Initial (and incidental) diagnosis of plasma cell neoplasm in the liver and gastrointestinal tract – Lessons to be learnt from two cases and literature review

Extramedullary plasma cell neoplasms are an infrequently reported phenomenon in the literature to date as they can pose a diagnostic challenge due to their wide range of clinical presentation. In this review, first we present two cases of extramedullary plasma cell neoplasms involving the liver and the duodenum in which the identification of monoclonal plasma cell populations were incidental findings in the background of other disorders. With these cases and review of literature, we would like to illustrate that although plasma cells can be found under physiological conditions in many tissues, atypical distribution patterns and cytologic atypia should prompt additional workup that can identify incidental plasma cell disease at an extramedullary site

Lyophilization provides long-term stability for a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine

Lipid nanoparticle (LNP)-formulated nucleoside-modified mRNA vaccines have proven to be very successful in the fight against the coronavirus disease 2019 (COVID-19) pandemic. They are effective, safe, and can be produced in large quantities. However, the long-term storage of mRNA-LNP vaccines without freezing is still a challenge. Here, we demonstrate that nucleoside-modified mRNA-LNPs can be lyophilized, and the physicochemical properties of the lyophilized material do not significantly change for 12 weeks after storage at room temperature and for at least 24 weeks after storage at 4??C. Importantly, we show in comparative mouse studies that lyophilized firefly luciferase-encoding mRNA-LNPs maintain their high expression, and no decrease in the immunogenicity of a lyophilized influenza virus hemagglutinin-encoding mRNALNP vaccine was observed after 12 weeks of storage at room temperature or for at least 24 weeks after storage at 4??C. Our studies offer a potential solution to overcome the longterm storage-related limitations of nucleoside-modifie

Role of ion transporters in the bile acid-induced esophageal injury

Barrett's esophagus (BE) is considered to be the most severe complication of gastro-esophageal reflux disease (GERD), in which the prolonged, repetitive episodes of combined acidic and biliary reflux result in the replacement of the squamous esophageal lining by columnar epithelium. Therefore, acid extruding mechanisms of esophageal epithelial cells (EECs) may play an important role in the defence. Our aim was to identify the presence of acid/base transporters on EECs and to investigate the effect of bile acids on their expressions and functions. Human EEC lines (CP-A and CP-D) was acutely exposed to bile acid cocktail (BAC) and the changes in intracellular pH (pHi) and Ca2+ concentration ([Ca2+]i) were measured by microfluorometry. mRNA and protein expression of ion transporters were investigated by RT-PCR, Western Blot and immunohistochemistry. We have identified the presence of Na+/H+ exchanger (NHE), Na+/HCO3- cotransporter (NBC) and a Cl- dependent HCO3- secretory mechanism in CP-A and CP-D cells. Acute administration of BAC stimulated HCO3- secretion in both cell lines and the NHE activity in CP-D cells by an IP3-dependent calcium release. Chronic administration of BAC to EECs increased the expression of ion transporters compared to non-treated cells. Similar expression pattern was observed in biopsy samples from BE compared to normal epithelium. We have shown that acute administration of bile acids differently alters ion transport mechanisms of EECs, whereas chronic exposure to bile acids increases the expression of acid/base transporters. We speculate that these adaptive processes of EECs, represent an important mucosal defence against the bile acid-induced epithelial injury

Modeling Esophagitis Using Human Three-Dimensional Organotypic Culture System

Esophagitis, whether caused by acid reflux, allergic responses, graft-versus-host disease, drugs, or infections, is a common condition of the gastrointestinal tract affecting nearly 20% of the US population. The instigating agent typically triggers an inflammatory response. The resulting inflammation is a risk factor for the development of esophageal strictures, Barrett esophagus, and esophageal adenocarcinoma. Research into the pathophysiology of these conditions has been limited by the availability of animal and human model systems. Three-dimensional organotypic tissue culture (OTC) is an innovative three-dimensional multicellular in vitro platform that recapitulates normal esophageal epithelial stratification and differentiation. We hypothesized that this platform can be used to model esophagitis to better understand the interactions between immune cells and the esophageal epithelium. We found that human immune cells remain viable and respond to cytokines when cultured under OTC conditions. The acute inflammatory environment induced in the OTC significantly affected the overlying epithelium, inducing a regenerative response marked by increased cell proliferation and epithelial hyperplasia. Moreover, oxidative stress from the acute inflammation induced DNA damage and strand breaks in epithelial cells, which could be reversed by antioxidant treatment. These findings support the importance of immune cell-mediated esophageal injury in esophagitis and confirms the utility of the OTC platform to characterize the underlying molecular events in esophagitis

Implementing continuous auditing processes in Quality Management

The aim of this thesis work was to create an internal quality audit system for Sallila Energia Oy. The thesis work is based on the ISO standards, that the Sallila Energia follows. The logic behind the internal quality audit system also works for other standards and supports an organization in achieving compliance and performance through continuous development. Altogether, the standards were parsed into 441 requirements, consisting of four different standards. The internal auditing system contains each of these requirements with one row per requirement. The row contains information of whether it has been completed or not (marked with either “k” for compliance or “?” for need of further specifications or development before compliance), action to be taken and further information regarding the implementation of the potential change or changes. The implementation was supported by the PDSA (Plan-Do-Study-Act) theory, of which the plan and do-phases were part of this thesis work. Findings of this paper show that continuous internal auditing routines function as a base for the development of organizational process planning, and that the internal auditing can raise the organization from being standard complying to being a platform for organizational performance through continuous auditing principles. The internal audit system can be found in Appendix IV