Heat-Conducting, Compressible Mixtures with Multicomponent Diffusion: Construction of a Weak Solution

We investigate a coupling between the compressible Navier'stokes-Fourier system and the full Maxwell'stefan equations. This model describes the motion of a chemically reacting heat-conducting gaseous mixture. The viscosity coefficients are density-dependent functions vanishing in a vacuum and the internal pressure depends on species concentrations. By several levels of approximation we prove the global-in-time existence of weak solutions on the three-dimensional torus

Approximate solutions to a model of two-component reactive flow

We consider a model of motion of binary mixture, based on the compressible Navier-Stokes system. The mass balances of chemically reacting species are described by the reaction-diffusion equations with generalized form of multicomponent difiusion ux. Under a special relation between the two density dependent viscosity coefficients and for singular cold pressure we construct the weak solutions passing through several levels of approximation

Chemically reacting mixtures in terms of degenerated parabolic setting

The paper analyzes basic mathematical questions for a model of chemically reacting mixtures. We derive a model of several (finite) component compressible gas taking rigorously into account the thermodynamical regime. Mathematical description of the model leads to a degenerate parabolic equation with hyperbolic deviation. The thermodynamics implies that the diffusion terms are non-symmetric, not positively defined, and cross-diffusion effects must be strongly marked. The mathematical goal is to establish the existence of weak solutions globally in time for arbitrary number of reacting species. A key point is an entropy-like estimate showing possible renormalization of the system. © 2013 AIP Publishing LLC

Pharmacogene expression during progression of metabolic dysfunction-associated steatotic liver disease: Studies on mRNA and protein levels and their relevance to drug treatment

\ua9 2024. Metabolic dysfunction-associated steatotic liver disease (MASLD) is common worldwide. Genes and proteins contributing to drug disposition may show altered expression as MASLD progresses. To assess this further, we undertook transcriptomic and proteomic analysis of 137 pharmacogenes in liver biopsies from a large MASLD cohort. We performed sequencing on RNA from 216 liver biopsies (206 MASLD and 10 controls). Untargeted mass spectrometry proteomics was performed on a 103 biopsy subgroup. Selected RNA sequencing signals were replicated with an additional 187 biopsies. Comparison of advanced MASLD (fibrosis score 3/4) with milder disease (fibrosis score 0–2) by RNA sequencing showed significant alterations in expression of certain phase I, phase II and ABC transporters. For cytochromes P450, CYP2C19 showed the most significant decreased expression (30 % of that in mild disease) but significant decreased expression of other CYPs (including CYP2C8 and CYP2E1) also occurred. CYP2C19 also showed a significant decrease comparing the inflammatory form of MASLD (MASH) with non-MASH biopsies. Findings for CYP2C19 were confirmed in the replication cohort. Proteomics on the original discovery cohort confirmed decreased levels of several CYPs as MASLD advanced but this decrease was greatest for CYP2C19 where levels fell to 40 % control. This decrease may result in decreased CYP2C19 activity that could be problematic for prescription of drugs activated or metabolized by CYP2C19 as MASLD advances. More limited decreases for other P450s suggest fewer issues with non-CYP2C19 drug substrates. Negative correlations at RNA level between CYP2C19 and several cytokine genes provided initial insights into the mechanism underlying decreased expression

Breast carcinoma and anaplastic gastric carcinoma with pleural metastases in patient after mastectomy 30 years ago

We describe a case of two simultaneous malignancies - anaplastic gastric carcinoma with pleural metastases and left breast carcinoma. These malignancies were recognized in 78-year old woman after right mastectomy performed 30 years ago. Additionaly, during diagnostic procedures rectal polypus found during colonoscopy occurred to be adenoma tubulovillosum. Her parents died from malignancies - mother from gastric cancer and father from pulmonary carcinoma. One should remember that there is always possibility of simultaneous development of more than one primary malignancies in one patient and neoplastic disease is an important cancer risk factor. This observation confirms the important role of genetic factors in the pathogenesis of malignant diseases

Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance

Background & Aims: Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages. Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR. Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2–4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5–8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2–4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD. Lay summary: MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy

Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: diagnostic and mechanistic relevance

Background & Aims: Serum microRNAs (miRNAs) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages.Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 NAFLD cases representing the complete NAFLD spectrum and 10 population controls). MiRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional NAFLD cases and 15 population controls by quantitative reverse transcriptase-polymerase chain reaction.Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages but miR-193a-5p consistently the showed increased levels in all comparisons. Relative to NAFL/NASH with mild fibrosis (stage 0/1), three miRNAs (miR-193a-5p, miR-378d and miR378d) were increased in cases with NASH and clinically significant fibrosis (stage 2-4), seven (miR193a-5p, miR-378d, miR-378e, miR-320b, c, d & e) increased in cases with NAFLD Activity Score (NAS) 5-8 compared with lower NAS, and three (miR-193a-5p, miR-378d, miR-378e) increased but one (miR-19b-3p) decreased in steatosis, activity, and fibrosis "activity" (SAF-A) score 2-4 compared with lower SAF-A. The significant findings for miR-193a-5p were replicated in the additional NAFLD cohort. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n=80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD

Evaluation von Nährmedien für in-vitro Langzeitstudien mit Candida Mischbiofilmen auf medizinischem Silikon

Einleitung: Candida Mischbiofilme verkürzen die Verweildauer von Stimmprothesen bei laryngektomierten Patienten. In vitro Studien zur Testung der Biofilmresistenz neuer Kunststoffmaterialien zeigen eine fehlende Vergleichbarkeit durch Anwendung verschiedener Nährmedien und Inkubationsprotokolle auf. Ziel der Studie ist die in vitro Evaluation von Standard Nährmedien zur Langzeitsimulation von Candida Mischbiofilmen auf medizinischem Silikon in Bezug auf Wachstumskinetik und morphologische Struktur.Methoden: Candida spezies und Bakterien wurden von explantierten Stimmprothesen isoliert. Reine Candida und bakterielle Mischbiofilme wurden mit folgenden Nährmedien auf je 12 Plättchen auf Silikonplättchen gezüchtet: YPD, YNB, M199, Spider Medium, RPMI-1640 2% Glukose, TSB und FBS. Die makroskopische Biofilmbildung wurde kontinuierlich über 22 Tage Inkubation gemessen und danach die Biofilmstrukturen elektronenmikroskopisch untersucht.Ergebnisse: Kontinuierliche Biofilmbildung konnte mit FBS für reine Candida und bakterielle Mischbiofilme erreicht werden. Spider Medium und YPD unterstützten die Bildung von reinen Candida Mischbiofilmen, während bakterielle Mischbiofilme geringeres Wachstum zeigten. YNB, M199, RPMI und TSB zeigten keine makroskopisch zu in vivo Bedingungen vergleichbare Biofilmentwicklung. Elektronenmikroskopisch konnten nährmedienspezifische Unterschiede in der Struktur der extrazellulären Polysaccharidmatrix und der Hyphenbildung festgestellt werden.Schlussfolgerung: In vitro Untersuchungen zu Biofilmresistenz von Stimmprothesenmaterialien erfordern Standardprotokolle. Candida Nährmedien scheinen sich großteils nicht für in vitro Langzeitstudien mit Mischbiofilmkompositionen, wie sie auf explantierten Stimmprothesen vorliegen, zu eignen.Der Erstautor gibt keinen Interessenkonflikt an