Here, we present the low-temperature (∼600 °C) solution combustion method for the fabrication of CoFe2O4, NiFe2O4, and Co0.5Ni0.5Fe2O4 nanoparticles (NPs) of 12–64 nm range in pure cubic spinel ...structure, by adjusting the oxidant (nitrate ions)/reductant (glycine) ratio in the reaction mixture. Although nitrate ions/glycine (N/G) ratios of 3 and 6 were used for the synthesis, phase-pure NPs could be obtained only for the N/G ratio of 6. For the N/G ratio 3, certain amount of Ni2+ cations was reduced to metallic nickel. The NH3 gas generated during the thermal decomposition of the amino acid (glycine, H2NCH2COOH) induced the reduction reaction. X-ray diffraction (XRD), Raman spectroscopy, vibrating sample magnetometry, and X-ray photoelectron spectroscopy techniques were utilized to characterize the synthesized materials. XRD analyses of the samples indicate that the Co0.5Ni0.5Fe2O4 NPs have lattice parameter larger than that of NiFe2O4, but smaller than that of CoFe2O4 NPs. Although the saturation magnetization (M s) of Co0.5Ni0.5Fe2O4 NPs lies in between the saturation magnetization values of CoFe2O4 and NiFe2O4 NPs, high coercivity (H c, 875 Oe) of the NPs indicate their hard ferromagnetic behavior. Catalytic behavior of the fabricated spinel NPs revealed that the samples containing metallic Ni are active catalysts for the degradation of 4-nitrophenol in aqueous medium.
Patients admitted with acute variceal bleeding (AVB) and Child‐Pugh C score (CP‐C) or Child‐Pugh B plus active bleeding at endoscopy (CP‐B+AB) are at high risk for treatment failure, rebleeding, and ...mortality. A preemptive transjugular intrahepatic portosystemic shunt (p‐TIPS) has been shown to improve survival in these patients, but its use in clinical practice has been challenged and not routinely incorporated. The present study aimed to further validate the role of preemptive TIPS in a large number of high‐risk patients. This multicenter, international, observational study included 671 patients from 34 centers admitted for AVB and high risk of treatment failure. Patients were managed according to current guidelines, and use of drugs and endoscopic therapy (D+E) or p‐TIPS was based on individual center policy. p‐TIPS in the setting of AVB is associated with a lower mortality in CP‐C patients compared with D+E (1 year mortality 22% vs. 47% in D+E group; P = 0.002). Mortality rate in CP‐B+AB patients was low, and p‐TIPS did not improve it. In CP‐C and CP‐B+AB patients, p‐TIPS reduced treatment failure and rebleeding (1‐year cumulative incidence function probability of remaining free of the composite endpoint: 92% vs. 74% in the D+E group; P = 0.017) and development of de novo or worsening of previous ascites without increasing rates of hepatic encephalopathy. Conclusion: p‐TIPS must be the treatment of choice in CP‐C patients with AVB. Because of the strong benefit in preventing further bleeding and ascites, p‐TIPS could be a good treatment strategy for CP‐B+AB patients.
In this paper, a procedure is established for calculating the load flow probability density function in an electrical power network, taking into account the presence of wind power generation. The ...probability density function of the power injected in the network by a wind turbine is first obtained by utilizing a quadratic approximation of its power curve. With this model, the DC power flow of a network is calculated, considering the probabilistic nature of the power injected or consumed by the generators and the loads.
The relationship between acute-on-chronic liver failure (ACLF) and acute variceal bleeding (AVB) is poorly understood. Specifically, the prevalence and prognosis of ACLF in the context of AVB is ...unclear, while the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management in patients with ACLF has not been described to date.
A multicenter, international, observational study was conducted in 2,138 patients from 34 centers between 2011 and 2015. ACLF was defined and graded according to the EASL-CLIF consortium definition. Placement of pre-emptive TIPS (pTIPS) was based on individual center policy. Patients were followed-up for 1 year, until death or liver transplantation. Cox regression and competing risk models (Gray's test) were used to identify independent predictors of rebleeding or mortality.
At admission, 380/2,138 (17.8%) patients had ACLF according to EASL-CLIF criteria (grade 1: 38.7%; grade 2: 39.2%; grade 3: 22.1%). The 42-day rebleeding (19% vs. 10%; p <0.001) and mortality (47% vs. 10%; p <0.001) rates were higher in patients with ACLF and increased with ACLF grades. Of note, the presence of ACLF was independently associated with rebleeding and mortality. pTIPS placement improved survival in patients with ACLF at 42 days and 1 year. This effect was also observed in propensity score matching analysis of 66 patients with ACLF, of whom 44 received pTIPs and 22 did not.
This large multicenter international real-life study identified ACLF at admission as an independent predictor of rebleeding and mortality in patients with AVB. Moreover, pTIPS was associated with improved survival in patients with ACLF and AVB.
Acute variceal bleeding is a deadly complication of liver cirrhosis that results from severe portal hypertension. This study demonstrates that the presence of acute-on-chronic liver failure (ACLF) is the strongest predictor of mortality in patients with acute variceal bleeding. Importantly, patients with ACLF and acute variceal (re)bleeding benefit from pre-emptive (early) placement of a transjugular intrahepatic portosystemic shunt.
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•Variceal bleeding is frequently associated with ACLF in cirrhosis.•ACLF is independently associated with rebleeding and mortality.•Patients with variceal bleeding and ACLF can benefit from a pre-emptive (early) TIPS.
Incorporation of plasmonic nanoparticles (NPs) has been considered recently to increase the absorption efficiency and/or the photocurrent of dye sensitized solar cells (DSSCs). However, metal NPs ...introduced in DSSCs make direct contact with iodide/triiodide-based liquid electrolyte, creating several problems such as recombination of charge-carriers, back reaction of photogenerated carriers, and corrosion of introduced metal NPs. For freshly prepared cells, charge-carrier recombination has been assumed as the principal process affecting the overall efficiency on DSSs. In this paper, through detailed optical and electrical characterization of gold nanoparticle-incorporated DSSCs and utilization of total electron density model, we demonstrate that the common perception that bare Au nanoparticles (NPs) act as recombination or back reactions centers cannot explain the photovoltaic behaviors of plasmonic DSSCs fully. Introduced plasmonic nanoparticles reduce electron injection efficiency in DSSCs, keeping the electron collection efficiency unchanged. Reduction of electron injection efficiency in plasmonic DSSCs is associated with an upward shift of the conduction band due to Au nanoparticle incorporation.
Fabrication of phase-pure well-crystalline BiFeO3 submicroparticles in large scale is of great importance for the utilization of this rhombohedrally distorted perovskite material in applications such ...as memory storage and spintronic devices and visible photocatalyst for the degradation of organic pollutants. In fact, because of the narrow temperature range of phase stabilization, the fabrication of phase-pure BiFeO3 in large scale remained elusive. We present the synthesis of phase-pure BiFeO3 particles of submicrometric dimensions (246–330 nm average size) through the adjustment of oxidizing/reducing agent ratio in solution combustion process utilizing glycine as reducing agent and nitrate precursors as oxidizing agent. Utilizing X-ray diffraction and Raman spectroscopy, we demonstrate that the BiFeO3 submicroparticles synthesized at equivalence ratio (Φe) close to 0.5 do not contain undesired impurities such as Bi2Fe4O9 and Bi24Fe2O39. Moreover, the submicroparticles are highly crystalline, possessing high room temperature magnetic moment and stable antiferromagnetic behavior across a wide temperature range. The superparamagnetic behavior at low magnetic field manifested by impurities attached to the BiFeO3 submicroparticles might lead to their use as effective magnetically separable photocatalysts.
Antibiotic prophylaxis reduces the risk of infection and mortality in patients with cirrhosis and acute variceal bleeding (AVB). This study examines the incidence of, and risk factors for, bacterial ...infections during hospitalization in patients with AVB on antibiotic prophylaxis.
A post hoc analysis was performed using the database of an international, multicenter, observational study designed to examine the role of pre-emptive transjugular intrahepatic portosystemic shunts in patients with cirrhosis and AVB. Data were collected on patients with cirrhosis hospitalized for AVB (n = 2,138) from a prospective cohort (October 2013-May 2015) at 34 referral centers, and a retrospective cohort (October 2011-September 2013) at 19 of these centers. The primary outcome was incidence of bacterial infection during hospitalization.
A total of 1,656 patients out of 1,770 (93.6%) received antibiotic prophylaxis; third-generation cephalosporins (76.2%) and quinolones (19.0%) were used most frequently. Of the patients on antibiotic prophylaxis, 320 patients developed bacterial infection during hospitalization. Respiratory infection accounted for 43.6% of infections and for 49.7% of infected patients, and occurred early after admission (median 3 days, IQR 1-6). On multivariate analysis, respiratory infection was independently associated with Child-Pugh C (odds ratio OR 3.1; 95% CI 1.4-6.7), grade III-IV encephalopathy (OR 2.8; 95% CI 1.8-4.4), orotracheal intubation for endoscopy (OR 2.6; 95% CI 1.8-3.8), nasogastric tube placement (OR 1.7; 95% CI 1.2-2.4) or esophageal balloon tamponade (OR 2.4; 95% CI 1.2-4.9).
Bacterial infections develop in almost one-fifth of patients with AVB despite antibiotic prophylaxis. Respiratory infection is the most frequent, is an early event after admission, and is associated with advanced liver failure, severe hepatic encephalopathy and use of nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.
Bacterial infections develop during hospitalization in close to 20% of patients with acute variceal bleeding despite antibiotic prophylaxis. Respiratory bacterial infections are the most frequent and occur early after admission. Respiratory infection is associated with advanced liver disease, severe hepatic encephalopathy and a need for a nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.
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•Bacterial infections still occur in around one-fifth of patients with cirrhosis and acute variceal bleeding despite antibiotic prophylaxis.•Respiratory bacterial infections are the most frequent, occurring early after admission.•Respiratory infections are related to the severity of cirrhosis, presence of severe hepatic encephalopathy and airway manipulation.•Over 50% of the bacteria isolated in this series were resistant to third-generation cephalosporines.
Clinically significant portal hypertension (CSPH), defined as a hepatic venous pressure gradient (HVPG) ≥10 mmHg, persists 24 weeks after sustained virological response (SVR) in up to 78% of patients ...with HCV-related cirrhosis treated with direct-acting antivirals. These patients remain at risk of decompensation. However, long-term paired clinical and hemodynamic data are not available for this population.
We conducted a prospective multicenter study in 226 patients with HCV-related cirrhosis and CSPH who achieved SVR after antiviral therapy. Patients with CSPH 24 weeks after end of treatment (SVR24) were offered another hemodynamic assessment 96 weeks after end of treatment (SVR96).
All patients were clinically evaluated. Out of 176 patients with CSPH at SVR24, 117 (66%) underwent an HVPG measurement at SVR96. At SVR96, 55/117 (47%) patients had HVPG <10 mmHg and 53% had CSPH (65% if we assume persistence of CSPH in all 59 non-evaluated patients). The proportion of high-risk patients (HVPG ≥16 mmHg) diminished from 41% to 15%. Liver stiffness decreased markedly after SVR (median decrease 10.5 ± 13 kPa) but did not correlate with HVPG changes (30% of patients with liver stiffness measurement <13.6 kPa still had CSPH). Seventeen (7%) patients presented with de novo/additional clinical decompensation, which was independently associated with baseline HVPG ≥16 mmHg and history of ascites.
Patients achieving SVR experienced a progressive reduction in portal pressure during follow-up. However, CSPH may persist in up to 53–65% of patients at SVR96, indicating persistent risk of decompensation. History of ascites and high-risk HVPG values identified patients at higher risk of de novo or further clinical decompensation.
As a major complication of cirrhosis, clinically significant portal hypertension (CSPH) is associated with adverse clinical outcomes. Herein, we show that CSPH persists at 96 weeks in just over half of patients with HCV-related cirrhosis, despite HCV elimination by direct-acting antivirals. Despite viral cure, patients with CSPH at the start of antiviral treatment remain at long-term risk of hepatic complications and should be managed accordingly.
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•HVPG ≥10 mmHg persists 2 years after therapy in 53–65% of patients with HCV-related cirrhosis despite HCV eradication.•Changes in liver stiffness do not correlate with changes in HVPG after a sustained virological response.•Baseline HVPG ≥16 mmHg and ascites identify patients with persistent CSPH and risk of decompensation.
Reversible and sub-lethal stresses to the mitochondria elicit a program of compensatory responses that ultimately improve mitochondrial function, a conserved anti-aging mechanism termed mitohormesis. ...Here, we show that harmol, a member of the beta-carbolines family with anti-depressant properties, improves mitochondrial function and metabolic parameters, and extends healthspan. Treatment with harmol induces a transient mitochondrial depolarization, a strong mitophagy response, and the AMPK compensatory pathway both in cultured C2C12 myotubes and in male mouse liver, brown adipose tissue and muscle, even though harmol crosses poorly the blood-brain barrier. Mechanistically, simultaneous modulation of the targets of harmol monoamine-oxidase B and GABA-A receptor reproduces harmol-induced mitochondrial improvements. Diet-induced pre-diabetic male mice improve their glucose tolerance, liver steatosis and insulin sensitivity after treatment with harmol. Harmol or a combination of monoamine oxidase B and GABA-A receptor modulators extend the lifespan of hermaphrodite Caenorhabditis elegans or female Drosophila melanogaster. Finally, two-year-old male and female mice treated with harmol exhibit delayed frailty onset with improved glycemia, exercise performance and strength. Our results reveal that peripheral targeting of monoamine oxidase B and GABA-A receptor, common antidepressant targets, extends healthspan through mitohormesis.
The DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT) inhibits the killing of tumor cells by alkylating agents, and its loss in cancer cells is associated with hypermethylation of the ...MGMT CpG island. Thus, methylation of MGMT has been correlated with the clinical response to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in primary gliomas. Here, we investigate whether the presence of MGMT methylation in gliomas is also a good predictor of response to another emergent alkylating agent, temozolomide.
Using a methylation-specific PCR approach, we assessed the methylation status of the CpG island of MGMT in 92 glioma patients who received temozolomide as first-line chemotherapy or as treatment for relapses.
Methylation of the MGMT promoter positively correlated with the clinical response in the glioma patients receiving temozolomide as first-line chemotherapy (n = 40). Eight of 12 patients with MGMT-methylated tumors (66.7%) had a partial or complete response, compared with 7 of 28 patients with unmethylated tumors (25.0%; P = 0.030). We also found a positive association between MGMT methylation and clinical response in those patients receiving BCNU (n = 35, P = 0.041) or procarbazine/1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (n = 17, P = 0.043) as first-line chemotherapy. Overall, if we analyze the clinical response of all of the first-line chemotherapy treatments with temozolomide, BCNU, and procarbazine/1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea as a group in relation to the MGMT methylation status, MGMT hypermethylation was strongly associated with the presence of partial or complete clinical response (P < 0.001). Finally, the MGMT methylation status determined in the initial glioma tumor did not correlate with the clinical response to temozolomide when this drug was administered as treatment for relapses (P = 0.729).
MGMT methylation predicts the clinical response of primary gliomas to first-line chemotherapy with the alkylating agent temozolomide. These results may open up possibilities for more customized treatments of human brain tumors.
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