Reductive cross-coupling allows the direct C-C bond formation between two organic halides without the need for preformation of an organometallic reagent. A method has been developed for the reductive ...cross-coupling of nonaromatic, heterocyclic bromides with aryl or heteroaryl bromides. The developed conditions use an air-stable Ni(II) source in the presence of a diamine ligand and a metal reductant to allow late-stage incorporation of saturated heterocyclic rings onto aryl halides in a functional-group tolerant manner.
Chronic pain is a common manifestation of Ehlers-Danlos syndrome and hypermobility spectrum disorders; thus it is often suggested that patients undergo generic interdisciplinary pain rehabilitation, ...despite there being little evidence to support this decision. The aim of this study is to examine the effectiveness of standard rehabilitation programmes for chronic pain on patients with Ehlers-Danlos syndrome and hypermobility spectrum disorders, compared with patients with other chronic pain disorders.
Data, collected between 2008 and 2016, were extracted from a Swedish national registry. The patient data comprised of 406 cases with Ehlers-Danlos syndrome or hypermobility spectrum disorders, 784 cases with a whiplash-related diagnosis, 3713 cases with diagnoses relating to spinal pain, and 2880 cases of fibromyalgia.
The differences between groups on key outcome measures from pre- to 1-year follow-up after interdisciplinary pain rehabilitation were analysed using linear mixed effects models. Sensitivity analysis in the form of pattern-mixture modelling was conducted to discern the impact of missing data.
No significant differences were found in improvements from pre- to 1-year follow-up for patients with Ehlers-Danlos syndrome or hypermobility spectrum disorder compared with other diagnostic groups regarding measures of health-related quality of life, mental health, or fatigue. At follow-up, differences in pain interference (d = -0.34 (95% confidence interval 95% CI -0.5 to -0.18)), average pain (d = 0.22 (95% CI 0.11-0.62)) and physical functioning (d = 2.19 (95% CI 1.61-2.77)) were detected for the group with spinal-related diagnoses in relation to those with EDS/HSD, largely due to pre-treatment group differences. Sensitivity analysis found little evidence for missing data influencing the results.
This study suggests that patients with Ehlers-Danlos syndrome/hypermobility spectrum disorders may benefit from inclusion in an interdisciplinary pain rehabilitation programme.
The azaborine motif provides a unique opportunity to develop core isosteres by inserting B-N units in place of C═C bonds within aromatic scaffolds, creating new pseudoaromatic building blocks that ...retain comparable structural features. Previous synthetic routes to the 1,3,2-benzodiazaborole core have used organoboron dichlorides and boronic acids as the boron precursors. The transformation developed herein utilizes entirely bench stable starting materials, including organotrifluoroborates, enabling a wider array of substrate analogues under facile reaction conditions. Furthermore, physical, structural, and electronic properties of these compounds were explored computationally to understand the influence of the B-N replacement on the structure, aromaticity, and isosteric viability of these analogues.
Conditions have been developed for the reductive cross-coupling of 3-bromo-2,1-borazaronaphthalenes with primary and secondary alkyl iodides. This method allows direct alkylation of azaborine cores, ...providing efficient access to functionalized isosteres of naphthalene derivatives.
Forging new C(sp3)–C(sp3) bonds to central positions within a peptide backbone is critical for the development of new therapeutics and chemical probes. Currently, there are no methods for ...decarboxylating Asp and Glu side chains solid-phase photochemically or using such radicals to form peptide macrocycles. Herein, electron-donor-acceptor complexes between Hantzsch ester and on-resin peptide N-hydroxyphthalimide radical precursors are used to access these radicals, demonstrated with two-carbon homologations and homologation cyclizations of Atosiban and RGDf.
Longhorn beetles (Cerambycidae) are a diverse family of beetles that can cause considerable damage as forest pests and vectors of pathogens, as well as being important components of forest food webs ...and ecosystem functionality. In recent years, numerous cerambycid pheromones have been identified, revealing some broad general patterns in functionality in terms of sex or aggregation‐sex pheromones in different subfamilies and different types of compounds characterizing the pheromones of various cerambycid taxa. Here, we describe the identification of the aggregation‐sex pheromones of the Eurasian longhorn beetle Aromia moschata moschata (L.) (Cerambycinae; tribe Callichromatini) and the North American species Holopleura marginata LeConte (Cerambycinae; Holopleurini), as part of an ongoing effort to extend the taxonomic coverage of identified cerambycid pheromones and to expand the prospects for cerambycid monitoring into the study of biodiversity and ecosystem services. Both species were found to use the novel pheromone compound p‐mentha‐1,3‐dien‐9‐ol, which also attracted significant numbers of the longhorn beetle Xestoleptura crassipes (LeConte) (Lepturinae; Lepturini) in trials in California. p‐Mentha‐1,3‐dien‐9‐ol represents a class of pheromone compounds novel to both tribes (Callichromatini and Holopleurini), further increasing the chemical space of identified pheromones within the subfamily Cerambycinae. This compound is also noteworthy because it represents an entirely different chemical class of pheromones than the monoepoxide (E)‐2‐cis‐6,7‐epoxynonenal, previously reported as an aggregation‐sex pheromone for the invasive Asian congener Aromia bungii (Faldermann).
A number of alkynyl pinacolboronates bearing various functional groups were synthesized according to literature methods. These were then stereoselectively reduced to the cis-alkenyl pinacolboronates ...via hydroboration with dicyclohexylborane followed by chemoselective protodeboronation using acetic acid. Treatment with potassium hydrogen fluoride smoothly converted these to the corresponding potassium organotrifluoroborates.
An approach to access azaborininones (carbonyl-containing, boron-based heterocyclic scaffolds) using simple reagents and conditions from both organotrifluoroborates and boronic acids is described. An ...inexpensive, common reagent, SiO
, was found to serve as both a fluorophile and desiccant to facilitate the annulation process across three different azaborininone platforms. Computational analysis of some of the cores synthesized in this study was undertaken to compare the azaborininones with the analogous carbon-based heterocyclic systems. Computationally derived pK
values, NICS aromaticity calculations, and electrostatic potential surfaces revealed a unique isoelectronic/isostructural relationship between these azaborines and their carbon isosteres that changed based on boron connectivity. Correlation to experimentally derived data supports the computational findings.
A uniquely stable acyl potassium trifluoroborate, potassium (2-phenylacetyl)trifluoroborate, has been synthesized and isolated. In the presence of an activating Lewis acid, this reagent reacts with ...azides to form amides in good yields.
Atopic dermatitis is a common and debilitating skin condition characterized by intense itching and chronic inflammation. Research on behavioral treatments with high accessibility is needed.
To ...investigate the efficacy of a highly scalable internet-delivered cognitive behavior therapy (CBT) for adults with atopic dermatitis.
This randomized clinical trial from a medical university in Stockholm, Sweden, included 102 adults with atopic dermatitis, recruited from across Sweden, who received 12 weeks of internet-delivered CBT (March 29, 2017, to February 16, 2018). The first participant provided screening data on November 27, 2016, and the last 1-year follow-up assessment was conducted on June 28, 2019.
Participants were randomized in a 1:1 ratio to 12 weeks of therapist-guided internet-delivered CBT (n = 51) or a control condition (n = 51) that gave instructions about standard care.
The primary outcome was the between-group difference in mean reduction of atopic dermatitis symptoms as measured by the Patient-Oriented Eczema Measure and modeled intention to treat during the 12-week treatment period.
A total of 102 participants (mean SD age, 37 11 years; 83 81% female) were recruited and randomized. The primary analysis indicated that participants receiving internet-delivered CBT, relative to the controls, had a significantly larger mean weekly reduction in symptoms of atopic dermatitis as measured with the Patient-Oriented Eczema Measure (B = 0.32; 95% CI, 0.14-0.49; P < .001), with a moderate to large, controlled effect size after treatment (d = 0.75; 95% CI, 0.32-1.16). Secondary analyses indicated that internet-delivered CBT also produced significantly larger reductions in itch intensity, perceived stress, sleep problems, and depression. Gains were sustained at 12 months of follow-up. Treatment satisfaction was high, and therapists spent a mean (SD) of 39.7 (34.7) minutes per treated patient providing internet-delivered CBT.
Internet-delivered CBT appears to be efficacious for reducing symptoms of atopic dermatitis, despite requiring minimal therapist resources. Thus, internet-delivered CBT has the potential to increase access to effective adjunct behavioral treatment for patients with this common skin condition.
ClinicalTrials.gov Identifier: NCT03051958.
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