A multistakeholder approach to innovations in NAFLD care

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent globally and requires multidisciplinary care. Here, we report key findings of a NAFLD care workshop, address knowledge gaps and highlight a path to optimise healthcare resource use, to improve outcomes in patients with steatotic liver disease

Ride Dynamics - Ride Safety - Driver's Place

Neue Sensorik und Algorithmen zur Auswertung insbesondere von Bilddaten führten 2018 zu einer Vielzahl von neuen oder verbesserten Assistenzsystemen im Traktor. Diese können auch als erste Schritte zum autonomen Fahren gesehen werden, wobei durch die Komplexität und Vielzahl der Aufgaben noch großer Forschungsbedarf besteht. Da der Mensch im Traktor wenigstens mittelfristig nicht zu ersetzen ist, sind neben den Unterstützungssystemen auch Komfort und Ergonomiethemen weiterhin von großer Bedeutung.New sensors and algorithms especially for image processing lead in 2018 to numerous new assistance systems for tractors. These can be seen as the first steps towards autonomous driving. Due the complexity and the multitude of task carried out by tractors, there is still a lot of research needed in this field. As the human will not be replaced in the medium-term by automatic systems, the areas of research focusing on comfort and ergonomics will continue to be important

Toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease

Toll-like receptors (TLRs) in the liver compartment have repeatedly been attributed to the development of non-alcoholic fatty liver disease (NAFLD). Knowledge on TLR expression in blood cells and their relation to intestinal microbiota and NAFLD development is limited. Here, we determined TLR expression patterns in peripheral blood mononuclear cells (PBMCs) of NAFLD patients and controls, their relation to intestinal microbiota and the impact of TLRs found altered in NAFLD development. Markers of intestinal permeability in blood and TLR mRNA expression in PBMCs were determined in 37 NAFLD patients and 15 age-matched healthy controls. Fecal microbiota composition was evaluated in 21 NAFLD patients and 9 controls using 16S rRNA gene amplicon sequencing. Furthermore, TLR1−/− and C57BL/6 mice (n = 5–6/group) were pair-fed a liquid control or a fat-, fructose- and cholesterol-rich diet. Intestinal microbiota composition and markers of intestinal permeability like zonulin and bacterial endotoxin differed significantly between groups with the latter markers being significantly higher in NAFLD patients. Expression of TLR1-8 and 10 mRNA was detectable in PBMCs; however, only TLR1 expression, being higher in NAFLD patients, were significantly positively correlated with the prevalence of Holdemanella genus while negative correlations were found with Gemmiger and Ruminococcus genera. TLR1−/− mice were significantly protected from the development of diet-induced NAFLD when compared to wild-type mice. While intestinal microbiota composition and permeability differed significantly between NAFLD patients and healthy subjects, in PBMCs, only TLR1 expression differed between groups. Still, targeting these alterations might be a beneficial approach in the treatment of NAFLD in some patients.Fil: Baumann, Anja. Universidad de Viena; AustriaFil: Nier, Anika. Universidad de Viena; AustriaFil: Hernández Arriaga, Angélica. Universidad de Hohenheim; AlemaniaFil: Brandt, Annette. Universidad de Viena; AustriaFil: Lorenzo Pisarello, Maria Jose. Universidad de Viena; Austria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Jin, Cheng J.. Universitat Jena; AlemaniaFil: Pilar, Esther. Universidad de Viena; AustriaFil: Camarinha-Silva, Amélia. Universidad de Hohenheim; AlemaniaFil: Schattenberg, Jörn M.. University Medical Center of the Johannes Gutenberg; AlemaniaFil: Bergheim, Ina. Universidad de Viena; Austri

Transaminase Level of Severity and Mortality of COVID-19 Patients at RSUD Dr. Saiful Anwar Malang

Background: Extend of lung injury, inflammation due to SARS COV-2 can also cause liver injury. Liver injury in COVID-19 patients can be caused by the direct effect on the liver, cholangiocyte role, activation of the immune system, drug-induced liver injury, and hypoxic injury. Hepatocyte necrosis could increase the transaminase. Therefore, transaminase increase may reveal the inflammation severity. Aim: This study aims to know the relationship of transaminase to the severity and mortality of COVID-19 patients. Method: A retrospective study of 177 COVID-19 patients hospitalized at Saiful Anwar Hospital Malang. The data were taken from the medical record of COVID-19 patients. The level of transaminase was taken on admission. The severity criteria of COVID-19 were taken from the Indonesian COVID-19 Guidelines. Chi-Square Test and Pearson Correlation Test were used as the statistical analysis with a significance of 0.05 (p=0.05) and a confidence interval of 95% (CI=95%). Results: From the correlation test, the AST had R=0.42 (p < 0.001) for severity and R=0.17 (p < 0.001) for mortality. The ALT had R=0.33 (p < 0.001) of severity and R=0.28 (p < 0.001) of mortality. Conclusion: There was a significant relationship between AST and ALT in the severity and mortality

The Use of Imatinib Mesylate as a Lifesaving Treatment of Chronic Myeloid Leukemia Relapse after Bone Marrow Transplantation

We describe the response of imatinib as lifesaving treatment of chronic myeloid leukemia (CML) relapse in seven patients who underwent allogeneic bone marrow transplantation (alloBMT) at our institution over a period of 4 years. Retrospective analysis of their medical records revealed that a mean age at transplant was 45.2 years. The median time to diagnosis was 7.4 years after transplant. At relapse, four, two, and one patients were classified as having hematologic, major molecular, and cytogenetic relapse, respectively. At imatinib initiation, five had CML in a chronic phase, while one patient was diagnosed as having accelerated phase and blast crisis. All these patients could be evaluated for the therapeutic efficacy. At a mean of follow-up of 1.9 years of therapy, all evaluable patients achieved major molecular response without compromising safety. Consistent with available data, our results indicate that imatinib is safe and effective treatment option for patients with relapse after BMT

The role of necroptotic extracellular vesicles in NAFLD pathogenesis

Tese de mestrado, Ciências Biofarmacêuticas, 2022, Universidade de Lisboa, Faculdade de Farmácia.As vesículas extracelulares (EVs), envolvidas na comunicação intercelular e a necroptose, uma via de necrose regulada, cuja maquinaria facilita o tráfico endosomal e a geração de EVs, foram recentemente implicadas na patogénese de fígado gordo não alcoólico (NAFLD). Neste trabalho tivemos como objetivo caracterizar o papel funcional da maquinaria necroptótica na geração de EVs provenientes de hepatócitos (Hep-EVs) e o seu impacto na função dos hepatócitos com sobrecarga lípidica. Hep-EVs foram isoladas por precipitação a partir de células AML12 wild-type (WT), deficientes em Ripk3 e em Mlkl na presença ou ausência de 125 µM ácido palmítico (PA) durante 24h, sendo depois caracterizadas por immunoblotting e análise de rastreamento de nanoparticulas. De seguida, após 1h de pré-exposição a 10 µg/mL Hep-EVs, os hepatócitos foram incubados com 125 µM PA por 48h, seguido de avaliação da morte celular e do metabolismo lípidico. Os nossos resultados mostram que a incubação com PA aumenta a secreção de Hep-EVs, um fenótipo que é dependente da maquinaria necroptótica. Em contraste com os hepatócitos Mlkl-/-, os hepatócitos Ripk3-/- estiveram protegidos da morte celular provocada pelo PA, a qual por sua vez não foi afetada pela exposição a EVs. Ainda assim, as EVs derivadas de células WT tratadas com PA aumentaram ainda mais os níveis de RIPK3 em células WT tratadas com PA, um efeito que foi anulado pela deficiência em Ripk3. De igual modo, embora os hepatócitos Ripk3-/- tenham uma expressão aumentada de enzimas lipogénicas, estas células apresentaram menor acumulação lipídica, a qual foi ainda mais reduzida pela incubação com Ripk3-/- Hep-EVs. Este efeito foi concomitante com o aumento da expressão de marcadores de β-oxidação e autofagia. Por fim, as células Ripk3-/- apresentam níveis diminuídos de NLRP3 e Tgf-β, indicando que a RIPK3 pode regular a ativação do inflamassoma e a sinalização profibrogénica após sobrecarga lipídica. Em conclusão, a deficiência em Ripk3 protegeu os hepatócitos da lipotoxicidade, acompanhada pela redução da expressão de mediadores pró-inflamatórios e fibrogénicos, bem como alterações no metabolismo lipídico. Além disso, EVs necroptóticos podem ter um papel na comunicação hepatocelular, particularmente afetando o metabolismo lipídico e os níveis de RIPK3 nos hepatócitos vizinhos, provavelmente contribuindo para a patogénese de NAFLD.Both extracellular vesicles (EVs) involved in intercellular communication and necroptosis, a regulated necrotic cell death routine whose machinery facilitates endosomal trafficking and EV generation have been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here, we aimed to elucidate the functional role of the necroptotic machinery in the generation of hepatocyte-derived EVs (Hep-EVs) and their implication in hepatocellular function after fat overload. Hep-EVs were isolated by precipitation from wild-type (WT) receptor-interacting protein kinase 3 (Ripk3)-deficient and mixed lineage kinase domain-like protein (Mlkl)-deficient AML-12 cells in the presence or absence of 125 µM palmitic acid (PA) for 24h, after which they were characterized by immunoblotting and nanoparticle tracking analysis. Then, after 1h pre-treatment with Hep-EVs (10 μg protein/mL), hepatocytes were exposed to 125 µM PA for 48h, followed by biochemical assessment of cell death and lipid metabolism. Our results showed that PA increases the secretion of Hep-EVs, a phenotype dependent on the necroptotic machinery. In contrast to Mlkl-/- hepatocytes, Ripk3-/- hepatocytes were protected from PA-induced cell death, which in turn was not affected by Hep-EV exposure. Still, PA-treated WT cell-derived EVs further increased RIPK3 protein levels in PA-treated WT cells, an effect that was abrogated by Ripk3 deficiency. Similarly, although Ripk3-/- hepatocytes display increased expression of the de novo lipogenesis enzymes, these cells displayed lower levels of fat accumulation, which were further decreased following incubation with Ripk3-/- Hep-EVs. This effect was concomitant with increased expression of β-oxidation and autophagy markers. Lastly, we showed that Ripk3-/- hepatocytes displayed decreased levels of NLRP3 and transforming growth factor-β, indicating that RIPK3 may regulate inflammasome activation and pro-fibrogenic signaling upon fat overload. In conclusion, Ripk3 deficiency protected hepatocytes from lipotoxicity, accompanied by reduced expression of proinflammatory and profibrogenic mediators, as well as changes in lipid metabolism. Further, necroptotic EVs may have a role in hepatocellular communication, particularly by affecting lipid metabolism and RIPK3 levels in neighbouring hepatocytes, likely contributing to NAFLD pathogenesis.Instituto de Investigação do Medicamento (iMed.ULisboa)

Tractor Hydraulics

Die Entwicklungstendenzen im Bereich der Traktorhydraulik konzentrieren sich neben der Effizienzsteigerung vor allem auf die Verbesserung des dynamischen Systemverhaltens und der Bedienbarkeit. Dies wird verstärkt durch den Einsatz von Verdrängersteuerungen und aufgelösten Steuerkanten angestrebt. Lastfühligkeit wird nun auch mit Closed-Center-Systemen erreicht. Bewährte hochwertige Technologie setzt sich zunehmend in geringeren Leistungsklassen durch.Main focus of research and application in tractor hydraulics is besides efficiency enhancement on improved system conduct and operability. This is more and more achieved by application of displacement control and separate meter-in and meter-out. Like in open center systems closed center systems are now available with load sensitive behaviour. State of the art high technology trickles down to machines with lower power level