Serotonin reduction in post-acute sequelae of viral infection.

Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, which impacts serotonin storage; and enhanced MAO-mediated serotonin turnover. Peripheral serotonin reduction, in turn, impedes the activity of the vagus nerve and thereby impairs hippocampal responses and memory. These findings provide a possible explanation for neurocognitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes.

The enteric nervous system relays psychological stress to intestinal inflammation.

Mental health profoundly impacts inflammatory responses in the body. This is particularly apparent in inflammatory bowel disease (IBD), in which psychological stress is associated with exacerbated disease flares. Here, we discover a critical role for the enteric nervous system (ENS) in mediating the aggravating effect of chronic stress on intestinal inflammation. We find that chronically elevated levels of glucocorticoids drive the generation of an inflammatory subset of enteric glia that promotes monocyte- and TNF-mediated inflammation via CSF1. Additionally, glucocorticoids cause transcriptional immaturity in enteric neurons, acetylcholine deficiency, and dysmotility via TGF-ß2. We verify the connection between the psychological state, intestinal inflammation, and dysmotility in three cohorts of IBD patients. Together, these findings offer a mechanistic explanation for the impact of the brain on peripheral inflammation, define the ENS as a relay between psychological stress and gut inflammation, and suggest that stress management could serve as a valuable component of IBD care.

Retro-Diels-Alder decomposition of norbornadiene mediated by a cationic magnesium complex.

First evidence for the coordination of norbornadiene (nbd) and dicyclopentadiene (dcpd) with the main group metal Mg is provided by the crystal structures of adducts with cationic ß-diketiminate (BDI) Mg complexes. While the dcpd complex is thermally stable, [(BDI)Mg+·nbd][B(C6F5)4-] shows slow room temperature retro-Diels-Alder decomposition to give a complex with the cation (BDI)Mg(C5H5)Mg(BDI)+.

[Cost minimization analysis of flexible ENT-endoscopes]. / Kostenvergleichsanalyse von flexiblen HNO-Endoskopen.

BACKGROUND: Reprocessing of complex instruments like flexible ENT-endoscopes with and without working channel are challanging for clinics and private practices. Aim of the study was to analyse the costs of an examination with a reusable endoscope-system and to compare it with two single-use endoscope-systems. MATERIAL AND METHODS: A cost minimization analysis was performed at the Department of Otorhinolaryngology, Head and Neck Surgery of the University Medical Center in Mainz, Germany. The local reusable endoscopy-system was compared with two single-use endoscopy-systems of Ambu and Karl Storz. RESULTS: Overall costs per examination with a reusable-scope were 23.03 € (11.60 € investment costs + 5.09 € repair costs + 6.34 € reprocessing costs). The single-use Endoscopy-system of Ambu resulted in 120.43 € per examination (120.00 € acquisition costs + 0.43 € storage costs). Overall costs for the single-use endoscopy-system of Karl Storz were 223.44 € per examination (investment costs for monitors 3.01 € + 220.00 € acquisition costs + 0.43 € storage costs). DISCUSSION: Flexible single-use ENT-endoscopy-systems generate higher costs in comparison to conventional reusable ones. But there are also advantages from the medical and economical side. CONCLUSION: A smart mix of reusable and single-use endoscopy systems seems therefore usefull.

Unsupported Mg-Alkene Bonding.

The first intermolecular early main group metal-alkene complexes were isolated. This was enabled by using highly Lewis acidic Mg centers in the Lewis base-free cations (Me BDI)Mg+ and (tBu BDI)Mg+ with B(C6 F5 )4 - counterions (Me BDI=CH[C(CH3 )N(DIPP)]2 , tBu BDI=CH[C(tBu)N(DIPP)]2 , DIPP=2,6-diisopropylphenyl). Coordination complexes with various mono- and bis-alkene ligands, typically used in transition metal chemistry, were structurally characterized for 1,3-divinyltetramethyldisiloxane, 1,5-cyclooctadiene, cyclooctene, 1,3,5-cycloheptatriene, 2,3-dimethylbuta-1,3-diene, and 2-ethyl-1-butene. In all cases, asymmetric Mg-alkene bonding with a short and a long Mg-C bond is observed. This asymmetry is most extreme for Mg-(H2 C=CEt2 ) bonding. In bromobenzene solution, the Mg-alkene complexes are either dissociated or in a dissociation equilibrium. A DFT study and AIM analysis showed that the C=C bonds hardly change on coordination and there is very little alkene→Mg electron transfer. The Mg-alkene bonds are mainly electrostatic and should be described as Mg2+ ion-induced dipole interactions.

Highly Active Superbulky Alkaline Earth Metal Amide Catalysts for Hydrogenation of Challenging Alkenes and Aromatic Rings.

Two series of bulky alkaline earth (Ae) metal amide complexes have been prepared: Ae[N(TRIP)2 ]2 (1-Ae) and Ae[N(TRIP)(DIPP)]2 (2-Ae) (Ae=Mg, Ca, Sr, Ba; TRIP=SiiPr3 , DIPP=2,6-diisopropylphenyl). While monomeric 1-Ca was already known, the new complexes have been structurally characterized. Monomers 1-Ae are highly linear while the monomers 2-Ae are slightly bent. The bulkier amide complexes 1-Ae are by far the most active catalysts in alkene hydrogenation with activities increasing from Mg to Ba. Catalyst 1-Ba can reduce internal alkenes like cyclohexene or 3-hexene and highly challenging substrates like 1-Me-cyclohexene or tetraphenylethylene. It is also active in arene hydrogenation reducing anthracene and naphthalene (even when substituted with an alkyl) as well as biphenyl. Benzene could be reduced to cyclohexane but full conversion was not reached. The first step in catalytic hydrogenation is formation of an (amide)AeH species, which can form larger aggregates. Increasing the bulk of the amide ligand decreases aggregate size but it is unclear what the true catalyst(s) is (are). DFT calculations suggest that amide bulk also has a noticeable influence on the thermodynamics for formation of the (amide)AeH species. Complex 1-Ba is currently the most powerful Ae metal hydrogenation catalyst. Due to tremendously increased activities in comparison to those of previously reported catalysts, the substrate scope in hydrogenation catalysis could be extended to challenging multi-substituted unactivated alkenes and even to arenes among which benzene.

Alkene Transfer Hydrogenation with Alkaline-Earth Metal Catalysts.

The alkene transfer hydrogenation (TH) of a variety of alkenes has been achieved with simple AeN''2 catalysts [Ae=Ca, Sr, Ba; N''=N(SiMe3 )2 ] using 1,4-cyclohexadiene (1,4-CHD) as a H source. Reaction of 1,4-CHD with AeN''2 gave benzene, N''H, and the metal hydride species N''AeH (or aggregates thereof), which is a catalyst for alkene hydrogenation. BaN''2 is by far the most active catalyst. Hydrogenation of activated C=C bonds (e.g. styrene) proceeded at room temperature without polymer formation. Unactivated (isolated) C=C bonds (e.g. 1-hexene) needed a higher temperature (120 °C) but proceeded without double-bond isomerization. The ligands fully control the course of the catalytic reaction, which can be: 1) alkene TH, 2) 1,4-CHD dehydrogenation, or 3) alkene polymerization. DFT calculations support formation of a metal hydride species by deprotonation of 1,4-CHD followed by H transfer. Convenient access to larger quantities of BaN''2 , its high activity and selectivity, and the many advantages of TH make this a simple but attractive procedure for alkene hydrogenation.