Virtual Trauma Meeting as a Component of Undergraduate Orthopaedic Education.

Introduction: Virtual teaching has proven effective for medical students during the COVID-19 pandemic. This study is the first to describe an undergraduate orthopaedic teaching strategy in the format of virtual trauma meetings (VTM).

Methods: Clinical medical students from the Universities of Bristol and Cardiff were invited to attend five VTM between October and November 2020.

Cerebral amyloid angiopathy distribution in older people: A cautionary note.

Introduction: Radiolabeled ligands for fibrillar amyloid beta (Aβ) peptides are used in positron emission tomography (PET) for dementia diagnosis. Current ligands do not discriminate parenchymal amyloid plaques from cerebral amyloid angiopathy (CAA).

Methods: We undertook neuropathological examination of 65 older people (81.

Use of Surgical Adhesive Tape to Maintain Tension on Intrafocal K-Wires for Easy Reduction and Fixation of Complex Intra-Articular Distal Radius Fractures.

Maintaining reduction during fixation of complex intra-articular distal radius fractures with dorsal comminution can be challenging. We describe an operative technique where reduction is achieved with temporary intrafocal Kirschner wires (K-wires), and held using surgical adhesive tape wrapped around the hand, whilst a volar plate is applied to achieve rigid fixation. This is a simple, inexpensive method used at our institutions which allows fixation of these fractures without the need for an operative assistant.

On-Resin Macrocyclization of Peptides Using Vinyl Sulfonamides as a Thiol-Michael "Click" Acceptor.

Macrocyclization of linear peptides imparts improved stability to enzymatic degradation and increases potency of function. Many successful macrocyclization of peptides both in solution and on-resin have been achieved but are limited in scope as they lack selectivity, require long reaction times, or necessitate heat. To overcome these drawbacks a robust and facile strategy was developed employing thiol-Michael click chemistry via an N-methyl vinyl sulfonamide.

Blue-light activated rapid polymerization for defect-free bulk Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) crosslinked networks.

A visible-light (470 nm wavelength) sensitive Type II photoinitiator system is developed for bulk Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions in crosslinked networks. The accelerated photopolymerization eliminates UV-mediated azide decomposition allowing for the formation of defect-free glassy networks which exhibit a narrow glass transition temperature.

Dynamic Bonds in Covalently Crosslinked Polymer Networks for Photoactivated Strengthening and Healing.

A photoactivated-strengthening polymer network is reported. This approach incorporates dynamic bonds into the network architecture, which enables a secondary polymerization triggered by UV light. Three attributes of this material are demonstrated, including: i) there is simultaneous photoinduced strengthening and healing after the material is severed, ii) bulk property changes are spatially confined via photopatterning, and iii) there is permanent shape change post-irradiation.

Gold(I)-promoted heterocyclization of internal alkynes: a comparative study of direct metallate 5-endo-dig cyclization versus a stepwise cyclization.

With cationic gold catalysts, internal alkynes bearing both propargylic acyloxy groups and tosylamide pronucleophiles were found to cyclize to give either five- or six-membered ring nitrogen heterocycles. A wide variety of gold catalysts, counterions, and solvents were examined to elucidate their effect on product distribution. In most cases, the direct 5-endo-dig cyclization was found to be the major pathway leading to good yields of dehydropyrrolidine products.

Removal of ruthenium using a silica gel supported reagent.

A solid-supported isocyanide ligand was developed to destroy active metathesis catalysts and to remove ruthenium byproducts from metathesis reactions. This method was able to significantly reduce the concentration of residual ruthenium from the organic products of several alkene and ene-yne metathesis reactions, under a variety of different conditions.

Probing a 2-aminobenzimidazole library for binding to RNA internal loops via two-dimensional combinatorial screening.

There are many potential RNA drug targets in bacterial, viral, and human transcriptomes. However, there are few small molecules that modulate RNA function. This is due, in part, to a lack of fundamental understanding about RNA-ligand interactions including the types of small molecules that bind to RNA structural elements and the RNA structural elements that bind to small molecules.

Geminal alkene-alkyne cross metathesis using a relay strategy.

A relay strategy was employed to achieve an intermolecular ene-yne metathesis between 1,1-disubstituted alkenes and alkynes. The relay serves to activate an unreactive alkene which will not participate in ene-yne metathesis. The new relay cross ene-yne metathesis gives rise to 1,1,3-trisubstituted-1,3-dienes previously inaccessible by direct ene-yne metathesis methods.

Alkene metathesis approach to β-unsubstituted anti-allylic alcohols and their use in ene-yne metathesis.

The synthesis of β-unsubstituted, anti-allylic alcohols using a catalytic Evans aldol reaction conjoined with a relay-type ring-closing alkene metathesis is reported. The metathesis step serves to remove a β-alkenyl group, which facilitated the aldol step. The β-substituted enals serve as acrolein surrogates.

Influencing uptake and localization of aminoglycoside-functionalized peptoids.

The development of small-molecule therapeutics that target RNA remains a promising field but one hampered with considerable challenges that include programming high affinity, specificity, cell permeability, and favorable pharmacokinetic profiles. Previously, we employed the use of peptoids to modularly display RNA-binding modules to enhance binding affinity and specificity by altering valency and the distance between ligand modules. Herein, factors that affect uptake, localization, and toxicity of peptoids that display a kanamycin derivative into a variety of mammalian cells lines are reported.

Controlling the specificity of modularly assembled small molecules for RNA via ligand module spacing: targeting the RNAs that cause myotonic muscular dystrophy.

Myotonic muscular dystrophy types 1 and 2 (DM1 and DM2, respectively) are caused by expansions of repeating nucleotides in noncoding regions of RNA. In DM1, the expansion is an rCUG triplet repeat, whereas the DM2 expansion is an rCCUG quadruplet repeat. Both RNAs fold into hairpin structures with periodically repeating internal loops separated by two 5'GC/3'CG base pairs.

Rational design of ligands targeting triplet repeating transcripts that cause RNA dominant disease: application to myotonic muscular dystrophy type 1 and spinocerebellar ataxia type 3.

Herein, we describe the design of high affinity ligands that bind expanded rCUG and rCAG repeat RNAs expressed in myotonic dystrophy type 1 (DM1) and spinocerebellar ataxia type 3. These ligands also inhibit, with nanomolar IC(50) values, the formation of RNA-protein complexes that are implicated in both disorders. The expanded rCUG and rCAG repeats form stable RNA hairpins with regularly repeating internal loops in the stem and have deleterious effects on cell function.