Epigenetic regulation of 15-lipoxygenase-1 expression in human chondrocytes by promoter methylation.

OBJECTIVE AND DESIGN: 15-Lipoxygenase-1 (15-LOX-1) catalyzes the biosynthesis of many anti-inflammatory and immunomodulatory lipid mediators and was reported to have protective properties in several inflammatory conditions, including osteoarthritis (OA). This study was designed to evaluate the expression of 15-LOX-1 in cartilage from normal donors and patients with OA, and to determine whether it is regulated by DNA methylation. METHODS: Cartilage samples were obtained at autopsy from normal knee joints and from OA-affected joints at the time of total knee joint replacement surgery. The expression of 15-LOX-1 was evaluated using real-time polymerase chain reaction (PCR). The role of DNA methylation in 15-LOX-1 expression was assessed using the DNA methyltransferase inhibitor 5-Aza-2'-desoxycytidine (5-Aza-dC). The effect of CpG methylation on 15-LOX-1 promoter activity was evaluated using a CpG-free luciferase vector. The DNA methylation status of the 15-LOX-1 promoter was determined by pyrosequencing. RESULTS: Expression of 15-LOX-1 was upregulated in OA compared to normal cartilage. Treatment with 5-Aza-dC increased 15-LOX-1 mRNA levels in chondrocytes, and in vitro methylation decreased 15-LOX-1 promoter activity. There was no difference in the methylation status of the 15-LOX-1 gene promoter between normal and OA cartilage. CONCLUSION: The expression level of 15-LOX-1 was elevated in OA cartilage, which may be part of a repair process. The upregulation of 15-LOX-1 in OA cartilage was not associated with the methylation status of its promoter, suggesting that other mechanisms are involved in its upregulation.

Use of IMMPACT Recommendations to Explore Pain Phenotypes in People with Knee Osteoarthritis.

OBJECTIVE: Knee osteoarthritis (OA) is a disease of multiple phenotypes of which a chronic pain phenotype (PP) is known. Previous PP studies have focused on one domain of pain and included heterogenous variables. We sought to identify multidimensional PPs using the IMMPACT recommendations and their relationship to clinical outcomes. METHODS: Participants >40 years of age with knee OA having a first-time orthopedic consultation at five university affiliated hospitals in Montreal, Quebec, and Hamilton (Canada) were recruited. Latent profile analysis was used to determine PPs (classes) using variables recommended by IMMPACT. This included pain variability, intensity and qualities, somatization, anxiodepressive symptoms, sleep, fatigue, pain catastrophizing, neuropathic pain, and quantitative sensory tests. We used MANOVA and χ2 tests to assess differences in participant characteristics across the classes and linear and Poisson regression to evaluate the association of classes to outcomes of physical performance tests, self-reported function and provincial healthcare data. RESULTS: In total, 343 participants were included (mean age 64 years, 64% female). Three classes were identified with increasing pain burden (class3 > class1), characterized by significant differences across most self-report measures and temporal summation, and differed in terms of female sex, younger age, lower optimism and pain self-efficacy. Participants in class2 and class3 had significantly worse self-reported function, stair climb and 40 m walk tests, and higher rates of healthcare usage compared to those in class1. CONCLUSIONS: Three distinct PPs guided by IMMPACT recommendations were identified, predominated by self-report measures and temporal summation. Using this standardized approach may improve PP study variability and comparison.

Impact of Degree of Ionization and PEGylation on the Stability of Nanoparticles of Chitosan Derivatives at Physiological Conditions.

Nowadays, the therapeutic efficiency of small interfering RNAs (siRNA) is still limited by the efficiency of gene therapy vectors capable of carrying them inside the target cells. In this study, siRNA nanocarriers based on low molecular weight chitosan grafted with increasing proportions (5 to 55%) of diisopropylethylamine (DIPEA) groups were developed, which allowed precise control of the degree of ionization of the polycations at pH 7.4. This approach made obtaining siRNA nanocarriers with small sizes (100-200 nm), positive surface charge and enhanced colloidal stability (up to 24 h) at physiological conditions of pH (7.4) and ionic strength (150 mmol L-1) possible. Moreover, the PEGylation improved the stability of the nanoparticles, which maintained their colloidal stability and nanometric sizes even in an albumin-containing medium. The chitosan-derivatives displayed non-cytotoxic effects in both fibroblasts (NIH/3T3) and macrophages (RAW 264.7) at high N/P ratios and polymer concentrations (up to 0.5 g L-1). Confocal microscopy showed a successful uptake of nanocarriers by RAW 264.7 macrophages and a promising ability to silence green fluorescent protein (GFP) in HeLa cells. These results were confirmed by a high level of tumor necrosis factor-α (TNFα) knockdown (higher than 60%) in LPS-stimulated macrophages treated with the siRNA-loaded nanoparticles even in the FBS-containing medium, findings that reveal a good correlation between the degree of ionization of the polycations and the physicochemical properties of nanocarriers. Overall, this study provides an approach to enhance siRNA condensation by chitosan-based carriers and highlights the potential of these nanocarriers for in vivo studies.

Lymphocyte transformation test reveals low prevalence of true metal hypersensitivity among pre-operative total knee arthroplasty patients.

PURPOSE: The aims of this study were to determine the prevalence of metal hypersensitivity, and identify pre-operative factors which could predict susceptibility to hypersensitivity reactions among patients scheduled for primary total knee arthroplasty (TKA). The present study used a testing method consistent with the recognised biological response to metals. METHODS: A prospective cross-sectional analysis of 220 patients was conducted. All patients received a testing protocol using lymphocyte transformation test to evaluate reactivity to possible contents of orthopaedic implants. Test response is interpreted as stimulation index (SI) values. A comprehensive questionnaire was used to evaluate prior exposure. Patients were categorised according to SI values and the odds ratios (OR) were calculated as comparative effect measure for each predetermined prior exposure factor. RESULTS: The prevalence of metal sensitivity response was 28% (n = 61) among patients with susceptibility to at least one agent (SI = 2 to 4.9), and 3.2% (n = 7) among patients with true hypersensitivity (SI ≥ 5). The population-weighted prevalence, adjusted for sampling weights of symptomatic knee osteoarthritis, was SI ≥ 5 = 4.7% (95% CI 0.4-11.8%) and SI ≥ 2 = 35.2% (95% CI 24.8-48.6%). Stimulation index levels of response to materials were markedly varied with the highest being aluminium. Female sex, smoking history, cutaneous reaction to jewellery, occupational exposure, and dental procedures were among factors shown to increase the odds of having higher reactivity response to tested metals. Nevertheless, patients with well-functioning prior contralateral TKA did not appear at greater risk of having either sensitivity or susceptibility with odds ratio (OR) = 0.2 (95% CI 0.01-3.2), p: NS and OR = 0.6 (95% CI 0.3-1.2), p: NS, respectively. Prior positive patch test was neither predictor of susceptibility to hypersensitivity OR = 1.2 (95% CI 0.6-2.6) p: NS nor predictor of true hypersensitivity OR = 0.7 (95% CI 0.08-6.1), p: NS. CONCLUSION: Among patients scheduled for primary TKA with no prior clinical features of metal allergy the prevalence of true hypersensitivity to at least one metal is just over 3%. Patients are likely to encounter a material to which they have pre-existing susceptibility to hypersensitivity. With certain prior exposure factors, there was increased susceptibility to metal hypersensitivity reaction evoking an acquired condition. LEVEL OF EVIDENCE: Level II, prospective cross-sectional study.

Efficacy of cryotherapy in the treatment of cutaneous horn associated with papillomatosis in a dog.

Cutaneous horn is a skin disease with low incidence and few citations in the literature. This report describes a dog with multiple cutaneous lesions of papillomatosis and one giant cutaneous horn on the face. Two sessions of cryotherapy achieved complete remission of the lesions.

La corne cutanée est une maladie de la peau à faible incidence et peu citée dans la littérature. Cet article décrit un chien avec de multiples lésions cutanées de papillomatose et une corne cutanée géante sur la face. Deux séances de cryothérapie ont permis d'obtenir une rémission complète des lésions.

Los cuernos cutáneos son una lesion patológica de baja incidencia y con escasas menciones en la literatura. Este artículo describe un caso de un perro con multiples lesiones cutáneas de papilomatosis y un cuerno cutáneo gigante en la cara. Dos sesiones de crioterapia consiguieron una remisión completa de las lesiones.

O corno cutâneo é uma doença cutânea com baixa incidência e poucas citações na literatura. Este relato descreve um cão com múltiplas lesões cutâneas características de papilomatose e um corno cutâneo gigante na face. Houve remissão completa das lesões após duas sessões de crioterapia.

The pathophysiology of immunoporosis: innovative therapeutic targets.

BACKGROUND: The physiological balance between bone resorption and bone formation is now known to be mediated by a cascade of events parallel to the classic osteoblast-osteoclast interaction. Thus, osteoimmunology now encompasses the role played by other cell types, such as cytokines, lymphocytes and chemokines, in immunological responses and how they help modulate bone metabolism. All these factors have an impact on the RANK/RANKL/OPG pathway, which is the major pathway for the maturation and resorption activity of osteoclast precursor cells, responsible for osteoporosis development. Recently, immunoporosis has emerged as a new research area in osteoimmunology dedicated to the immune system's role in osteoporosis. METHODS: The first part of this review presents theoretical concepts on the factors involved in the skeletal system and osteoimmunology. Secondly, existing treatments and novel therapeutic approaches to treat osteoporosis are summarized. These were selected from to the most recent studies published on PubMed containing the term osteoporosis. All data relate to the results of in vitro and in vivo studies on the osteoimmunological system of humans, mice and rats. FINDINGS: Treatments for osteoporosis can be classified into two categories. They either target osteoclastogenesis inhibition (denosumab, bisphosphonates), or they aim to restore the number and function of osteoblasts (romozumab, abaloparatide). Even novel therapies, such as resolvins, gene therapy, and mesenchymal stem cell transplantation, fall within this classification system. CONCLUSION: This review presents alternative pathways in the pathophysiology of osteoporosis, along with some recent therapeutic breakthroughs to restore bone homeostasis.

Advanced practice physiotherapy for adults with spinal pain: a systematic review with meta-analysis.

OBJECTIVE: To appraise the available evidence on advanced practice physiotherapy (APP) models of care (MoC) in specialized secondary care such as orthopaedic, rheumatology or neurosurgery outpatients' clinics for adults with spinal pain. METHODS: Systematic review with meta-analysis. Electronic searches were conducted up to July 2020 in Medline, Embase, Cochrane CENTRAL and CINAHL. Studies on APP MoC in specialized secondary care for adults with spinal pain were included. RESULTS: Eighteen studies (n = 9405), including two randomized controlled trials and sixteen observational studies were included. One study was considered at high quality, fourteen studies were considered of moderate quality and three were considered of low quality. Pooled results for change in disability for patients with spinal pain reported no significant difference between APP and usual medical care (UMC). Mean wait time for initial consultation was lower with APP (1-9.4 weeks) than with UMC MoC (23-65 weeks). Following the implementation of APP MoC, wait time for a consultation with a medical specialist was reduced (6-16 weeks). Physiotherapists in APP MoC managed independently 89.2% of the patients referred (n = 8393). Stakeholders and patients reported high satisfaction with APP care. CONCLUSIONS: APP MoC and UMC likely result in comparable pain, disability and quality of life improvement for adults with spinal pain. However, APP MoC have the potential to improve health care access by reducing wait time for consultation in specialized care and maintaining a high level of satisfaction among stakeholders and patients.

Economic evaluation of advanced practice physiotherapy models of care: a systematic review with meta-analyses.

BACKGROUND: The objective of this systematic review is to appraise evidence on the economic evaluations of advanced practice physiotherapy (APP) care compared to usual medical care. METHODS: Systematic searches were conducted up to September 2021 in selected electronic bibliographical databases. Economic evaluation studies on an APP model of care were included. Economic data such as health care costs, patient costs, productivity losses were extracted. Methodological quality of included studies was assessed with the Effective Public Health Practice Project tool and the Critical Appraisal Skills Programme checklist. Meta-analyses were performed and mean differences (MD) in costs per patient were calculated using random-effect inverse variance models. Certainty of the evidence was assessed with the GRADE Approach. RESULTS: Twelve studies (n = 14,649 participants) including four randomized controlled trials, seven analytical cohort studies and one economic modeling study were included. The clinical settings of APP models of care included primary, emergency and specialized secondary care such as orthopaedics, paediatrics and gynaecology. The majority of the included participants were adults with musculoskeletal disorders (n = 12,915). Based on low quality evidence, health system costs including salaries, diagnostic tests, medications, and follow-up visits were significantly lower with APP care than with usual medical care, at 2 to 12-month follow-up (MD: - 145.02 €/patient; 95%CI: - 251.89 to - 38.14; n = 7648). Based on low quality evidence, patient costs including travel and paid medication prescriptions, or treatments were significantly higher with APP care compared to usual medical care, at 2 to 6-month follow-up (MD: 22.18 €/patient; 95%CI: 0.40 to 43.96; n = 1485). Based on very low quality evidence, no significant differences in productivity losses per patient were reported between both types of care (MD: 450 €/patient; 95%CI: - 80 to 970; n = 819). CONCLUSIONS: This is the first systematic review and meta-analysis on the economic evaluation of APP models of care. Low quality evidence suggests that APP care might result in lower health care costs, but higher patient costs compared to usual medical care. Costs differences may vary depending on various factors such as the cost methodology used and on the clinical setting. More evidence is needed to evaluate cost benefits of APP models of care.

Barriers to Family Resilience in Caregivers of People Who Have Schizophrenia.

PURPOSE: To explore the barriers to family resilience in caregivers of people who have schizophrenia. DESIGN: A qualitative descriptive approach was used. METHODS: Semistructured interviews were conducted with family caregivers of patients with schizophrenia registered at the psychiatry outpatient unit of a hospital center. Content analysis was performed on audio-recorded and verbatim-transcribed interviews. The consolidated criteria for reporting qualitative research (COREQ) checklist was applied to this study. RESULTS: A total of 31 family caregivers participated, the majority of whom were female (71%) with an average age of 57.5 years. Most participants lived with and cared for their relative (90.3%). The caregiver role was assumed mostly by mothers (54.8%) and fathers (22.6%). Barriers to family resilience in caregivers of people experiencing schizophrenia broadly fall under five categories: lack of knowledge about the disease, social stigma, expressed emotion, involvement in the relationship, and blame. CONCLUSIONS: In view of the paucity of studies exploring and understanding the barriers to family resilience, this study presents itself as one of the first in this area. There are different barriers to family resilience. This research provides an overview and an understanding of key barriers to family resilience in caregivers of people experiencing schizophrenia. CLINICAL RELEVANCE: There is a need for nurses to help families to be resilient. By understanding the barriers to resilience, nurses are able to focus on these factors and help families to remove or reduce their influence.

Efficacy of oral sarolaner against Lynxacarus radovskyi in naturally infested cats.

BACKGROUND: Lynxacarus radovskyi is a fur mite of cats. Several classes of ectoparasiticides have shown success for treatment, including an isoxazoline. OBJECTIVES: To evaluate the efficacy of a single oral dose of sarolaner for the treatment of L. radovskyi mites in naturally infested cats. ANIMALS: Fourteen adult cats (six males and eight females), naturally infested with L. radovskyi. METHODS AND MATERIALS: Animals were randomized according to sex and average pretreatment mite count. The cats were assigned to two groups of seven cats each. The treated group received one 10 mg sarolaner tablet, corresponding to a dose of 2-4 mg/kg body weight, and the control group received no treatment. From each cat, three trichograms consisting of approximately 50 hairs each were collected from the dorsal neck, lateral thigh and perineum/tail region (total of nine samples per cat). The severity of infestation was scored on a scale of 0 (no parasites) to 4 (>50 mites) at baseline and days 7, 15, 30, 45 and 60 post-treatment. Efficacy was compared between the treatment and control groups using the arithmetic mean reduction of the mite score; results were analysed using the Kruskal-Wallis test followed by the Student-Newtman-Keuls test, with significance set at P < 5%. RESULTS: The efficacy of oral sarolaner was >95% at Day 30 post-treatment. Statistical differences were first observed between the means of the control and treated groups 15 days post-treatment. CONCLUSION: A single oral dose of sarolaner effectively eliminated L. radovskyi in most cats.

A blinded, randomized, placebo-controlled trial of the safety of oclacitinib in cats.

BACKGROUND: Oclacitinib is a Janus kinase (JAK) 1 enzyme inhibitor and blocks JAK1-dependent cytokines and is used to control pruritus. Studies available in cats are very limited and as there is a potential role for oclacitinib in the control of pruritus in this specie, the aim of this study was to evaluate the safety and clinical effects of oral oclacitinib maleate in healthy cats. RESULTS: Thirty mixed-breed cats weighing from 2.1 to 5.3 kg each were randomly allocated to three treatment groups of 10 animals each. Cats in two groups received oclacitinib at 1 mg/kg or 2 mg/kg q 12 h orally for 28 days. Cats in the third group were given placebo tablets (cornstarch) q 12 h orally for 28 days. Oclacitinib maleate was well tolerated during the study and few adverse events were observed in treated cats. Clinical signs of toxicity were not observed in any animals treated at 1 mg/kg. Gastrointestinal clinical signs observed in the 2 mg/kg group included vomiting in two of the 10 cats and soft stools in two cats. One cat treated with placebo also exhibited soft stools. No significant differences were observed between the groups for hematologic analyses performed during the study. There was a slight increase in neutrophils and monocytes and a decrease in eosinophil mean counts in treated cats. Mean renal and liver enzymes remained normal throughout the entire study. A small, but significant increase in fructosamine levels was observed for both treated groups compared with placebo; however, values remained within the normal reference range. There were no significant difference between treated groups and the placebo group for urine specific gravity, pH, or urine protein to creatinine ratio mean values. CONCLUSIONS: Oclacitinib maleate was well tolerated by cats at 1 mg/kg and 2 mg/kg and appeared to be safe for this species when administered orally twice daily for 28 days. More studies would be needed to demonstrate if oclacitinib maleate may be a suitable alternative to treat pruritic cats.

Effect of intracortical bone properties on the phase velocity and cut-off frequency of low-frequency guided wave modes (20-85 kHz).

The assessment of intracortical bone properties is of interest since early-stage osteoporosis is associated with resorption in the endosteal region. However, understanding the interaction between ultrasonic guided waves and the cortical bone structure remains challenging. The purpose of this work is to investigate the effect of intracortical bone properties on the ultrasonic response obtained at low-frequency (<100 kHz) using an axial transmission configuration. The semi-analytical finite element method was used to simulate the propagation of guided waves in a waveguide with realistic geometry and material properties. An array of 20 receivers was used to calculate the phase velocity and cut-off frequency of the excited modes using the two-dimensional Fourier transform. The results show that the position of the emitter around the circumference of the bone is an important parameter to control since it can lead to variations of up to 10 dB in the amplitude of the transmitted modes. The cut-off frequency of the high order modes was, however, only slightly affected by the circumferential position of the emitter, and was sensitive mainly to the axial shear modulus. The phase velocity and cut-off frequency in the 20-85 kHz range are promising parameters for the assessment of intracortical properties.

Elucidating the Role of Protandim and 6-Gingerol in Protection Against Osteoarthritis.

Protandim and 6-gingerol, two potent nutraceuticals, have been shown to decrease free radicals production through enhancing endogenous antioxidant enzymes. In this study, we evaluated the effects of these products on the expression of different factors involved in osteoarthritis (OA) process. Human OA chondrocytes were treated with 1 ng/ml IL-1ß in the presence or absence of protandim (0-10 µg/ml) or 6-gingerol (0-10 µM). OA was induced surgically in mice by destabilization of the medial meniscus (DMM). The animals were treated weekly with an intraarticular injection of 10 µl of vehicle or protandim (10 µg/ml) for 8 weeks. Sham-operated mice served as controls. In vitro, we demonstrated that protandim and 6-gingerol preserve cell viability and mitochondrial metabolism and prevented 4-hydroxynonenal (HNE)-induced cell mortality. They activated Nrf2 transcription factor, abolished IL-1ß-induced NO, PGE2 , MMP-13, and HNE production as well as IL-ß-induced GSTA4-4 down-regulation. Nrf2 overexpression reduced IL-1ß-induced HNE and MMP-13 as well as IL-1ß-induced GSTA4-4 down-regulation. Nrf2 knockdown following siRNA transfection abolished protandim protection against oxidative stress and catabolism. The activation of MAPK and NF-κB by IL-1ß was not affected by 6-gingerol. In vivo, we observed that Nrf2 and GSTA4-4 expression was significantly lower in OA cartilage from humans and mice compared to normal controls. Interestingly, protandim administration reduced OA score in DMM mice. Altogether, our data indicate that protandim and 6-gingerol are essential in preserving cartilage and abolishing a number of factors known to be involved in OA pathogenesis. J. Cell. Biochem. 118: 1003-1013, 2017. © 2016 Wiley Periodicals, Inc.

An overview of the role of lipid peroxidation-derived 4-hydroxynonenal in osteoarthritis.

BACKGROUND: Over the years, many theories have been proposed and examined to better explain the etiology and development of osteoarthritis (OA). The characteristics of joint destruction are one of the most important aspects in disease progression. Therefore, investigating different factors and signaling pathways involved in the alteration of extracellular matrix (ECM) turnover, and the subsequent catabolic damage to cartilage holds chief importance in understanding OA development. Among these factors, reactive oxygen species (ROS) have been at the forefront of the physiological and pathophysiological OA investigation. FINDINGS: In the last decades, research studies provided an enormous volume of data supporting the involvement of ROS in OA. Most interestingly, published data regarding the effect of exogenous antioxidant therapy in OA lack conclusive results from clinical trials to back up in vitro data. Accordingly, it is rational to suggest that there are other reactive species in OA that are not taken into account. Thus, our present review is focused on our current understanding of the involvement of lipid peroxidation-derived 4-hydroxynonenal (HNE) in OA. CONCLUSION: Our findings, like those in the literature, illustrate the central role played by HNE in the regulation of a number of factors involved in joint homeostasis. HNE could thus be considered as an attractive therapeutic target in OA.

Simulation of acoustic guided wave propagation in cortical bone using a semi-analytical finite element method.

Axial transmission techniques have been extensively studied for cortical bone quality assessment. However, the modeling of ultrasonic guided waves propagation in such a complex medium remains challenging. The aim of this paper is to develop a semi-analytical finite element method to simulate the propagation of guided waves in an irregular, multi-layer, and heterogeneous bone cross-section modeled with anisotropic and viscoelastic material properties. The accuracy of the simulations was verified against conventional time-domain three-dimensional finite element. The method was applied in the context of axial transmission in bone to investigate the feasibility of first arrival signal (FAS) to monitor degradation of intracortical properties at low frequency. Different physiopathological conditions for the intracortical region, varying from healthy to osteoporotic, were monitored through FAS velocity using a 10-cycle tone burst excitation centered at 32.5 kHz. The results show that the variation in FAS velocity is mainly associated with four of the eight modes supported by the waveguide, varying with velocity values between 550 and 700 m/s along the different scenarios. Furthermore, the FAS velocity is shown to be associated with the group velocity of the mode with the highest relative amplitude contribution at each studied scenario. However, because of the evolution of the mode with the highest contribution, the FAS velocity is shown to be limited to discriminate intracortical bone properties at low frequency.

The role of resolvin D1 in the regulation of inflammatory and catabolic mediators in osteoarthritis.

OBJECTIVE AND DESIGN: Resolvin D1 (RvD1), an omega-3 fatty acid derivative, has shown remarkable properties in resolving inflammation, promoting tissue repair and preserving tissue integrity. In this study, we investigated RvD1 effects on major processes involved in osteoarthritis (OA) pathophysiology. MATERIALS AND METHODS: Human OA chondrocytes were treated with either 1 ng/ml interleukin-1ß (IL-1ß) or 20 µM 4-hydroxynonenal (HNE), then treated or not with increased concentrations of RvD1 (0-10 µM). RvD1 levels were measured by enzyme immunoassay in synovial fluids from experimental dog model of OA and sham operated dogs obtained from our previous study. Cell viability was evaluated by 3-(4,5-dimethyl-thiazoyl)-2,5-diphenyl-SH-tetrazolium bromide assay. Parameters related to inflammation, catabolism and apoptosis were determined by enzyme-linked immunosorbent assay, Western blotting, and quantitative polymerase chain reaction. Glutathione (GSH) was assessed by commercial kit. The activation of mitogen-activated protein kinases and nuclear factor-kappaB (NF-κB) pathways was evaluated by Western blot. RESULTS: We showed that RvD1 levels were higher in synovial fluids from OA joint compared to controls. In OA human chondrocytes, we demonstrated that RvD1 was not toxic up to 10 µM and stifled IL-1ß-induced cyclooxygenase 2, prostaglandin E2, inducible nitric oxide synthase, nitric oxide, and matrix metalloproteinase-13. Our study of signalling pathways revealed that RvD1 suppressed IL-1ß-induced activation of NF-κB/p65, p38/MAPK and JNK(1/2). Moreover, RvD1 prevented HNE-induced cell apoptosis and oxidative stress, as indicated by inactivation of caspases, inhibition of lactate dehydrogenase release, and increased levels of Bcl2 and AKT, as well as GSH. CONCLUSION: This is the first in vitro study demonstrating the beneficial effect of RvD1 in OA. That RvD1 abolishing a number of factors known to be involved in OA pathogenesis renders it a clinically valuable agent in prevention of the disease.

Art and Plastic Surgery.

UNLABELLED: The roots of science and art of plastic surgery are very antique. Anatomy, drawing, painting, and sculpting have been very important to the surgery and medicine development over the centuries. Artistic skills besides shape, volume, and lines perception can be a practical aid to the plastic surgeons' daily work. An overview about the interactions between art and plastic surgery is presented, with a few applications to rhinoplasty, cleft lip, and other reconstructive plastic surgeries. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Periprosthetic fractures of the acetabulum during cup insertion: posterior column stability is crucial.

Periprosthetic hip fractures around acetabular components are rare with little information available to guide surgical management of these complex injuries. A retrospective review of intraoperative isolated acetabular periprosthetic fractures from three tertiary surgical units was done. A total of 32 patients were identified with 9 initially missed. Acetabular components were stable (type 1) in 11 patients with no failures; unstable (type 2) in 12 patients and treated with supplemental fixation. Non-union and displacement were correlated with absent posterior column plating. Missed fractures (type 3) had the highest reoperation rate. Anterior patterns all healed, whereas fractures with posterior column instability had a 67% failure rate. Periprosthetic acetabular fracture can heal successfully with posterior column stability. Plating is mandatory for large posterior wall fragments to achieve osteointegration.

Sorbitol-modified hyaluronic acid reduces oxidative stress, apoptosis and mediators of inflammation and catabolism in human osteoarthritic chondrocytes.

OBJECTIVE AND DESIGN: Our study was designed to elucidate the precise molecular mechanisms by which sorbitol-modified hyaluronic acid (HA/sorbitol) exerts beneficial effects in osteoarthritis (OA). METHODS: Human OA chondrocytes were treated with increasing doses of HA/sorbitol ± anti-CD44 antibody or with sorbitol alone and thereafter with or without interleukin-1beta (IL-1ß) or hydrogen peroxide (H2O2). Signal transduction pathways and parameters related to oxidative stress, apoptosis, inflammation, and catabolism were investigated. RESULTS: HA/sorbitol prevented IL-1ß-induced oxidative stress, as measured by reactive oxygen species, p47-NADPH oxidase phosphorylation, 4-hydroxynonenal (HNE) production and HNE-metabolizing glutathione-S-transferase A4-4 expression. Moreover, HA/sorbitol stifled IL-1ß-induced metalloproteinase-13, nitric oxide (NO) and prostaglandin E2 release as well as inducible NO synthase expression. Study of the apoptosis process revealed that this gel significantly attenuated cell death, caspase-3 activation and DNA fragmentation elicited by exposure to a cytotoxic H2O2 dose. Examination of signaling pathway components disclosed that HA/sorbitol prevented IL-1ß-induced p38 mitogen-activated protein kinase and nuclear factor-kappa B activation, but not that of extracellular signal-regulated kinases 1 and 2. Interestingly, the antioxidant as well as the anti-inflammatory and anti-catabolic effects of HA/sorbitol were attributed to sorbitol and HA, respectively. CONCLUSIONS: Altogether, our findings support a beneficial effect of HA/sorbitol in OA through the restoration of redox status and reduction of apoptosis, inflammation and catabolism involved in cartilage damage.