Wrist fusion in peripheral paralysis.

In cases of paralysis of the upper limb, wrist fusion is useful in selected indications, especially when there are little to no tendon transfers available to restore finger function and wrist extension. Wrist fusion is particularly useful in the sequelae of brachial plexus lesions and in total paralysis of the radial nerve with hand drop and preserved wrist flexors. Numerous fusion techniques have been proposed. In cases of sequelae of brachial plexus lesions, locking of pronation-supination is associated with the wrist fusion. The use of anatomical plates has dropped the non-union and complication rates.

Pyruvate Aldol Condensation Product: A Metabolite That Escaped Synthetic Preparation for Over a Century.

The homoaldol condensation product of pyruvate, 2-methyl-4-oxopent-2-enedioic acid (OMPD), has been recently implicated as a catabolic intermediate in the bacterial degradation of lignin and previously identified from other biological sources in reports ranging over 60 years. Yet, while a preparation of the pyruvate homoaldol product precursor, 4-hydroxy-4-methyl-2-oxoglutaric acid (HMOG/Parapyruvate), was first reported in 1901, there has not been a complete published synthesis of OMPD. Analyses of reaction mixtures have helped identify zymonic acid, the lactone of HMOG, as the direct precursor to OMPD. The reaction appears to proceed through an acid- or base-mediated ring opening that does not involve formal lactone hydrolysis. In addition to a preparative protocol, we provide a proposed mechanism for the formation of methylsuccinic acid that arises from the nonoxidative decarboxylation of OMPD. Finally, we calculated the relative stability of the isomers of OMPD and found Z-OMPD to be the lowest in energy. These computations also support our observations that Z-OMPD is the most abundant isomer across a range of pH values.

Imidazolium-Catalyzed Synthesis of an Imidazolium Catalyst.

The chemistry of imidazolium-catalyzed imidazolium synthesis was studied as part of an effort to develop a plausible prebiotic synthesis of a small catalytic molecule capable of catalyzing its own synthesis. Specifically, we investigated the one-pot 1-ethyl-3-methylimidazolium acetate (EMIM-Ac) catalyzed synthesis of 1,3-dibutyl-4,5-difuryl-imidazolium acetate (DBDFIM-Ac) from furfural, n-butylamine, formaldehyde, and acetic acid at 80 °C. Liu et al. (2012) had previously demonstrated the first reaction of the synthetic process, the EMIM-Ac catalyzed benzoin condensation of furfural that yields furoin. Our early studies established the second reaction of the synthetic process, the multicomponent reaction of furoin, n-butylamine, formaldehyde, and acetic acid that yields the imidazolium salt, DBDFIM-Ac. Studies of the complete two-reaction process that uses furfural for the synthesis of DBDFIM-Ac showed that the highest yield of DBDFIM-Ac was obtained when the mole ratio of n-butylamine, formaldehyde, and acetic acid relative to furfural was respectively (0.5:0.25:0.25:1.0-furfural), or one-half of the stoichiometric ratio (1.0:0.5:0.5:1.0-furfural). A time course study of the process showed transient formation of furoin, the obligatory reaction intermediate. DBDFIM-Ac and the imidazolium side product, 1,3-dibutyl-4,5-trifuryl-imidazolium acetate (DBTFIM-Ac), were stable under the reaction conditions. Imidazolium products (DBDFIM and DBTFIM) and the furoin intermediate were not formed in control reactions (80 °C, 24 h) in which EMIM catalyst was either absent or replaced with an equal volume of acetonitrile or DMF. The imidazolium product, DBDFIM-Ac, was shown to catalyze the synthesis of structurally similar 1,3-dipentyl-4,5-difuryl-imidazolium acetate (DPDFIM-Ac) from furfural, n-pentylamine, formaldehyde, and acetic acid at 80 °C.

Long-term functional outcomes after surgical treatment of nonspecific thoracic outlet syndrome: Retrospective study of 70 cases at a mean of 8 years' follow-up.

Our objective was to study the clinical and functional outcomes after surgical treatment of nonspecific thoracic outlet syndrome (TOS) using a supraclavicular approach. We included every patient with TOS who was treated surgically by the same surgeon at a single hospital between 1999 and 2014 with a minimum follow-up of 4 years. The primary outcome was the overall evaluation of the function by the QuickDASH Score. Secondary outcomes included functional, subjective outcomes, pain levels, and neuropathic features. The clinical outcome of 70 cases was evaluated with a mean follow-up of 8.5 years. The improvement in the QuickDASH Score was significant with an average change of 38 points. Mean pain intensity was reduced postoperatively by 1.6 points from 5.1/10 to 3.5/10. Persistent pain rate at 4/10 or more remained in 56% of cases. These cases were mostly neuropathic. The surgical procedure significantly reduced the number of patients suffering from paresthesia, numbing or weakness. The possibility of sequelae and the persistence of neuropathic pain means the surgical indication should be limited to patients with significant functional disability despite well-conducted rehabilitation. The long-term functional outcomes in patients undergoing TOS was mostly good but could be improved by addressing residual neuropathic pain symptoms.

Monosaccharides and Their Derivatives in Carbonaceous Meteorites: A Scenario for Their Synthesis and Onset of Enantiomeric Excesses.

Carbonaceous meteorites provide the best glimpse into the solar system's earliest physical and chemical processes. These ancient objects, ~4.56 billion years old, contain evidence of phenomena ranging from solar system formation to the synthesis of organic compounds by aqueous and (likely) low-temperature photolytic reactions. Collectively, chemical reactions resulted in an insoluble kerogen-like carbon phase and a complex mixture of discrete soluble compounds including amino acids, nucleobases, and monosaccharide (or "sugar") derivatives. This review presents the documented search for sugars and their derivatives in carbonaceous meteorites. We examine early papers, published in the early 1960s, and note the analytical methods used for meteorite analysis as well as conclusions on the results. We then present the recent finding of sugar derivatives including sugar alcohols and several sugar acids: The latter compounds were found to possess unusual "d" enantiomeric (mirror-image) excesses. After discussions on the possible roles of interstellar grain chemistry and meteorite parent body aqueous activity in the synthesis of sugar derivatives, we present a scenario that suggests that most of Earth's extraterrestrial sugar alcohols (e.g., glycerol) were synthesized by interstellar irradiation and/or cold grain chemistry and that the early solar disk was the location of the initial enantiomeric excesses in meteoritic sugar derivatives.

Enantiomer excesses of rare and common sugar derivatives in carbonaceous meteorites.

Biological polymers such as nucleic acids and proteins are constructed of only one-the d or l-of the two possible nonsuperimposable mirror images (enantiomers) of selected organic compounds. However, before the advent of life, it is generally assumed that chemical reactions produced 50:50 (racemic) mixtures of enantiomers, as evidenced by common abiotic laboratory syntheses. Carbonaceous meteorites contain clues to prebiotic chemistry because they preserve a record of some of the Solar System's earliest (∼4.5 Gy) chemical and physical processes. In multiple carbonaceous meteorites, we show that both rare and common sugar monoacids (aldonic acids) contain significant excesses of the d enantiomer, whereas other (comparable) sugar acids and sugar alcohols are racemic. Although the proposed origins of such excesses are still tentative, the findings imply that meteoritic compounds and/or the processes that operated on meteoritic precursors may have played an ancient role in the enantiomer composition of life's carbohydrate-related biopolymers.

Hydrolytic Fitness of N-glycosyl Bonds: Comparing the Deglycosylation Kinetics of Modified, Alternative and Native Nucleosides.

Nature's selection of the contemporary nucleobases in RNA and DNA continues to intrigue the origin of life community. While the prebiotic synthesis of the N-glycosyl bond has historically been a central area of investigation, variations in hydrolytic stabilities among the N-glycosyl bonds may have presented an additional selection pressure that contributed to nucleobase and nucleoside evolution. To experimentally probe this hypothesis, a systematic kinetic analysis of the hydrolytic deglycosylation reactions of modified, alternative and native nucleosides was undertaken. Rate constants were measured as a function of temperature (at pH 1) to produce Arrhenius and Eyring plots for extrapolation to 37°C and determination of thermodynamic activation parameters. Rate enhancements based on the differences in reaction rates of deoxyribo- and ribo-glycosidic bonds were found to vary under the same conditions. Rate constants of deoxynucleosides were also measured across the pH range of 1 - 3 (at 50°C), which highlighted how simple changes to the heterocycle alone can lead to significant variation in deglycosylation rates. The contemporary nucleosides exhibited the slowest deglycosylation rates in comparison to the non-native/alternative nucleosides, which we suggest as experimental support for nature's selection of the fittest N-glycosyl bonds.

Actifit synthetic meniscal substitute: experience with 18 patients in Brest, France.

BACKGROUND: The management of post-meniscectomy pain is poorly standardised. Allogeneic transplantation may be appropriate in some patients after total meniscectomy. After partial meniscectomy, the synthetic meniscal substitute Actifit may constitute a valid option if the knee is stable or stabilised and aligned or re-aligned. The interconnected pore structure of Actifit promotes tissue regeneration from the meniscal wall. Arthroscopy is used to position the implant, which is then sutured to the remaining native meniscus using horizontal stitches and to the meniscal wall using vertical stitches. However, a burdensome programme of rigorous rehabilitation is required after Actifit implantation. HYPOTHESIS: We hypothesised that implantation of a meniscal substitute effectively alleviated pain without adversely affecting the knee. OBJECTIVES: To assess the intra-articular behaviour of Actifit and the outcomes of Actifit implantation in a prospective case-series of patients monitored using arthroscopy, pathology, and imaging studies, as well as the Lysholm score to assess clinical benefits on daily activities. MATERIALS AND METHODS: Between October 2009 and April 2012, 18 patients underwent Actifit implantation at the military hospital in Brest, France. All procedures were performed by the same surgeon, who had extensive experience with meniscal suturing. There were 13 males and 5 females aged 20 to 46 years. The medial meniscus was involved in 13 patients and the lateral meniscus in 5 patients. Actifit implantation was used alone in 6 patients and in combination with anterior cruciate ligament reconstruction and/or realignment osteotomy in 12 patients. All patients were followed-up for at least 2 years. RESULTS: The mean Lysholm score after 1 year was 92%, indicating excellent outcomes. Magnetic resonance imaging showed no damage to the implant or degeneration of the neighbouring cartilage. Histological examination of meniscal substitute biopsies taken 1 year after implantation showed polymer ingrowth by normal chondrocytes and fibrochondrocytes. The clinical and radiographic outcomes compared favourably with those seen after isolated procedures on bone or ligaments. DISCUSSION: Actifit has no deleterious effects on patients. The implant induces and promotes meniscal regeneration. Actifit constitutes a major addition to our therapeutic armamentarium. We provide convincing evidence that meniscal reconstruction can be highly beneficial in decreasing the risk of progression to knee osteoarthritis. LEVEL OF EVIDENCE: IV.

[Feasibility and relevance of an operating room safety checklist for developing countries: Study in a French hospital in Djibouti]. / Étude de la faisabilité et de la pertinence de la check-list au bloc opératoire pour un pays en développement : exemple d'un hôpital français à Djibouti.

INTRODUCTION: The use of the World Health Organization surgical safety checklist, mandatory in operating rooms (OR) in France, significantly reduces morbidity and mortality. Our objective was to evaluate the use of this checklist in the OR of a French military hospital in Djibouti (Horn of Africa). METHODS: The study was performed in three stages: a retrospective evaluation of the checklist use over the previous two months, to assess the utilization and completeness rates; provision of information to the OR staff; and thereafter, prospective evaluation for a one-month period of checklist use, the reasons for non-compliance, and the cases in which the checklist identified errors and thus prevented serious adverse events. RESULTS: The initial utilization rate was 49%, with only 24% complete. After staff training and during the study these rates reached 100% and 99%. The staff encountered language difficulties in 53% of cases, and an interpreter was available for 81% of them. The capacity of the surgical safety checklist to detect serious adverse events was highlighted. CONCLUSION: The utilization and completeness rates were initially worse than those observed in metropolitan French ORs, but a simple staff information program was rapidly effective. Language difficulties are frequent but an interpreter is often available, unlike in developed countries where language problems are uncommon and the availability of interpreters difficult. Moreover, this study illustrates the ability of the checklist to detect and therefore prevent potentially serious adverse events.

On the Origin of the Canonical Nucleobases: An Assessment of Selection Pressures across Chemical and Early Biological Evolution.

The native bases of RNA and DNA are prominent examples of the narrow selection of organic molecules upon which life is based. How did nature "decide" upon these specific heterocycles? Evidence suggests that many types of heterocycles could have been present on the early Earth. It is therefore likely that the contemporary composition of nucleobases is a result of multiple selection pressures that operated during early chemical and biological evolution. The persistence of the fittest heterocycles in the prebiotic environment towards, for example, hydrolytic and photochemical assaults, may have given some nucleobases a selective advantage for incorporation into the first informational polymers. The prebiotic formation of polymeric nucleic acids employing the native bases remains, however, a challenging problem to reconcile. Hypotheses have proposed that the emerging RNA world may have included many types of nucleobases. This is supported by the extensive utilization of non-canonical nucleobases in extant RNA and the resemblance of many of the modified bases to heterocycles generated in simulated prebiotic chemistry experiments. Selection pressures in the RNA world could have therefore narrowed the composition of the nucleic acid bases. Two such selection pressures may have been related to genetic fidelity and duplex stability. Considering these possible selection criteria, the native bases along with other related heterocycles seem to exhibit a certain level of fitness. We end by discussing the strength of the N-glycosidic bond as a potential fitness parameter in the early DNA world, which may have played a part in the refinement of the alphabetic bases.

Syntheses, thermal reactivities, and computational studies of aryl-fused quinoxalenediynes: effect of extended benzannelation on Bergman cyclization energetics.

A series of [b]-fused 6,7-diethynylquinoxaline derivatives have been synthesized through an imine condensation strategy to examine the effect of extended benzannelation on the thermal reactivity of enediynes. Absorption and emission spectra of the highly conjugated quinoxalenediynes were red-shifted approximately 100-200 nm relative to those of 1,2-diethynylbenzene. Strong exotherms indicative of enediyne cyclization were observed by differential scanning calorimetry, while solution cyclizations in the presence of 1,4-cyclohexadiene confirmed C(1)-C(6) Bergman cyclization. To provide further insight into Bergman cyclization energetics, computational studies were performed to compare changes in the cyclization enthalpy barrier, reaction enthalpy, and barrier of retro-Bergman ring-opening. Extension of benzannelation from 1,2-diethynylbenzene to either 2,3-diethynylnaphthalene or the 6,7-diethynylquinoxalines had a minimal effect on the cyclization barrier. In comparison, the enthalpies of cyclization were increased upon linearly extended benzannelation, which resulted in reduced barriers to retro-Bergman ring-opening. In addition, the orientation of extended benzannelation was found to have a significant effect on the cyclization endothermicity. In particular, 5,6-diethynylquinoxaline exhibited a 6.9 kcal/mol decrease in cyclization enthalpy compared to 6,7-diethynylquinoxaline due to increased aromatic stabilization energy in the respective angularly versus linearly fused azaacene cyclized products.

Refining the genetic alphabet: a late-period selection pressure?

The transition from genomic ribonucleic acid (RNA) to deoxyribonucleic acid (DNA) in primitive cells may have created a selection pressure that refined the genetic alphabet, resulting from the global weakening of the N-glycosyl bonds. Hydrolytic rupture of these bonds, termed deglycosylation, leaves an abasic site that is the single greatest threat to the stability and integrity of genomic DNA. The rates of deglycosylation are highly dependent on the identity of the nucleobases. Modifications made to the bases, such as deamination, oxidation, and alkylation, can further increase deglycosylation reaction rates, suggesting that the native bases provide optimum N-glycosyl bond stability. To protect their genomes, cells have evolved highly specific enzymes called glycosylases, associated with DNA repair, that detect and remove these damaged bases. In RNA, however, the occurrence of many of these modified bases is deliberate. The dichotomous behavior that cells exhibit toward base modifications may have originated in the RNA world. Modified bases would have been advantageous for the functional and structural repertoire of catalytic RNAs. Yet in an early DNA world, the utility of these heterocycles was greatly diminished, and their presence posed a distinct liability to the stability of cells' genomes. A natural selection for bases exhibiting the greatest resistance to deglycosylation would have ensured the viability of early DNA life, along with the recruitment of DNA repair.

Design, synthesis, and spectroscopic properties of extended and fused pyrrolo-dC and pyrrolo-C analogs.

The syntheses of four fluorescent nucleoside analogs, related to pyrrolo-C (PyC) and pyrrolo-dC (PydC) through the conjugation or fusion of a thiophene moiety, are described. A thorough photophysical analysis of the nucleosides, in comparison to PyC, is reported.

Radius graft pedicled on the anterior interosseous artery for recurrent ulnar nonunion.

Recurrent ulnar nonunion challenges the functional prognosis and raises major problems concerning the best therapeutic strategy to follow. The case of a female patient presenting recurrent nonunion of the ulnar diaphysis despite successive treatments is reported. The radius graft pedicled on the anterior interosseous artery from a retrograde approach obtained bone union in 3 months with no functional sequelae. For the first time, we propose a therapeutic alternative calling on a proximally pedicled anterior interosseous flap. This technique can be performed under locoregional anesthesia and does not sacrifice the main artery of the forearm. However, the size of the graft does not entirely compensate for segmentary bone loss. The radius graft pedicled on the anterior interosseus artery is an inventive technique that can solve the problem of difficult ulna nonunions without the disadvantages of vascularized fibula harvesting.

Painful medial knee compartment syndrome in over-45-year-olds. II--technical note: Biomechanical considerations: theoretic analysis of load distribution in the knee according to plane and to gait phase.

Varus deviation as defined by Thomine is the basis for understanding load distribution between the medial and lateral tibial plateau; it was originally defined in the frontal plane. Analysis in the sagittal and horizontal planes leads to a concept of varizing area. Varizing area sheds light on how, during gait, load predominates in the medial and posteromedial knee. It also accounts for the following two findings: (a) degenerative lesions are mainly medial, even when the mid-knee axis is normal; (b) degenerative lesions are mainly posterior.

Painful medial knee compartment syndrome in over-45 year-olds: I--medical or surgical management: a series of 174 patients.

INTRODUCTION: There is at present no consensus on the management of degenerative medial meniscus lesions in patients aged over 45 years without proven osteoarthritis, especially given that the causal relation between degenerative meniscal lesion and osteoarthritis remains controversial. A prospective multicenter non randomized study was therefore performed. The principal objective was to assess surgeons' practice in the management of degenerative medial meniscus lesions. The secondary objectives were to identify predictive and prognostic factors and to compare medical versus surgical attitudes so as to draw up an adapted treatment strategy. PATIENTS AND METHOD: One hundred and seventy-four patients were included between September 2008 and February 2010, and distributed between a surgical (n=104) and a medical group (n=70). Minimum follow-up was 6 months. Patient satisfaction and health-related quality of life on the SF-36 questionnaire were assessed at 6 months. RESULTS: No difference emerged between the surgical and medical groups. However, predictive factors for poor results were identified: overweight (p=0.005), cartilage lesions (p=0.035) and meniscus extrusion (p=0.006). DISCUSSION: Results clarified the relation between degenerative meniscus lesions and osteoarthritis, in terms of meniscal incompetence. Meniscal extrusion should be seen as an arthrogenic degenerative meniscus lesion. We recommend a management strategy based on terrain and imaging data (X-ray and MRI), with the aim of providing patient relief while conserving cartilage.

Model systems: how chemical biologists study RNA.

Ribonucleic acids are structurally and functionally sophisticated biomolecules and the use of models, frequently truncated or modified sequences representing functional domains of the natural systems, is essential to their exploration. Functional noncoding RNAs such as miRNAs, riboswitches, and, in particular, ribozymes, have changed the view of RNA's role in biology and its catalytic potential. The well-known truncated hammerhead model has recently been refined and new data provide a clearer molecular picture of the elements responsible for its catalytic power. A model for the spliceosome, a massive and highly intricate ribonucleoprotein, is also emerging, although its true utility is yet to be cemented. Such catalytic model systems could also serve as 'chemo-paleontological' tools, further refining the RNA world hypothesis and its relevance to the origin and evolution of life.

Split cervical spinal cord malformation and vertebral dysgenesis.

We report a case of vertebral malformation associated with diplomyelia believed to be a type II split cord malformation. Cervicothoracic level cases are exceptional. This article reports the case of an 11-year-old boy with no neurological symptoms who had not undergone surgery. The diagnosis was made during pregnancy by prenatal screening with ultrasound and MRI. Several embryological theories have been offered to provide an explanation for this syndrome. Close follow-up is mandatory. Surgery must only be considered if neurological deterioration occurs.