ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.Peer reviewe

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed

Transition Metal Complexes of a New Ylide-Like Silylene

2006 wurde in unserer Arbeitsgruppe das stabile Silylen 5 entwickelt. Ziel der Arbeit war es, Übergangsmetall-Silylen-Komplexe zu synthetisieren und deren Reaktivität zu untersuchen. Das Silylen 5 wurde mit verschiedenen Übergangsmetallverbindungen umgesetzt, dabei erwiesen sich halogenhaltige Verbindungen als ungeeignet. Als bevorzugte Methode zur Darstellung von Silylen-Komplexen erwies sich die Substitution. Dieses sechsgliedrige N-heterocyclische Silylen zeigt aufgrund seiner einzigartigen zwitterionischen Struktur eine sehr ungewöhnliche Reaktivität. Neben dem elektronenarmen Siliciumzentrum mit dem freien Elektronenpaar ist v.a. die elektronenreiche CH2-Gruppe im Ligandenrückgrat, die sehr leicht von Elektrophilen angegriffen werden kann, entscheidend für die Reaktivität verantwortlich. Diese fungiert im Silylen auch als Elektronenakzeptor und verringert die Elektronendichte innerhalb des Ringsystems. Dadurch verstärken sich die pi-Akzeptorfähigkeiten des Silylens erheblich. Dies zeigt sich z.B. darin, dass das Silylen 5 in der Lage ist ungewöhnliche und hochreaktive Übergangsmetallfragmente wie Ni0(eta.6-Aren) zu stabilisieren. Die Silylen-Ni0(eta.6-Aren)-Komplexe 42, 48, 49 und 50 sind thermisch bemerkenswert stabil. In C6D6-Lösung werden die Arenliganden in einer Gleichgewichtsreaktion ausgetauscht, was mittels NMR-Spektroskopie verfolgt werden konnte. Der Silylenligand behält dabei seine ylidartige Struktur und so können die elektronischen Eigenschaften des Liganden durch Addition von B(C6F5)3 an die exocyclische CH2-Gruppe variiert werden, während dieser am Metallzentrum koordiniert bleibt. Des Weiteren erhält man durch Substitution des eta.6-Toluolliganden in Verbindung 42 mit CO quantitativ den Silylen-Ni(CO)3-Komplex 56. Auch in diesem Fall behält der Silylenligand seine ylid-artige Struktur und addiert bereitwillig B(C6F5)3 oder ein Proton an die exocyclische CH2-Gruppe. Das freie Elektronenpaar am Siliciumzentrum ist im Komplex 56 durch die Koordination geschützt. Die Aktivierung von kleinen Molekülen mit Element-Wasserstoff-Bindungen wie z.B. H2O, HOTf, H2S oder PH3 gelingt somit über eine charakteristische 1,4-Addition an den Silylenliganden während dieser am Ni-Zentrum koordiniert bleibt. Sogar die Aktivierung von stark basischen Molekülen wie NH3 ist mit dem Silylen 5 als beteiligtem Liganden möglich. Die dabei gebildeten Verbindungen (57, 73, 74, 75, 78 und 79) können der Gruppe der basenstabilisierten Silylen-Komplexe zugeordnet werden. Durch diese Additionsreaktionen lassen sich die sigma-Donor-/pi-Akzeptoreigenschaften des Si(II)-Liganden über einen sehr weiten Bereich variieren, während dieser an das Metallzentrum gebunden bleibt. Mittels IR-Spektroskopie lassen sich diese elektronischen Eigenschaften anhand der n(CO)A1-Schwingungsfrequenzen sehr gut mit denen von Phosphanen und N-heterocyclischen Carbenen vergleichen. Mit den gewonnenen Kenntnissen über die Reaktivität des Silylenliganden konnte im Folgenden die Komplexität der Verbindungen weiter erhöht werden. Durch Addition von bifunktionellen Liganden mit einer E-H-Bindung (E = O, S, N) wird eine zweite Donorfunktion eingeführt, die für die Koordination an ein zweites Metallzentrum genutzt werden kann. Dies wurde am Beispiel der Addition eines Phosphinoalkohols zum Komplex 88 und anschließender Koordination an ein Rhodiumzentrum gezeigt. Eine weitere Methode zur Darstellung von heterobimetallischen Komplexen wurde durch die Deprotonierung des Hydroxysilylen-Komplexes 57 mit nBuLi zum dimeren Lithiumsilanolat 82 eröffnet.In 2006 the new stable silylene 5 was developed in our group. The objective of this work was to synthesize and investigate transition metal complexes with this particular silylene as ligand with regards to their structure and reactivity. Therefore silylene 5 was reacted in various ways with transition metal compounds. Halogen metal compounds were proven to be unsuitable as the starting material and the method of choice for synthesizing silylene complexes was found to be ligand substitution reactions. This six-membered N-heterocyclic silylene 5 exhibits an unique reactivity due to an unique ylide-like structure. Besides the electron lone pair at the silicon center, it has been shown, that the electron-rich CH2-group in the backbone is a potent nucleophile and exerts an essential influence on the reactivity. It shows remarkable electron acceptor qualities and lowers the electron density within the silylene ring system. This entails a stronger pi-acceptor capability at the silicon center and therefore, increases M→Si-backdonation as compared to other N-heterocyclic silylenes. As a result of the well-balancedsigma-donor/pi-acceptor abilities silylene 5 is capable to stabilize even highly reactive transition metal fragments like Ni0(eta.6-arene). The resulting silylene-Ni0(eta.6-arene) complexes 42, 48, 49 and 50 are thermally remarkable stable. NMR experiments reveal that the arene ligands are slowly exchanged by C6D6 in an equilibrium reaction. The exocyclic methylene group of silylene complex 42 retains its nucleophilic character. That offers the possibility to variate the electronic properties of the silylene ligand while being coordinated to the metal center by addition of B(C6F5)3. Furthermore, the eta.6-bound toluene ligand could be easily substituted by CO to yield quantitatively silylene-Ni(CO)3 complex 56, which still exhibits the ylide-like mesomeric structure and reacts readily with e.g. B(C6F5)3 or a proton at the exocyclic methylene group. The electron lone pair at the silicon center is protected by coordination to the metal center. Therefore, activation of small molecules with element-hydrogen bonds proceeds via a characteristic 1,4-addition at the silylene ligand without breaking the silicon-metal bond. With silylene 5 as a non-innocent ligand, even activation of strongly basic molecules like NH3 is possible. The formed addition products (57, 73, 74, 75, 78 and 79) are classified as base-stabilized silylene complexes. Starting from complex 56 the donor/acceptor abilities of the silylene ligand can be varied over a wide range while still being attached to the Ni(CO)3 fragment. The Ni(CO)3 moiety serves as an ideal probe in IR spectroscopy to estimate the electronic properties of the corresponding Si(II) ligands and allows to compare them with known phosphines and N-heterocyclic carbenes. With the knowledge gained about reactivity of the silylene as a ligand, the complexity of the formed compounds can be further expanded. By addition of bifunctional ligands with an E-H bond (E = O, S, N) a second donor function is introduced, which is suitable for the coordination to a second metal center. This has been shown e.g. by the addition of 3-(diphenylphosphino)propanol and subsequent coordination to a rhodium center. Another strategy for the synthesis of heterobimetallic complexes is opened up by the deprotonation of the hydroxysilylene complex 57 with nBuLi forming the dimeric lithium silanolate 82