Ultrasound-guided fasciotomy in forearm chronic exertional compartment syndrome: Preliminary results in 12 cases.

INTRODUCTION: Forearm chronic exertional compartment syndrome is a rare condition in athletes and musicians who perform repeated prolonged forced gripping movements. It mainly affects young men, and presents with cramp-like pain, beginning on the anteromedial side of the forearm and progressively extending to the entire circumference, and may be associated with muscle weakness and neurologic symptoms. The objective of this study was to report preliminary results of ultrasound-guided fasciotomy in the treatment of forearm chronic exertional compartment syndrome. MATERIAL AND METHODS: A single-center retrospective observational study was conducted. Forearm chronic exertional compartment syndrome was diagnosed on clinical presentation and pathological intramuscular pressure measurement, defined as >30 mmHg at 1 min after effort. The series comprised 7 men, with bilateral involvement. Mean age was 30 years. All patients were motorcyclists. The mean preoperative intramuscular pressure at 1 min after effort was 60.75 mmHg (range: 30-81 mmHg). The main study endpoint was change in pain on visual analogic scale. Secondary endpoints comprised patient satisfaction, change in competitive sports level, and time to return to sport. Complications were noted. RESULTS: Six patients (12 forearms) were evaluated. Mean follow-up was 22.5 months (range: 3-48 months). Mean pain rating was 7.3/10 (range: 6-9) preoperatively, and 0/10 postoperatively. All patients were satisfied with the procedure. Mean time to return to sports was 25.5 days (range: 21-30 days). No patients decreased their competitive sports level after the procedure. One patient presented a postoperative hematoma, not requiring surgery. CONCLUSION: Ultrasound-guided fasciotomy in the treatment of Forearm chronic exertional compartment syndrome is an innovative technique with promising preliminary results. LEVEL OF EVIDENCE: IV; retrospective cohort.

Treatment of scaphoid nonunion by arthroscopic cancellous bone grafting.

INTRODUCTION: In order to avoid Scaphoid Nonunion Advanced Collapse (SNAC) type osteoarthritis, which progressively affects the radial and midcarpal joints, several vascularized and non-vascularized grafting techniques have been described. Over the past decade, there has been growing interest in arthroscopic cancellous bone grafts for scaphoid nonunion. The aim of this novel prospective study was to assess the healing rate of scaphoid grafts under arthroscopy, and the prognostic factors for healing. MATERIAL AND METHODS: This prospective study was carried out across 10 centers between September 2019 and April 2021, in patients aged 16 to 65. Scaphoid nonunion grafting was performed arthroscopically. Union was assessed on CT scans and displacement correction angles were measured preoperatively and then at 3 and 6months. We assessed mobility, Jamar wrist strength, functional results as per the Patient Related Wrist Score (PRWE) and the Quick Disabilities of the Arm, Shoulder and Hand (Quick DASH) score. Risk factors for nonunion were assessed. RESULTS: We included 77 patients with a mean age of 24years (18 to 55years) with a mean time between trauma and treatment of nonunion of 34.8months (6 to 180months). The population was represented by 46 manual workers and 20 were smokers. In 42 cases, the nonunion was proximal, in Schernberg zone I or II. At the last follow-up of 12.9months on average (Standard Deviation: 8.7months), union was achieved in 72 patients (93.5%). The average duration of union was 3.4months (Standard Deviation 1.6). Among the 5 patients who did not heal, grafting was performed in addition to the fixation. We did not identify any contributory factors for nonunion. CONCLUSION: This study demonstrated the effectiveness of arthroscopic treatment of scaphoid nonunion with a union rate at least equivalent to pedicled vascularized grafts. Smoking and delayed treatment were no longer considered unfavorable prognostic factors in the context of arthroscopic treatment. LEVEL OF EVIDENCE: III.

Correction of residual humpback deformity after arthroscopic treatment of scaphoid non-union.

BACKGROUND: The aim of this study was to assess residual humpback deformity after arthroscopic treatment of scaphoid non-union. MATERIAL AND METHOD: We reviewed the medical records of 47 patients with scaphoid non-union who underwent arthroscopic treatment between 2012 and 2018. Patients who did not receive an intraoperative bone graft were excluded (10 patients), as were those who did not achieve bone union (three patients). The radiographic assessment consisted of pre- and postoperative radiographs and CT-scans. RESULTS: The radiolunate angle, scapholunate angle and Youm index were measured. At the final follow-up, the scapholunate angle was 54±8̊ (36-80̊) and the radiolunate angle was 11±7̊ (2-45̊). The scapholunate angle was significantly different between the preoperative measurement and the last follow-up; however, the radiolunate angle and Youm index did not change significantly. CONCLUSION: Our study found that arthroscopic treatment of scaphoid non-union with a cancellous bone graft taken from the distal radius results corrects the humpback deformity. LEVEL OF EVIDENCE: IV.

An Ultrasound-guided Percutaneous Surgical Technique for Trigger Finger Release Using a Minimally Invasive Surgical Knife.

Triggering of the finger at the A1 pulley is one of the most frequent pathologies encountered in hand surgery and a common cause of hand pain. Open release of the A1 pulley is currently still regarded as the golden-standard procedure. Nevertheless, there is an increasing interest in minimally invasive percutaneous techniques for the treatment of this condition. Current techniques range from percutaneous needle techniques without imaging, to the use of hook knives, with ultrasound guidance. Because of concerns about possible complications or incomplete releases, hand surgeons remain wary. The objective of this study was to introduce a new ultrasound-guided percutaneous surgical technique for trigger finger release, using a second-generation minimally invasive surgical knife. In this series of 78 releases, complete resolution of the symptoms was found in 98.7% of the cases. One recurrence of triggering was observed. There were no tendon injuries, infections, or neurovascular lesions recorded. This paper contains technical pearls and possible pitfalls to ensure the surgeon of a complete release and to avoid complications. A video of the technique was also included as Supplemental Digital Content (http://links.lww.com/BTH/A143). We can conclude that the procedure can be considered as safe and highly effective for the treatment of triggering at the A1 pulley.

Using Ultrasonography During the Fixation of Distal Radius and Finger Fractures.

Ultrasonography (US) is a noninvasive examination modality that is devoid of risk, both for the patient and the surgeon, compared with fluoroscopy. The principle is the same for distal radius and finger fractures: replace the fluoroscopy checks with US checks to reduce the patient's, surgeon's, and surgical team's exposure to radiation. In this article, the authors report their experience of the effectiveness of ultrasound imaging during the fixation of a distal radius and long finger fracture. They also describe equipment needed and surgical procedure.

Distal radius malunion in adults.

Distal radius malunion (DRMU) consists in a non-anatomical consolidation of a distal radius fracture. The resulting alteration of the articular or extra-articular radial anatomy impairs wrist function to a greater or lesser degree: Restricted ranges of motion, loss of strength, pain. There may also be nerve or tendon involvement. Adaptive carpal malalignment and ulnar-carpal impingement are also possible. Imaging assessment should at least include X-ray and CT; CT-arthrography is essential in intra-articular DRMU, which regularly progresses toward radiocarpal osteoarthritis. Surgical indications are guided by clinical assessment. Restoring distal radial anatomy requires osteotomy, according to type of DRMU: anterior or posterior opening or closing wedge. Bone or bone-substitute graft may need to be associated. Computerisation has improved planning and should be implemented, whenever possible. Ulnar osteotomy may be performed, isolated or associated to distal radial osteotomy. Palliative partial fusion or bone resection is possible in case of joint involvement or in patients with low functional demand.

Ribosomal protein eL42 contributes to the catalytic activity of the yeast ribosome at the elongation step of translation.

The GGQ minidomain of the ribosomal protein eL42 was previously shown to contact the CCA-arm of P-site bound tRNA in human ribosome, indicating a possible involvement of the protein in the catalytic activity. Here, using Schizosaccharomyces pombe (S. pombe) cells, we demonstrate that the GGQ minidomain and neighboring region of eL42 is critical for the ribosomal function. Mutant eL42 proteins containing amino acid substitutions within or adjacent to the GGQ minidomain failed to complement the function of wild-type eL42, and expression of the mutant eL42 proteins led to severe growth defects. These results suggest that the mutations in eL42 interfere with the ribosomal function in vivo. Furthermore, we show that some of the mutations associated with the conserved GGQ region lead to reduced activities in the poly(Phe) synthesis and/or in the peptidyl transferase reaction with respect to puromycin, as compared with those of the wild-type ribosomes. A pK value of 6.95 was measured for the side chain of Lys-55/Arg-55, which is considerably less than that of a Lys or Arg residue. Altogether, our findings suggest that eL42 contributes to the 80S ribosome's peptidyl transferase activity by promoting the course of the elongation cycle.

Affinity labelling in situ of the bL12 protein on E. coli 70S ribosomes by means of a tRNA dialdehyde derivative.

In this report, we have used periodate-oxidized tRNA (tRNAox) as an affinity laleling reagent to demonstrate that: (i) the bL12 protein contacts the CCA-arm of P-site bound tRNA on the Escherichia coli 70S ribosomes; (ii) the stoichiometry of labelling is one molecule of tRNAox bound to one polypeptide chain of endogenous bL12; (iii) cross-linking in situ of bL12 with tRNAox on the ribosomes provokes the loss of activity; (iv) intact tRNA protects bL12 in the 70S ribosomes against cross-linking with tRNAox; (v) both tRNAox and pyridoxal 5'-phosphate (PLP) compete for the same or for proximal cross-linking site(s) on bL12 inside the ribosome; (vi) the stoichiometry of cross-linking of PLP to the recombinant E. coli bL12 protein is one molecule of PLP covalently bound per polypeptide chain; (vii) the amino acid residue of recombinant bL12 cross-linked with PLP is Lys-65; (viii) Lys-65 of E. coli bL12 corresponds to Lys-53 of eL42 which was previously shown to cross-link with P-site bound tRNAox on human 80S ribosomes in situ; (ix) finally, E. coli bL12 and human eL42 proteins display significant primary structure similarities, which argues for evolutionary conservation of these two proteins located at the tRNA-CCA binding site on eubacterial and eukaryal ribosomes.

A STAT3-inhibitory hairpin decoy oligodeoxynucleotide discriminates between STAT1 and STAT3 and induces death in a human colon carcinoma cell line.

BACKGROUND: The Signal Transducer and Activator of Transcription 3 (STAT3) is activated in tumor cells, and STAT3-inhibitors are able to induce the death of those cells. Decoy oligodeoxynucleotides (dODNs), which bind to the DNA Binding Domain (DBD) of STAT3, are efficient inhibitors. However, they also inhibit STAT1, whose activity is essential not only to resistance to pathogens, but also to cell growth inhibition and programmed cell death processes. The aim of this study was to design STAT3-specific dODNs which do not affect STAT1-mediated processes. RESULTS: New dODNs with a hairpin (hpdODNs) were designed. Modifications were introduced, based on the comparison of STAT3- and STAT1-DBD interactions with DNA using 3D structural analyses. The designed hpdODNs were tested for their ability to inhibit STAT3 but not STAT1 by determining: i) cell death in the active STAT3-dependent SW480 colon carcinoma cell line, ii) absence of inhibition of interferon (IFN) γ-dependent cell death, iii) expression of STAT1 targets, and iv) nuclear location of STAT3 and STAT1. One hpdODN was found to efficiently induce the death of SW480 cells without interfering with IFNγ-activated STAT1. This hpdODN was found in a complex with STAT3 but not with STAT1 using an original in-cell pull-down assay; this hpdODN also did not inhibit IFNγ-induced STAT1 phosphorylation, nor did it inhibit the expression of the STAT1-target IRF1. Furthermore, it prevented the nuclear transfer of STAT3 but not that of IFNγ-activated STAT1. CONCLUSIONS: Comparative analyses at the atomic level revealed slight differences in STAT3 and STAT1 DBDs' interaction with their DNA target. These were sufficient to design a new discriminating hpdODN that inhibits STAT3 and not STAT1, thereby inducing tumor cell death without interfering with STAT1-dependent processes. Preferential interaction with STAT3 depends on oligodeoxynucleotide sequence modifications but might also result from DNA shape changes, known to modulate protein/DNA interactions. The finding of a STAT3-specific hpdODN establishes the first rational basis for designing STAT3 DBD-specific inhibitors.

Solution structure of a truncated anti-MUC1 DNA aptamer determined by mesoscale modeling and NMR.

Mucin 1 is a well-established target for the early diagnosis of epithelial cancers. The nucleotides of the S1.3/S2.2 DNA aptamer involved in binding to variable number tandem repeat mucin 1 peptides have been identified using footprinting experiments. The majority of these binding nucleotides are located in the 25-nucleotide variable region of the total aptamer. Imino proton and 2D NMR spectra of truncated and total aptamers in supercooled water reveal common hydrogen-bonding networks and point to a similar secondary structure for this 25-mer sequence alone or embedded within the total aptamer. NMR titration experiments confirm that the TTT triloop structure is the primary binding site and show that the initial structure of the truncated aptamers is conserved upon interaction with variable number tandem repeat peptides. The thermal dependence of the NMR chemical shift data shows that the base-paired nucleotides melt cooperatively at 47 ± 4°C. The structure of the 25-mer oligonucleotide was determined using a new combined mesoscale molecular modeling, molecular dynamics and NMR spectroscopy investigation. It contains three Watson-Crick pairs, three consecutive mispairs and four Watson-Crick pairs capped by a TTT triloop motif. The 3D model structures (PDB 2L5K) and biopolymer chain elasticity molecular models are consistent with both NMR and long unconstrained molecular dynamics (10 ns) in explicit water, respectively. Database Structural data are available in the Protein Data Bank and BioMagResBank databases under the accession numbers 2L5K and 17129, respectively.

Nucleic acid folding determined by mesoscale modeling and NMR spectroscopy: solution structure of d(GCGAAAGC).

Determination of DNA solution structure is a difficult task even with the high-sensitivity method used here based on simulated annealing with 35 restraints/residue (Cryoprobe 750 MHz NMR). The conformations of both the phosphodiester linkages and the dinucleotide segment encompassing the sharp turn in single-stranded DNA are often underdetermined. To obtain higher quality structures of a DNA GNRA loop, 5'-d(GCGAAAGC)-3', we have used a mesoscopic molecular modeling approach, called Biopolymer Chain Elasticity (BCE), to provide reference conformations. By construction, these models are the least deformed hairpin loop conformation derived from canonical B-DNA at the nucleotide level. We have further explored this molecular conformation at the torsion angle level with AMBER molecular mechanics using different possible (epsilon,zeta) constraints to interpret the 31P NMR data. This combined approach yields a more accurate molecular conformation, compatible with all the NMR data, than each method taken separately, NMR/DYANA or BCE/AMBER. In agreement with the principle of minimal deformation of the backbone, the hairpin motif is stabilized by maximal base-stacking interactions on both the 5'- and 3'-sides and by a sheared G.A mismatch base pair between the first and last loop nucleotides. The sharp turn is located between the third and fourth loop nucleotides, and only two torsion angles beta6 and gamma6 deviate strongly with respect to canonical B-DNA structure. Two other torsion angle pairs epsilon3,zeta3 and epsilon5,zeta5 exhibit the newly recognized stable conformation BIIzeta+ (-70 degrees, 140 degrees). This combined approach has proven to be useful for the interpretation of an unusual 31P chemical shift in the 5'-d(GCGAAAGC)-3' hairpin.

Dinucleotide TpT and its 2'-O-Me analogue possess different backbone conformations and flexibilities but similar stacked geometries.

UV irradiation at 254 nm of 2'-O,5-dimethyluridylyl(3'-5')-2'-O,5-dimethyluridine (1a) and of natural thymidylyl(3'-5')thymidine (1b) generates the same photoproducts (CPD and (6-4)PP; responsible for cell death and skin cancer). The ratios of quantum yields of photoproducts obtained from 1a (determined herein) to that from 1b are in a proportion close to the approximately threefold increase of stacked dinucleotides for 1a compared with those of 1b (from previous circular dichroism results). 1a and 1b however are endowed with different predominant sugar conformations, C3'-endo (1a) and C2'-endo (1b). The present investigation of the stacked conformation of these molecules, by unrestrained state-of-the-art molecular simulation in explicit solvent and salt, resolves this apparent paradox and suggests the following main conclusions. Stacked dinucleotides 1a and 1b adopt the main characteristic features of a single-stranded A and B form, respectively, where the relative positions of the backbone and the bases are very different. Unexpectedly, the geometry of the stacking of two thymine bases, within each dinucleotide, is very similar and is in excellent agreement with photochemical and circular dichroism results. Analyses of molecular dynamics trajectories with conformational adiabatic mapping show that 1a and 1b explore two different regions of conformational space and possess very different flexibilities. Therefore, even though their base stacking is very similar, these molecules possess different geometrical, mechanical, and dynamical properties that may account for the discrepancy observed between increased stacking and increased photoproduct formations. The computed average stacked conformations of 1a and 1b are well-defined and could serve as starting models to investigate photochemical reactions with quantum dynamics simulations.

Thoracolumbar fractures surgically treated by "in situ contouring".

This is a retrospective study on a series of 70 patients with thoracolumbar fractures (TL), surgically treated by the in situ bending technique (ISB). Its purpose is to show the performances and limits of the ISB technique for the early correction of post-traumatic spine deformities as well as to estimate the overall outcome in this series and to discuss the indications for anterior grafting. Although the management of limbs fractures is a cleared issue today, spine fractures management is still a matter of debate. Surgical treatment progresses fast, while indications, the fixation techniques, fracture reduction options, and associated grafting are still blurry. Seventy patients with TL fractures, mean age 40.3 years (20-80) were treated by posterior fusion with a standard construct and deformity reduction by means of the ISB technique. Mean follow-up was 30.7 months (12-78). Pre- and post-operative deformity was evaluated and the relative deformity as defined by Farcy's sagittal index (SIF) was analyzed. Thirty-eight patients underwent anterior interbody grafting. The pre-operative SIF decreased from 16.98 to 1.62 degrees (15.36 degrees decrease). Eighty percent of patients were normo- or hyper-corrected. The loss of correction during the follow-up occurred within the disc (SIF: -2.24 degrees , vertebral kyphosis 0.94 degrees , p<0.001), and was lower in patients who underwent secondary anterior grafting (-5.21 degrees vs.-1.18 degrees , p=0.002). Clinical outcome is good (Oswestry=29.75) and seems to be better in cases of double approach (20.71 vs. 37.,4, p=0.001). Sepsis occurred in ten cases, and two patients experienced construct dismounting. One patient had a retroperitoneal hematoma that required embolization. Seventy-one percent of operated patients went back to their previous work after surgery. Spine fractures deserve an efficient treatment. The ISB technique improves post traumatic kyphosis. This results is maintained at long term if the posterior fusion is associated with anterior grafting in cases where the correction within the disc exceeds 50% of the total correction.

Spectroscopic and structural impact of a stem base-pair change in DNA hairpins: GTTC-ACA-GAAC versus GTAC-ACA-GTAC.

Successive investigations over the last decade have revealed and confirmed a stable loop closure in a family of d-[GTAC-5Pur6N7N-GTAC] hairpins, where 5Pur6N7N is a AAA, GAG and AXC loop (X being any nucleotide). The trinucleotide loop is characterized by a well defined 5Pur-7N mispairing mode, and by upfield chemical shifts for three sugar protons of the apical nucleotide 6N. The GTTC-ACA-GAAC DNA hairpin, of interest for its likely involvement in Vibrio cholerae genome mutations, has now been investigated. The GTAC-ACA-GTAC DNA hairpin has also been studied because it is intermediate between the other structures, as it contains the loop of the hairpin under consideration and the stem of the above family. The two hairpins with the ACA loop are stable. They show the same mispairing mode and similar upfield shifts as the previous family, but GTTC-ACA-GAAC seems to be slightly less compact than any other. GTTC-ACA-GAAC is remarkable in that it exhibits a B(II) character for the phosphate-ester conformation at 8Gp9A, together with a swing of the upper hairpin into the major groove that, in particular, brings 6CH1' roughly as close to 7AH2 as to 6CH6. These unexpected structural features are qualitatively deduced from (1)H and (31)P NMR spectra, and confirmed by Raman spectroscopy. This comparative study shows that not only the loop sequence but also the stem sequence may control hairpin structures.

In vitro selection of halo-thermophilic RNA reveals two families of resistant RNA.

The "RNA world" hypothesis proposes that early in the evolution of life, RNA was responsible both for the storage and transfer of genetic information and for the catalysis of biochemical reactions. One of the problems of the hypothesis is that RNA is known to be temperature sensitive. Nevertheless, different types of sequences with a thermostable phenotype may exist. In order to test this possibility, we applied an in vitro evolution method (SELEX) to isolate RNA molecules that are resistant at high temperatures (80 degrees C for 65 h) and high salt concentrations (2 M NaCl). The sequences of the resulting cloned halo-thermophilic RNAs can be grouped in two families (I and II) possessing very different thermal and chemical stabilities and very different secondary structures. The selected RNA molecules illustrate two different possibilities leading to thermal resistance which may be related to primitive conditions. We propose that members of family I constitute a good means of storing sequence information while members of family II are less efficient but replicate faster in early steps of the SELEX. These selected RNA behaviors may be related to primitive conditions and could allow to define limits for survival, and demonstrate that what is at stake for RNA molecules, as for living organisms, is survival and reproduction.

Biopolymer Chain Elasticity: A novel concept and a least deformation energy principle predicts backbone and overall folding of DNA TTT hairpins in agreement with NMR distances.

A new molecular modelling methodology is presented and shown to apply to all published solution structures of DNA hairpins with TTT in the loop. It is based on the theory of elasticity of thin rods and on the assumption that single-stranded B-DNA behaves as a continuous, unshearable, unstretchable and flexible thin rod. It requires four construction steps: (i) computation of the tri-dimensional trajectory of the elastic line, (ii) global deformation of single-stranded helical DNA onto the elastic line, (iii) optimisation of the nucleoside rotations about the elastic line, (iv) energy minimisation to restore backbone bond lengths and bond angles. This theoretical approach called 'Biopolymer Chain Elasticity' (BCE) is capable of reproducing the tri-dimensional course of the sugar-phosphate chain and, using NMR-derived distances, of reproducing models close to published solution structures. This is shown by computing three different types of distance criteria. The natural description provided by the elastic line and by the new parameter, Omega, which corresponds to the rotation angles of nucleosides about the elastic line, offers a considerable simplification of molecular modelling of hairpin loops. They can be varied independently from each other, since the global shape of the hairpin loop is preserved in all cases.

DNA tri- and tetra-loops and RNA tetra-loops hairpins fold as elastic biopolymer chains in agreement with PDB coordinates.

The biopolymer chain elasticity (BCE) approach and the new molecular modelling methodology presented previously are used to predict the tri- dimensional backbones of DNA and RNA hairpin loops. The structures of eight remarkably stable DNA or RNA hairpin molecules closed by a mispair, recently determined in solution by NMR and deposited in the PDB, are shown to verify the predicted trajectories by an analysis automated for large numbers of PDB conformations. They encompass: one DNA tetraloop, -GTTA-; three DNA triloops, -AAA- or -GCA-; and four RNA tetraloops, -UUCG-. Folding generates no distortions and bond lengths and bond angles of main atoms of the sugar-phosphate backbone are well restored upon energy refinement. Three different methods (superpositions, distance of main chain atoms to the elastic line and RMSd) are used to show a very good agreement between the trajectories of sugar-phosphate backbones and between entire molecules of theoretical models and of PDB conformations. The geometry of end conditions imposed by the stem is sufficient to dictate the different characteristic DNA or RNA folding shapes. The reduced angular space, consisting of the new parameter, angle Omega, together with the chi angle offers a simple, coherent and quantitative description of hairpin loops.