Anxiety and depression symptoms among patients with long COVID: a retrospective cohort study.

Patients suffering from post-acute sequelae of COVID-19 (PASC) have a higher prevalence of anxiety and depression than the general population. The long-term trajectory of these sequelae is still unfolding. To assess the burden of anxiety and depression among patients presenting to the University of Iowa Hospitals and Clinics (UIHC) post-COVID-19 clinic, we analyzed how patient factors influenced Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) scores. In this retrospective cohort study, the GAD-7 and PHQ-9 questionnaire scores of patients presenting to the UIHC post-COVID clinic between March 2021-February 2022 (N = 455) were compared to the scores of a sample of patients presenting to the general internal medicine (GIM) clinic during the same period (N = 94). Our analysis showed that patients with an absent history of depression on their electronic medical record (EMR) problem list scored significantly higher on the GAD-7 (mean difference -1.62, 95% CI -3.12 to -0.12, p = 0.034) and PHQ-9 (mean difference -4.45, 95% CI -5.53 to -3.37, p < 0.001) questionnaires compared to their similar counterparts in the GIM clinic. On the other hand, patients with an absent history of anxiety on their EMR problem list scored significantly higher on the GAD-7 (mean difference -2.90, 95% CI -4.0 to -1.80, p < 0.001) but not on the PHQ-9 questionnaire (p = 0.196). Overall, patients with PASC may have experienced a heavier burden of newly manifest anxiety and depression symptoms compared to patients seen in the GIM clinic. This suggests that the mental health impacts of PASC may be more pronounced in patients with no prior history of anxiety or depression.

Exploring Conformational Landscapes Along Anharmonic Low-Frequency Vibrations.

We aim to automatize the identification of collective variables to simplify and speed up enhanced sampling simulations of conformational dynamics in biomolecules. We focus on anharmonic low-frequency vibrations that exhibit fluctuations on time scales faster than conformational transitions but describe a path of least resistance toward structural change. A key challenge is that harmonic approximations are ill-suited to characterize these vibrations, which are observed at far-infrared frequencies and are easily excited by thermal collisions at room temperature. Here, we approached this problem with a frequency-selective anharmonic (FRESEAN) mode analysis that does not rely on harmonic approximations and successfully isolates anharmonic low-frequency vibrations from short molecular dynamics simulation trajectories. We applied FRESEAN mode analysis to simulations of alanine dipeptide, a common test system for enhanced sampling simulation protocols, and compared the performance of isolated low-frequency vibrations to conventional user-defined collective variables (here backbone dihedral angles) in enhanced sampling simulations. The comparison shows that enhanced sampling along anharmonic low-frequency vibrations not only reproduces known conformational dynamics but can even further improve the sampling of slow transitions compared to user-defined collective variables. Notably, free energy surfaces spanned by low-frequency anharmonic vibrational modes exhibit lower barriers associated with conformational transitions relative to representations in backbone dihedral space. We thus conclude that anharmonic low-frequency vibrations provide a promising path for highly effective and fully automated enhanced sampling simulations of conformational dynamics in biomolecules.

Linear and Nonlinear Dielectric Response of Intrinsically Disordered Proteins.

Linear and nonlinear dielectric responses of solutions of intrinsically disordered proteins (IDPs) were analyzed by combining molecular dynamics simulations with formal theories. A large increment of the linear dielectric function over that of the solvent is found and related to large dipole moments of IDPs. The nonlinear dielectric effect (NDE) of the IDP far exceeds that of the bulk electrolyte, offering a route to interrogate protein conformational and rotational statistics and dynamics. Conformational flexibility of the IDP makes the dipole moment statistics consistent with the gamma/log-normal distributions and contributes to the NDE through the dipole moment's non-Gaussian parameter. The intrinsic non-Gaussian parameter of the dipole moment combines with the protein osmotic compressibility in the nonlinear dielectric susceptibility when dipolar correlations are screened by the electrolyte. The NDE is dominated by dipolar correlations when electrolyte screening is reduced.

Formation of a diiron-(µ-η1:η1-CN) complex from acetonitrile solution.

The activation of C-C bonds by transition-metal complexes is of continuing interest and acetonitrile (MeCN) has attracted attention as a cyanide source with comparatively low toxicity for organic cyanation reactions. A diiron end-on µ-η1:η1-CN-bridged complex was obtained from a crystallization experiment of an open-chain iron-NHC complex, namely, µ-cyanido-κ2C:N-bis{[(acetonitrile-κN)[3,3'-bis(pyridin-2-yl)-1,1'-(methylidene)bis(benzimidazol-2-ylidene)]iron(II)} tris(hexafluorophosphate), [Fe2(CN)(C2H3N)2(C25H18N6)2](PF6)3. The cyanide appears to originate from the MeCN solvent by C-C bond cleavage or through carbon-hydrogen oxidation.

Synthesis, characterization, and biomedical evaluation of ethylene-bridged tetra-NHC Pd(ii), Pt(ii) and Au(iii) complexes, with apoptosis-inducing properties in cisplatin-resistant neuroblastoma cells.

Synthesis and characterization of the first two cyclic ethylene-bridged tetradentate NHC ligands, with an unsaturated (imidazole) and saturated backbone (2-imidazoline), are described. Complexes of both ligands containing palladium(ii) have been obtained. For platinum(ii) and gold(iii), only the unsaturated tetracarbene complexes could be isolated. The attempts to synthesize a methylene-bridged 2-imidazoline macrocycle are also described. Furthermore, a novel bisimidazolinium ligand precursor and its open-chain PdII and PtII tetracarbene complexes are obtained. Finally, it is shown that the unsaturated gold(iii) tetracarbene is able to induce apoptosis in malignant SK-N-AS neuroblastoma cells via the mitochondrial and ROS pathway and overcomes resistance to cisplatin in vitro.

Intravenous iron therapy for patients with iron deficiency and heart failure: a systematic review and meta-analysis of randomized controlled trials.

Introduction: Heart failure (HF) presents a significant health challenge, with intravenous (IV) iron therapy considered a potential treatment avenue. Method: We assessed IV iron therapy's efficacy in HF patients with concurrent iron deficiency versus standard of care. Primary outcomes included the composite of HF hospitalizations or cardiovascular-related mortality, HF hospitalizations, and all-cause, HF, and cardiovascular mortality rates. Secondary measures encompassed improvements in New York Heart Association functional classification, quality of life, 6-minute walk test, left ventricular ejection fraction, and adverse events. We used a random-effects model to compute relative risk (RR) or mean difference (MD) with 95% confidence intervals (CIs). Results: Based on an analysis of 14 randomized controlled trials involving 6614 patients, IV iron therapy significantly reduced composite outcome (RR: 0.84, 95% CI: 0.73, 0.96; P = 0.01) and HF hospitalizations (RR: 0.74, 95% CI: 0.61, 0.89; P = 0.002) compared to standard of care. Mortality rates showed no significant difference. IV iron therapy improved New York Heart Association functional classification, quality of life, and 6-minute walk test, with no major impact on left ventricular ejection fraction. Adverse events remained stable. Conclusions: IV iron therapy holds promise for diminishing HF hospitalizations and enhancing quality of life and 6-minute walk test in HF patients. Yet, its effect on all-cause or cardiovascular mortalities appears limited.

The European Polysaccharide Network of Excellence (EPNOE) research roadmap 2040: Advanced strategies for exploiting the vast potential of polysaccharides as renewable bioresources.

Polysaccharides are among the most abundant bioresources on earth and consequently need to play a pivotal role when addressing existential scientific challenges like climate change and the shift from fossil-based to sustainable biobased materials. The Research Roadmap 2040 of the European Polysaccharide Network of Excellence (EPNOE) provides an expert's view on how future research and development strategies need to evolve to fully exploit the vast potential of polysaccharides as renewable bioresources. It is addressed to academic researchers, companies, as well as policymakers and covers five strategic areas that are of great importance in the context of polysaccharide related research: (I) Materials & Engineering, (II) Food & Nutrition, (III) Biomedical Applications, (IV) Chemistry, Biology & Physics, and (V) Skills & Education. Each section summarizes the state of research, identifies challenges that are currently faced, project achievements and developments that are expected in the upcoming 20 years, and finally provides outlines on how future research activities need to evolve.