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

Neuroinflammatory processes in cognitive disorders:Is there a role for flavonoids and n-3 polyunsaturated fatty acids in counteracting their detrimental effects?

Neuroinflammatory processes are known to contribute to the cascade of events culminating in the neuronal damage that underpins neurodegenerative disorders such as Parkinson's and Alzheimer's disease. With the ageing population and increased cases of neurodegenerative diseases, there is a crucial need for the development of new strategies capable to prevent, delay the onset or treat brain dysfunction and associated cognitive decline. Growing evidence sheds light on the use of dietary polyphenols and n-3 long chain polyunsaturated fatty acids to improve cognitive performances and reduce the neuroinflammatory and oxidative stress responses occurring with age and neurodegenerative pathologies. This review will summarise the most recent information related to the impact and mechanisms underlying the neuroinflammatory processes in neurodegenerative disorders. We will also detail the current evidence indicating that flavonoids and n-3 polyunsaturated fatty acids are strong candidate in preventing neuroinflammation and modulating age-related memory decline, and will describe the potential mechanisms of action underlying their neuroprotective effects. As such, these dietary bioactives represent important precursor molecules in the quest to develop of a new generation of drugs capable of counteracting neuroinflammation and neurodegenerative diseases

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

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

The Third EAHN Meeting in Turin: A Roundup

Turin, the home of a lively community of historians and a city that has attracted the interest of architectural and urban historians across the whole 20th century, was chosen to host the Third EAHN Meeting in 2014. In accordance with the network's spirit of enhancing communication and encouraging the exchange of research outputs well beyond the boundaries of the European framework, the Third Meeting welcomed a large international community of scholars who delivered and discussed 157 papers and discussion positions. With the aim of recording some of the major outcomes of this very intense programme, seven delegates were asked to review the key issues emerging from the conference sessions, and to outline their underlying methodologies. The result is a cross-section of the discipline that highlights a composite tableau of approaches to the study of the built environment and raises a series of issues affecting our area of investigation, its competencies, instruments, and objects of research