Characterization of the Leucocyte Immunoglobulin-like Receptor B4 (Lilrb4) Expression in Microglia

Kretzschmar F, Piecha R, Jahn J, Potru P, Spittau B. Characterization of the Leucocyte Immunoglobulin-like Receptor B4 (Lilrb4) Expression in Microglia. Biology. 2021;10(12): 1300.As resident innate immune cells of the CNS, microglia play important essential roles during physiological and pathological situations. Recent reports have described the expression of Lilrb4 in disease-associated and aged microglia. Here, we characterized the expression of Lilrb4 in microglia in vitro and in vivo in comparison with bone marrow-derived monocytes and peritoneal macrophages in mice. Using BV2 cells, primary microglia cultures as well as ex vivo isolated microglia and myeloid cells in combination with qPCR and flow cytometry, we were able to provide a comprehensive characterization of Lilrb4 expression in distinct mouse myeloid cells. Whereas microglia in vivo display low expression of Lilrb4, primary microglia cultures present high levels of surface LILRB4. Among the analyzed peripheral myeloid cells, peritoneal macrophages showed the highest expression levels of Lilrb4. Moreover, LPS treatment and inhibition of microglial TGFβ signaling resulted in significant increases of LILRB4 cell surface levels. Taken together, our data indicate that LILRB4 is a reliable surface marker for activated microglia and further demonstrate that microglial TGFβ signaling is involved in the regulation of Lilrb4 expression during LPS-induced microglia activation

Controlled Attenuation Parameter (CAP) for the assessment of alcoholic hepatic steatosis:biopsy-controlled diagnostic accuracy and role of detoxification

This book concerns the foundations of epistemic modality. I examine the nature of epistemic modality, when the modal operator is interpreted as concerning both apriority and conceivability, as well as states of knowledge and belief. The book demonstrates how epistemic modality relates to the computational theory of mind; metaphysical modality; deontic modality; the types of mathematical modality; to the epistemic status of undecidable propositions and abstraction principles in the philosophy of mathematics; to the apriori-aposteriori distinction; to the modal profile of rational propositional intuition; and to the types of intention, when the latter is interpreted as a modal mental state. Each essay is informed by either epistemic logic, modal and cylindric algebra or coalgebra, intensional semantics or hyperintensional semantics. The book's original contributions include theories of: (i) epistemic modal algebras and coalgebras; (ii) cognitivism about epistemic modality; (iii) two-dimensional truthmaker semantics, and interpretations thereof; (iv) the ground-theoretic ontology of consciousness; (v) fixed-points in vagueness; (vi) the modal foundations of mathematical platonism; (vii) a solution to the Julius Caesar problem based on metaphysical definitions availing of notions of ground and essence; (viii) the application of epistemic two-dimensional semantics to the epistemology of mathematics; and (ix) a modal logic for rational intuition. I develop, further, a novel approach to conditions of self-knowledge in the setting of the modal $\mu$-calculus, as well as novel epistemicist solutions to Curry's and the liar paradoxes. Solutions to previously intransigent issues concerning the first-person concept, the distinction between fundamental and derivative truths, and the unity of intention and its role in decision theory, are developed along the way

Performance of non-invasive fibrosis scores in non-alcoholic fatty liver disease with and without morbid obesity

Background!#!Non-invasive scores, such as the non-alcoholic fatty liver disease (NAFLD) Fibrosis Score (NFS), are increasingly used for liver fibrosis assessment in patients with NAFLD. The aim of this study was to assess the applicability and reliability of non-invasive fibrosis scores in NAFLD patients with and without morbid obesity.!##!Methods!#!Three hundred sixty-eight patients with biopsy-proven NAFLD identified between January 2012 and December 2015 were studied; 225 with morbid obesity (biopsy obtained during bariatric surgery) and 143 patients without (termed as 'conventional').!##!Results!#!Median age was 47 years, 57% were female. Median body mass index (BMI) was 42.9 kg/m!##!Conclusions!#!Our data suggest that FIB-4 score is an accurate predictor of advanced fibrosis in NAFLD throughout all BMI stages. Without adjustment, NFS tends to overestimate fibrosis in morbidly obese NAFLD patients. This problem may be solved by implementation of an upper BMI limit (for NFS) or adjustment of diagnostic thresholds

Efficacy of Retreatment After Failed Direct-acting Antiviral Therapy in Patients With HCV Genotype 1-3 Infections

Hepatitis C virus infection is causing chronic liver disease, cirrhosis, and hepatocellular carcinoma. By combining direct-acting antivirals (DAAs), high sustained virologic response rates (SVRs) can be achieved. Resistance-associated substitutions (RASs) are commonly observed after DAA failure, and especially nonstructural protein 5A (NS5A) RASs may impact retreatment options.$^{1-3}$ Data on retreatment of DAA failure patients using first-generation DAAs are limited.$^{4-7}$ Recently, a second-generation protease- and NS5A-inhibitor plus sofosbuvir (voxilaprevir/velpatasvir/sofosbuvir [VOX/VEL/SOF]) was approved for retreatment after DAA failure.$^{8}$ However, this and other second-generation regimens are not available in many resource-limited countries or are not reimbursed by regular insurance, and recommendations regarding the selection of retreatment regimens using first-generation DAAs are very important. This study aimed to analyze patients who were re-treated with first-generation DAAs after failure of a DAA combination therapy