Percutaneous distal clavicle excision for acromioclavicular joint arthritis: our experience and early results of a novel surgical technique.

PURPOSE: Symptomatic acromioclavicular joint (ACJ) osteoarthritis causes pain and limitations in activities of daily living. Open and arthroscopic distal clavicle excision techniques have been described with good outcomes. However, both techniques have their own sets of advantages and disadvantages. This study describes a novel technique of percutaneous distal clavicle excision for symptomatic ACJ osteoarthritis and our two-year results. METHODS: Fifteen consecutive patients underwent percutaneous distal clavicle excision for ACJ arthritis. These patients had failed a trial of conservative treatment. The ACJ was confirmed as the pain generator with an intraarticular steroid/lignocaine injection, and shoulder MRI was used to exclude alternative pain generators in the shoulder. They had a minimum of two years of follow-up. RESULTS: At a mean of 26.8 months postoperatively, the mean VAS pain score was 0, and the mean Constant score for the shoulder was 87.3 points (range 50-94), which corresponded to 1 good, 1 very good and 13 excellent results. The mean SF-36 score was 94.9 points (range 65-100). There were statistically significant improvements in the VAS scores, Constant shoulder scores and SF-36 scores at one year and two years of follow-up (p < 0.05). Three unique complications, namely subcutaneous emphysema, "missing" of the distal clavicle and thermal skin injury, were encountered. Our surgical technique has since been modified to circumvent these complications. CONCLUSION: Our novel technique of percutaneous distal clavicle excision yields a 93.3% good-to-excellent results based on the Constant shoulder score and durable pain relief based on VAS at two years.

STAT3 Expression and Activity are Up-Regulated in Diffuse Large B Cell Lymphoma of Dogs.

BACKGROUND: The Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathways play important roles in the pathogenesis of diffuse large B cell lymphoma (DLBCL) in humans, and up-regulated STAT3 expression and activity are associated with worse clinical outcome in humans. No studies have evaluated the JAK-STAT signaling pathway in DLBCL of dogs. HYPOTHESIS: STAT3 pathway is deregulated in DLBCL in dogs. We aim to assess the expression, activation, and cellular localization of STAT3 and mitogen-activated protein kinase ERK1/2 in DLBCL of dogs. ANIMALS: Forty-three client-owned dogs diagnosed with DLBCL by histopathology METHODS: Retrospective analysis of DLBCL in dogs, including patient characteristics and treatment, immunohistochemistry, and protein expressions by Western blot. RESULTS: A higher percentage of STAT3 and p-STAT3 immunolabelled cells were observed in DLBCL of dogs when compared to normal canine lymph nodes. In STAT3 immunolabelled cells, STAT3 has higher nuclear expression in lymphoma samples than in normal or reactive lymph nodes. In addition to up-regulated STAT3 expression and activation, mitogen-activated kinase ERK1/2 activation is up-regulated in DLBCL of dogs. CONCLUSION AND CLINICAL IMPORTANCE: Compared with the normal canine lymph node, DLBCL of dogs has up-regulated STAT3 pathway. Our results support future investigation of JAK inhibitors in the treatment of DLBCL in dogs.

Multiple limb salvage attempts for diabetic foot infections: is it worth it?

AIMS: Limb salvage for diabetic foot infections often require multiple procedures. Some patients will eventually end up with below knee amputation (BKA) when all limb salvage attempts fail. We seek to study the patients' ability to return to normal life, functional status, prosthesis usage and perspectives on multiple limb salvage procedures that culminated in BKA to review if they would undertake a similar path if their situation was repeated. PATIENTS AND METHODS: A total of 41 patients who underwent BKA between July 2011 and June 2013 were reviewed. They were divided into primary and creeping (prior multiple salvage procedures) amputations. The Barthel's Index (BI) and the Reintegration to Normal Living Index (RNLI) were used. A questionnaire was used to identify whether the patient would undergo the same multiple attempts at limb salvage again if faced with the same problem. RESULTS: All patients had a good mean BI of 14.2 (3 to 20) and RNLI of 73.2 (31 to 100). There was no difference in prosthesis usage, BI and RNLI between both groups. We found that 16 (94.1%) out of 17 patients with creeping amputation would undergo the same multiple salvage procedures if given a similar option. Conversely, only 15 (62.5%) patients with primary amputation would do the same again while the other nine (37.5%) patients choose to do everything possible to save their leg if faced with a similar situation (p = 0.001). CONCLUSION: Most patients preferred to undergo multiple procedures to salvage the limb from diabetic foot infection even if it ultimately concluded with a BKA. All the patients had a moderately good functional outcome and ability to return to normal living after BKA. Cite this article: Bone Joint J 2017;99-B:1502-7.

JAK1/2 Inhibitors AZD1480 and CYT387 Inhibit Canine B-Cell Lymphoma Growth by Increasing Apoptosis and Disrupting Cell Proliferation.

BACKGROUND: Canine diffuse large B-cell lymphoma (DLBCL) is a common and aggressive hematologic malignancy. The lack of conventional therapies with sustainable efficacy warrants further investigation of novel therapeutics. The Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways play important roles in the pathogenesis of hematologic malignancies in humans including DLBCLs. AZD1480 and CYT387 are novel JAK1/2 inhibitors that have been used in clinical trials for treating various hematologic cancers in humans. No studies have characterized the antitumor effects of JAK inhibitors on DLBCL in dogs. HYPOTHESIS/OBJECTIVES: We hypothesize that JAK1/2 inhibitors AZD1480 and CYT387 can effectively inhibit growth of canine DLBCL in vitro. We aim to assess the antitumor activity of AZD1480 and CYT387 in canine DLBCL and to determine the underlying mechanisms of action. METHODS: In vitro study of canine lymphoma cell growth, proliferation, and apoptosis by viability, proliferation and apoptosis assays. RESULTS: A significant decrease in viable canine lymphoma cells was observed after AZD1480 and CYT387 treatments. In addition, AZD1480 and CYT387 treatment resulted in decreased lymphoma cell proliferation and increased early apoptosis. CONCLUSION AND CLINICAL IMPORTANCE: AZD1480 and CYT387 inhibit canine lymphoma cell growth in a dose-dependent manner. Our findings justify further phase I/II clinical investigations of the safety and efficacy of JAK1/2 inhibitors in canine DLBCL and suggest new opportunities for novel anticancer therapies.

miR-520h is crucial for DAPK2 regulation and breast cancer progression.

This corrects the article DOI: 10.1038/onc.2015.168.

A comparison of necrotising fasciitis in diabetics and non-diabetics: a review of 127 patients.

AIMS: Diabetes mellitus is the most common co-morbidity associated with necrotising fasciitis. This study aims to compare the clinical presentation, investigations, Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score, microbiology and outcome of management of this condition in diabetic and non-diabetic patients. PATIENTS AND METHODS: The medical records of all patients with surgically proven necrotising fasciitis treated at our institution between 2005 and 2014 were reviewed. Diagnosis of necrotising fasciitis was made on findings of 'dishwater' fluid, presence of greyish necrotic deep fascia and lack of bleeding on muscle dissection found intra-operatively. Information on patients' demographics, presenting symptoms, clinical signs, investigations, treatment and outcome were recorded and analysed. RESULTS: A total of 127 patients with surgically proven necrotising fasciitis were included in this study. In all, 78 (61.4%) were diabetic and 49 (38.6%) were non-diabetic. Diabetics tended to have polymicrobial infections (p = 0.03), renal impairment (p < 0.001), end-stage renal disease (p = 0.001) and multiple co-morbidities (p < 0.001). They presented atypically, with less tenderness (p = 0.042) and less hypotension (p = 0.034). This resulted in higher rates of misdiagnosis (p = 0.038) and a longer time to surgery (p = 0.05) leading to longer hospital stays (p = 0.043) and higher rates of amputation (p = 0.045). However, the rate of mortality is comparable (p = 0.525). A LRINEC score of > 8 appears to be more sensitive in diabetic patients (p < 0.001). However, the increased sensitivity in diabetic patients may be related to hyperglycemia and electrolyte abnormalities associated with renal impairment in these patients. CONCLUSION: The LRINEC score must be used with caution in diagnosing necrotising fasciitis in diabetic patients. A high index of suspicion is key to the early diagnosis and subsequent management of these patients. Cite this article: Bone Joint J 2016;98-B:1563-8.

Management of sports injuries of the foot and ankle: An update.

Injuries to the foot in athletes are often subtle and can lead to a substantial loss of function if not diagnosed and treated appropriately. For these injuries in general, even after a diagnosis is made, treatment options are controversial and become even more so in high level athletes where limiting the time away from training and competition is a significant consideration. In this review, we cover some of the common and important sporting injuries affecting the foot including updates on their management and outcomes. Cite this article: Bone Joint J 2016;98-B:1299-1311.

miR-520h is crucial for DAPK2 regulation and breast cancer progression.

MicroRNAs (miRNAs) are small RNAs that suppress gene expression by their interaction with 3'untranslated region of specific target mRNAs. Although the dysregulation of miRNAs has been identified in human cancer, only a few of these miRNAs have been functionally documented in breast cancer. Thus, defining the important miRNA and functional target involved in chemoresistance is an urgent need for human breast cancer treatment. In this study, we, for the first time, identified a key role of miRNA 520h (miR-520h) in drug resistance. Through protecting cells from paclitaxel-induced apoptosis, expression of miR-520h promoted the drug resistance of human breast cancer cells. Bioinformatics prediction, compensatory mutation and functional validation further confirmed the essential role of miR-520h-suppressed Death-associated protein kinase 2 (DAPK2) expression, as restoring DAPK2 abolished miR-520h-promoted drug resistance, and knockdown of DAPK2 mitigated cell death caused by the depletion of miR-520h. Furthermore, we observed that higher level of miR-520h is associated with poor prognosis and lymph node metastasis in human breast cancer patients. These results show that miR-520h is not only an independent prognostic factor, but is also a potential functional target for future applications in cancer therapeutics.

Clinically relevant heterotopic ossification after elbow fracture surgery: a risk factors study.

BACKGROUND: Heterotopic ossification (HO) is a common complication of elbow fracture surgery that can significantly impair function and range of motion (ROM). Whereas numerous studies have assessed HO after hip trauma or replacement surgery, few data have been reported on the prevalence and risk factors of HO after elbow fractures. HYPOTHESIS: Our objective was to investigate the prevalence and risk factors of clinically relevant HO after elbow fracture surgery under the hypothesis that the ability to identify high-risk patients would improve treatment tailoring and assist in meeting patient expectations. MATERIALS AND METHODS: We retrospectively included consecutive patients who had surgery for elbow injuries between January 2007 and December 2011. Patient demographics, operative details, and radiographs were reviewed. RESULTS: Of 124 elbows in 122 patients, 38 (30.6%) had HO and 26 (21%) clinically relevant HO. The prevalence of clinically relevant HO was highest in floating elbow injury, followed by combined olecranon and radial head fractures, types A and B distal humerus fractures, and terrible triad injury. By multiple logistic regression, factors that independently predicted clinically relevant HO were fracture-dislocation (OR, 4.87; 95%CI, 1.78-13.29; P=0.002) and longer time to surgery (P<0.05). Of the 26 patients with clinically relevant HO, 6 (23%) eventually required revision elbow surgery to improve ROM. DISCUSSION: HO of the elbow occurred in almost one-third of our patients with surgically treated elbow fractures. Fracture-dislocation of the elbow and longer time to surgery independently predicted HO responsible for ROM loss. Clinically relevant HO was associated with significant morbidity. LEVEL OF EVIDENCE: Level IV, retrospective study.

Inhibition of BMP signaling suppresses metastasis in mammary cancer.

Bone morphogenetic proteins (BMPs) are secreted cytokines/growth factors that have differing roles in cancer. BMPs are overexpressed in human breast cancers, but loss of BMP signaling in mammary carcinomas can accelerate metastasis. We show that human breast cancers display active BMP signaling, which is rarely downregulated or homozygously deleted. We hypothesized that systemic inhibition of BMP signaling in both the tumor and the surrounding microenvironment could prevent tumor progression and metastasis. To test this hypothesis, we used DMH1, a BMP antagonist, in MMTV.PyVmT expressing mice. Treatment with DMH1 reduced lung metastasis and the tumors were less proliferative and more apoptotic. In the surrounding tumor microenvironment, treatment with DMH1 altered fibroblasts, lymphatic vessels and macrophages to be less tumor promoting. These results indicate that inhibition of BMP signaling may successfully target both the tumor and the surrounding microenvironment to reduce tumor burden and metastasis.

In vivo monitoring of multiple trace metals in the brain extracellular fluid of anesthetized rats by microdialysis-membrane desalter-ICPMS.

We have developed an on-line analytical system involving microdialysis (MD) sampling, a carbohydrate membrane desalter (CMD), and an inductively coupled plasma mass spectrometer (ICPMS) system for the simultaneous determination of multiple trace metals in the extracellular fluid (ECF) in the brains of anesthetized rats. The microdialysate that perfused from the animal at a flow rate of 0.5 microL/min was on-line transferred to the CMD to remove the high-sodium matrix, followed by ICPMS measurement. The role of the CMD in this on-line system was investigated in detail. With prior addition of EDTA to the microdialysate to form anionic complexes of the metal analytes and the use of NH4Cl as a regenerant to exchange Na(+) with NH4(+) ions, both quantitative recovery of the trace metal analytes and quantitative removal of the sodium matrix could be achieved. Two experimental modes of the monitoring system were constructed. For those metals (e.g., Cu, Zn, and Mn) that existed at (sub)nanogram-per-milliliter concentrations in the microdialysate, the temporal resolution was 10 min when using a 10 microL loop for sample collection, followed by CMD and ICPMS; for those elements (e.g., Ca and Mg) that existed at microgram-per-milliliter levels (or greater), near-real-time analysis was possible because the microdialysate could be led, bypassing the sample loop, directly to the CMD for desalting without any time delay. Further improvement of the temporal resolution for the low-concentration elements was not possible without decreasing the detection limits of mass detection. Among the eight trace metals tested using this on-line system, the method detection limits for Cu, Zn, Mn, Co, Ni, and Pb reached subnanogram-per-milliliter levels; for electrolyte species such as Ca and Mg, the detection limits were in the range of 50-100 ng/mL. Analytical accuracy, expressed as spike recovery, was 100% +/- 15% for all of the elements tested. We demonstrate the applicability of the proposed system through the successful measurement of the basal values of Ca, Mg, Cu, Zn, and Mn in the ECF of a living rat brain and through in vivo monitoring of the concentration profiles of Mn and Pt in the ECF after the injection of drugs (MnCl2 and cisplatin) into the rats. This microdialysis system is the first to offer real-time, in vivo monitoring of trace elements such as Ca and Mg.

The role of the VEGF-C/VEGFR-3 axis in cancer progression.

Vascular endothelial growth factor (VEGF) receptor 3 (VEGFR-3) (also called VEGFR-3) is activated by its specific ligand, VEGF-C, which promotes cancer progression. The VEGF-C/VEGFR-3 axis is expressed not only by lymphatic endothelial cells but also by a variety of human tumour cells. Activation of the VEGF-C/VEGFR-3 axis in lymphatic endothelial cells can facilitate metastasis by increasing the formation of lymphatic vessels (lymphangiogenesis) within and around tumours. The VEGF-C/VEGFR-3 axis plays a critical role in leukaemic cell proliferation, survival, and resistance to chemotherapy. Moreover, activation of the VEGF-C/VEGFR-3 axis in several types of solid tumours enhances cancer cell mobility and invasion capabilities, promoting cancer cell metastasis. In this review, we discuss the novel function and molecular mechanism of the VEGF-C/VEGFR-3 axis in cancer progression.

An ELISA for antibodies against infectious bronchitis virus using an S1 spike polypeptide.

Using the whole infectious bronchitis virus (IBV) for detecting the antibody against IBV by enzyme-linked immunosorbent assay (ELISA) is a routine work in poultry industry. To prepare virus is time consuming and tedious. Furthermore, the whole viral antigen detects all antibodies against the viral structural proteins, including spike (S), nucleocapsid, matrix, and other proteins. Among those, S protein is related to neutralization. Thus, to develop and express protein fragment from S gene and to use the protein as a coating antigen for antibody detection against IBV are the purposes of this experiment. A partial S gene fragment (n.t. 1143-1665) was cloned into pRSET vectors and transformed into competent Escherichia coli (E. coli) BL21 (DE3). A 27.5 kDa fusion protein (S-fg, containing S1-F and partial S2-G antigenic sites) was successfully expressed, affinity-purified and detected specifically with chicken anti-IBV serum by Western blot. The expressed S-fg protein was used as a coating antigen for developing an ELISA (S-fg ELISA) for serum antibody detection in anti-IBV antisera from different IBV serotypes and in field sera. The results show that the S-fg fusion protein is highly cross-reactive among different IBV serotypes, and the S-fg ELISA is found to be a convenient, economical, and efficient method for antibody detection against IBV.

Anti-dsDNA autoantibody cross-reacts with the C-terminal hydrophobic cluster region containing phenylalanines in the acidic ribosomal phosphoprotein P1 to exert a cytostatic effect on the cells.

The present study was an attempt to map the epitope in P1 protein which may cross-react with anti-dsDNA. In addition to wild-type P1, the genes of its C-terminal mutants were cloned and expressed. The binding activity of these proteins with anti-dsDNA was determined by Western blot and ELISA. The P1 mutants with complete deletion of the acidic charge and hydrophobic clusters, deletion of the hydrophobic cluster, or replacement of the phenylanlanines with alanine in the hydrophobic cluster lost the binding activity. Moreover, P1 mutants with mutation at the serine phosphorylation sites (positions 102 and 105) retained their binding activities with anti-dsDNA. However, those with mutation at the serine phosphorylation sites and without the hydrophobic cluster lost their binding activities. These findings suggest that phenylalanines in the C-terminal hydrophobic cluster region of ribosomal P proteins are essential to their cross-reactivity with anti-dsDNA.

Signal transduction by a protease cascade.

The dorsoventral axis of the Drosophila embryo is determined by a spatial cue generated by ovarian somatic cells. This cue is communicated to the embryo through an extracellular serine protease cascade active only on the ventral side of the embryo. Studies of the proteases and somatically expressed proteins involved in this signalling process suggest a working model for how the protease cascade is locally activated hours after the ovarian somatic cells have degenerated.

REM sleep eye movement counts correlate with visual imagery in dreaming: a pilot study.

Based on the findings of our previously published positron emission tomography study, we proposed that recorded eye movements during REM sleep are visually targeted saccades. In the present study, we examined the correlation between the number of eye movements in REM sleep (EM) and visual imagery in dreaming (V) and provided further support for our proposal. All the observations (N = 11) were made with one individual to eliminate interindividual variation and were made during the second REM sleep period to control for a time-of-night effect. V, with or without dream report length partialled out, was strongly associated with EM only in the 1-min interval immediately preceding awakening. The time course of the association suggests that the strong EM-V association reflects a phasic, localized activation of the eye-movement-control system in association with REM sleep eye movements.

Abundance, parity, and Japanese encephalitis virus infection of mosquitoes (Diptera:Culicidae) in Sepang District, Malaysia.

A 2-yr study of Japanese encephalitis (JE) virus in Sepang District, Selangor, Malaysia, was carried out to identify the mosquito vectors and to determine their seasonal abundance, parity, and infection rates. In total, 81,889 mosquitoes belonging to 9 genera and > 50 species were identified from CDC trap collections augmented with dry ice during 1992 and 1993. Culex tritaeniorhynchus Giles and Culex gelidus Giles were the most abundant species, and both increased in numbers with increases in rainfall. Overall, 45 JE virus isolations were made from 7 species-Cx. tritaeniorhynchus (24), Cx. gelidus (12), Culex fuscocephala Theobald (2), Aedes butleri Theobald (4), Culex quinquefasciatus Say (1), Aedes lineatopennis Ludlow (1), and Aedes (Cancraedes) sp. (1). Based on elevated abundance and JE infection rates, Cx. tritaeniorhynchus appears to be the most important vector of JE virus in Sepang.

Assessment of the ability of propoxur, methomyl, and aldicarb, three carbamate insecticides, to induce micronuclei in vitro in cultured Chinese hamster ovary cells and in vivo in BALB/c mice.

Three carbamate insecticides (propoxur, methomyl, and aldicarb) were evaluated for their ability to induce micronuclei (MN) in vitro using cultured Chinese hamster ovary (CHO) cells, and in vivo in mouse bone marrow erythrocytes. In vitro, all three insecticides induced a significant increase in micronucleated binucleate cells, which was generally both dose and sample time dependent. The in vivo studies involved treating male BALB/c mice by different routes, either once or on 3 consecutive days, followed by multiple or single sampling. Treatment by intraperitoneal injection or oral gavage induced a significant increase in micronucleated reticulocytes (MNRETs) in peripheral blood. For all three chemicals, the MN response depended on sample time and the number of treatments, while for aldicarb, the response depended also on the route of exposure. These positive results demonstrate that propoxur, methomyl, and aldicarb are capable of inducing structural and/or numerical chromosomal aberrations in mammalian cells either in vitro or in vivo. Furthermore, based on the results obtained, on optimal in vivo MN protocol for carbamate insecticides is a single treatment followed by blood sampling at 24 and 48 hr after treatment.

Neoplastic response in Japanese medaka and channel catfish exposed to N-methyl-N'-nitro-N-nitrosoguanidine.

Japanese medaka (Oryzias latipes) and channel catfish (Ictalurus punctatus) were investigated for carcinogenic response following a 28-day, 3 x/wk pulse exposure to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Five-wk-old medaka were exposed at concentrations of 0, 0.5, and 1.0 mg/L, and 5-mo-old catfish at concentrations of 0, 0.1, and 0.5 mg/L. In medaka, a total of 19 tumors including 2 branchioblastomas, 6 thyroid follicular adenomas and 1 adenocarcinoma, and 11 subcutaneous fibrosarcomas were observed in 16 of 96 MNNG-exposed fish. In catfish, a total of 37 tumors including 4 squamous cell carcinomas and 16 papillomas, 3 lipomas, 1 fibroma, 1 osteosarcoma, 4 branchioblastomas, 6 thymic epithelial tumors, and 2 generalized lymphosarcomas were observed in 34 of 172 MNNG-exposed fish. The induction of neoplasms in medaka was primarily in the gill, thyroid, and subcutis of the cervical and trunk regions, whereas in catfish skin, thymus, oro-pharynx, and hemopoietic tissues were also commonly affected. In both species, the neoplastic response was considered to be related to direct exposure of the tissues to MNNG. Some of these tumors have not been reported in the literature in either natural or experimental fish. The results also suggest species-specific differences in carcinogenic response following MNNG exposure.