Comparison of two ways of altering carpal tunnel pressure with ultrasound surface wave elastography

Higher carpal tunnel pressure is related to the development of carpal tunnel syndrome. Currently, the measurement of carpal tunnel pressure is invasive and therefore, a noninvasive technique is needed. We previously demonstrated that speed of wave propagation through a tendon in the carpal tunnel measured by ultrasound elastography could be used as an indicator of carpal tunnel pressure in a cadaveric model, in which a balloon had to be inserted into the carpal tunnel to adjust the carpal tunnel pressure. However, the method for adjusting the carpal tunnel pressure in the cadaveric model is not applicable for the in vivo model. The objective of this study was to utilize a different technique to adjust carpal tunnel pressure via pressing the palm and to validate it with ultrasound surface wave elastography in a human cadaveric model. The outcome was also compared with a previous balloon insertion technique. Results showed that wave speed of intra-carpal tunnel tendon and the ratio of wave speed of intra-and outer-carpal tunnel tendons increased linearly with carpal tunnel pressure. Moreover, wave speed of intra carpal tunnel tendon via both ways of altering carpal tunnel pressure showed similar results with high correlation. Therefore, it was concluded that the technique of pressing the palm can be used to adjust carpal tunnel pressure, and pressure changes can be detected via ultrasound surface wave elastography in an ex vivo model. Future studies will utilize this technique in vivo to validate the usefulness of ultrasound surface wave elastography for measuring carpal tunnel pressure.     

Statics of the Ribosomal Exit Tunnel: Implications for Cotranslational Peptide Folding, Elongation Regulation, and Antibiotics Binding

A sophisticated interplay between the static properties of the ribosomal exit tunnel and its functional role in cotranslational processes is revealed by constraint counting on topological network representations of large ribosomal subunits from four different organisms. As for the global flexibility characteristics of the subunit, the results demonstrate a conserved stable structural environment of the tunnel. The findings render unlikely that deformations of the tunnel move peptides down the tunnel in an active manner. Furthermore, the stable environment rules out that the tunnel can adapt widely so as to allow tertiary folding of nascent chains. Nevertheless, there are local zones of flexible nucleotides within the tunnel, between the peptidyl transferase center and the tunnel constriction, and at the tunnel exit. These flexible zones strikingly agree with previously identified folding zones. As for cotranslational elongation regulation, flexible residues in the β-hairpin of the ribosomal L22 protein were verified, as suggested previously based on structural results. These results support the hypothesis that L22 can undergo conformational changes that regulate the tunnel voyage of nascent polypeptides. Furthermore, rRNA elements, for which conformational changes have been observed upon interaction of the tunnel wall with a nascent SecM peptide, are less strongly coupled to the subunit core. Sequences of coupled rigid clusters are identified between the tunnel and some of these elements, suggesting signal transmission by a domino-like mechanical coupling. Finally, differences in the flexibility of the glycosidic bonds of bases that form antibiotics-binding crevices within the peptidyl transferase center and the tunnel region are revealed for ribosomal structures from different kingdoms. In order to explain antibiotics selectivity, action, and resistance, according to these results, differences in the degrees of freedom of the binding regions may need to be considered.     

The ribosomal tunnel as a functional environment for nascent polypeptide folding and translational stalling

As the nascent polypeptide chain is being synthesized, it passes through a tunnel within the large ribosomal subunit and emerges at the solvent side where protein folding occurs. Despite the universality and conservation of dimensions of the ribosomal tunnel, a functional role for the ribosomal tunnel is only beginning to emerge: Rather than a passive conduit for the nascent chain, accumulating evidence indicates that the tunnel plays a more active role. In this article, we discuss recent structural insights into the role of the tunnel environment, and its implications for protein folding, co-translational targeting and translation regulation.     

Reducing Mouse Anxiety during Handling: Effect of Experience with Handling Tunnels

Handling stress is a well-recognised source of variation in animal studies that can also compromise the welfare of research animals. To reduce background variation and maximise welfare, methods that minimise handling stress should be developed and used wherever possible. Recent evidence has shown that handling mice by a familiar tunnel that is present in their home cage can minimise anxiety compared with standard tail handling. As yet, it is unclear whether a tunnel is required in each home cage to improve response to handling. We investigated the influence of prior experience with home tunnels among two common strains of laboratory mice: ICR(CD-1) and C57BL/6. We compared willingness to approach the handler and anxiety in an elevated plus maze test among mice picked up by the tail, by a home cage tunnel or by an external tunnel shared between cages. Willingness to interact with the handler was much greater for mice handled by a tunnel, even when this was unfamiliar, compared to mice picked up by the tail. Once habituated to handling, C57BL/6 mice were most interactive towards a familiar home tunnel, whereas the ICR strain showed strong interaction with all tunnel handling regardless of any experience of a home cage tunnel. Mice handled by a home cage or external tunnel showed less anxiety in an elevated plus maze than those picked up by the tail. This study shows that using a tunnel for routine handling reduces anxiety among mice compared to tail handling regardless of prior familiarity with tunnels. However, as home cage tunnels can further improve response to handling in some mice, we recommend that mice are handled with a tunnel provided in their home cage where possible as a simple practical method to minimise handling stress.     

A comparison of flexor tenosynovectomy, open carpal tunnel release, and open carpal tunnel release with flexor tenosynovectomy in the treatment of carpal tunnel syndrome

The purpose of this study was to identify the advantages and disadvantages of performing a flexor tenosynovectomy without dividing the transverse carpal ligament, an open carpal tunnel release, and an open carpal tunnel release with flexor tenosynovectomy in the treatment of carpal tunnel syndrome. From 1990 to 1998, a retrospective study was done in which a flexor tenosynovectomy was performed in 133 patients without division of the transverse carpal ligament and compared with 68 patients who had an open carpal tunnel release and 75 patients who had an open carpal tunnel release and flexor tenosynovectomy. Patients were followed up for an average period of 30 weeks with history and physical findings and nerve conduction velocities and for an average period of 2.6 years with telephone interviews. There was a 2.3 percent incidence of pillar pain in the flexor tenosynovectomy group, which may explain the earlier return to their regular jobs at an average time of 9.9 weeks, compared with 10.7 weeks for the carpal tunnel release group and 12.0 weeks for the carpal tunnel release/flexor tenosynovectomy group. The latter two groups had an incidence of pillar pain of 12.1 percent and 25.3 percent, respectively. Postoperative grip strength was statistically significantly improved in the flexor tenosynovectomy group compared with the other two groups, where adjustments were made for sex and preoperative grip strengths with standard error of adjusted means. In the flexor tenosynovectomy group, 20.6 percent of patients had a previous open or endoscopic carpal tunnel release with recurrent carpal tunnel syndrome, compared with 5.2 percent in the open carpal tunnel release group and 21.6 percent in the open carpal tunnel release with flexor tenosynovectomy group. Excisional biopsies of flexor tenosynovium in the flexor tenosynovectomy, open carpal tunnel release, and open carpal tunnel release with flexor tenosynovectomy groups revealed an incidence of fibrosis in 89.2 percent, 88.9 percent, and 87.7 percent of specimens, respectively. Edema was a frequent finding, but an active inflammatory response was seldom seen. The findings in this study indicate that because of a significant decrease in pillar pain, a flexor tenosynovectomy in the treatment of carpal tunnel syndrome would likely benefit workers who use the palm of the hand in heavy manual or highly repetitive work by allowing them to return to regular duty sooner.     

Structural insight into the role of the ribosomal tunnel in cellular regulation

Nascent proteins emerge out of ribosomes through an exit tunnel, which was assumed to be a firmly built passive path. Recent biochemical results, however, indicate that the tunnel plays an active role in sequence-specific gating of nascent chains and in responding to cellular signals. Consistently, modulation of the tunnel shape, caused by the binding of the semi-synthetic macrolide troleandomycin to the large ribosomal subunit from Deinococcus radiodurans, was revealed crystallographically. The results provide insights into the tunnel dynamics at high resolution. Here we show that, in addition to the typical steric blockage of the ribosomal tunnel by macrolides, troleandomycin induces a conformational rearrangement in a wall constituent, protein L22, flipping the tip of its highly conserved beta-hairpin across the tunnel. On the basis of mutations that alleviate elongation arrest, the tunnel motion could be correlated with sequence discrimination and gating, suggesting that specific arrest motifs within nascent chain sequences may induce a similar gating mechanism.     

Queue Size Determines the Width of Tunnels in the Formosan Subterranean Termite (Isoptera: Rhinotermitidae)

We present a model of tunnel excavation by termites that requires no pheromone labeling of soil or work sites, but instead relies on tactile interactions and individuals who actively orient their movement. Potential termite excavators moved from the tunnel origin towards the distal end of the tunnel and formed a queue behind those termites at the digging face. Delayed termites excavated soil laterally from the tunnel wall at a position governed by their position in the queue of termites. By examining excavation under artificially induced conditions of longer and shorter queues of termites at the tunnel end, we showed that tunnel width increased with increased queue size and the rate of lateral excavation in a process we termed “digging pressure.”     

Evaluation of the carpal tunnel based on 3-D reconstruction from MRI

While deviated wrist postures have been linked to the development of carpal tunnel syndrome, the relative contributions of posture-related changes in size, shape and volume of the carpal tunnel contribute to median nerve compression are unclear. The purpose of this study was two-fold: (1) to reconstruct the carpal tunnel from MRI data in neutral and non-neutral (30 degrees extension, 30 degrees flexion) wrist postures, and (2) to evaluate errors associated with off-axis imaging. Three-dimensional reconstruction of the carpal tunnels of 8 volunteers from the university community revealed that the orientation of the carpal tunnel was not directly explained by external wrist angle. The average orientation of the carpal tunnel was extended in all postures, ranging from 25 degrees +/-9 degrees in extension, 13 degrees +/-5 degrees in neutral and 4 degrees +/-4 degrees in the flexed wrist. Changing the orientation of the imaging plane to be perpendicular to the reconstructed carpal tunnel revealed that axial images overestimated cross-sectional area by an average of nearly 10% in extension, 4% in neutral and less than 1% in flexion. Similarly, adjusting the imaging plane to be perpendicular to external wrist angle overestimated cross-sectional area by an average of 2% in extension, 4% in neutral and 24% in flexion. Distortion of the carpal tunnel shape also became evident with rotation of the imaging plane. The data suggest that correction for the orientation of the carpal tunnel itself to be more appropriate than relying on external wrist angle. Computerized reconstruction provided detailed anatomic visualization of the carpal tunnel, and has created the framework to develop a biomechanical model of the carpal tunnel. Similar reconstruction of the tissue structures passing through (median nerve and flexor tendons) and entering the carpal tunnel (muscle tissue) will enable evaluation and partitioning of median nerve injury mechanisms.     

Folding zones inside the ribosomal exit tunnel

Helicity of membrane proteins can be manifested inside the ribosome tunnel, but the determinants of compact structure formation inside the tunnel are largely unexplored. Using an extended nascent peptide as a molecular tape measure of the ribosomal tunnel, we have previously demonstrated helix formation inside the tunnel. Here, we introduce a series of consecutive polyalanines into different regions of the tape measure to monitor the formation of compact structure in the nascent peptide. We find that the formation of compact structure of the polyalanine sequence depends on its location. Calculation of free energies for the equilibria between folded and unfolded nascent peptides in different regions of the tunnel shows that there are zones of secondary structure formation inside the ribosomal exit tunnel. These zones may have an active role in nascent-chain compaction.     

Aerodynamic corrections for the flight of birds and bats in wind tunnels

Few wind tunnel studies of animal flight have controlled or corrected for distortions to behaviour, physiology or flight aerodynamics representing the difference between flight in the tunnel and flight in free air. Aerodynamic correction factors are derived based on lifting-line theory and the method of images for an animal flying freely within closed- and open-section wind tunnels; the method is very similar to that used to model flight in ground effect, and as in ground effect the corrections to induced drag may be substantial. These correction factors are used to estimate bound wing circulation, drag and mechanical power for comparison with free flight, and to derive testable predictions of optimum flight strategies for an animal in a tunnel. In an open-section tunnel, mechanical power is increased compared to free flight, and the animal should fly at the tunnel centre. In a closed tunnel mechanical power is usually reduced, and substantial savings are available, particularly at low speeds, if the animal flies close to the tunnel roof. Anecdotal observations confirm that birds and bats adopt this strategy. The mechanical power-speed curve in a closed tunnel is flatter than the curve for free flight, and this may explain the flat metabolic power-speed curves for birds and bats obtained in some measurements.     

The incidence of recurrence after endoscopic carpal tunnel release

Endoscopic carpal tunnel release has been used to decompress the median nerve in carpal tunnel syndrome for over the past decade, with an advantage (over the traditional "open" release) being decreased pain in the postoperative period. The goals of this study were to attempt to define the recurrence rate after endoscopic carpal tunnel release and to determine if it differs from that of open technique. The charts of 191 consecutive carpal tunnel syndrome patients treated operatively at the University of Missouri were reviewed. For this study, recurrent carpal tunnel syndrome was defined as documented cases in which the symptoms had resolved following surgical release but subsequently recurred, requiring surgical rerelease of the carpal tunnel. All endoscopic releases were performed using the Chow two-portal technique. Statistical analysis was performed using Fisher's exact test. A total of 103 patient hands had open carpal tunnel releases; 88 were endoscopically released. Total follow-up time (from the initial release) averaged 29 months for the open group and 22 months for the endoscopic group. There were no recurrences in the open group and six recurrences in the endoscopic group (7 percent, p = 0.008). All six recurrences were in worker's compensation patients. The median time between endoscopic release and rerelease was 8.5 months. There seems to be a statistically higher incidence of recurrence of carpal tunnel syndrome after endoscopic release compared with the traditional "open" release in our cases. Although the pathogenesis of this increased rate of recurrence is not clear, this should be considered when planning surgical release of the volar carpal ligament for carpal tunnel syndrome.     

贵州独山中泥盆世动藻迹生态习性探讨

贵州独山中泥盆统产有丰富的遗迹化石Zoopkycos,现从其产出的特征和古生态等方面对其生活习性进行探讨。认为分布于静水、贫氧、有机质丰富环境的Zoopkycos为螺旋向上的内生觅食构造;边缘管一端通过中央通道与海水相通,呈“J”形;蹼状构造系造迹生物觅食区域的扩大、边缘管增大而形成;同一个体的Zoopkycos可以分出许多的与蹼状构造变化规律相近的、具同一边缘管的觅食序列(food-system),每一觅食序列的边缘管具有一端向上与中央通道相通,另一端向下与相邻觅食序列的边缘管相联;螺旋的疏密、大小与相对沉积速度有关。产于独山地区中泥盆统的Zoopkycos的造迹生物可能是星虫类(sipunculids)。     

The binding and release of oxygen and hydrogen peroxide are directed by a hydrophobic tunnel in cholesterol oxidase

The usage by enzymes of specific binding pathways for gaseous substrates or products is debated. The crystal structure of the redox enzyme cholesterol oxidase, determined at sub-angstrom resolution, revealed a hydrophobic tunnel that may serve as a binding pathway for oxygen and hydrogen peroxide. This tunnel is formed by a cascade of conformational rearrangements and connects the active site with the exterior surface of the protein. To elucidate the relationship between this tunnel and gas binding and release, three mutant enzymes were constructed to block the tunnel or its putative gate. Mutation of the proposed gating residue Asn485 to Asp or tunnel residue Phe359 or Gly347 to Trp or Asn reduces the catalytic efficiency of oxidation. The K mO 2 increases from 300 +/- 35 microM for the wild-type enzyme to 617 +/- 15 microM for the F359W mutant. The k cat for the F359W mutant-catalyzed reaction decreases 13-fold relative to that of the wild-type-catalyzed reaction. The N485D and G347N mutants could not be saturated with oxygen. Transfer of hydride from the sterol to the flavin prosthetic group is no longer rate-limiting for these tunnel mutants. The steady-state kinetics of both wild-type and tunnel mutant enzymes are consistent with formation of a ternary complex of steroid and oxygen during catalysis. Furthermore, kinetic cooperativity with respect to molecular oxygen is observed with the tunnel mutants, but not with the wild-type enzyme. A rate-limiting conformational change for binding and release of oxygen and hydrogen peroxide, respectively, is consistent with the cooperative kinetics. In the atomic-resolution structure of F359W, the indole ring of the tryptophan completely fills the tunnel and is observed in only a single conformation. The size of the indole is proposed to limit conformational rearrangement of residue 359 that leads to tunnel opening in the wild-type enzyme. Overall, these results substantiate the functional importance of the tunnel for substrate binding and product release.     

On the use of the antibiotic chloramphenicol to target polypeptide chain mimics to the ribosomal exit tunnel

The ribosomal exit tunnel had recently become the centre of many functional and structural studies. Accumulated evidence indicates that the tunnel is not simply a passive conduit for the nascent chain, but a rather functionally important compartment where nascent peptide sequences can interact with the ribosome to signal translation to slow down or even stop. To explore further this interaction, we have synthesized short peptides attached to the amino group of a chloramphenicol (CAM) base, such that when bound to the ribosome these compounds mimic a nascent peptidyl-tRNA chain bound to the A-site of the peptidyltransferase center (PTC). Here we show that these CAM-peptides interact with the PTC of the ribosome while their effectiveness can be modulated by the sequence of the peptide, suggesting a direct interaction of the peptide with the ribosomal tunnel. Indeed, chemical footprinting in the presence of CAM-P2, one of the tested CAM-peptides, reveals protection of 23S rRNA nucleotides located deep within the tunnel, indicating a potential interaction with specific components of the ribosomal tunnel. Collectively, our findings suggest that the CAM-based peptide derivatives will be useful tools for targeting polypeptide chain mimics to the ribosomal tunnel, allowing their conformation and interaction with the ribosomal tunnel to be explored using further biochemical and structural methods.     

Nascent peptide side chains induce rearrangements in distinct locations of the ribosomal tunnel

Although we have numerous structures of ribosomes, none disclose side-chain rearrangements of the nascent peptide during chain elongation. This study reports for the first time that rearrangement of the peptide and/or tunnel occurs in distinct regions of the tunnel and is directed by the unique primary sequence of each nascent peptide. In the tunnel mid-region, the accessibility of an introduced cysteine to a series of novel hydrophilic maleimide reagents increases with increasing volume of the adjacent chain residue, a sensitivity not manifest at the constriction and exit port. This surprising result reveals molecular movements not yet resolvable from structural studies. These findings map solvent-accessible volumes along the tunnel and provide novel insights critical to our understanding of allosteric communication within the ribosomal tunnel, translational arrest, chaperone interaction, folding, and rates of elongation.     

Analysis of forces of ACL reconstructions at the tunnel entrance: is tunnel enlargement a biomechanical problem?

Bone tunnel enlargement is a common phenomenon following reconstruction of the anterior cruciate ligament (ACL). Biomechanical and biological factors have been reported as potential causes of this problem. However, there is no analysis of forces between the graft and bone, as the graft changes direction at the bone tunnel entrance. The purpose of this study was to study these 'redirecting forces'. Magnetic resonance images of 10 patients with an ACL reconstruction (age: 26+/-6.8 years) were used to determine the angle between graft and drill holes. Vector analysis was used to calculate the direction and magnitude of the perpendicular component of the force between the bone tunnel and the graft at the entrance of the bone tunnel. Force components were projected into the radiographically important sagittal and coronal planes. Tension of ACL reconstructions was recorded during passive knee motion in 10 cadaveric knee experiments (age: 28.9+/-10.6 years) and the tension multiplied with the force component for each plane. Results are reported for the coronal and sagittal planes, respectively: For -10 degrees of extension, the percentages of graft tension were determined to be 17+/-7 (max: 26; min: 7%) and 26+/-9 (max: 39; min: 16%) for the tibia. They were 59+/-6 (max: 66; min: 48%) and 99+/-1 (max: 1.00; min: 99%) for the femur. Force components were 14.68+/-6.54 and 25.73+/-12.96 N for the tibial tunnel. For the femoral tunnel, they were 52.48+/-19.03 and 90.77+/-32.06 N. Percentages of graft tension and force components were significantly higher for the femoral tunnel compared with the tibial tunnel. Moreover, in the sagittal direction, force components for the femoral tunnel were significantly higher compared with the coronal plane (Wilcoxon test, p < 0.01). The differences in force components calculated in this study corresponds with the amount of tunnel enlargement in the radiographic planes in the literature providing evidence that biomechanical forces play a key role in postoperative tunnel expansion.     

东湖通道工程对沿线底泥细菌群落结构和多样性的影响

为调查东湖通道工程对沿线底泥细菌群落结构和多样性可能造成的影响, 随着隧道施工的进程, 在东湖通道沿线的3个湖区中的19个采样点进行了3次采样, 通过PCR-DGGE结合分子克隆技术, 分析了细菌群落的群落结构及多样性。3批样品共检出细菌类群分别为5门18属、6门17属、5门11属。在门水平上, 底泥中的优势菌是变形菌门, 但其在总量中的比例随施工进程逐渐下降, 依次为86%、80.6%和43.9%。在属水平上, 施工初期的优势菌是埃希氏杆菌属, 施工后期却是Steroidobacter。通道施工初期, 汤菱湖、郭郑湖的湖心区域在属水平上的群落结构相似性较高, 与团湖差异显著; 接近施工区样点与远离施工区样点的底泥细菌群落存在显著差异; 因施工形成的临时封闭水域与敞水区除均有埃希氏杆菌属外, 其他菌属类群差异显著。施工后期的汤菱湖、郭郑湖及团湖的湖心区的底泥微生物群落结构趋于相似; 接近施工区样点与远离施工区样点的底泥细菌群落差异不显著; 封闭区和敞水区有相似的细菌群落结构。施工期间, 细菌群落的多样性指数的最高点都有出现在靠近施工区的位置。各批次样点的Simpson_1-D指数、Shannon_H指数、Margalef指数, 均随着施工进程而逐渐增加。因此, 东湖通道修建对通道沿线近距离的底泥细菌的群落结构和多样性产生了较显著的影响, 这种影响是暂时性还是持续性的, 尚需通道完工回填后的长期评估。研究将为进一步探讨通道修建等人为强干扰活动对浅水湖泊的可能环境影响和制定合理的生态修复策略提供理论基础和数据支撑。     

Carpal tunnel syndrome in hemodialysed patients]

A case of carpal tunnel syndrome in female patient treated with hemodialyses for 10 years is presented. Surgical management was applied with positive result. Histological examination of tissue collected during surgery has shown the deposits of amyloid-like substance in carpal tunnel. The authors discuss current concepts of carpal tunnel syndrome pathogenesis in hemodialysed patients.     

Regional Discrimination and Propagation of Local Rearrangements along the Ribosomal Exit Tunnel

All proteins, from bacteria to man, are made in the ribosome and are elongated, one residue at a time, at the peptidyl transferase center. This growing peptide chain wends its way through the ribosomal tunnel to the exit port, ~ 100 Å from the peptidyl transferase center. We have identified locations in the tunnel that sense and respond to single side chains of the nascent peptide to induce local conformational changes. Moreover, side-chain sterics and rearrangements deep in the tunnel influence the disposition of residues 45 Å away at the exit port and are consistent with side-chain-induced axial retraction of the peptide backbone. These coupled responses are neither haphazard nor uniform along the tunnel. Rather, they are confined to discriminating zones in the tunnel and are sequence specific. Such discerning communication may contribute to folding events and mechanisms governing sequence-specific signaling between different regions of the tunnel during translation.