which was transcriptionally upregulated in response to CysC, was required for the CysC-induced sAPPα secretion. Knockdown of SIRT1 abolished CysC-triggered ADAM10 upregulation and sAPPα production. Taken together, our results demonstrated that exogenously applied CysC can direct amyloidogenic APP processing to non-amyloidgenic pathway in brain endothelial cells, mediated by proteasomal degradation of BACE1 and SIRT1-mediated ADAM10 upregulation. Our study unveils previously unrecognized protective role of CysC in APP processing.

There may be significant difference between measurement of end-tidal carbon dioxide partial pressure (PetCO2) and arterial carbon dioxide partial pressure (PaCO2) during one-lung ventilation with low tidal volume for thoracic surgeries. Transcutaneous carbon dioxide partial pressure (PtcCO2) monitoring can be used continuously to evaluate PaCO2 in a noninvasive fashion. In this study, we compared the accuracy between PetCO2 and PtcCO2 in predicting PaCO2 during prolonged one-lung ventilation with low tidal volume for thoracic surgeries.Eighteen adult patients who underwent thoracic surgeries with one-lung ventilation longer than two hours were included in this study. Their PetCO2, PtcCO2, and PaCO2 values were collected at five time points before and during one-lung ventilation. Agreement among measures was evaluated by Bland-Altman analysis.Ninety sample sets were obtained. The bias and precision when PtcCO2 and PaCO2 were compared were 4.1 ± 6.5 mmHg during two-lung ventilation and 2.9 ± 6.1 mmHg during one-lung ventilation. Those when PetCO2 and PaCO2 were compared were -11.8 ± 6.4 mmHg during two-lung ventilation and -11.8 ± 4.9 mmHg during one-lung ventilation. The differences between PtcCO2 and PaCO2 were significantly lower than those between PetCO2 and PaCO2 at all five time-points (p < 0.05).PtcCO2 monitoring was more accurate for predicting PaCO2 levels during prolonged one-lung ventilation with low tidal volume for patients undergoing thoracic surgeries.

CONTEXT:Stress response induced by surgery is proposed to play an important role in the pathogenesis of postoperative cognitive dysfunction. OBJECTIVE:To investigate the association between postoperative serum cortisol level and occurrence of cognitive dysfunction early after coronary artery bypass graft surgery. DESIGN:Prospective cohort study. SETTING:Two teaching hospitals. PATIENTS:One hundred and sixth-six adult patients who were referred to elective coronary artery bypass graft surgery from March 2008 to December 2009. INTERVENTION:None. MAIN OUTCOME MEASURES:Neuropsychological tests were completed one day before and seven days after surgery. Cognitive dysfunction was defined using the same definition as used in the ISPOCD1-study. Blood samples were obtained in the first postoperative morning for measurement of serum cortisol concentration. Multivariate Logistic regression analyses were performed to assess the relationship between serum cortisol level and occurrence of postoperative cognitive dysfunction. RESULTS:Cognitive dysfunction occurred in 39.8% (66 of 166) of patients seven days after surgery. Multivariate Logistic regression analysis showed that high serum cortisol level was significantly associated with the occurrence of postoperative cognitive dysfunction (odds ratio [OR] 2.603, 95% confidence interval [CI] 1.371-4.944, P = 0.003). Other independent predictors of early postoperative cognitive dysfunction included high preoperative New York Heart Association functional class (OR 0.402, 95% CI 0.207-0.782, P = 0.007), poor preoperative Grooved Pegboard test score of nondominant hand (OR 1.022, 95% CI 1.003-1.040, P = 0.020), use of penehyclidine as premedication (OR 2.565, 95% CI 1.109-5.933, P = 0.028), and occurrence of complications within seven days after surgery (OR 2.677, 95% CI 1.201-5.963, P = 0.016). CONCLUSIONS:High serum cortisol level in the first postoperative morning was associated with increased risk of cognitive dysfunction seven days after coronary artery bypass graft surgery.

Bacterial wilt is a common disease that causes severe yield and quality losses in many plants. In the present study, we used the model Ralstonia solanacearum-Arabidopsis thaliana pathosystem to study transcriptional changes associated with wilt disease development. Susceptible Col-5 plants and RRS1-R-containing resistant Nd-1 plants were root-inoculated with R. solanacearum strains harbouring or lacking the matching PopP2 avirulence gene. Gene expression was marginally affected in leaves during the early stages of infection. Major changes in transcript levels took place between 4 and 5 days after pathogen inoculation, at the onset of appearance of wilt symptoms. Up-regulated genes in diseased plants included ABA-, senescence- and basal resistance-associated genes. The influence of the plant genetic background on disease-associated gene expression is weak although some genes appeared to be specifically up-regulated in Nd-1 plants. Inactivation of some disease-associated genes led to alterations in the plant responses to a virulent strain of the pathogen. In contrast to other pathosystems, very little overlap in gene expression was detected between the early phases of the resistance response and the late stages of disease development. This observation may be explained by the fact that above-ground tissues were sampled for profiling whereas the bacteria were applied to root tissues. This exhaustive analysis of Arabidopsis genes whose expression is modulated during bacterial wilt development paves the way for dissecting plant networks activated by recognition of R. solanacearum effectors in susceptible plants.

Background: 5S rRNA is a highly conserved ribosomal component. Eukaryotic 5S rRNA and its associated proteins (5S rRNA system) have become very well understood. Giardia lamblia was thought by some researchers to be the most primitive extant eukaryote while others considered it a highly evolved parasite. Previous reports have indicated that some aspects of its 5S rRNA system are simpler than that of common eukaryotes. We here explore whether this is true to its entire system, and whether this simplicity is a primitive or parasitic feature. Methodology/Principal Findings: By collecting and confirming pre-existing data and identifying new data, we obtained almost complete datasets of the system of three isolates of G. lamblia, two other parasitic excavates (Trichomonas vaginalis, Trypanosoma cruzi), and one free-living one (Naegleria gruberi). After comprehensively comparing each aspect of the system among these excavates and also with those of archaea and common eukaryotes, we found all the three Giardia isolates to harbor a same simplified 5S rRNA system, which is not only much simpler than that of common eukaryotes but also the simplest one among those of these excavates, and is surprisingly very similar to that of archaea; we also found among these excavates the system in parasitic species is not necessarily simpler than that in free-living species, conversely, the system of free-living species is even simpler in some respects than those of parasitic ones. Conclusion/Significance: The simplicity of Giardia 5S rRNA system should be considered a primitive rather than parasitically-degenerated feature. Therefore, Giardia 5S rRNA system might be a primitive system that is intermediate between that of archaea and the common eukaryotic model system, and it may reflect the evolutionary history of the eukaryotic 5S rRNA system from the archaeal form. Our results also imply G. lamblia might be a primitive eukaryote with secondary parasitically-degenerated features. [ABSTRACT FROM AUTHOR]

BackgroundThe current worldwide pandemic of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, and the mortality rate of critical ill patients remains high. The purpose of this study was to identify factors that early predict the progression of COVID-19 from severe to critical illness.MethodsThis retrospective cohort study included adult patients with severe or critical ill COVID-19 who were consecutively admitted to the Zhongfaxincheng campus of Tongji Hospital (Wuhan, China) from February 8 to 18, 2020. Baseline variables, data at hospital admission and during hospital stay, as well as clinical outcomes were collected from electronic medical records system. The primary endpoint was the development of critical illness. A multivariable logistic regression model was used to identify independent factors that were associated with the progression from severe to critical illness.ResultsA total of 138 patients were included in the analysis; of them 119 were diagnosed as severe cases and 16 as critical ill cases at hospital admission. During hospital stay, 19 more severe cases progressed to critical illness. For all enrolled patients, longer duration from diagnosis to admission (odds ratio [OR] 1.108, 95% CI 1.022-1.202; P = 0.013), pulse oxygen saturation at admission ConclusionsHigher neutrophil count and lower lymphocyte count at admission were early independent predictors of progression to critical illness in severe COVID-19 patients.

BackgroundFemoral nerve block (FNB) is one of the first-line analgesic methods for patients following lower extremity surgery. However, FNB with local anesthetics alone exert limited potency and supplemental opioids are often required. Dexmedetomidine (DEX) has been used to improve the analgesic effects of FNB. The present systematic review and meta-analysis were conducted to evaluate the effectiveness of DEX as an adjuvant to local anesthetics for FNB.MethodsRandomized controlled trials comparing the effects of DEX versus sham control in combination with local anesthetics for FNB were included in this meta-analysis. Postoperative pain scores, duration of analgesic effects, and postoperative narcotic consumption were outcomes of interest. This research was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements.ResultsA total of 9 studies encompassing 580 participants were included for data synthesis after critical evaluation. DEX as an adjuvant with local anesthetics for FNB significantly relieved pain intensity at 12, 24 and 48 hours after surgery, both at rest (standardized mean difference -1.34 [95% CI -1.87 to -0.82], PConclusionDEX as an adjuvant to local anesthetics for FNB improves analgesia, prolongs analgesic duration and reduces supplemental opioid consumption; but increases hypotension.

This study aimed to explore the efficacy and mechanism of Chanling Gao (CLG), a compound Chinese medicine, on colorectal cancer (CRC). A model of transplanted CRC was established in nude mice. The mice were treated 7 days after CRC transplantation with either Capecitabine or CLG for 3 weeks. On the 28th day after the operation, CRC growth and liver metastasis were assessed by morphology, the changes in the expression of HIF-1α (hypoxia inducible factor-1α), stromal cell-derived factor-1 alpha (SDF-1α), CXCR4 (C-X-C chemokine receptor type 4), PI3K, and Akt in the transplanted tumor and SDF-1α and CXCR4 in the liver were detected by Western blot and immunohistochemistry. The protein contents of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and collagen IV in the serum and transplanted tumor and SDF-1α and CXCR4 in liver tissues were detected by enzyme-linked immunosorbent assay. In the Capecitabine and high dose CLG groups, the growth and liver metastasis of CRC were significantly inhibited, the protein levels of HIF-1α, SDF-1α, CXCR4, MMP-2, VEGF, PI3K, Akt, P-PI3K and P-Akt in the transplanted tumor were lower, while the content of collagen IV in the transplanted tumor was higher, than in Model group. A high dose of CLG inhibited the growth of transplanted tumor and liver metastasis of CRC in nude mice, probably by inhibiting the HIF-1α/SDF-1α-CXCR4/PI3K-Akt signaling pathway reducing the synthesis and release of VEGF and degradation of collagen IV.

BACKGROUND:Delirium is a frequent complication after cardiac surgery and its occurrence is associated with poor outcomes. The purpose of this study was to investigate the impact of perioperative dexmedetomidine administration on the incidence of delirium in elderly patients after cardiac surgery. METHODS:This randomized, double-blinded, and placebo-controlled trial was conducted in two tertiary hospitals in Beijing between December 1, 2014 and July 19, 2015. Eligible patients were randomized into two groups. Dexmedetomidine (DEX) was administered during anesthesia and early postoperative period for patients in the DEX group, whereas normal saline was administered in the same rate for the same duration for patients in the control (CTRL) group. The primary endpoint was the incidence of delirium during the first five days after surgery. Secondary endpoints included the cognitive function assessed on postoperative days 6 and 30, the overall incidence of non-delirium complications within 30 days after surgery, and the all-cause 30-day mortality. RESULTS:Two hundred eighty-five patients were enrolled and randomized. Dexmedetomidine did not decrease the incidence of delirium (4.9% [7/142] in the DEX group vs 7.7% [11/143] in the CTRL group; OR 0.62, 95% CI 0.23 to 1.65, p = 0.341). Secondary endpoints were similar between the two groups; however, the incidence of pulmonary complications was slightly decreased (OR 0.51, 95% CI 0.26 to 1.00, p = 0.050) and the percentage of early extubation was significantly increased (OR 3.32, 95% CI 1.36 to 8.08, p = 0.008) in the DEX group. Dexmedetomidine decreased the required treatment for intraoperative tachycardia (21.1% [30/142] in the DEX group vs 33.6% [48/143] in the CTRL group, p = 0.019), but increased the required treatment for postoperative hypotension (84.5% [120/142] in the DEX group vs 69.9% [100/143] in the CTRL group, p = 0.003). CONCLUSIONS:Dexmedetomidine administered during anesthesia and early postoperative period did not decrease the incidence of postoperative delirium in elderly patients undergoing elective cardiac surgery. However, considering the low delirium incidence, the trial might have been underpowered. TRIAL REGISTRATION:ClinicalTrials.gov NCT02267538.