Republication of "Ankle Fracture-Dislocations: A Review".

Ankle fractures are common musculoskeletal injuries that may result in tibiotalar joint dislocations. Ankle fracture-dislocations occur via similar mechanisms as ankle fractures, although the persistence or magnitude of the deforming force is sufficient to disrupt any remaining bony or soft-tissue stability. Ankle fracture-dislocations likely represent distinct clinical entities, as the pathology, management, and patient outcomes following these injuries differ from those seen in more common ankle fractures without dislocation.

Does the frailty index predict discharge disposition and length of stay at the hospital and rehabilitation facilities?

Introduction: Many geriatric hip fracture patients utilize significant healthcare resources and require an extensive recovery period after surgery. There is an increasing awareness that measuring frailty in geriatric patients may be useful in predicting mortality and perioperative complications and may be useful in helping guide treatment decisions. The primary purpose of the study is to investigate whether the frailty index predicts discharge disposition from the hospital and discharge facility and length of stay.

Anatomy, Classification, and Management of Ankle Fractures Involving the Posterior Malleolar Fragment: A Literature Review.

Unlabelled: The posterior malleolar fragment is frequently involved in rotational ankle fractures, but diagnosis and definitive management remains controversial. Ankle fractures with a posterior malleolar component that are not identified and treated in a timely manner may contribute significantly to future comorbidities, including continued pain, instability, and the development of arthritis. This article highlights the anatomic features of posterior malleolar ankle fractures, the classification schemes used, and discusses the various nonsurgical and surgical methods currently used.

Structural Basis of TLR2/TLR1 Activation by the Synthetic Agonist Diprovocim.

Diprovocim is a recently discovered exceptionally potent, synthetic small molecule agonist of TLR2/TLR1 and has shown significant adjuvant activity in anticancer vaccination against murine melanoma. Since Diprovocim bears no structural similarity to the canonical lipopeptide ligands of TLR2/TLR1, we investigated how Diprovocim interacts with TLR2/TLR1 through in vitro biophysical, structural, and computational approaches. We found that Diprovocim induced the formation of TLR2/TLR1 heterodimers as well as TLR2 homodimers in vitro.

Diprovocims: A New and Exceptionally Potent Class of Toll-like Receptor Agonists.

A screen conducted with nearly 100000 compounds and a surrogate functional assay for stimulation of an immune response that measured the release of TNF-α from treated human THP-1 myeloid cells differentiated along the macrophage line led to the discovery of the diprovocims. Unique to these efforts and of special interest, the screening leads for this new class of activators of an immune response came from a compound library designed to promote cell-surface receptor dimerization. Subsequent comprehensive structure-activity relationship studies improved the potency 800-fold over that of the screening leads, providing diprovocim-1 and diprovocim-2.

Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti-PD-L1 to eliminate melanoma in mice.

Successful cancer immunotherapy entails activation of innate immune receptors to promote dendritic cell (DC) maturation, antigen presentation, up-regulation of costimulatory molecules, and cytokine secretion, leading to activation of tumor antigen-specific cytotoxic T lymphocytes (CTLs). Here we screened a synthetic library of 100,000 compounds for innate immune activators using TNF production by THP-1 cells as a readout. We identified and optimized a potent human and mouse Toll-like receptor (TLR)1/TLR2 agonist, Diprovocim, which exhibited an EC of 110 pM in human THP-1 cells and 1.

Cozen's deformity: resolved by guided growth.

Proximal tibial metaphyseal fractures in children can lead to progressive and symptomatic tibial valgus. Corrective osteotomy has been abandoned, due to frequent complications, including recurrent valgus deformity. While spontaneous remodelling has been reported, this is not predictable.

An unusual variant of perilunate fracture dislocations.

Trans-scaphoid, trans-radial styloid, trans-triquetral perilunate fracture dislocations are rare. We describe a 19-year-old male who suffered this injury after crashing his bicycle. He underwent open reduction internal fixation and percutaneous pinning.

Discovery and Structure-Activity Relationships of the Neoseptins: A New Class of Toll-like Receptor-4 (TLR4) Agonists.

Herein, we report studies leading to the discovery of the neoseptins and a comprehensive examination of the structure-activity relationships (SARs) of this new class of small-molecule mouse Toll-like receptor 4 (mTLR4) agonists. The compounds in this class, which emerged from screening an α-helix mimetic library, stimulate the immune response, act by a well-defined mechanism (mouse TLR4 agonist), are easy to produce and structurally manipulate, exhibit exquisite SARs, are nontoxic, and elicit improved and qualitatively different responses compared to lipopolysaccharide, even though they share the same receptor.

TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS.

Structurally disparate molecules reportedly engage and activate Toll-like receptor (TLR) 4 and other TLRs, yet the interactions that mediate binding and activation by dissimilar ligands remain unknown. We describe Neoseptins, chemically synthesized peptidomimetics that bear no structural similarity to the established TLR4 ligand, lipopolysaccharide (LPS), but productively engage the mouse TLR4 (mTLR4)/myeloid differentiation factor 2 (MD-2) complex. Neoseptin-3 activates mTLR4/MD-2 independently of CD14 and triggers canonical myeloid differentiation primary response gene 88 (MyD88)- and Toll-interleukin 1 receptor (TIR) domain-containing adaptor inducing IFN-beta (TRIF)-dependent signaling.

Positive communication paradigm decreases early recurrence in clubfoot treatment.

Background: The Ponseti method has become the treatment standard for idiopathic clubfoot. Deformity recurrence is most commonly attributed to premature abandonment of the requisite abduction orthosis. A study in 2009 from our center revealed a high rate of deformity recurrence in our patient population.

Total synthesis of lepadiformine alkaloids using N-Boc α-amino nitriles as trianion synthons.

Lepadiformine A, B, and C were synthesized in an enantiomerically pure form using a reductive cyclization strategy. N-Boc α-amino nitriles were deprotonated and alkylated with enantiomerically pure dibromides to afford the first ring. The products were manipulated to introduce phosphate leaving groups, and subsequent reductive lithiation followed by intramolecular alkylation formed the second ring with high stereoselectivity.

Fully substituted carbon centers by diastereoselective spirocyclization: stereoselective synthesis of (+)-lepadiformine C.

Reductive lithiation of N-Boc alpha-amino nitriles generated alpha-amino alkyllithium reagents with unexpected selectivity. The intermediate radical prefers to align with the nitrogen lone pair, and this interaction leads to an A(1,3)-strain effect that biases the conformation of the radical. In cyclohexane rings with alpha-substituents the net effect is an inversion of configuration on reductive lithiation.

Reductive spiroannulation of nitriles with secondary electrophiles.

The scope of reductive decyanation and spiroannulation reactions has been expanded to include secondary electrophiles for potentially useful transformations. Secondary phosphates and chlorides, as well as terminal epoxides, cyclize in a stereospecific fashion. Both endo and exo modes of cyclization were observed with terminal epoxides.