Patients after organ transplantation have impaired immune response after vaccination against the SARS-CoV-2 virus. So far, published studies have reported quite different response rates to SARS-CoV-2 ...vaccination, ranging from 15-79% in liver and kidney transplant recipients. Up to one year after the first vaccine dose, we analyzed the humoral and cellular immune response of 21 liver transplant (LTX) patients after vaccination with mRNA vaccines compared with 28 kidney transplant (KTX) patients. We evaluated IgG against the SARS-CoV-2 spike protein as well as SARS-CoV-2 specific T cells using an ELISpot assay that detected IFN-γ- and/or IL-2-expressing T cells. We found a cellular and/or humoral immune response in 100% of the LTX patients compared with 68% of the KTX patients. Antibody titers against the spike protein of SARS-CoV-2 were significantly higher in the LTX group, and significantly more LTX patients had detectable specific IL-2-producing T cells. The immunosuppression applied in our LTX cohort was lower compared with the KTX cohort (14% triple therapy in LTX patients vs. 79% in KTX patients). One year after the first vaccination, breakthrough infections could be detected in 41% of all organ transplant patients. None of those patients suffered from a severe course of COVID-19 disease, indicating that a partial vaccination response seemed to offer protection to immunosuppressed patients. The better immune response of LTX patients after SARS-CoV-2 vaccination might be due to less intense immunosuppressive therapy compared with KTX patients.
In most human cancers, a large number of proteins with driver mutations are involved in tumor development, implying that multiple fine tuners are involved in cancer formation and/or maintenance. A ...useful strategy for cancer therapy may therefore be to target multiple cancer type-specific fine tuners. Furthermore, genome-wide association studies of tumor samples have identified a large number of long noncoding (lnc)RNA associated with various types of tumor. In this context we have previously found that C20orf204 (a splice variant of Linc00176) RNA contains a 189 amino acid (AA) long open reading frame (C20orf204-189AA) that is expressed predominantly in hepatocellular carcinoma (HCC). We report here that a protein, C20orf204-189AA, was detected in the nucleus of 14 out of 20 primary HCC, but not in control livers. Strikingly, overexpression of C20orf204-189AA enhanced cell proliferation and ribosomal RNA transcription. C20orf204-189AA is co-localized, and interacted with nucleolin via the C-terminal and with ribosomal RNA via the N-terminal domain. Furthermore, the expression of C20orf204-189AA upregulates the protein level of nucleolin. Nucleolin and C20orf204 mRNA levels in HCC are correlated with tumor differentiation grade and patient survival, suggesting that C20orf204-189AA is a cancer type-specific fine tuner in some HCC that presents itself for potential targeting therapy and cancer biomarker. Thus, cancer cells exhibit remarkable transcriptome alterations partly by adopting cancer-specific splicing isoforms of noncoding RNAs and may participate in tumor development.
•Solubility and dissolution kinetics of GaN under ammonoacidic and -basic conditions.•Results suggest a significant refinement of raw gravimetric literature data.•Change from normal to retrograde ...solubility at high temperatures is discussed.•Potentially relevant, reactor-material related sources of errors are addressed.
Solubility and dissolution kinetics of GaN are investigated, as they represent essential parameters for ammonothermal crystal growth of GaN. In situ X-ray imaging is applied to monitor the dissolving crystal. Both ammonoacidic and ammonobasic conditions are investigated. Compared to NH4F, the dissolution is generally much slower using NaN3 mineralizer, leading to a much longer time needed to establish a saturated solution. The solubility of GaN at 540°C and 260MPa in supercritical ammonia with a molar concentration of NaN3 of 0.72mmol/ml is determined to be 0.15±0.01mol%. This suggest a severe refinement of raw gravimetric literature data also for alkali metal based mineralizers, as we reported previously for ammonium halide mineralizers. The order of magnitude is in good agreement with refined gravimetric solubility data (Griffiths et al., 2016). The apparent discrepancy between the literature and this work regarding the temperature range in which retrograde solubility occurs is discussed. A possible reason for the occurrence of retrograde solubility at high temperatures is described. The paper is complemented by a section pointing out and partially quantifying potential, reactor-material-dependent sources of errors.
Zusammenfassung
In dieser Forschungsnotiz wird ein laufendes Forschungsprojekt vorgestellt, das Hausbesuche im Kindes- und Erwachsenenschutz in verschiedenen Regionen der deutschsprachigen Schweiz ...untersucht. Für zwei Zeiträume (1960 bis 1980; 2000 bis 2020) wird rekonstruiert, aufgrund welcher fachlichen Überlegungen Hausbesuche bei Abklärungen von Gefährdungen im Kindes- und Erwachsenenschutz in Auftrag gegeben wurden/werden, wie sie abliefen/ablaufen, welches Wissen dabei produziert wurde/wird und wie dieses Wissen anschliessend prozessiert und entscheidungsrelevant gemacht wurde/wird. Die Untersuchung basiert auf einer qualitativen Analyse von Personenakten sowie auf einer Interviewstudie mit Fachkräften und von behördlichen Hausbesuchen betroffenen Menschen. Weiter werden teilnehmende Beobachtungen von Hausbesuchen durchgeführt.
Hemodialysis patients (HDP) and kidney transplant recipients (KTR) have a high risk of infection with SARS-CoV-2 with poor clinical outcomes. Because of this, vaccination of these groups of patients ...against SARS-CoV-2 is particularly important. However, immune responses may be impaired in immunosuppressed and chronically ill patients. Here, our aim was to compare the efficacy of an mRNA-based vaccine in HDP, KTR, and healthy subjects.
In this prospective observational cohort study, the humoral and cellular response of prevalent 192 HDP, 50 KTR, and 28 healthy controls (HC) was assessed 1, 2, and 6 months after the first immunization with the BNT162b2 mRNA vaccine.
After 6 months, 97.5% of HDP, 37.9% of KTR, and 100% of HC had an antibody response. Median antibody levels were 1539.7 (±3355.8), 178.5 (±369.5), and 2657.8 (±2965.8) AU/mL in HDP, KTR, and HC, respectively (
≤ 0.05). A SARS-CoV-2 antigen-specific cell response to vaccination was found in 68.8% of HDP, 64.5% of KTR, and 90% of HC.
The humoral response rates to mRNA-based vaccination of HDPs are comparable to HCs, but antibody titers are lower. Furthermore, HDPs have weaker T-cell response to vaccination than HCs. KTRs have very low humoral and antigen-specific cellular response rates and antibody titers, which requires other vaccination strategies in addition to booster vaccination.
Introduction: The literature on liver transplantation (LT) for cirrhosis-associated hepatocellular carcinoma (cirr-HCC) in elderly patients (≥65 years of age) is scarce. The aim of this study was ...therefore to analyze the outcome after LT for cirr-HCC in elderly patients in our single-center experience. Methods: All consecutive patients who underwent LT for cirr-HCC at our center were identified from our prospectively collected LT database and stratified into an elderly (≥65 years) and a younger (<65 years) cohort. Perioperative mortality as well as Kaplan-Meier estimations of overall (OS) and recurrence-free survival (RFS) were compared between age strata. A subgroup analysis was performed for patients with HCC only inside Milan criteria. For further oncological comparison, outcome in the subgroup of elderly LT recipients with HCC inside Milan was also compared to a group of elderly patients undergoing liver resection for cirr-HCC inside Milan extracted from our institutional liver resection database. Results: Out of 369 consecutive patients with cirr-HCC who underwent LT between 1998 and 2022 at our center, we identified 97 elderly (with a subgroup of 14 septuagenarians) and 272 younger LT patients. 5- and 10-year OS in elderly compared to younger LT patients was 63% and 52% versus 63% and 46% (p = 0.67), respectively, while 5- and 10-year RFS was 58% and 49% versus 58% and 44% (p = 0.69). 5-/10-year OS and RFS in 50 elderly LT recipients with HCC inside Milan were 68%/55% and 62%/54%, respectively, which compared to 46%/38% (p = 0.07) and 26%/14% (p < 0.0001) in elderly patients after liver resection for cirr-HCC inside Milan. Conclusion: Our results in almost 100 elderly patients after LT for cirr-HCC show that older age per se should not be considered a contraindication to LT and that selected elderly patients older than 65 and even 70 years benefit from LT as much as younger ones.
The article presents the empirical findings of a multi-site ethnography in two organizations in Swiss street-level bureaucracy. We examined both a municipal child welfare office and the police force ...of a medium-sized city. The focus was on the question as to whether and how ethnic differentiation takes place in such public agencies and what role it plays at work. The findings suggest that un/doing ethnicity follows an instrumental logic and that it is executed in manifold and ambivalent ways.
(1) Background: Dialysis patients and recipients of a kidney allograft are at high risk for infection with SARS-CoV-2. It has been shown that the development of potent neutralizing humoral immunity ...against SARS CoV-2 leads to an increased probability of survival. However, the question of whether immunocompromised patients develop antibodies has not yet been sufficiently investigated; (2) Methods: SARS-CoV-2 antibodies were examined in hemodialysis patients on the waiting list for kidney transplantation as well as patients after kidney transplantation. Patients were interviewed about symptoms and comorbidities, BMI, and smoking history; (3) Results: SARS-CoV-2 antibodies were found in 16 out of 259 patients (6%). The trend of infections here reflects the general course of infection in Germany with a peak in November/December of 2020. Remarkably, patients on the waiting list experienced only mild disease. In contrast, transplanted patients had to be hospitalized but recovered rapidly from COVID-19. Most interesting is that all immunosuppressed patients developed antibodies against SARS-CoV-2 after infection; (4) Conclusions: Even with extensive hygiene concepts, an above-average number of patients were infected with SARS-CoV-2 during the second wave of infections in Germany. Because SARS-CoV-2 infection triggered the formation of antibodies even in these immunocompromised patients, we expect vaccination to be effective in this group of patients. Thus, dialysis patients and patients after kidney transplantation should be given high priority in vaccination programs.
Macrophages play central roles in inflammatory reactions and initiation of immune responses during infections. More than 80% of total tissue macrophages are described to be located in the liver as ...liver-resident macrophages, also named Kupffer cells (KCs). While studies in mice have established a central role of liver-resident KCs in regulating liver inflammation, their phenotype and function are not well-characterized in humans. Comparing paired human liver and peripheral blood samples, we observed significant differences in the distribution of macrophage (Mφ) subsets, with lower frequencies of CD14
CD16
and higher frequencies of CD14
CD16
Mφ in human livers. Intrahepatic Mφ consisted of diverse subsets with differential expression of CD49a, a liver-residency marker previously described for human and mice NK cells, and VSIG4 and/or MARCO, two recently described human tissue Mφ markers. Furthermore, intrahepatic CD49a
Mφ expressed significantly higher levels of maturation and activation markers, exhibited higher baseline levels of TNF-α, IL-12, and IL-10 production, but responded less to additional
TLR stimulation. In contrast, intrahepatic CD49a
Mφ were highly responsive to stimulation with TLR ligands, similar to what was observed for CD49a
monocytes (MOs) in peripheral blood. Taken together, these studies identified populations of CD49a
, VSIG4
, and/or MARCO
Mφ in human livers, and demonstrated that intrahepatic CD49a
Mφ differed in phenotype and function from intrahepatic CD49a
Mφ as well as from peripheral blood-derived monocytes.
Using activation tagging in the Arabidopsis Col-0 rps2-101C background, we identified a mutant (FMO1-3D) that showed virtually no symptoms after inoculation with virulent Pseudomonas syringae pv. ...tomato DC3000 bacteria. The dominant, gain-of-function phenotype of the FMO1-3D mutant is due to over-expression of a class 3 flavin-containing mono-oxygenase (FMO). We recapitulated the FMO1-3D mutant phenotype in independent transgenic Col-0 lines over-expressing the FMO1 cDNA under the control of the 35S CaMV promoter. The increased basal resistance observed in the FMO1-3D mutant was also effective against the taxonomically unrelated downy mildew-causing pathogen Hyaloperonospora parasitica. By investigating the progeny from crosses of the FMO1-3D mutant with the NahG transgenic line, we showed that the enhanced basal resistance phenotype was dependent on the accumulation of salicylic acid. FMO1-3D plants showed wild-type resistant reactions after inoculation with avirulent bacteria, indicating that the R-gene-mediated defence physiology was not compromised by FMO1 over-expression. Transcripts of the class 3 FMO1 gene accumulated within 6 h after inoculation of wild-type Col-0 plants with avirulent Pst + avrRpt2 cells. Moreover, a T-DNA insertion into the FMO1 gene resulted in enhanced susceptibility to virulent Pseudomonas and Hyaloperonospora parasitica, suggesting that expression of the FMO1 gene is a hitherto undescribed component of the plant's resistance repertoire. We discuss the possibility that the FMO may participate in the detoxification of virulence factors produced by pathogens.
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