The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes

The thymus plays distinct roles in the pathogenesis of the different Myasthenia gravis (MG) subtypes. Inflammatory, neoplastic and age-related alterations of the thymus are of pivotal relevance for the initiation of anti-acetylcholine receptor (AChR) autoimmunity in early onset MG, thymoma-associated MG and, likely, late onset MG, respectively. By contrast, the thymus is presumably not related to MG that is due to autoantibodies to the muscle specific kinase, MuSK. Finally, the role of the thymus is still obscure in MG defined by antibodies against the agrin receptor LRP4 and in MG without all of the above autoantibdies (triple sero-negative MG) since these MG subtypes have been described only recently and thymectomy has not been their standard treatment. This review aims to give an update on intrathymic mechanisms of tolerance breakdown in MG, including abnormal T cell selection and activation, the role of thymic myoid cells, the autoimmune regulator (AIRE) and regulatory T cells.     

Activation of RhoA,B,C by Yersinia Cytotoxic Necrotizing Factor (CNFy) Induces Apoptosis in LNCaP Prostate Cancer Cells

Prostate cancer is the most common malignancy, accounting for about 25% of all incident cases among men in industrialized countries. The human androgen-dependent prostate cancer cell line LNCaP, which is derived from a metastatic lesion of human prostatic adenocarcinoma, is frequently used to study prostate cancer associated signaling pathways in vitro. Recently it was described that Rho GTPase activation in these cells leads to apoptotic responses. We used the bacterial toxins CNFy and CNF1, which specifically and directly activate Rho GTPases by deamidation of a single glutamine. We asked whether these Rho activators could induce apoptosis in LNCaP cells. Our results indicate that RhoA activation, induced by CNFy, does lead to intrinsic apoptosis of the cells. Analysis of the underlying signaling pathway reveals that apoptosis induction requires the activity of Rho kinase (ROCK) and myosin activation, an apoptotic pathway previously identified in cancer stem cells.     

Consensus statement on prevention and management of adverse effects following rejuvenation procedures with hyaluronic acid‐based fillers

Facial fillers play an important role in the correction of facial changes associated with ageing. They offer quick treatments in the outpatient setting with minimal subsequent downtime that provide predictable, natural‐looking, long‐lasting results. Adverse reactions after hyaluronic acid injections tend to be mild or moderate and rather temporary. However, as with all injected or implanted biomaterials, severe adverse events can occur and patients must be fully informed of potential risks prior to undergoing treatment. A panel of experts from Germany (D), Austria (A) and Switzerland (CH) developed recommendations, and this study provides the ‘DACH Consensus Recommendations’ from this group specifically on the use of hyaluronic acid fillers. The aim is to help clinicians recognize potential risks and to provide guidance on how best to treat adverse events if they arise. Contraindications to hyaluronic acid fillers are also detailed, and ways to prevent adverse events occurring are discussed. Hyaluronic acid‐based products are claimed to be very close to an ideal tissue augmentation agent; nevertheless, profound medical, anatomical and product knowledge are of paramount importance to minimize the occurrence of adverse reactions.     

Enzymes Enhance Biofilm Removal Efficiency of Cleaners

Efficient removal of biofilms from medical devices is a big challenge in health care to avoid hospital-acquired infections, especially from delicate devices like flexible endoscopes, which cannot be reprocessed using harsh chemicals or high temperatures. Therefore, milder solutions such as enzymatic cleaners have to be used, which need to be carefully developed to ensure efficacious performance. In vitro biofilm in a 96-well-plate system was used to select and optimize the formulation of novel enzymatic cleaners. Removal of the biofilm was quantified by crystal violet staining, while the disinfecting properties were evaluated by a BacTiter-Glo assay. The biofilm removal efficacy of the selected cleaner was further tested by using European standard (EN) for endoscope cleaning EN ISO 15883, and removal of artificial blood soil was investigated by treating TOSI (Test Object Surgical Instrument) cleaning indicators. Using the process described here, a novel enzymatic endoscope cleaner was developed, which removed 95% of Staphylococcus aureus and 90% of Pseudomonas aeruginosa biofilms in the 96-well plate system. With a >99% reduction of CFU and a >90% reduction of extracellular polymeric substances, this cleaner enabled subsequent complete disinfection and fulfilled acceptance criteria of EN ISO 15883. Furthermore, it efficiently removed blood soil and significantly outperformed comparable commercial products. The cleaning performance was stable even after storage of the cleaner for 6 months. It was demonstrated that incorporation of appropriate enzymes into the cleaner enhanced performance significantly.