Single-Molecule Identification of the Isomers of a Lipidic Antibody Activator

Molecular structural elucidation can be accomplished by different techniques, such as nuclear magnetic resonance or X-ray diffraction. However, the former does not give information about the three-dimensional atomic arrangement, and the latter needs crystallizable solid samples. An alternative is direct, real-space visualization of the molecules by cryogenic scanning tunneling microscopy (STM). This technique is usually limited to thermally robust molecules because an annealing step is required for sample deposition. A landmark development has been the coupling of STM with electrospray deposition (ESD), which smooths the process and widens the scope of the visualization technique. In this work, we present the on-surface characterization of air-, light-, and temperature-sensitive rhamnopolyene with relevance in molecular biology. Supported by theoretical calculations, we characterize two isomers of this flexible molecule, confirming the potential of the technique to inspect labile, non-crystallizable compounds

Iodine(III)-Mediated Selective Intermolecular C–H Amination for the Chemical Diversification of Tryptamines

Defined hypervalent iodine reagents of the general structure PhI­[N­(SO₂R)­(SO₂R′)]₂ promote the selective direct C–H-amination of the indole core of various tryptamines. Starting from a general C2-amination strategy, subsequent transformations enable a variety of site-selective functionalizations, which proceed with noteworthy high chemoselectivity and provide an overall access to structurally diversified products

Preferential Adsorption from Binary Mixtures on Graphite: The n-Decane−n-Heptan-1-ol System

The competitive adsorption of n-decane and n-heptan-1-ol adsorbed from the binary liquid mixture onto graphite has been studied using differential scanning calorimetry, incoherent quasielastic neutron scattering, and 1H and 2H nuclear magnetic resonance. A solid monolayer is identified at all bulk solution compositions with a melting temperature that varies with bulk composition in a manner resembling the bulk behavior. Incoherent elastic neutron scattering, IQNS, and nuclear magnetic resonance, NMR, data indicate that decane is preferentially adsorbed onto the surface over most of the composition range, heptanol being the principal surface component only at very high heptanol concentrations. NMR is proved, for the first time, to be an efficient tool to provide independent information on each component of the system

Ti/Ni-Mediated Inter- and Intramolecular Conjugate Addition of Aryl and Alkenyl Halides and Triflates

In this work, we show that the unique combination of a nickel catalyst and Cp₂TiCl allows the direct conjugate addition of aryl and alkenyl iodides, bromides, and to a lesser extent, chlorides and triflates to α,β-unsaturated carbonyls at room temperature, without requiring the previous formation of an organometallic nucleophile. The reaction proceeds inter- and intramolecularly with good functional group compatibility, which is key for the development of free protecting group methodologies. Carbo- and heterocycles of five- and six-membered rings are obtained in good yields. Moreover, some insights about the mechanism involved have been obtained from cyclic voltammetry, UV–vis, and HRTEM measurements

Ti(III)-Catalyzed Cyclizations of Ketoepoxypolyprenes: Control over the Number of Rings and Unexpected Stereoselectivities

We describe a new strategy to control the number of cyclization steps in bioinspired radical (poly)­cyclizations involving epoxypolyenes containing keto units positioned along the polyene chain. This approach provides an unprecedentedly straightforward access to natural terpenoids with pendant unsaturated side chains. Additionally, in the case of bi- and tricyclizations, decalins with <i>cis</i> stereochemistry have been obtained as a consequence of the presence of the ketone. The preferential formation of <i>cis</i>-fused adducts was rationalized using DFT calculations. This result is completely unprecedented in biomimetic cyclizations and permits the access to natural terpenoids with this stereochemistry, as well as to non-natural analogues

Ti(III)-Catalyzed Cyclizations of Ketoepoxypolyprenes: Control over the Number of Rings and Unexpected Stereoselectivities

We describe a new strategy to control the number of cyclization steps in bioinspired radical (poly)­cyclizations involving epoxypolyenes containing keto units positioned along the polyene chain. This approach provides an unprecedentedly straightforward access to natural terpenoids with pendant unsaturated side chains. Additionally, in the case of bi- and tricyclizations, decalins with <i>cis</i> stereochemistry have been obtained as a consequence of the presence of the ketone. The preferential formation of <i>cis</i>-fused adducts was rationalized using DFT calculations. This result is completely unprecedented in biomimetic cyclizations and permits the access to natural terpenoids with this stereochemistry, as well as to non-natural analogues

Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world

Background Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months. Methods European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as &gt;= 50% and &gt;= 75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response. Results Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0-55.0) years. At baseline, the median of MHD was 20.0 (14.0-28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p&lt;0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p&lt;0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models. Conclusions This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success

Surgical treatment trends and outcomes for anal fistula: fistulotomy is still accurate and safe. Results from a nationwide observational study

PurposeThe aim of the present study was to analyse current surgical treatment preferences for anal fistula (AF) and its subtypes and nationwide results in terms of success and complications.MethodsA retrospective multicentre observational cohort study was conducted. The study period was 1 year (2019), with a follow-up period of at least 1 year. A descriptive analysis of patient characteristics and trends regarding technical options was performed. Univariate and multivariate Cox regression models were used to analyse factors associated with healing and faecal incontinence (FI).ResultsFifty-one hospitals were involved, providing data on 1628 patients with AF. At a median follow-up of 18.3 (9.9-28.3) months, 1231 (75.9%) patients achieved healing, while 390 (24.1%) did not; failure was catalogued as persistence in 279 (17.2.0%) patients and as recurrence in 111 (6.8%). On multivariate analysis, factors associated with healing were fistulotomy (OR 5.5; 95% CI 3.8-7.9; p &lt; 0.001), simple fistula (OR 2.1; 95% CI 1.5-2.8; p &lt; 0.001), single tract (HR 1.9; 95% CI 1.3-2.8; p &lt; 0.001) and number of preparatory surgeries (none vs. 3; HR 1.8; 95% CI 1.2-2.8; p = 0.006). Regarding de novo FI, in the multivariate analysis previous anal surgery (OR 1.5, 95% CI 1.0-2.4, p = 0.037), age (OR 1.02, 95% CI 1.00-1.04, p = 0.002) and being female (OR 1.7, 95% CI 1.1-2.5, p = 0.008) were statistically related.ConclusionsAnal fistulotomy is the most used procedure for AF, especially for simple AF, with a favourable overall balance between healing and continence impairment. Sphincter-sparing or minimally invasive sphincter-sparing techniques resulted in lower rates of healing. In spite of their intended sphincter-sparing design, a certain degree of FI was observed for several of these techniques