Endotoxin activity and leukocytic STAT3 mRNA alterations differ according to age in lipopolysaccharide-challenged calves.

The objective of this study was to investigate the age difference in the response to endotoxin in calves related to the plasma endotoxin activity and mRNA expression of cytokines. Fifteen calves were divided into three groups: control (191 ± 21 days), weaning (162.4 ± 17.5 days), and calf (22.4 ± 8.2 days). The weaning and calf groups received 2.5 µg/kg of ultrapure O111:B4 LPS in 10 mL of each autologous serum, whereas the control calves received a similar volume of saline. Blood samples were collected at 0, 0.5, 1, 2, 4, 8, 12, and 24 h. Liver samples were collected by ultrasound-guided liver biopsy at 0, 2, 4, and 24 h. Plasma endotoxin activity was measured by the limulus amebocyte lysate kinetic turbidimetric assay. The mRNA expression level of GAPDH, TLR-4, NF-κB2, TNF-α, IL-6, and STAT3 in leukocytes and the liver was measured by real-time PCR. Following LPS challenge, the maximal plasma endotoxin activity, and leukocytic expression of TLR4, NF-κB2, TNF-α, and STAT3 were reached at 0.5, 4, 2-4, 2-4, and 4 h, respectively, in weaning and calf groups. The endotoxin activity in calf remained high until 2 h. Furthermore, the expression of leukocytic STAT3 mRNA in calf was not significantly different from the pre-value. In contrast, STAT3 mRNA in weaning markedly increased at 2 and 4 h. Therefore, this study provides new information to the literature of immune and inflammatory responses in calves.

Mechanical regulation of bone homeostasis through p130Cas-mediated alleviation of NF-κB activity.

Mechanical loading plays an important role in bone homeostasis. However, molecular mechanisms behind the mechanical regulation of bone homeostasis are poorly understood. We previously reported p130Cas (Cas) as a key molecule in cellular mechanosensing at focal adhesions. Here, we demonstrate that Cas is distributed in the nucleus and supports mechanical loading-mediated bone homeostasis by alleviating NF-κB activity, which would otherwise prompt inflammatory processes. Mechanical unloading modulates Cas distribution and NF-κB activity in osteocytes, the mechanosensory cells in bones. Cas deficiency in osteocytes increases osteoclastic bone resorption associated with NF-κB-mediated RANKL expression, leading to osteopenia. Upon shear stress application on cultured osteocytes, Cas translocates into the nucleus and down-regulates NF-κB activity. Collectively, fluid shear stress-dependent Cas-mediated alleviation of NF-κB activity supports bone homeostasis. Given the ubiquitous expression of Cas and NF-κB together with systemic distribution of interstitial fluid, the Cas-NF-κB interplay may also underpin regulatory mechanisms in other tissues and organs.

Use of collagen/chitosan sponges mineralized with hydroxyapatite for the repair of cranial defects in rats.

In traumatology, we encounter several clinical challenges that involve extensive bone loss primarily related to trauma, conditions that can be treated with autologous grafts. A good alternative is the use of synthetic biomaterials as substitutes. These polymers provide a suitable environment for the growth of new bone and vascular tissue, which are essential for repair. Collagen/hydroxyapatite composites have proven to be biocompatible and to behave mechanically. Furthermore, the addition of chitosan contributes to the formation of a three-dimensional structure that permits cell adhesion and proliferation, thus improving osteogenesis. The aim of this study was to evaluate bone formation during the repair of bone defects experimentally induced in the skull of rats and grafted with a polymer blend consisting of bovine tendon collagen and chitosan combined with hydroxyapatite. Thirty animals were used for the creation of a defect in the left parietal bone and were divided into three groups of 10 animals each: a control group without biomaterial implantation, a group receiving the blend of collagen and chitosan, and a group receiving this blend combined with hydroxyapatite. Each group was subdivided and the animals were sacrificed 3 or 8 weeks after surgery. After sacrifice, the skulls were removed for macroscopic photodocumentation and radiographic examination. The samples were processed for histological evaluation of new bone formation at the surgical site. Macroscopic and radiographic analysis demonstrated the biocompatibility of the blends. Histologically, the formation of new bone occurred in continuity with the edges of the defect, with the observation of higher volumes in the grafted groups compared to control. Mineralization of sponges did not stimulate bone neoformation, with bone repair being incomplete over the experimental period. In conclusion, mineralization by the addition of hydroxyapatite should be better studied. However, the collagen/chitosan sponges used in this study are suitable to stimulate osteogenesis in cranial defects, although this process is slow and not sufficient to achieve complete bone regeneration over a short period of time.

Correction: Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells.

The authors report that there is a mistake in the representative picture of Fig. 4D (top row: PC3-miR1260b inh-0h) in the original version. The correct version of Fig. 4 with the original pictures for both PC3 miR-NC inh-0h and PC3-miR1260b inh-0h are provided below.

Thumb boutonnière deformity without rheumatoid arthritis or trauma.

Boutonnière deformity of the thumb without rheumatoid arthritis or trauma is not widely recognised. This study aimed to investigate its prevalence, relation to sex and age, and identifying factors associated with the extensor mechanism using ultrasonography. We examined 248 thumbs from 127 participants who were asymptomatic for hand disorders and had no history of hand injury. Boutonnière deformity was identified in 20 thumbs of 17 participants and was significantly more prevalent among elderly participants than among young participants. No significant differences in sex or hand dominance were noted. The deformity had a significant effect on range of motion and grip and pinch strengths. The extensor pollicis brevis (EPB) tendon was significantly narrower in affected thumbs than in non-affected thumbs. The prevalence of boutonnière deformity without rheumatoid arthritis or trauma was 13%, and the deformity was associated with advanced age and a narrow EPB tendon. LEVEL OF EVIDENCE: III.

Efficacy and safety of collagenase Clostridium histolyticum injection for Dupuytren's contracture in non-Caucasian Japanese patients (CORD-J Study): the first clinical trial in a non-Caucasian population.

To assess the efficacy, safety and pharmacokinetics of 0.58 mg collagenase Clostridium histolyticum injections for the treatment of Dupuytren's contracture in Japanese patients, we conducted a phase III, multicentre, uncontrolled, open-label clinical study in patients with Dupuytren's contracture. Of the 77 patients, 66 achieved clinical success in the primary treated joint (86%; 95% confidence interval: 76% to 93%), confirming the efficacy of collagenase Clostridium histolyticum injections. More improvement was seen in the metacarpophalangeal joints than in the proximal interphalangeal joints (94% versus 73%). The main adverse reaction was a local reaction in the injected hand. No tendon rupture or anaphylactic reactions were seen. The concentrations of collagenase Clostridium histolyticum were below the lower limit of quantification in plasma samples at all time points. As seen in global studies in Caucasian patients, a corrective effect on Dupuytren's contracture and good tolerance were observed in most non-Caucasian (Asian) Japanese patients. LEVEL OF EVIDENCE: Level 3.

Scaphoid nonunion with carpal ligament injury - radiological, arthroscopical assessment and clinical results.

The purpose of this study was to review the clinical results of carpal ligaments injuries with scaphoid nonunion. We hypothesized that scaphoid nonunion with carpal ligament injury is associated with clinical result. We retrospectively reviewed 60 cases of -Herbert screw fixation with bone graft for scaphoid nonunions. Scapholunate (SL) and lunotriquetral (LT) ligaments lesions were confirmed by arthroscopy. Approximately half of the nonunion scaphoid cases had carpal ligaments injuries. At final follow-up evaluation, wrist function as evaluated by the Mayo wrist score was excellent in 34 patients, good in 16 patients, fair in 8 patients, and poor in 2 patients. Cases with both SL/LT ligaments injuries tended to have decreased wrist flexion-extension motion. Our results suggest that there is an indication for arthroscopy in scaphoid nonunion if surgical fixation is offered to avoid detrimental effects of an undiagnosed ligament tear.

Morphological characteristics of olecranon fractures in adults : a Computed Tomography-based study.

The aim of this study was to identify the fragment's shape by evaluating olecranon fractures. We examined the CT images of 48 olecranon fractures (28 women and 20 men). Mean age was 59.9 years. On the olecranon's posterior surface, we measured the distance between the apex of the olecranon fragment and the radial edge of the flat spot on the short axis and the width of the flat spot on the same short axis. The tip radial ratio (i.e., the tip radial edge to the flat spot width) was derived from these parameters. The mean tip radial edge was 1.96 mm, and the flat spot width was 12.64 mm ; therefore, the tip radial ratio was 0.15 mm. Radial inclination on the articular surface was 30.55°. Our findings confirmed our hypothesis that the fracture lines run from the proximal ulnar side to the distal radial side on the olecranon's posterior and articular surfaces.

Effects of depression and inflammatory factors on chronic conditions of the wrist.

AIMS: Chronic conditions of the wrist may be difficult to manage because pain and psychiatric conditions are correlated with abnormal function of the hand. Additionally, intra-articular inflammatory cytokines may cause pain. We aimed to validate the measurement of inflammatory cytokines in these conditions and identify features associated with symptoms. PATIENTS AND METHODS: The study included 38 patients (18 men, 20 women, mean age 43 years) with a chronic condition of the wrist who underwent arthroscopy. Before surgery, the Self-Rating Depression Scale (SDS), Hand20 questionnaire and a visual analogue scale (VAS) for pain were used. Cytokine and chemokine levels in the synovial fluid of the wrist were measured using enzyme-linked immunosorbent assays and correlations between the levels with pain were analysed. Gene expression profiles of the synovial membranes were assessed using quantitative polymerase chain reaction. RESULTS: Older patients had high pre-operative Hand20 scores. One-year post-operative Hand20 and VAS scores and pre-operative VAS scores correlated with SDS scores. Post-operative VAS scores negatively correlated with the expression of nerve growth factor and SDS scores positively correlated with the expression of tumour necrosis factor-alpha and negatively correlated with the expression of tumour necrosis factor-converting enzyme. CONCLUSION: There was a positive correlation between depression and chronic conditions of the wrist. Levels of some cytokines correlate with pain and depression. Additionally, cytokines may be important in the assessment and treatment of chronic conditions of the wrist and depression. Cite this article: Bone Joint J 2016;98-B:961-8.

Feasibility study of collagen membranes derived from bovine pericardium and intestinal serosa for the repair of cranial defects in ovariectomised rats.

The indication of biomaterials has increased substantially in the regenerative therapy of bone defects. However, in addition to evaluating the physicochemical properties of biomaterials, the quality of the recipient tissue is also essential for the osseointegration of implants, as abnormalities in bone metabolism, such as gonadal hormone deficiency, can influence bone healing. This study evaluated the osteoregenerative capacity of collagen membranes derived from bovine pericardium and intestinal serosa in the repair of cranial defects in ovariectomised rats. Thirty female Wistar rats were submitted to surgical creation of a 5-mm cranial bone defect. The rats were divided into a control group (not ovariectomised) and an ovariectomised group. The non-ovariectomised group was divided into three subgroups: control (G1) in which the defect was not filled with the biomaterial, and two subgroups (G2 and G3) that received the bovine pericardium- and serosa-derived collagen membranes, respectively. The ovariectomised group was divided into the same subgroups (G4, G5, and G6). The animals were sacrificed 8 weeks after surgery. The calvaria were removed for macroscopic and radiographic photodocumentation and processed for histomorphometric analysis of bone healing at the surgical site. Macroscopic, radiological, and microscopic analyses demonstrated the biocompatibility of the implanted collagen membranes, as indicated by the absence of infiltration and signs of inflammation at the surgical site. Histologically, discrete immature bone neoformation projecting from the margins of the defect was observed at the surgical site in ovariectomised groups when compared to the non-ovariectomised groups. The volume of newly formed bone was significantly higher in the non-ovariectomised groups (G1: 7.83%±1.32; G2: 21.33%±1.96; and G3: 22.83%±0.98) compared to the respective ovariectomised subgroups (G4: 3.16%±0.75; G5: 16.83%±0.98; and G6: 16.16%±0.75), thus demonstrating the deleterious effects of ovariectomy on bone homeostasis. Higher volumes of newly formed bone were observed in the groups receiving the membrane grafts (G2, G3, G5, and G6) compared to the control groups (G1 and G4). In conclusion, the bilateral ovariectomy compromises the ability to repair bone lesions grafted with osteoconductive biomaterials as in the case of collagen membranes derived from both bovine pericardium and intestinal serosa.

Teletriage for patients with traumatic finger injury directing emergency medical transportation services to appropriate hospitals: a pilot project in Nagoya City, Japan.

INTRODUCTION: Emergency medical technicians in Japan have experienced difficulties in identifying hospitals that will accept patients with severe finger injuries. We developed and managed a system named Interactive Teletriage using mobile phone photos to aid efficient patient transportation. The aim of this study was to investigate features related to the transportation of patients with severe finger injuries and to evaluate the feasibility of this system. MATERIALS AND METHODS: We prospectively analysed data from the medical association of Aichi Prefecture and the Nagoya City Fire Department in Japan. We investigated features related to the transportation of 474 patients with severe finger injuries in Nagoya from 2010 to 2013: 100 in 2010, 134 in 2011, 125 in 2012, and 115 in 2013. We began using Teletriage in August 2011 and compared the periods before and after its implementation. RESULTS: The time of injury showed two different peaks from 09:00 to 11:00h and at 13:00h. The number of patients injured during each weekday was generally the same, while cases on Saturdays and Sundays reflected 70% and 47% of the weekday average, respectively. Of the 474 patients, 395 (83%) were accepted to hospitals after 3 or fewer requests for admission: 160 of 202 (79.2%) before and 235 of 272 (86.4%) after Teletriage, constituting a significant increase (p=0.039). Furthermore, the number of patients who required 4 or more requests significantly decreased after implementation of Teletriage (p=0.039): 42 patients (20.8%) before and 37 (13.6%) after Teletriage. Our data showed that as the number of requests until final determination increased, the transportation period increased. Furthermore, the mean transportation period significantly decreased from 22.3min before to 18.1min after Teletriage (p=0.021). As the number of requests until final determination increased, the proportion of patients transported to Level I and II hospitals decreased; conversely, the proportion of patients transported to Level III, IV, and V hospitals increased. CONCLUSIONS: Our results indicated that the implementation of Teletriage has the potential to ease the problem of emergency medical transportation for those with severe finger injuries.

Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation.

BACKGROUND: Predictive biomarkers for the recurrence of hepatocellular carcinoma (HCC) have great benefit in the selection of treatment options, including liver transplantation (LT), for HCC. The purpose of this study was to identify specific microRNAs (miRs) in exosomes from the serum of patients with recurrent HCC and to validate these molecules as novel biomarkers for HCC recurrence. METHODS: We employed microarray-based expression profiling of miRs derived from exosomes in the serum of HCC patients to identify a biomarker that distinguishes between patients with and without HCC recurrence after LT. This was followed by the validation in a separate cohort of 59 HCC patients who underwent living related LT. The functions and potential gene targets of the recurrence-specific miRs were analysed using a database, clinical samples and HCC cell lines. RESULTS: We found that miR-718 showed significantly different expression in the serum exosomes of HCC cases with recurrence after LT compared with those without recurrence. Decreased expression of miR-718 was associated with HCC tumour aggressiveness in the validated cohort series. We identified HOXB8 as a potential target gene of miR-718, and its upregulation was associated with poor prognosis. CONCLUSION: Circulating miRs in serum exosomes have potential as novel biomarkers for predicting HCC recurrence.