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The aim of this study was to investigate the correlation of wrist extension strength (WES) and grip strength (GS) using a radial nerve block, and to determine the WES required to prevent the “wrist flexion phenomenon” (antagonistic WES) when making a fist. We tested 14 arms in seven healthy males. WES and GS were measured before blocking as standard WES and standard GS. All participants then had radial nerve blocks with mepivacaine hydrochloride. During the recovery process from radial nerve blockade, WES and GS were recorded every 5 minutes. There was a very strong correlation between WES and GS (p < 0.0001). The mean antagonistic WES was 51% of standard WES, and the mean GS, recorded at the same time, was 66% of standard GS. [ABSTRACT FROM PUBLISHER]

Purpose: The primary objective of this study was to compare the long-term survival rates of silicone metacarpophalangeal (MCP) arthroplasties between two major implants in patients with rheumatoid arthritis, using implant fracture as an end point. We also evaluated the difference in postoperative function between patients with fractured and intact implants as a secondary objective., Methods: A retrospective cohort study was conducted on 372 fingers of 133 hands that underwent silicone MCP arthroplasty between January 2000 and June 2019 (mean follow-up, 7.6 years). The survival rates of Swanson-type and Sutter-type implants were compared, using implant fracture as the end point after a radiographic evaluation. Clinical measures and upper limb functional assessments using the Disabilities of the Arm, Shoulder, and Hand (DASH) score were performed in the nested cohort., Results: The 10.6-year survival rates for implant fracture of Swanson- and Sutter-type implants were 86.2% and 9.4%, respectively, with significantly higher survival noted for Swanson-type implants. The Sutter-type implant showed increased susceptibility to fracture in all four fingers compared to the Swanson-type implant. Implant fractures were primarily observed at the stem-hinge junction. There were no significant differences in upper limb function between the fractured and intact implant groups., Conclusions: Sutter-type implants were found to be more prone to fracture compared with Swanson-type implants. However, implant fractures did not significantly affect upper limb function., Type of Study/level of Evidence: Prognosis IV., Competing Interests: Conflicts of Interest No benefits in any form have been received or will be received related directly or indirectly to the subject of this article., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Single-molecule enzyme activity-based enzyme profiling (SEAP) is a methodology to globally analyze protein functions in living samples at the single-molecule level. It has been previously applied to detect functional alterations in phosphatases and glycosidases. Here, we expand the potential for activity-based biomarker discovery by developing a semi-automated synthesis platform for fluorogenic probes that can detect various peptidases and protease activities at the single-molecule level. The peptidase/protease probes were prepared on the basis of a 7-amino-4-methylcoumarin fluorophore. The introduction of a phosphonic acid to the core scaffold made the probe suitable for use in a microdevice-based assay, while phosphonic acid served as the handle for the affinity separation of the probe using Phos-tag. Using this semi-automated scheme, 48 fluorogenic probes for the single-molecule peptidase/protease activity analysis were prepared. Activity-based screening using blood samples revealed altered single-molecule activity profiles of CD13 and DPP4 in blood samples of patients with early-stage pancreatic tumors. The study shows the power of single-molecule enzyme activity screening to discover biomarkers on the basis of the functional alterations of proteins., Competing Interests: Declaration of interests S.S. and Y.K. are cofounders, employees, and shareholders of Cosomil, Inc. H.H., N.I., and M.S. are employees of Cosomil, Inc. T.M. and K.H., are advisors and shareholders of Cosomil, Inc. R.W. and T. Komatsu are cofounders, advisors, and shareholders of Cosomil, Inc. S.S., Y.K., R.W., Y.U., and T. Komatsu are inventors of a patent describing the SAS-based probe synthesis., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: One of the mechanisms of the efficacy of extracorporeal shock wave therapy (ESWT) for impaired muscle coordination of limbs is the destruction of Acetylcholine receptors (AChRs) at neuromuscular junction. The highly increased density of AChRs can change the acoustic impedance, and this change of the acoustic impedance can be the reason that radial shock wave (rESW) destroy AChRs selectively. However, the relationship between applied energy of rESWs and the therapeutic efficacy remains unclear, although some studies compared the clinical efficacy of rESWT between high- and low-energy applications. This study aimed to compare the CMAP change among different energy and pulses of rESW application., Methods: Male Sprauger-Dawley rats were used. A device that generates radial shock waves pneumatically, was used to apply the following six patterns of radial extracorporeal shockwaves in different energy flux densities and pulses to the right calf of each rat: 1, 8000 pulses at 0.045 mJ/mm 2 ; 2, 4000 pulses at 0.09 mJ/mm 2 ; 3, 2000 pulses at 0.18 mJ/mm 2 ; 4, 4000 pulses at 0.045 mJ/mm 2 ; 5, 2000 pulses at 0.09 mJ/mm 2 ; 6, 1000 pulses at 0.18 mJ/mm 2 . Left calf muscles were considered controls., Results: There was a significant reduction in CMAP amplitude between control and rESW-exposed muscles in the group applied 4000 pulses with EFD at 0.09 mJ/mm 2 and the group applied 2000 pulses with EFD at 0.18 mJ/mm 2 . However, the group applied 8000 pulses with EFD at 0.045 mJ/mm 2 and all groups which was exposed to total 180 mJ rESW application did not show a significantly decreased CMAP amplitude compared with the untreated side., Conclusions: Total energy and energy flux density correlate with a decrease in CMAP amplitude by rESW application. These findings could be availed by clinicians in actual clinical setting for the proper application of rESW., Competing Interests: Declaration of competing interest All authors, their immediate family, and any research foundation with which they are affiliated did not receive any financial payments or other benefits from any commercial entity related to the subject of this article., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: The traditional curriculum for medical students in Japan does not include sufficient opportunities for students to develop their skills for musculoskeletal (MSK) examination and clinical reasoning and diagnosis. Therefore, an effective programme is required to help medical students and residents improve their clinical skills in MSK. This paper aims to assess the clinical skills of medical students who have participated in a peer role-playing simulation programme using a mini clinical evaluation exercise (mini-CEX)., Methods: Participants were 90 female medical students who were completing their first orthopaedic clinical clerkship. They were divided into two groups. The simulation group participated in a role-play focussed on MSK cases as low-fidelity simulation, a structured debriefing with the course supervisor, and a self-reflection on Day 1 (n = 64). The control group did not participate in the role-play due to randomised clerkship schedules (n = 26). On Day 2 of the intervention, we observed and assessed all participants' performances during MSK outpatient encounters using the mini-CEX. We compared the mini-CEX score between the simulation group and the control group; the Wilcoxon rank-sum test was used for statistical analysis., Results: The mini-CEX scores for physical examination, clinical reasoning and diagnosis, and overall clinical competency were significantly higher in the simulation group than in the control group (p < .05, physical examination: p = .014, clinical reasoning: p = .042, overall: p = .016). These findings suggest that medical students who partake in a peer role-playing simulation programme could experience improved clinical skills for physical examination, clinical reasoning and diagnosis, and overall clinical competency in real-life MSK outpatient encounters., Conclusions: Through a mini-CEX assessment, our findings indicate that medical students who participated in our peer role-playing simulation programme have improved clinical skills. Peer role-playing as a low-fidelity simulation and practical educational opportunity will enable educators to polish the competency of medical students in musculoskeletal physical examinations and clinical reasoning and diagnosis in a clinical setting.

We encountered a case of capitellum fracture with radial head dislocation in which it was challenging to diagnose whether the dislocation was coincident with the fracture or this was chronic dislocation that presented before the fracture. Chronic radial head dislocation may be congenital or could occur in patients with untreated post-traumatic dislocation, although diagnosis is particularly challenging if the radial head dislocation is unilateral. Classical capitellum fracture involves anterosuperior bone fragment dislocation. However, in the present case, the bone fragment was present beneath the radial head, which suggests chronic radial head dislocation. When the bone fragment appears in a different position than usual, every effort should be made to understand the pathophysiology by reviewing the mechanism of onset, disease history, and imaging.

A new polyenyl-α-pyrone polyketide, aspopyrone A (1), was isolated from a culture broth of Okinawan plant-associated Aspergillus sp. TMPU1623 by solvent extraction, ODS column chromatography, and preparative HPLC (ODS). The structure of 1 was assigned based on NMR experiments. Compound 1 exhibited protein tyrosine phosphatase (PTP) 1B and T-cell PTP (TCPTP) inhibitory activities with IC 50 values of 6.7 and 6.0 μM, respectively.

Cladosporamide A (1), a new protein tyrosine phosphatase (PTP) 1B inhibitor, was isolated together with a known prenylated flavanone derivative (2) from the culture broth of an Indonesian marine sponge-derived Cladosporium sp. TPU1507 by solvent extraction, ODS column chromatography, and preparative HPLC (ODS). The structure of 1 was elucidated based on 1D and 2D NMR data. Compound 1 modestly inhibited PTP1B and T-cell PTP (TCPTP) activities with IC 50 values of 48 and 54 μM, respectively. The inhibitory activity of 2 against PTP1B (IC 50  = 11 μM) was approximately 2-fold stronger than that against TCPTP (IC 50  = 27 μM).

Purpose: Imaging criteria for diagnosing compressive ulnar neuropathy at the elbow (UNE) have recently been established as the maximum ulnar nerve cross-sectional area (UNCSA) upon magnetic resonance imaging (MRI) and/or ultrasonography (US). However, the levels of maximum UNCSA and diagnostic cutoff values have not yet been established. We therefore analyzed UNCSA by MRI and US in patients with UNE and in controls., Methods: We measured UNCSA at 7 levels in 30 patients with UNE and 28 controls by MRI and at 15 levels in 12 patients with UNE and 24 controls by US. We compared UNCSA as determined by MRI or US and determined optimal diagnostic cutoff values based on receiver operating characteristic curve analysis., Results: The UNCSA was significantly larger in the UNE group than in controls at 3, 2, 1, and 0 cm proximal and 1, 2, and 3 cm distal to the medial epicondyle for both modalities. The UNCSA was maximal at 1 cm proximal to the medial epicondyle for MRI (16.1 ± 3.5 mm 2 ) as well as for US (17 ± 7 mm 2 ). A cutoff value of 11.0 mm 2 for MRI and US was found to be optimal for differentiating between patients with UNE and controls, with an area under the receiver operating characteristic curve of 0.95 for MRI and 0.96 for US. The UNCSA measured by MRI was not significantly different from that by US. Intra-rater and interrater reliabilities for UNCSA were all greater than 0.77. The UNCSA in the severe nerve dysfunction group of 18 patients was significantly larger than that in the mild nerve dysfunction group of 12 patients., Conclusions: By measuring UNCSA with MRI or US at 1 cm proximal to the ME, patients with and without UNE could be discriminated at a cutoff threshold of 11.0 mm 2 with high sensitivity, specificity, and reliability., Type of Study/level of Evidence: Diagnostic III., (Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Introduction: This study assesses the effect of radial extracorporeal shock wave (rESW) exposure on neuromuscular transmission and neuromuscular junction (NMJ) morphology., Methods: We applied 2,000 rESWs at 0.18 mJ/mm 2 and a frequency of 15 Hz to the right calf of male rats, measured the compound muscle action potential (CMAP), and examined NMJ morphology using electron microscopy. Left calf muscles were used as controls., Results: rESW exposure significantly reduced CMAP amplitude without delayed latency in exposed muscles compared with controls. All rESW-exposed muscles exhibited NMJs with irregular end plates. Mean interjunctional fold interval was significantly increased compared with controls. However, axon terminals and muscle fibers surrounding NMJs with irregular end plates were unchanged., Discussion: This localized destruction of end plates may be caused by differences in acoustic impedance induced by the density of acetylcholine receptors. These results provide a possible mechanism for the effectiveness of rESW treatment for spasticity and dystonia. Muscle Nerve 57: 466-472, 2018., (© 2017 Wiley Periodicals, Inc.)

A model Post-Termination Complex (PoTC) used for the discovery of Ribosome Recycling Factor (RRF) was purified and characterized by cryo-electron microscopic analysis and biochemical methods. We established that the model PoTC has mostly one tRNA, at the P/E or P/P position, together with one mRNA. The structural studies were supported by the biochemical measurement of bound tRNA and mRNA. Using this substrate, we establish that the release of tRNA, release of mRNA and splitting of ribosomal subunits occur during the recycling reaction. Order of these events is tRNA release first followed by mRNA release and splitting almost simultaneously. Moreover, we demonstrate that IF3 is not involved in any of the recycling reactions but simply prevents the re-association of split ribosomal subunits. Our finding demonstrates that the important function of RRF includes the release of mRNA, which is often missed by the use of a short ORF with the Shine-Dalgarno sequence near the termination site.

Background and Aim: Gastroesophageal reflux disease (GERD) and psychological stress are associated with sleep disturbances. The aim of the present study was to examine the prevalence of sleep disturbances, anxiety, and depression by GERD subtypes and to identify factors associated with sleep disturbances in general population., Methods: A total of 2002 Japanese subjects, who underwent annual health checkups, were enrolled and asked to fill out a questionnaire, including the frequency scale for the symptoms of GERD (FSSG), Athens Insomnia Scale (AIS), Rome III questionnaire, and Hospital Anxiety and Depression Scale (HADS). GERD was divided into asymptomatic erosive reflux disease (a-ERD), symptomatic ERD (s-ERD), and non-erosive reflux disease (NERD), according to the presence or absence of esophageal mucosal injury on endoscopy, and the FSSG scores. Sleep disturbances were diagnosed in subjects with AIS score ≥6., Results: Prevalence of sleep disturbances was significantly higher in GERD subjects than in controls (35.9 and 14.7%, respectively), especially, in the NERD group (45.1%). Sleep duration was significantly shorter in the s-ERD group compared with other groups. Subjects in the NERD and s-ERD groups showed higher HADS scores, resulting in higher incidences of anxiety and depression than those in the control and a-ERD groups. Reflux symptoms, anxiety, depression, and coexisting functional dyspepsia, but not the presence of esophageal mucosal injury, were associated with an increased odds ratio for sleep disturbances., Conclusion: There were significant positive associations among reflux symptoms, psychological stress, and sleep disturbance in Japanese adults. Further studies investigating the efficacy of therapy are needed.

Background/aims: Approximately 20-40% of patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI) treatment. The acid-inhibitory effect of vonoprazan, a novel potassium-competitive acid blocker (P-CAB), is significantly greater when compared to the effect of PPIs. We investigated the efficacy of vonoprazan treatment for PPI-refractory GERD and factors associated with P-CAB non-response., Methods: We enrolled 277 GERD patients receiving continuous PPI therapy. Subjects completed a self-report questionnaire including the frequency scale for the symptoms of GERD (FSSG). Patients with PPI-refractory GERD received 20 mg of vonoprazan once daily for 8 weeks. After that, subjects completed the same questionnaire, and the results were used to identify P-CAB responders and non-responders., Results: Twenty-eight patients were identified as P-CAB responders and 26 were non-responders. Vonoprazan treatment significantly decreased scores of FSSG, nighttime symptom, and Athens Insomnia Scale. Multivariate analysis demonstrated co-existing functional dyspepsia (FD; OR 4.94) and the presence of sleep disturbances (OR 4.34) was associated with P-CAB non-response, whereas alcohol consumption was inversely associated., Conclusions: Vonoprazan treatment might be appropriate as a promising new strategy for PPI-refractory GERD. Co-existing FD, sleep disturbances, and alcohol abstinence were significantly associated with P-CAB non-response. Other therapeutic options should be considered in patients with these factors., (© 2017 S. Karger AG, Basel.)

Background: Several studies have reported a significant association between sleep disturbance and inflammatory bowel disease (IBD). The aim of the present study is to compare the clinical characteristics and the health-related quality of life (HR-QOL) of Japanese IBD patients with or without sleep disturbances, and to investigate the risk factors for disease flare in these patients., Methods: IBD patients were asked to complete a self-administered questionnaire including the Pittsburg sleep quality index and the 8-item short-form health survey. The information about disease flare within 1 year from enrollment in the study was analyzed with a multiple logistic regression model to identify risk factors for IBD flare-ups., Results: The prevalence of sleep disturbances was 44.1 % (60 out of 136 IBD patients). Use of sleep medications was significantly higher in IBD patients with sleep disturbances whereas use of immuno modulators was significantly higher in IBD patients without sleep disturbances. The scores from all HR-QOL domains were significantly lower in patients with sleep disturbances than in patients without sleep disturbances. Fifty-one patients (37.5 %) had disease flare within 1 year from enrollment in the study and sleep disturbances were identified as a significant risk factor for disease flare (OR 3.09, 95 % CI 1.47-6.43)., Conclusions: Our results indicate that sleep disturbances are common in Japanese IBD patients and are associated with poorer HR-QOL. Since the presence of sleep disturbances is a significant risk factor for IBD flare-ups, we encourage physicians to perform a careful examination of sleep disturbances in IBD patients.

Objective Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances; however, the detailed differences in the characteristics of sleep disturbances between GERD and non-GERD patients are unknown. The aim of the present study was to analyze the clinical characteristics as well as health-related quality of life in GERD and non-GERD patients with sleep disturbances. Methods Three hundred and fifty patients, including 124 patients with GERD and 226 patients without GERD, completed a self-administered questionnaire that evaluated clinical information. The Pittsburg Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) and 8-item Short-Form Health Survey (SF-8) were also used. Sleep disturbance was considered to be present if the PSQI was >5.5. Results The prevalence of sleep disturbances was significantly higher in the GERD patients (66/124, 53.9%) than in the non-GERD patients (89/226, 39.3%). Depression and anxiety were significantly more common in the subjects with sleep disturbances than in those without sleep disturbances, although there were no differences between the GERD and non-GERD patients. Among the subjects with sleep disturbances, daytime sleepiness was more common in the GERD patients than in the non-GERD patients. The subjects with sleep disturbances had a poorer health-related quality of life. The physical components of quality of life were impaired, particularly in the GERD patients with sleep disturbances. Conclusion GERD patients with sleep disturbances commonly experience daytime sleepiness and an impaired health-related quality of life, especially in terms of physical components.

Objective: Glossopharyngeal neuralgia (GN) is a rare disease often clinically misdiagnosed as trigeminal neuralgia. An endovascular provocative test has been applied to assist in making the diagnosis of GN caused by vascular compression. We similarly used endovascular provocative techniques to identify the causative vessel and to evaluate the indication for microvascular decompression (MVD) in two patients., Methods: Two patients had severe retroauricular and pharyngeal pain that could not be controlled by medical therapy. Magnetic resonance imaging and magnetic resonance angiography showed a high-riding right posterior inferior cerebellar artery (PICA). We decided to apply the endovascular provocation test to prove the assumed GN and identify potential indications for MVD., Result: A loop of the PICA appeared to compress the glossopharyngeal nerve in the first patient. In this patient, a microcatheter was inserted into the right PICA, decreasing the GN. The patient underwent MVD, resulting in complete pain relief. In the second patient, a microcatheter was inserted into the right PICA, and an attack of typical GN occurred, with pain in the posterior region of the tongue, tonsils, oropharynx, and larynx. The patient's severe pain was clearly different from this typical GN caused by the microcatheter provocation test, and MVD was not performed., Conclusion: The diagnosis of GN is sometimes complex. The endovascular provocative technique may allow identification of GN caused by vascular compression., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Although efficacious clinical results have been reported after vein wrapping for the treatment of recurrent compressive neuropathy, the mechanism of nerve protection remains uncertain., Methods: Eight-week-old male Wistar rats (n = 90) were randomly divided into three groups: sham procedure, chronic constriction injury, and chronic constriction injury plus vein wrapping. Mechanical withdrawal thresholds and walking patterns were measured with use of von Frey filaments and the CatWalk system, respectively. We investigated L4-L5 dorsal root ganglia immunohistochemically at fourteen days postsurgery and sciatic nerves histologically at fourteen days and again five months postsurgery. Concentrations of several sciatic neurotrophic factors in the ligated sciatic nerves were quantified with use of ELISA (enzyme-linked immunosorbent assay)., Results: In behavioral tests, the rats in which the chronic constriction injury had been followed by vein wrapping displayed significantly greater pain responses than the sham group, and the group with untreated chronic constriction injury showed greater pain responses than the vein-wrapping group (both p &lt; 0.05). Immunoreactive markers of inflammation and nerve damage, calcitonin gene-related peptide (CGRP) and activating transcription factor-3 (ATF3), were upregulated in dorsal root ganglion neurons in the constriction-injury and vein-wrapping groups compared with those in the sham group, with greater upregulation in the constriction-injury group than in the vein-wrapping group (both p &lt; 0.01). Histologic observation showed marked nerve degeneration and scar tissue formation around the sciatic nerve in the constriction-injury group, but these effects were prevented to some extent in the vein-wrapping group. Vascular endothelial growth factor (VEGF) levels at one and three days postsurgery and hepatocyte growth factor (HGF) levels at three, seven, fourteen, and twenty-eight days postsurgery were significantly higher in the vein-wrapping group than in the other groups (p &lt; 0.05)., Conclusions: Vein wrapping decreased pain-associated behavior and nerve damage caused by chronic constriction injury. VEGF and HGF produced in response to vein grafts may play a mechanistic role., Clinical Relevance: These findings may lead to development of new therapies employing growth factors, with or without other materials, that simulate vein wrapping.

Purpose: Clinically, neuropathic pain is frequent and intense following brachial plexus injury. It is thought that brachial plexus pain is not generated by avulsed roots, but rather by non-avulsed roots, since the avulsed root could not possibly transmit action potentials to central nerves. The aim of this study was to evaluate pain behavior and activation of sensory neurons in a brachial plexus avulsion (BPA) model in rats., Methods: Fifteen male Wistar rats were used. In the BPA group, the C8-T1 roots were avulsed from the spinal cord with forceps at the lower trunk level (n = 5). In the naïve group, rats did not receive any procedures (n = 5). In the sham-operated group, the lower trunk was simply exposed (n = 5). Mechanical hyperalgesia of forelimbs corresponding to C6 and C7 dermatomes was measured using von Frey filaments every third day for 3 weeks. Activation of DRG neurons was immunohistochemically examined using anti-ATF3 (a marker for neuron activation) antibodies 21 days after surgery. Von Frey and immunohistochemical data between groups were analyzed using a Kruskal-Wallis test, followed by Mann-Whitney U tests. Bonferroni corrections were performed., Results: Animals in the BPA group displayed significant mechanical hyperalgesia at the dermatome innervated by uninjured nerves continuing through day 21 compared with animals in the sham-operated group. ATF3-immunoreactive small and large DRG neurons were significantly activated in the BPA group (10.6 ± 9.5 and 5.2 ± 4.1 %, 39.7 ± 6.7 and 25.2 ± 10.3 %, 78.0 ± 9.1 and 53.7 ± 29.3 %) compared with the sham-operated group (0.7 ± 0.9 and 0 ± 0 %, 2.8 ± 2.0 and 1.0 ± 2.0 %, 3.9 ± 2.7 and 8.6 ± 10.1 %) at every level of C5, 6, and 7. In the naïve group, no DRG neurons were activated. ATF3-immunoreactive small and large DRG neurons were significantly activated at the level of C7 compared with C6 and C5, and significantly activated at the level of C6 compared with C5 in the BPA group., Conclusions: Expression of ATF3 in uninjured DRG neurons may contribute to pain following brachial plexus avulsion injury. Consequently, spared spinal sensory nerves may represent therapeutic targets for treatment of this pain.

Background: This is the first study to objectively assess the athletic ability of school-age congenital clubfoot patients., Methods: Forty-six feet of 30 patients (18 boys, 12 girls) were evaluated in this study. Nine patients were treated conservatively, 8 patients underwent percutaneous tenotomy of the Achilles tendon, and 13 patients were treated with extensive soft-tissue release. The mean age at the investigation was 9.2±1.9 years, and the mean follow-up period was 8.3±2.9 years. Athletic ability was evaluated by calculating Z-scores for the patients' scores in 5 physical fitness tests routinely performed nationwide at elementary schools: 50-meter run; standing long jump; repetition side steps; 20-meter shuttle run; and sit-ups. The Z-scores were calculated based on data published as the nationwide standards., Results: Of the 148 scores recorded for the 5 tests for the 30 clubfoot patients, 143 scores (96.6%) were higher than the -2 SD value. The mean Z-scores were as follows: -0.32 for 50-meter run; -0.16 for standing long jump; -0.24 for 20-meter shuttle run; 0.22 for repetition side steps; and 0.06 for sit-ups. None of the events showed any significant differences among the three treatment groups., Conclusions: Congenital clubfoot with satisfactory treatment did not significantly impair the athletic performance., Level of Evidence: Prognostic level III.

Study Design: We measured the response of the behavior and spinal glial activation to anti-nerve growth factor receptor (p75 neurotrophin receptor [p75NTR]) antibodies in the rat brachial plexus avulsion (BPA) model., Objective: The aim of this study was to investigate the effect of anti-p75NTR antibodies on nociceptive behavior and activation of spinal microglia in the rat BPA model., Summary of Background Data: Tanezumab (anti-nerve growth factor antibody) treatment is associated with pain reduction and improvement in function, but with several complications., Methods: Thirty male Wistar rats were used. In the BPA group, the C8-T1 roots were avulsed from the spinal cord with forceps at the lower trunk level and 10 μL of saline was applied locally (n = 10). In the anti-p75NTR group, the C8-T1 roots were avulsed and 10 μL of anti-p75NTR antibody was applied locally (n = 10). In a sham-operated group, the lower trunk was simply exposed (n = 10). Mechanical hyperalgesia and pain-induced walking patterns were measured using von Frey filaments (Stoelting, Wood Dale, IL) and the CatWalk gait analysis (Noldus Information Technology, the Netherlands) system every third day for 3 weeks. Activation of astrocytes and microglia was immunohistochemically examined in the spinal cord using anti-glial fibrillary acidic protein (GFAP) and anti-Iba1 antibodies both 7 and 21 days after surgery., Results: Animals in the BPA group displayed significant mechanical hyperalgesia that continued through day 21 compared with animals in the sham-operated group, and mechanical hyperalgesia in the anti-p75NTR group was significantly improved 6 days after the operation. Regarding pain-induced gait analysis via CatWalk, animals in the BPA group displayed a significantly greater pain-like gait pattern than the p75 group for up to 3 weeks. Levels of GFAP-immunoreactive astrocytes and Iba1-immunoreactive microglia in the anti-p75NTR group were significantly reduced compared with the BPA group., Conclusion: Our results suggest that p75NTR contributes to neuropathic pain associated with BPA, and that inhibition of p75NTR reduces neuropathic pain., Level of Evidence: N/A.

The mechanisms for the cytotoxicity of staphylococcal Panton-Valentine leukocidin (PVL), a pore-forming toxin consisting of LukS-PV and LukF-PV, in human immune cells are still unclear. Because LukS-PV binds to ganglioside GM1, a constituent of detergent-resistant membrane microdomains (DRMs) of the plasma membrane, the role of DRMs in PVL cytotoxicity was examined in human polymorphonuclear neutrophils (PMNs), monocytes, HL-60 cells, and THP-1 cells. PVL binding capacities in HL-60 and THP-1 cells were higher than those in PMNs and monocytes; however, the PVL concentration to obtain more than 80% cell lysis in HL-60 cells was 10 times higher than that in PMNs and PVL even at such concentration induced < 10% cell lysis in THP-1 cells. After incubation of PMNs with LukS-PV, more than 90% of LukS-PV bound to the detergent-soluble membranes. Subsequent incubation with LukF-PV at 4 °C induced the accumulation of more than 70% of PVL components and 170- to 220-kDa complex formation in DRMs in an actin-independent manner. However, only 30% of PVL was found, and complex formation was under detectable level in DRMs in HL-60 cells. PVL did not accumulate in DRMs in THP-1 cells. Our observations strongly indicate that PVL accumulation in DRMs is essential for PVL cytotoxicity., (© 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.)

It is known that free nerve endings are degenerated after application of shock waves. We therefore hypothesized that the application of shock waves to muscle induces dysfunction of neuromuscular transmission at neuromuscular junctions. We investigated changes in neuromuscular transmission in response to shock wave application. Sprague-Dawley rats were used in this study. Two thousand shock waves at an energy flux density of 0.18 mJ/mm(2) were applied to their right calf muscles. Neuromuscular junctions of gastrocnemius muscles were evaluated using rhodamine-α-bungarotoxin on the day of treatment (n  =  5). Amplitude and latency of compound muscle action potentials were measured on the day of treatment and 1, 2, 4, 6, and 8 weeks after treatment (n  =  10, each group). Degenerated acetylcholine receptors existed in all treated muscles. Although the action potential amplitude on the treated side was significantly less than on the control side from the day of treatment (25.1 ± 7.8 vs. 34.5 ± 9.1, p  =  0.012) to 6 weeks (27.9 ± 7.2 vs. 34.5 ± 7.2, p  =  0.037), there was no significant difference at 8 weeks. There was no significant difference in transmission latency between the groups. The application of shock waves to muscle induced a transient dysfunction of nerve conduction at neuromuscular junctions., (Copyright © 2012 Orthopaedic Research Society.)

The aim of this study was to investigate the correlation of wrist extension strength (WES) and grip strength (GS) using a radial nerve block, and to determine the WES required to prevent the "wrist flexion phenomenon" (antagonistic WES) when making a fist. We tested 14 arms in seven healthy males. WES and GS were measured before blocking as standard WES and standard GS. All participants then had radial nerve blocks with mepivacaine hydrochloride. During the recovery process from radial nerve blockade, WES and GS were recorded every 5 minutes. There was a very strong correlation between WES and GS (p < 0.0001). The mean antagonistic WES was 51% of standard WES, and the mean GS, recorded at the same time, was 66% of standard GS.

During translation, ribosomes stall on mRNA when the aminoacyl-tRNA to be read is not readily available. The stalled ribosomes are deleterious to the cell and should be rescued to maintain its viability. To investigate the contribution of some of the cellular translation factors on ribosome rescuing, we provoked stalling at AGA codons in mutants that affected the factors and then analyzed the accumulation of oligopeptidyl (peptides of up to 6 amino acid residues, oligopep-)-tRNA or polypeptidyl (peptides of more than 300 amino acids in length, polypep-)-tRNA associated with ribosomes. Stalling was achieved by starvation for aminoacyl-tRNA(Arg4) upon induced expression of engineered lacZ (β-galactosidase) reporter gene harboring contiguous AGA codons close to the initiation codon or at internal codon positions together with minigene ATGAGATAA accompanied by reduced peptidyl-tRNA hydrolase (Pth). Our results showed accumulations of peptidyl-tRNA associated with ribosomes in mutants for release factors (RF1, RF2, and RF3), ribosome recycling factor (RRF), Pth, and transfer-messenger RNA (tmRNA), implying that each of these factors cooperate in rescuing stalled ribosomes. The role of these factors in ribosome releasing from the stalled complex may vary depending on the length of the peptide in the peptidyl-tRNA. RF3 and RRF rescue stalled ribosomes by "drop-off" of peptidyl-tRNA, while RF1, RF2 (in the absence of termination codon), or Pth may rescue by hydrolyzing the associated peptidyl-tRNA. This is followed by the disassembly of the ribosomal complex of tRNA and mRNA by RRF and elongation factor G., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The ribosome-recycling factor (RRF) and elongation factor-G (EF-G) disassemble the 70S post-termination complex (PoTC) into mRNA, tRNA, and two ribosomal subunits. We have determined cryo-electron microscopic structures of the PoTC·RRF complex, with and without EF-G. We find that domain II of RRF initially interacts with universally conserved residues of the 23S rRNA helices 43 and 95, and protein L11 within the 50S ribosomal subunit. Upon EF-G binding, both RRF and tRNA are driven towards the tRNA-exit (E) site, with a large rotational movement of domain II of RRF towards the 30S ribosomal subunit. During this intermediate step of the recycling process, domain II of RRF and domain IV of EF-G adopt hitherto unknown conformations. Furthermore, binding of EF-G to the PoTC·RRF complex reverts the ribosome from ratcheted to unratcheted state. These results suggest that (i) the ribosomal intersubunit reorganizations upon RRF binding and subsequent EF-G binding could be instrumental in destabilizing the PoTC and (ii) the modes of action of EF-G during tRNA translocation and ribosome-recycling steps are markedly different.

Purpose: Although the end-to-side nerve repair technique has been used clinically, it has not yet produced consistent motor and sensory recovery in patients. The aim of this study was to investigate whether end-to-side double nerve grafts display more axonal regeneration compared with a single nerve graft in a rat lower limb preparation., Methods: The lower limbs of 96 Wister rats were used in experiments comparing single and double end-to-side nerve grafts. Left peroneal nerves were harvested and grafted between the right peroneal and tibial nerves. A single graft was attached end-to-side to the peroneal and tibial nerves through an epineural window (single graft group, n = 24). Two grafts were performed in the same manner in the double graft group (n = 24). The peroneal nerve was exposed in positive controls (n = 24) and no graft was performed in negative controls (n = 24). We recorded action potentials and moist weights of the left tibialis anterior muscle at each time point. Fluoro-Gold-labeled (Fluorochrome, Denver, CO) dorsal root ganglion neurons from L1 to L6 were counted using fluorescence microscopy and compared among the 4 groups., Results: In both single and double groups, the amplitude and the tibialis anterior muscle weight increased significantly compared with negative controls but remained lower than those measured in positive controls. There was no significant difference between single and double groups. In Fluoro-Gold-labeled neurons, there was also no significant difference between single and double groups., Conclusions: The study showed that regeneration of motor and sensory nerve fibers was possible using 2 end-to-side nerve grafts. However, there was no significant difference between single and double grafts. This might suggest a therapeutic limitation of nerve transplants using 2 end-to-side nerve grafts., Clinical Relevance: Double end-to-side repair attracts both motor and sensory axons, and this results in a medium degree of recovery of function; however, double end-to-side nerve grafting does not appear to offer any advantage over a single end-to-side graft., (Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Pathomechanisms of injured-nerve pain have not been fully elucidated. Radicular pain and chronic constriction injury models have been established; however, producing these models is complicated. A sciatic nerve-pinch injury is easy to produce but the reliability of this model for evaluating pain behavior has not been examined. The current study evaluated pain-related behavior and change in pain markers in the dorsal root ganglion (DRG) of rats in a simple, sciatic nerve-pinch injury model. In the model, the sciatic nerve was pinched for 2 s using forceps (n = 20), but not injured in sham-operated animals (n = 20). Mechanical and thermal hyperalgesia were measured every second day for 2 weeks using von Frey filaments and a Hargreaves device. Calcitonin gene-related peptide (CGRP), activating transcription factor-3 (ATF-3), phosphorylated p38 mitogen activated protein (Map) kinase (p-p38), and nuclear factor-kappa B (NF-κB; p65) expression in L5 DRGs were examined at 4 and 7 days after surgery using immunohistochemistry. The proportion of neurons immunoreactive for these markers was compared between the two groups. Mechanical (during 8 days) and thermal hyperalgesia (during 6 days) were found in the pinch group rats, but not in the sham-operated animals (p < 0.05); however, hyperalgesia was not significant from days 10 to 14. CGRP, ATF-3, p-p38, and NF-κB expression in L5 DRGs was upregulated in the nerve-injured rats compared with the sham-operated rats (p < 0.01). Our results indicate that a simple sciatic nerve pinch produced pain-related behavior. Upregulation of the pain-marker expression in the nerve-injury model suggested it could be used as a model of pain. However, it was not considered as suitable for long-term studies.

Purpose: Nerve growth factor (NGF), via the high-affinity receptor, tyrosine kinase A, has been widely reported as a mediator of pain caused by inflammation. A clinical trial has suggested that anti-NGF antibody is effective for pain caused by osteoarthritis of the knee. However, adverse events such as headache (8.9%), upper respiratory tract infection (7.3%), and paresthesia (6.8%) were reported. We hypothesized that inhibition of the low-affinity NGF receptor, p75 neurotrophin receptor (p75NTR), is also effective for joint pain and may reduce side effects. This study examined suppression of pain behavior and expression of pain-inducing neuropeptides such as calcitonin gene-related peptide (CGRP) and p75NTR in dorsal root ganglia neurons by a p75NTR inhibitory antibody in a rat model of wrist joint inflammatory pain., Methods: We injected complete Freund's adjuvant (CFA) into the wrist joint of rats and used this as a model of inflammatory pain. We applied 10 microL of saline (CFA + saline group; n = 20) or 1, 10, or 50 microL of a p75NTR inhibitory antibody (CFA + p75NTR inhibitory antibody group; n = 40) directly to the inflamed joint in the rats. Mechanical hyperalgesia was measured for 2 weeks using von Frey filaments. We assessed CGRP and p75NTR expression in C8 dorsal root ganglia immunochemically. Adverse events such as loss of weight and/or appetite, constipation, and infection were examined., Results: p75NTR inhibitory antibody reduced mechanical hyperalgesia caused by CFA (p<.05 vs controls) in the rat model (p<.01 vs saline), without any adverse events. We found that 10 and 50 microL of a p75NTR inhibitory antibody were more effective for pain, without a significant difference between doses. CGRP and p75NTR immunoreactivity was upregulated in the CFA + saline groups compared with a control group (p<.01). However, direct p75NTR inhibitory antibody application decreased CGRP and p75NTR expression after wrist inflammation (p<.01)., Conclusions: p75NTR inhibition may be a therapeutic target for inflamed joint pain treatment with reduced adverse events., (Copyright 2010. Published by Elsevier Inc.)

A rare case of trigeminal neuralgia, caused by a branch of the superior cerebral artery running through the trigeminal nerve, was successfully treated by microvascular decompression. The nerve gap at the arterial penetration point was widened by the dissection of the epineurium to obtain sufficient mobilization of the artery and decompression of the nerve. This technique would be useful for securing neurovascular decompression, as well as for avoiding postoperative hypesthesia owing to the neurotomy described in previous reports. Preparing for such a rare case is important as preoperative magnetic resonance imaging (MRI) often fails to disclose precise diagnoses.

The authors present a rare case of cervical myelopathy caused by dropped head syndrome. This 68-year-old woman presented with her head hanging forward. After 1 month, she was admitted to the medical service because of head drop progression. Examination of biopsy specimens from her cervical paraspinal muscles showed nonspecific myopathic features without inflammation, and isolated neck extensor myopathy was diagnosed. The patient's condition did not respond to the administration of corticosteroids. During follow up as an outpatient, the patient's head drop continued to gradually progress. At 1 year after onset, she developed bilateral weakness of the upper and lower extremities, clumsiness of the hands, and gait disturbance. A radiograph of the cervical spine obtained in a standing position showed a pronounced kyphotic deformity and instability at the level of C4-5. Magnetic resonance imaging demonstrated spinal cord compression at C-3 and C-4. The patient underwent a C3-4 laminectomy and occipitocervicothoracic fixation. Gait and hand coordination gradually improved, and she was able to walk with no support 1 month postoperatively. Surgical fixation was beneficial in this patient with dropped head syndrome, myelopathy, and cervical instability.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) possessing the Panton-Valentine leukocidin (PVL) gene (luk(PV)) is associated with skin and soft tissue infections, osteomyelitis, and necrotizing pneumonia. There are geographically two types of CA-MRSA: one (sequence type ST30) that is worldwide (pandemic) and the other (sequence types, e.g., ST1, ST8 or ST80) that is continent-specific. The pandemic type, but not continent-specific type, possessed the bone sialoprotein-adhesin gene (bbp), which was associated with osteomyelitis. No recent hospital-acquired MRSA had the bbp gene, while past PVL-positive nosocomial outbreak-derived strains did possess it. The collagen-adhesin gene (cna) was associated with pandemic CA-MRSA, though with positive cases even in continent-specific CA-MRSA and PVL-negative Japanese region-specific CA-MRSA. Thus, the pandemic type is characterized by the combination of luk(PV) and bbp (and cna) genes. A specific real-time PCR assay for the bbp gene was developed, and dual assay for bbp and luk(PV) in one test tube became possible.

Ribosome recycling, the last step in translation, is now accepted as an essential process for prokaryotes. In 2005, three laboratories showed that ribosome-recycling factor (RRF) and elongation factor G (EF-G) cause dissociation of ribosomes into subunits, solving the long-standing problem of how this essential step of translation occurs. However, there remains ongoing controversy regarding the other actions of RRF and EF-G during ribosome recycling. We propose that the available data are consistent with the notion that RRF and EF-G not only split ribosomes into subunits but also participate directly in the release of deacylated tRNA and mRNA for the next round of translation.

Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), produces superantigenictoxins, such as toxic shock syndrome toxin-1 (TSST-1). TSST-1 abnormally activates T cells to overproduce inflammatory cytokines (such as tumor necrosis factor-alpha, interleukin-2, and interferon-gamma) leading to shock. In this study, we investigated the inhibitory effect of antimicrobial agents and anisodamine (a Chinese herbal extract) on TSST-1-induced cytokine production. Among the macrolides and related agents examined, azithromycin and rokitamycin showed the greatest inhibitory activity against the TSST-1-induced cytokine production. This inhibitory effect was similar to that of anisodamine, which, however, had no inhibitory activity against bacterial growth. Vancomycin, teicoplanin, arbekacin, and linezolid (anti-MRSA and related agents) had no significant inhibitory effect on cytokine production. The inhibitory effect of the drugs on cell proliferation was not significant. These data indicate that some antimicrobial agents, e.g., azithromycin and rokitamycin, manifest anti-superantigenic toxin activity through the inhibition of cytokine production, just like anisodamine.

Large-scale nosocomial outbreaks of Serratia marcescens septicaemia in Japan have had a fatality rate of 20-60% within 48 h. As a countermeasure, a real-time PCR assay was constructed for the rapid diagnosis of S. marcescens septicaemia. This assay indeed detected S. marcescens in clinical blood specimens (at ca. 10(2)CFU ml(-1)), at a frequency of 0.5% in suspected cases of septicaemia. In mice, the assay provided estimates of blood S. marcescens levels at various infectious stages: namely, 10(7) to 10(8)CFU ml(-1) at a fatal stage (resulting in 100% death), 10(4)-10(5)CFU ml(-1) at a moderately fatal stage (resulting in 50% or more death), and <10(3)CFU ml(-1) at a mild stage (resulting in 100% survival), consistent with actual CFU measurements. Blood bacterial levels could be an important clinical marker that reflects the severity of septicaemia. The simultaneous detection of S. marcescens and the carbapenem resistance gene was also demonstrated.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was collected from children with bullous impetigo in 2003 and 2004. One strain collected in 2003 was Panton-Valentine leucocidin (PVL) positive. In 2004, a multiple-drug-resistant PVL(+) CA-MRSA strain was isolated from an athlete with a cutaneous abscess. These strains were analyzed by multilocus sequence typing, spa typing, agr typing, coagulase typing, staphylococcal cassette chromosome mec (SCCmec) typing, PCR assay for 30 virulence genes, drug susceptibility testing, pulsed-field gel electrophoresis, and for plasmids. The two Japanese PVL(+) CA-MRSA strains belonged to the globally extant ("pandemic") sequence type 30 (ST30) with SCCmec IV. A transmissible, multiple-drug resistance plasmid emerged in such ST30 strains. The PVL(-) CA-MRSA strains ("domestic" CA-MRSA) accumulated for bullous impetigo, exhibiting new genotypes. Hospital-acquired MRSA of ST91 (but not pandemic ST5) shared common features with the PVL(-) CA-MRSA strain.

A new category of methicillin-resistant Staphylococcus aureus (MRSA), called community-acquired MRSA (CA-MRSA), has emerged worldwide. In contrast to previous MRSA, most CA-MRSA carries the Panton-Valentine leukocidin (PVL) genes (lukPVSF) as a virulence genetic trait. Sequence analysis of the lukPVSF gene of a Japanese isolate demonstrated that the gene has more similarity to methicillin-susceptible S. aureus from France than MRSA from the United States. Based on the sequences, we developed a real-time PCR assay for the three key genes of CA-MRSA; that is, lukPVSF, mecA (for methicillin resistance), and spa (for S. aureus). Dual or triple assay for lukPVSF, mecA, and spa in one test tube became possible. The detection limit of the assay with probe and SYBR Green methods was between 2.7 and 2.7 x 10(1) CFU/ml. The assay detected PVL-positive MRSA in clinical (blood) isolates.

Shiga toxin (Stx)-producing Escherichia coli (STEC) is associated with hemolytic uremic syndrome (HUS). High inflammatory cytokine [interleukin (IL)-6 and IL-8] levels and low anti-inflammatory cytokine (IL-10) levels are indicators of a high risk for developing HUS in STEC-infected children. In this study, we investigated inhibitory action of telithromycin, a ketolide, against STEC and against Stx and lipopolysaccharide (LPS). Telithromycin inhibited in vitro STEC growth without inducing Stx phage, in marked contrast to norfloxacin. Stx markedly induced inflammatory (but not anti-inflammatory) cytokine production in human peripheral blood monocytes, while LPS induced both inflammatory and anti-inflammatory cytokine production. Telithromycin selectively inhibited the IL-6 and IL-8 production from Stx-stimulated (but not LPS-stimulated) monocytes. The drug did not significantly inhibit IL-10 production. Our data suggest that Stx plays a crucial role in the stimulation of inflammatory cytokines and such inflammatory response is inhibited by telithromycin, an anti-bacterial agent.

Shiga toxin (Stx)-producing Escherichia coli (STEC), an important cause of hemolytic uremic syndrome, was completely killed by (60)Co irradiation at 1 x l0(3) gray (1 kGy) or higher. However, a low dose of irradiation (0.1-0.3 kGy) markedly induced Stx phage from STEC. Stx production was observed in parallel to the phage induction. Inactivation of Stx phage required a higher irradiation dose than that for bacterial killing. Regarding Stx, cytotoxicity was susceptible to irradiation, but cytokine induction activity was more resistant than Stx phage. The findings suggest that (1). although (60)Co irradiation is an effective means to kill the bacteria, it does induce Stx phage at a lower irradiation dose, with a risk of Stx phage transfer and emergence of new Stx-producing strains, and (2). irradiation differentially inactivates some activities of Stx.

The motility of Helicobacter pylori was maximum at 37 degrees C and at pH 6. A newly developed proton pump inhibitor, rabeprazole (RPZ), and its thioether derivative (RPZ-TH) markedly inhibited the motility of H. pylori. The concentrations of the drug necessary to inhibit 50% of the motility were 0.25, 16, 16, and >64 microgram/ml for RPZ-TH, RPZ, lansoprazole, and omeprazole, respectively. No such inhibitory effects were observed with H(2) blockers or anti-H. pylori agents. The motilities of Campylobacter jejuni and C. coli-but not those of Vibrio cholerae O1 and O139, Vibrio parahaemolyticus, Salmonella enterica serovar Typhimurium, and Proteus mirabilis-were also inhibited. Prolonged incubation with RPZ or RPZ-TH inhibited bacterial growth of only H. pylori, except for a turbid colony mutant. The results indicate that RPZ and RPZ-TH have a characteristic inhibitory effect against the motility of H. pylori (spiral-shaped bacteria), which is distinguished from that against bacterial growth.