Moderne vor Ort

Die Protagonisten des Buches Camillo Sitte, Otto Wagner, Josef Maria Olbrich, Joseph August Lux, Oskar Strnad und Felix Augenfeld schufen von den spaten 1880er Jahren bis 1938 uber die Zasur des Weltkriegs hinaus eine moderne und ortspezifische Architektur. Den Bedurfnissen einer modernen Massengesellschaft wollten sie mit differenzierten Stadtraumen und kontextuell eingebundenen Bauten Rechnung tragen. In der Formulierung dieser ortspezifischen Variante einer dezidiert modernen Architektur spielten neuentwickelte, nicht-historistische Vergangenheitsbezuge eine wichtige Rolle wie etwa die Entdeckung der vernakularen Architektur der Wiener Innenstadt und der Vorstadte aus dem Vormarz. In funf unterschiedlich zugeschnittenen Kapiteln werden architektonische Schlusselwerke und Theorien in ihrem unmittelbaren Entstehungskontext rekontextualisiert

Mitochondrial genes are altered in blood early in Alzheimer's disease

Although mitochondrial dysfunction is a consistent feature of Alzheimer's disease in the brain and blood, the molecular mechanisms behind these phenomena are unknown. Here we have replicated our previous findings demonstrating reduced expression of nuclear-encoded oxidative phosphorylation (OXPHOS) subunits and subunits required for the translation of mitochondrial-encoded OXPHOS genes in blood from people with Alzheimer's disease and mild cognitive impairment. Interestingly this was accompanied by increased expression of some mitochondrial-encoded OXPHOS genes, namely those residing closest to the transcription start site of the polycistronic heavy chain mitochondrial transcript (MT-ND1, MT-ND2, MT-ATP6, MT-CO1, MT-CO2, MT-C03) and MT-ND6 transcribed from the light chain. Further we show that mitochondrial DNA copy number was unchanged suggesting no change in steady-state numbers of mitochondria. We suggest that an imbalance in nuclear and mitochondrial genome-encoded OXPHOS transcripts may drive a negative feedback loop reducing mitochondrial translation and compromising OXPHOS efficiency, which is likely to generate damaging reactive oxygen species

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

0333 Eine Architektenmonographie als Abrechnung

Otto Wagner was already honoured with a monograph during his lifetime. What may at first glance appear to be a tribute to the architect and his life’s work by the well-known cultural journalist Joseph August Lux reveals itself, in the context of the author’s other writings, as a relatively undisguised attack on the cultural establishment of the Austro-Hungarian monarchy and its art policies. In his Wagner monograph, Lux elaborated on the theme of the artist suffering from the incomprehension of those in power – a motif he had previously developed in several of his novels. Lux too, despite the wide circulation of his books, saw himself as a victim of cultural policy, and thus as a kindred interpreter of Wagner’s creative work and suffering

Moderne vor Ort

Die Protagonisten des Buches Camillo Sitte, Otto Wagner, Josef Maria Olbrich, Joseph August Lux, Oskar Strnad und Felix Augenfeld schufen von den spaten 1880er Jahren bis 1938 uber die Zasur des Weltkriegs hinaus eine moderne und ortspezifische Architektur. Den Bedurfnissen einer modernen Massengesellschaft wollten sie mit differenzierten Stadtraumen und kontextuell eingebundenen Bauten Rechnung tragen. In der Formulierung dieser ortspezifischen Variante einer dezidiert modernen Architektur spielten neuentwickelte, nicht-historistische Vergangenheitsbezuge eine wichtige Rolle wie etwa die Entdeckung der vernakularen Architektur der Wiener Innenstadt und der Vorstadte aus dem Vormarz. In funf unterschiedlich zugeschnittenen Kapiteln werden architektonische Schlusselwerke und Theorien in ihrem unmittelbaren Entstehungskontext rekontextualisiert