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The Haynes® 718 Ni-base superalloy has been investigated by use of modern material characterization, metallographic and heat treatment equipment. Grain growth annealing experiments at temperatures in the range of 1050 – 1200 oC (1323–1473K) for time durations in the range of 20 min-22h have been conducted. The kinetic equations and an Arrhenius-type equation have been applied to compute the grain-growth exponent n and the activation energy for grain growth, Qg, for the investigated alloy. The grain growth exponent, n, was computed to be in the range of 0.066-0.206; and the n values have been critically discussed in relation to the literature. The activation energy for grain growth, Qg, for the investigated alloy has been computed to be around 440 kJ/mol; and the Qg data for the investigated alloy has been compared with other metals and alloys and ceramics; and critically analyzed in relation to our results.

Introduction Waiting list mortality is high in patients awaiting liver transplantation (LT). Despite the use of the Model for Endstage Liver Disease (MELD) score, patients with severe hyponatremia have an even worse waiting list survival. We assessed the impact of mild hyponatremia on LT waiting list survival and overall survival. We also aim to identify if there are any patient groups that are underserved in the MELD based allocation system. Methodology Data were collected from 3 transplant centers located in The Netherlands, Germany, and the United States of America. Serum bilirubin, creatinine, sodium, and international normalized ratio (INR) were collected and MELD scores calculated using the standard formula. Mild hyponatremia was defined as serum sodium level of 130-134 mmol/L. Results In total 1658 patients were included in this study. A strong correlation was found between serum sodium and overall and waiting list survival (P < 0.001). Post-LT survival was also significantly decreased in the mild hyponatremia group (P < 0.001). Waiting list survival for patients with serum sodium levels 130-134 mmol/L was worse compared to patients with normal sodium levels in all three centers together and each center individually (P < 0.001). Waiting list and overall survival was significantly worse in the 166 patients with cholestatic liver disease compared to patients with non-cholestatic liver disease (P = 0.041; P = 0.005). Post-LT survival also was significantly worse in this group (P = 0.022). Conclusion Mild hyponatremia is associated with significantly worse waiting list survival in patients awaiting LT. It is also associated with increased post-LT mortality. Patients listed for cholestatic liver disease may be underserved in the current allocation model. Serum sodium should therefore have a more prominent role in liver allocation. [ABSTRACT FROM AUTHOR]

Abstract Background A decrease in the need for liver transplantations (LTX) in Primary Biliary Cirrhosis (PBC), possibly related to treatment with ursodeoxycholic acid (UDCA), has been reported in the USA and UK. The aim of this study was to assess LTX requirements in PBC over the past 20 years in the Netherlands. Methods Analysis of PBC transplant data of the Dutch Organ Transplant Registry during the period 1988-2008, including both absolute and proportional numbers. The indication for LTX was categorized as liver failure, hepatocellular carcinoma or poor quality of life (severe fatigue or pruritus). Data were analysed for two decades: 1.1.1988-31.12.1997 (1st) and 1.1.1998-31.12.2007 (2nd). The severity of disease was quantified using MELD scores. To fit lines which show trends over time we applied a linear regression model. Results A total of 110 patients (87% women) was placed on the waiting list. 105 patients were transplanted (1st: 61, 2nd: 44), 5 (5%) died while listed. The absolute annual number of LTX for PBC slightly decreased during the 20 year period, the proportional number decreased significantly. At the time of LTX the mean age was 53.6 yrs. (1st: 53.4, 2nd: 53.8), the mean MELD score 13.9 (1st:14.5, 2nd:13.0). The median interval from diagnosis to LTX was 90.5 months (1st:86.5, 2nd: 93.5). 69% of patients was treated with UDCA (1st 38%, 2nd 82%). Conclusions Over the past 20 years the absolute number of LTX for PBC in the Netherlands showed a tendency to decrease whereas the proportional decrease was significant. There was a trend over time toward earlier transplantation.

This work represents an effective design of a temperature regulated PV module by integrating phase change materials for Malaysian weather condition. Through the numerical analysis and experimental investigation it has been shown that if a PCM layer of width 0.02 m of RT 35 is used as a cooling arrangement with a PV module, the surface temperature of the module is reduced by 10°C, which remains constant for a period of 4–6 hours. This reduction of temperature implies the increase in conversion efficiency of the module. Experiment as well as investigation has been carried out considering typical Malaysian weather. Obtained result has been validated by using experimental prototype and comparative analysis. [ABSTRACT FROM AUTHOR]

Intravenous immunoglobulin ( IVIg) is used to treat autoimmune and systemic inflammatory diseases caused by derailment of humoral and cellular immunity. In this study we investigated whether IVIg treatment can modulate regulatory T cells ( Tregs) in humans in vivo. Blood was collected from IVIg-treated patients with immunodeficiency or autoimmune disease who were treated with low-dose ( n = 12) or high-dose ( n = 15) IVIg before, immediately after and at 7 days after treatment. Percentages and activation status of circulating CD4+ CD25+forkhead box protein 3 ( FoxP3+) Tregs and of conventional CD4+ FoxP3− T-helper cells ( Tconv) were measured. The suppressive capacity of Tregs purified from blood collected at the time-points indicated was determined in an ex-vivo assay. High-dose, but not low-dose, IVIg treatment enhanced the activation status of circulating Tregs, as shown by increased FoxP3 and human leucocyte antigen D-related ( HLA- DR) expression, while numbers of circulating Tregs remained unchanged. The enhanced activation was sustained for at least 7 days after infusion, and the suppressive capacity of purified Tregs was increased from 41 to 70% at day 7 after IVIg treatment. The activation status of Tconv was not affected by IVIg. We conclude that high-dose IVIg treatment activates Tregs selectively and enhances their suppressive function in humans in vivo. This effect may be one of the mechanisms by which IVIg restores imbalanced immune homeostasis in patients with autoimmune and systemic inflammatory disorders. [ABSTRACT FROM AUTHOR]

Herpes simplex virus (HSV) hepatitis is a rare and potential life-threatening disease. The diagnosis of HSV hepatitis is hampered by its indifferent clinical presentation, which necessitates confirmatory laboratory data to identify HSV in the affected liver. However, liver biopsies are often contraindicated in the context of coagulopathy, are prone to sampling errors and have low sensitivity in mild HSV hepatitis cases. There is an unmet need for less invasive diagnostic tools. The diagnostic and therapeutic value of HSV DNA load and liver enzyme level kinetics was determined in five patients with HSV hepatitis and twenty disease controls with HSV-DNAemia without hepatitis. At time of hospitalization, patients with HSV hepatitis had a higher median (± interquartile range) HSV DNA load (6.0 × 10±1.2 × 10) compared to disease controls (171 ± 2845). Viral DNA load correlated with liver transaminase levels and disease severity. Antiviral treatment led to rapid decline of HSV DNA load and improvement of liver function of patients with HSV hepatitis. The data advocate the prompt and consecutive quantification of the HSV DNA load and liver enzyme levels in plasma of patients suspected of HSV hepatitis as well as those under antiviral treatment. [ABSTRACT FROM AUTHOR]

Purpose: To establish optimal management of patients with an umbilical hernia complicated by liver cirrhosis and ascites. Methods: Patients with an umbilical hernia and liver cirrhosis and ascites were randomly assigned to receive either elective repair or conservative treatment. The primary endpoint was overall morbidity related to the umbilical hernia or its treatment after 24 months of follow-up. Secondary endpoints included the severity of these hernia-related complications, quality of life, and cumulative hernia recurrence rate. Results: Thirty-four patients were included in the study. Sixteen patients were randomly assigned to elective repair and 18 to conservative treatment. After 24 months, 8 patients (50%) assigned to elective repair compared to 14 patients (77.8%) assigned to conservative treatment had a complication related to the umbilical hernia or its repair. A recurrent hernia was reported in 16.7% of patients who underwent repair. For the secondary endpoint, quality of life through the physical (PCS) and mental component score (MCS) showed no significant differences between groups at 12 months of follow-up (mean difference PCS 11.95, 95% CI − 0.87 to 24.77; MCS 10.04, 95% CI − 2.78 to 22.86). Conclusion: This trial could not show a relevant difference in overall morbidity after 24 months of follow-up in favor of elective umbilical hernia repair, because of the limited number of patients included. However, elective repair of umbilical hernia in patients with liver cirrhosis and ascites appears feasible, nudging its implementation into daily practice further, particularly for patients experiencing complaints. Trial registration: Clinicaltrials.gov, NCT01421550, on 23 August 2011. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) represents one of the foremost causes of acute hepatitis globally. Although there is no proven medication for hepatitis E, pegylated interferon-α (IFN-α) has been used as off-label drug for treating HEV. However, the efficacy and molecular mechanisms of how IFN signalling interacts with HEV remain undefined. As IFN-α has been approved for treating chronic hepatitis C (HCV) for decades and the role of interferon signalling has been well studied in HCV infection, this study aimed to comprehensively investigate virus-host interactions in HEV infection with focusing on the IFN signalling, in comparison with HCV infection. A comprehensive screen of human cytokines and chemokines revealed that IFN-α was the sole humoral factor inhibiting HEV replication. IFN-α treatment exerted a rapid and potent antiviral activity against HCV, whereas it had moderate and delayed anti-HEV effects in vitro and in patients. Surprisingly, blocking the basal IFN pathway by inhibiting JAK1 to phosphorylate STAT1 has resulted in drastic facilitation of HEV, but not HCV infection. Gene silencing of the key components of JAK-STAT cascade of the IFN signalling, including JAK1, STAT1 and interferon regulatory factor 9 (IRF9), stimulated HEV infection. In conclusion, compared to HCV, HEV is less sensitive to IFN treatment. In contrast, the basal IFN cascade could effectively restrict HEV infection. This bears significant implications in management of HEV patients and future therapeutic development. [ABSTRACT FROM AUTHOR]

Further understanding of the molecular biology and pathogenesis of hepatocellular carcinoma (HCC) is crucial for future therapeutic development. SMAD4, recognized as an important tumor suppressor, is a central mediator of transforming growth factor beta (TGFB) and bone morphogenetic protein (BMP) signaling. This study investigated the role of SMAD4 in HCC. Nuclear localization of SMAD4 was observed in a cohort of 140 HCC patients using tissue microarray. HCC cell lines were used for functional assay in vitro and in immune-deficient mice. Nuclear SMAD4 levels were significantly increased in patient HCC tumors as compared with adjacent tissues. Knockdown of SMAD4 significantly reduced the efficiency of colony formation and migratory capacity of HCC cells in vitro and was incompatible with HCC tumor initiation and growth in mice. Knockdown of SMAD4 partially conferred resistance to the anti-growth effects of BMP ligand in HCC cells. Importantly, simultaneous elevation of SMAD4 and phosphorylated SMAD2/3 is significantly associated with poor patient outcome after surgery. Although high levels of SMAD4 can also mediate an antitumor function by coupling with phosphorylated SMAD1/5/8, this signaling, however, is absent in majority of our HCC patients. In conclusion, this study revealed a highly non-canonical tumor-promoting function of SMAD4 in HCC. The drastic elevation of nuclear SMAD4 in sub-population of HCC tumors highlights its potential as an outcome predictor for patient stratification and a target for personalized therapeutic development. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a complex and heterogeneous disease, often associated with underlying conditions, like cirrhosis or other relevant co-morbidities that worsen the prognosis and make the clinical management more challenging. Current recommendations emphasize the importance of a multidisciplinary approach for the management of HCC patients and stress the crucial role of careful prevention and the management of cirrhosis-associated complications. This article discusses the importance of a multidisciplinary approach in the treatment of HCC patients. Current recommendations for the treatment of cirrhotic patients with HCC are also reviewed. [ABSTRACT FROM AUTHOR]

The present study focused on thermal conductivity and viscosity of alumina nanoparticles, at low volume concentrations of 0.01-1.0 % dispersed in the mixture of ethylene glycol and water (mass ratio, 60:40). Sodium dodeobcylbenzene sulfonate (SDBS) was applied for better dispersion and stability of alumina nanoparticles and study of its influence on both thermal conductivity and viscosity. The thermal conductivity established polynomial enhancement pattern with increase of volume concentration up to 0.1 % while linear enhancement was obtained at higher concentrations. In addition, thermal conductivity was enhanced with the rise of temperature. However, the augmentation was negligible compared to that obtained with increase of volume concentration. In contrast, viscosity data showed remarkable reduction with increase of temperature. Meanwhile, viscosity of nanofluids enhanced with loading of alumina nanoparticles. Thermal conductivity and viscosity measurements showed higher values over theoretical predictions. Results showed SDBS at different concentrations has distinct influence on thermal conductivity and viscosity of nanofluid. [ABSTRACT FROM AUTHOR]

Background: Open cholecystectomy (OC) is often preferred over laparoscopic cholecystectomy (LC) in patients with liver cirrhosis and portal hypertension, but evidence is lacking to support this practice. This meta-analysis aimed to clarify which surgical technique is preferable for symptomatic cholecystolithiasis in patients with liver cirrhosis. Methods: A meta-analysis was conducted according to the PRISMA guidelines. Articles published between January 1990 and October 2011 were identified from MEDLINE, Embase and the Cochrane Library. Randomized clinical trials (RCTs) comparing outcomes of OC versus LC for cholecystolithiasis in patients with liver cirrhosis were included. The quality of the RCTs was assessed using the Jadad criteria. Results: Following review of 1422 papers by title and abstract, a meta-analysis was conducted of four RCTs comprising 234 surgical patients. They provided evidence of at least level 2b on the Oxford Level of Evidence Scale, but scored poorly according to the Jadad criteria. Some 97·0 per cent of the patients had Child-Turcotte-Pugh (CTP) grade A or B liver cirrhosis. In all, 96·6 per cent underwent elective surgery. No postoperative deaths were reported. LC was associated with fewer postoperative complications (risk ratio 0·52, 95 per cent confidence interval (c.i.) 0·29 to 0·92; P = 0·03), a shorter hospital stay (mean difference − 3·05 (95 per cent c.i. − 4·09 to − 2·01) days; P < 0·001) and quicker resumption of a normal diet (mean difference − 27·48 (−30·96 to − 23·99) h; P < 0·001). Conclusion: Patients with CTP grade A or B liver cirrhosis who undergo LC for symptomatic cholecystolithiasis have fewer overall postoperative complications, a shorter hospital stay and resume a normal diet more quickly than those who undergo OC. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article discusses a study which compares the outcomes from orthotopic liver transplantation (OLT) using controlled graft donation after cardiac death (DCD) and that from OLT using graft donation after brain death (DBD). The study employs adult recipients in the Netherlands who undergo OLT from DCD and DBD donors from January 1, 2001 to December 31, 2006. The results show that the one and three-year survival rates in patients were the same for DCD and DBD transplants.

SUMMARY In experimental animals inhibition of T cell co-stimulation immediately after organ transplantation effectively prevents rejection. We investigated whether the expression of co-stimulatory molecules is enhanced in cadaveric liver transplants, whether their expression is influenced by the transplantation procedure, and whether variation in expression between liver transplants is related to the occurrence of acute rejection. Expression of CD80, CD86 and the macrophage marker CD68 were determined by immunohistochemistry in biopsies from 40 clinical liver transplants obtained at different time-points during the transplantation procedure, and in normal liver tissue obtained from 10 human livers. Expression of CD80 and CD86 on Kupffer cells was graded by comparison with CD68-staining. In a subgroup CD80 and CD86 mRNA was quantified by real-time detection polymerase chain reaction. CD86 was expressed in all liver transplants and normal livers on the majority of Kupffer cells. CD80 was absent or sporadically expressed in normal liver tissue, but in 18 of 40 liver transplants at least one-quarter of Kupffer cells expressed CD80. CD80- and CD86-mRNA and protein expression in liver transplants did not change during the warm ischaemic and reperfusion phases of the transplantation procedure. CD80-expression on Kupffer cells varied strongly between individual donor livers; this variation was, however, not significantly related to the occurrence of acute rejection after transplantation. In conclusion, in nearly half of cold-preserved cadaveric liver transplants an increased proportion of Kupffer cells express CD80 at the time of transplantation in comparison with normal liver tissue. The expression was not further induced by warm ischaemia and reperfusion. However, the observed variation in CD80-expression between liver transplants is not a accurate predictive measure for acute rejection. [ABSTRACT FROM AUTHOR]

Review: 223 refs. [ABSTRACT FROM AUTHOR]

The article presents research which dealt with fine-needle aspiration cytology in the diagnosis of acute rejection after liver transplantation. Core-needle biopsy is not applicable for this purpose due to its risk of complications and pain. On the other hand, the cytological fine-needle aspiration biopsy procedure serves as a safe and atraumatic alternative.

It is no secret that graphene, a two-dimensional single-layered carbon atom crystal lattice, has drawn tremendous attention due to its distinct electronic, surface, mechanical, and optoelectronic properties. Graphene also has opened up new possibilities for future systems and devices due to its distinct structure and characteristics which has increased its demand in a variety of applications. However, scaling up graphene production is still a difficult, daunting, and challenging task. Although there is a vast body of literature reported on the synthesis of graphene through conventional and eco-friendly methods, viable processes for mass graphene production are still lacking. This review focuses on the variety of unwanted waste materials, such as biowastes, coal, and industrial wastes, for producing graphene and its potential derivatives. Among the synthetic routes, the main emphasis relies on microwave-assisted production of graphene derivatives. In addition, a detailed analysis of the characterization of graphene-based materials is presented. This paper also highlights the current advances and applications through the recycling of waste-derived graphene materials using microwave-assisted technology. In the end, it would alleviate the current challenges and forecast the specific direction of waste-derived graphene future prospects and developments.

Background: Primary infection with or reactivation of Epstein-Barr virus (EBV) can occur after liver transplant (LT) and can lead to posttransplant lymphoproliferative disease (PTLD). In pediatric LT, an EBV-DNA viral load (EBV VL) monitoring strategy, including the reduction of immunosuppression, has led to a lower incidence of PTLD. For adult LT recipients with less primary infection and more EBV reactivation, it is unknown whether this strategy is effective., Objective: To examine the effect of an EBV VL monitoring strategy on the incidence of PTLD after LT in adults., Design: Cohort study., Setting: Two university medical centers in the Netherlands., Patients: Adult recipients of first LT in Leiden between September 2003 and January 2017 with an EBV VL monitoring strategy formed the monitoring group (M1), recipients of first LT in Rotterdam between January 2003 and January 2017 without such a strategy formed the contemporary control group (C1), and those who had transplants in Leiden between September 1992 and September 2003 or Rotterdam between 1986 and January 2003 formed the historical control groups (M0 and C0, respectively)., Measurements: Influence of EBV VL monitoring on incidence of PTLD., Results: After inverse probability of treatment weighting of the 4 groups to achieve a balance among the groups for important patient characteristics, differences within hospitals between the historical and recent era in cumulative incidences-expressed as the number of events per 1000 patients measured at 5-, 10-, and 15-year follow-up-showed fewer events in the contemporary era in both centers. This difference was considerably larger in the monitoring center, whereas the 95% CI included the null value of 0 for point estimates., Limitation: Retrospective, low statistical power, and incompletely balanced groups, and non-EBV PTLD cannot be prevented., Conclusion: Monitoring EBV VL may reduce PTLD incidence after LT in adults; larger studies are warranted., Primary Funding Source: None.

Background: Transplant recipients undergo significant changes in their medication regimen during follow-up and are at an increased risk for medication-related problems (MRPs)., Aim: This study aimed to compare the prevalence and types of MRPs and interventions in liver transplant recipients with and without an outpatient medication consultation by a clinical pharmacist as well as the satisfaction with information about medicines and medication adherence., Method: We performed a single-center, observational cohort study. A retro- and prospective cohort were used and subdivided in a group that did and did not receive a medication consultation. The prevalence and types of MRPs and interventions were identified and categorized. The satisfaction parameters were evaluated using validated questionnaires., Results: Included were 291 patients. In total, 368 MRPs were identified in 197 patients in the non-medication consultation cohort (median 1; range 1-3 per patient) and 248 MRPs in 94 patients in the medication consultation cohort (median 2; range 1-4 per patient). In the medication consultation cohort, significantly fewer MRPs as unnecessary drugs (17.3% versus 58.7%, p < 0.001), suboptimal therapy (2.4% versus 9.5%, p < 0.001), untreated indication (2.8% versus 6.8%, p = 0.040) and underdosed drugs (0.4% versus 6.3%, p < 0.001) were identified. In the non-medication consultation cohort significantly more patients used unnecessary drugs (72.1% versus 39.4%, p < 0.001) compared to the medication consultation cohort. Patients in both cohorts are satisfied with the information about medicines and reported a high medication adherence., Conclusion: Patients in the medication consultation cohort had significantly fewer MRPs and used significantly less unnecessary drugs. Including a clinical pharmacist to the post-transplant care has an added value., (© 2022. The Author(s).)

Although viruses are known to modify the free radical concentration in infected cells, the exact location and concentrations of such changes remain unknown. Although this information is important to understand the virus pathogenesis and design better anti-viral drugs or vaccines, obtaining it with the conventional free radical/ROS detection techniques is impossible. Here, we elucidate the utility of diamond magnetometry for studying the free radical response of baby hamster kidney-21 cells upon Semliki Forest virus infection. Specifically, we optically probe the alterations in free radical concentration near infectious viruses via measuring the spin-lattice relaxation (T 1 ) of NV defect ensembles embedded in intracellular nanodiamonds. We performed measurements both at random locations as well as close to the virus entry by conjugating viruses to nanodiamond sensors. We observed alterations of T 1 , which represent the intracellular free radical concentration during the viral replication process. Moreover, relaxometry is also used to monitor real-time free radical variation during the early infectious process., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)