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Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired haematopoietic stem cell disease characterized by complement-mediated intravascular hemolysis, thrombosis, and bone marrow failure. Eculizumab and ravulizumab are anti-C5 monoclonal antibodies that reduce hemolysis, anaemia and thrombotic risk, but are associated with increased risk of infection with encapsulated bacteria, including Neisseria meningitidis. We report a case of life-threatening infection by non-groupable Neisseria meningitidis in a young PNH patient treated with ravulizumab. Despite prompt admission to the intensive care unit, microbe isolation was delayed due to the negativity of capsular antigens, and the patient required intubation, dialysis, and transfusion support for pancytopenia. Notably, PNH disease activity remained controlled and no additional anti-C5 doses were administered. Increasing awareness regarding septic risk in PNH patients on complement inhibitors despite vaccinations is pivotal. A warning about serotypes generally not pathogenetic and not covered by vaccination, such as non-capsulated forms, is emerging.

Huntington disease (HD) is a neurodegenerative disorder caused by the expansion of a polyglutamine tract in the huntingtin (mHtt) protein. Here the authors suggest that mHtt promotes ribosome stalling and inhibits protein synthesis.

Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MCs) in extra-cutaneous organs. It could be divided into indolent SM, smoldering SM, SM with an associated hematologic (non-MC lineage) neoplasm, aggressive SM, and mast cell leukemia. SM is generally associated with the presence of a gain-of-function somatic mutation in KIT at codon 816. Clinical features could be related to MC mediator release or to uncontrolled infiltration of MCs in different organs. Whereas indolent forms have a near-normal life expectancy, advanced diseases have a poor prognosis with short survival times. Indolent forms should be considered for symptom-directed therapy, while cytoreductive therapy represents the first-line treatment for advanced diseases. Since the emergence of tyrosine kinase inhibitors (TKIs), KIT inhibition has been an attractive approach. Initial reports showed that only the rare KITD816V negative cases were responsive to first-line TKI imatinib. The development of new TKIs with activity against the KITD816V mutation, such as midostaurin or avapritinib, has changed the management of this disease. This review aims to focus on the available clinical data of therapies for SM and provide insights into possible future therapeutic targets.

Cyanobacteria are of major interest in freshwater ecosystems, since they are able to produce toxins with potentially negative impacts on the environment, health and thus on economics and society. It is therefore important for water management authorities to assess the manner in which cyanobacteria may evolve under climate change, especially in the Alpine Region where warming is projected by climate models to be more important than the global average. In this study, air temperature extremes under current climate were used as a proxy for future "average" climate forced by enhanced greenhouse gas concentrations. The impacts of extreme temperature events on cyanobacteria were analyzed in five deep peri-Alpine lakes, covering the entire trophic gradient and using a synoptic approach. Extreme air temperatures were observed to alter the biomass of the cyanobacteria community. In general, extreme hot events are associated with high biomass while extreme cold events are characterised by low biomass. However, the assessed air temperature extremes did not lead to a dominance of cyanobacteria over the other phytoplankton groups, which also showed responses in relative biomass change during extreme events. Both extreme hot and extreme cold events were seen to generate a loss of diversity among cyanobacteria. In addition, the use of extreme events as a proxy to "average" future climates is a useful approach to enhance possible impacts of future global warming on the biota in freshwater systems. The outcomes of a synoptic approach provide general responses and are a useful tool for further modelling purposes.

This work focuses on informal politics for the political elite level in the Czech Republic and proposes an actor-based view. It considers the relationship between formal and informal structures and the functions of informality. I analyse areas highly affected by informality: the justice system and anti-corruption agencies as well as state ministries and state monopolies distributing large amounts of money, and identify patterns of informality. Additionally, the work shows the effect of informality for the European level. The work concludes with a rather pessimistic view on the effects of informal politics in a democratic country.