The pathogenesis of tendinopathy and the primary biological change in the tendon that precipitates pathology have generated several pathoaetiological models in the literature. The continuum model of tendon pathology, proposed in 2009, synthesised clinical and laboratory-based research to guide treatment choices for the clinical presentations of tendinopathy. While the continuum has been cited extensively in the literature, its clinical utility has yet to be fully elucidated. The continuum model proposed a model for staging tendinopathy based on the changes and distribution of disorganisation within the tendon. However, classifying tendinopathy based on structure in what is primarily a pain condition has been challenged. The interplay between structure, pain and function is not yet fully understood, which has partly contributed to the complex clinical picture of tendinopathy. Here we revisit and assess the merit of the continuum model in the context of new evidence. We (1) summarise new evidence in tendinopathy research in the context of the continuum, (2) discuss tendon pain and the relevance of a model based on structure and (3) describe relevant clinical elements (pain, function and structure) to begin to build a better understanding of the condition. Our goal is that the continuum model may help guide targeted treatments and improved patient outcomes.

https://bjsm.bmj.com/content/bjsports/50/19/1187.full.pdf

Revisiting the continuum model of tendon pathology: what is its merit in clinical practice and research?

The translation of DNA sequences into corresponding biopolymers enables the production, function and evolution of the macromolecules of life. In contrast, methods to generate sequence-defined synthetic polymers with similar levels of control have remained elusive. Here, we report the development of a DNA-templated translation system that enables the enzyme-free translation of DNA templates into sequence-defined synthetic polymers that have no necessary structural relationship with nucleic acids. We demonstrate the efficiency, sequence-specificity and generality of this translation system by oligomerizing building blocks including polyethylene glycol, α-(D)-peptides, and β-peptides in a DNA-programmed manner. Sequence-defined synthetic polymers with molecular weights of 26 kDa containing 16 consecutively coupled building blocks and 90 densely functionalized β-amino acid residues were translated from DNA templates using this strategy. We integrated the DNA-templated translation system developed here into a complete cycle of translation, coding sequence replication, template regeneration and re-translation suitable for the iterated in vitro selection of functional sequence-defined synthetic polymers unrelated in structure to nucleic acids.

/pdf/enzyme-free-translation-of-dna-into-sequence-defined-9gxadwykwz.pdf

Enzyme-free translation of DNA into sequence-defined synthetic polymers structurally unrelated to nucleic acids

Publisher Summary This chapter presents the cross-interaction constants and discusses their applications for the characterization of TS structures for various types of reactions. Applications of the various cross-interaction constants to the elucidation of reaction mechanisms are discussed in the chapter. The use of the sign and magnitude allows us to predict the reaction types (IB- or TB-controlled in group-transfer and nucleophilic displacement reactions) and TS structures semiquantitatively. One of the most extensively investigated reactions in chemistry is nucleophilic substitution (S N ). In addition, S N -type reactions are most suitable for the application of cross-interaction constants as a measure of the TS structure. For these reasons, cross-interaction constants are determined and the TS structures are discussed for a large number of S N reactions in greater detail. As in any application of selectivity parameters from linear free energy relationships, cross-interaction constants reflect the TS structure only for the rate-determining step of a reaction. This means that interpretation of cross-interaction constants will not be clearcut and easy in a complex reaction, which proceeds in many steps with no identifiable single rate-determining step.

Cross-interaction constants and transition-state structure in solution

This review highlights recent research on Achilles tendon healing, and comments on the current clinical controversy surrounding the diagnosis and treatment of injury. The processes of Achilles tendon healing, as demonstrated through changes in its structure, composition, and biomechanics, are reviewed. Finally, a review of tendon developmental biology and mechano transductive pathways is completed to recognize recent efforts to augment injured Achilles tendons, and to suggest potential future strategies for therapeutic intervention and functional tissue engineering. Despite an abundance of clinical evidence suggesting that current treatments and rehabilitation strategies for Achilles tendon ruptures are equivocal, significant questions remain to fully elucidate the basic science mechanisms governing Achilles tendon injury, healing, treatment, and rehabilitation.

/pdf/the-achilles-tendon-fundamental-properties-and-mechanisms-4o2ubr6elc.pdf

The Achilles tendon: fundamental properties and mechanisms governing healing.

The (dys)functional extracellular matrix

Background
Tendinopathy (pain and tendon degeneration) is associated with repetitive use and mechanical overload. However, the etiology of tendinopathy remains unclear. Clarification of histologic and molecular changes of tendon to repetitive stress could provide better understanding of Achilles tendon disorders related to repetitive stress.

Tendinosis-like Histologic and Molecular Changes of the Achilles Tendon to Repetitive Stress: A Pilot Study in Rats

Elimination reactions of (E)- and (Z)-benzaldehyde O-pivaloyloximes 1 and 2 with DBU in MeCN have been investigated kinetically. The reactions are second order and exhibit substantial values of Hammett ρ and kH/kD values, and an E2 mechanism is evident. The rate of elimination from 2 is approximately 20 000-fold faster than that from 1. For reactions of 1 with DBU in MeCN, a Hammett ρ value of 2.4 ± 0.1, kH/kD = 2.7 ± 0.3, ΔH⧧ = 12.5 ± 0.2 kcal/mol, and ΔS⧧ = −31.0 ± 0.6 eu have been determined. The corresponding values for 2 are ρ = 1.4 ± 0.1, kH/kD = 7.8 ± 0.3, ΔH⧧ = 8.8 ± 0.1 kcal/mol, and ΔS⧧ = −23.6 ± 0.4 eu, respectively. The results indicate that the nitrile-forming anti eliminations from 2 proceed via a more symmetrical transition state with a smaller degree of proton transfer, less negative charge development at the β-carbon, and greater extent of triple-bond formation than that for the syn elimination.

Elimination Reactions of (E)- and (Z)-Benzaldehyde O-Pivaloyloximes. Transition-State Differences for the Syn and Anti Eliminations Forming Nitriles.

We present an unusual case of a 26-year-old man with muscular polyarteritis nodosa (PAN) with severe calf pain and gait disturbance. Magnetic resonance imaging of the lower limbs demonstrated highly increased signal intensity in both soleus muscles and the lateral head of the left gastrocnemius muscle. Biopsies of the soleus muscle showed acute necrotizing arteritis. The calf pain and limited range of motion of ankle dorsiflexion subsided from day 1 on administration of oral corticosteroid at high dosage and were completely resolved by 4 months. After tapering corticosteroid to 10 mg, symptoms recurred. A combined regimen of immunosuppressants was found to maintain symptomatic relief.Muscular PAN should be included in the differential diagnosis of a patient presenting with symptoms of acute or subacute calf pain. Although this muscular PAN was so far been benign, complete remission of the underlying process may be difficult to achieve.

Muscular polyarteritis nodosa.

Reaction d'elimination des dinitro-2,4 phenyloxime et picryloxime du benzaldehyde. Les resultats observes sont en faveur d'un mecanisme E2

Eliminations from (E)-O-Arylbenzaldoximes promoted by tertiary amines in acetonitrile. Effects of aryl substituents, base strength, and leaving group upon the nitrile-forming transition state.

Introduction

It is important to understand the presence of Martin-Gruber anastomosis in patients with complete ulnar neuropathy at the elbow. Case Report: We describe a patient with complete ulnar neuropathy at the elbow and Martin-Gruber anastomosis in the forearm, mimicking incomplete ulnar neuropathy with complete conduction block in the forearm segment. Ultrasonography of the ulnar nerve around the elbow demonstrated severe swelling of the ulnar nerve, which was compatible with severe ulnar neuropathy at the elbow. Conclusions: This case report demonstrates that combination of ultrasonography with electrophysiological studies can provide more detailed information about the changes of nerve structures and lesion sites. Muscle Nerve, 2013

Nam Soon Cho

Papers

Tendinosis-like Histologic and Molecular Changes of the Achilles Tendon to Repetitive Stress: A Pilot Study in Rats

Elimination Reactions of (E)- and (Z)-Benzaldehyde O-Pivaloyloximes. Transition-State Differences for the Syn and Anti Eliminations Forming Nitriles.

Muscular polyarteritis nodosa.

Eliminations from (E)-O-Arylbenzaldoximes promoted by tertiary amines in acetonitrile. Effects of aryl substituents, base strength, and leaving group upon the nitrile-forming transition state.

Electrophysiological and ultrasonographic findings in ulnar neuropathy with Martin-Gruber anastomosis.