Papers by Julio Fernandes
BMC Health Services Research, 2022
An amendment to this paper has been published and can be accessed via the original article.
<b>Copyright information:</b>Taken from "Abnormal insulin-like growth factor 1 s... more <b>Copyright information:</b>Taken from "Abnormal insulin-like growth factor 1 signaling in human osteoarthritic subchondral bone osteoblasts"Arthritis Research &amp; Therapy 2006;8(6):R177-R177.Published online 27 Nov 2006PMCID:PMC1794522. Cells were grown to confluence and incubated overnight in serum free medium. Cells were then exposed to 50 ng/ml insulin-like growth factor (IGF)-1 for various lengths of time, as indicated. After cell lysis in RIPA buffer and IP with an anti-IRS-1 antibody, co-immunoprecipitated Syp levels were visualized by immunoblotting with an anti-Syp antibody. A representative immunoblotting of three different experiments is presented. Determination of actin was used as the control for loading.
Inflammation Research, 2021
Background The physiological balance between bone resorption and bone formation is now known to b... more 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.
Ligaments and Ligamentoplasties, 1997
The posterior cruciate ligament (PCL) stands today as the anterior cruciate ligament (ACL) did so... more The posterior cruciate ligament (PCL) stands today as the anterior cruciate ligament (ACL) did some 20 years ago; it has replaced the ACL as the “enigma of the knee” [83]. The issue of surgical versus conservative treatment still remains disputed. Clinical and investigational research on injuries to the PCL lags far behind our understanding of the ACL. Acute injuries to the PCL may go unrecognized, and it is difficult to assign a strict chronological period to acute versus chronic injuries. The belief that injury to the PCL is a rare event is slowly being dispelled due to better imaging techniques and clinical acumen. The incidence of PCL tears is estimated to be 5%–20% of all ligament tears [12, 14, 42]. Most injuries to the PCL occur in either motor vehicle accidents or athletic events [31], and disruption of the PCL as an isolated injury does occur [13, 47, 71].
European Spine Journal, 2020
To appraise the available evidence on advanced practice physiotherapy (APP) models of care (MoC) ... more 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. 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. 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. 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.
BMC Health Services Research, 2021
Background The objective of this systematic review is to appraise evidence on the economic evalua... more 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...
Journal of Proteomics, 2021
The α,β-unsaturated aldehyde 4-hydroxynonenal (HNE) is formed through lipid peroxidation during o... more The α,β-unsaturated aldehyde 4-hydroxynonenal (HNE) is formed through lipid peroxidation during oxidative stress. As a highly reactive electrophile, it is able to form adducts with various biomolecules, including proteins. These protein modifications could modulate many signaling pathways, as well as cell differentiation and proliferation, and thus could be highly important in the context of the extracellular matrix and degradation of articular cartilage. This study specifically investigated the role of HNE as a bioactive molecule in chondrocytes of osteoarthritis (OA) patients. Chondrocyte extracts of OA and non-OA patients were analyzed for HNE binding using Western blot and bottom-up LC-MS/MS analyses. HNE-modified histones, H2A and H2B, and histone deacetylase were identified using anti-HNE antibodies. Furthermore, peptide sequencing and database searching revealed 95 distinct HNE-modified proteins and their exact modification sites, with 88 protein adducts being unique to OA chondrocytes. HNE-proteins of specific interest included histone H2A, H2B and H4, collagen alpha-3(VI) chain, eukaryotic initiation factor 4A-I, and nucleolar RNA helicase 2. Comparing their MS/MS spectra to those of HNE-modified standard peptides further validated the six HNE-proteins. SIGNIFICANCE: HNE binding to proteins has been shown to result in multiple abnormalities of chondrocyte phenotype and function, suggesting its contribution in OA development. Considering the increased levels of HNE in OA cartilage, this reactive aldehyde could play a role in OA. This work represents a clinically-relevant in vivo study to demonstrate the pathophysiological role of HNE in human OA. Since HNE binding can alter protein conformation and function, it remains highly relevant to study the effects of this modification in osteoarthritis.
The Journal of the Acoustical Society of America, 2019
Manuscript (TeX or Word only) Click here to access/download;Manuscript (TeX or Word only);Manuscr... more Manuscript (TeX or Word only) Click here to access/download;Manuscript (TeX or Word only);Manuscript.tex JASA/Sample JASA Article 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 cutoff frequency of the excited modes using the 2D 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 cutoff frequency of the high order modes was, however, only slightly affected by the circunferential position of the emitter, and was sensitive mainly to the axial shear modulus. The phase velocity and cutoff frequency in the 20-85 kHz range are promising parameters for the assessment of intracortical properties.
International journal of nanomedicine, 2018
Tumor necrosis factor-alpha (TNFα), a pro-inflammatory cytokine, has been shown to play a role in... more Tumor necrosis factor-alpha (TNFα), a pro-inflammatory cytokine, has been shown to play a role in the pathophysiology of rheumatoid arthritis. Silencing TNFα expression with small interfering RNA (siRNA) is a promising approach to treatment of the condition. Towards this end, our team has developed a modified chitosan (CH) nanocarrier, deploying folic acid, diethylethylamine (DEAE) and polyethylene glycol (PEG) (folate-PEG-CH-DEAE). The gene carrier protects siRNA against nuclease destruction, its ligands facilitate siRNA uptake via cell surface receptors, and it provides improved solubility at neutral pH with transport of its load into target cells. In the present study, nanoparticles were prepared with siRNA-TNFα, DEAE, and folic acid-CH derivative. Nanoparticle size and zeta potential were verified by dynamic light scattering. Their TNFα-knockdown effects were tested in a murine collagen antibody-induced arthritis model. TNFα expression was examined along with measurements of var...
Vascular health and risk management, 2018
Low-molecular-weight heparin (LMWH) is a recommended anticoagulant for thromboprophylaxis after m... more Low-molecular-weight heparin (LMWH) is a recommended anticoagulant for thromboprophylaxis after major orthopedic surgery. Dabigatran etexilate is an oral anticoagulant recognized as noninferior to LMWH. We aimed to assess the incidence of symptomatic venous thromboembolic events (VTEs) after discharge in patients who underwent joint replacement, using a hospital registry. Patients who underwent total knee and hip arthroplasty between September 2011 and March 2015 were selected. Subcutaneous enoxaparin (30 mg twice daily) was given during hospitalization. At discharge, patients received either enoxaparin 30 mg twice daily/40 mg once daily or dabigatran 220 mg/150 mg once daily. Patients were seen or called at 2, 6, and 12 weeks after surgery. Outcomes were the number of VTEs, including deep venous thrombosis, pulmonary embolism, and the number of major/minor bleeding events after discharge. After discharge, 1468 patients were prescribed enoxaparin and 904 dabigatran (1396 total knee ...
The Journal of the Acoustical Society of America, 2016
In this work, a semi-analytical finite-element method was on the propagation of acoustic guided w... more In this work, a semi-analytical finite-element method was on the propagation of acoustic guided wave. The simulations were performed with a realistic bone cross-sectional geometry by considering an axial transmission configuration. A point source excitation was applied using a toneburst centered at 35 kHz as the input signal. The propagating waves were monitored using out-of-plane displacement in the axial direction at 32 positions separated 4 mm apart. The properties of the endosteal region of cortical bone were varied from healthy to early osteoporotic conditions. The use of the two-dimensional Fourier transform (2DFFT) allowed the measurement of individual mode velocity, which was compared to the velocity typically measured using first arrival signal (FAS). The results have shown that variations in the velocity measured using 2DFFT were mainly associated to a low order flexural-like mode among the eight modes supported by the waveguide. Furthermore, the measured velocity decreased approximately 10/% du...
Inflammation research : official journal of the European Histamine Research Society ... [et al.], Jan 26, 2017
Over the years, many theories have been proposed and examined to better explain the etiology and ... more 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. 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 ...
Orthopaedics & traumatology, surgery & research : OTSR, Jan 19, 2017
Blood loss is a major concern in total knee arthroplasty (TKA) along with postoperative knee func... more Blood loss is a major concern in total knee arthroplasty (TKA) along with postoperative knee function. The present study explores the impact of tourniquet (T) and closed-suction drains (D) on these parameters in TKA. A prospective study was conducted on 111 patients admitted for TKA. Subjects were divided into three groups: 36 in group T+D+, 42 in T-D+ and 33 in T-D- (where T+: prolonged tourniquet use, T-: cementation-only tourniquet, D+: closed-suction drain use, and D-: no drain). No statistically significant differences were observed among the three groups(T+D+, T-D+ and T-D-) for total blood lost, hemoglobin levels over the first six postoperative weeks and blood transfusion rates. Intraoperative bleeding was significantly reduced in T+ subjects compared to T- subjects (100±88mL vs. 279±235mL respectively, p<0.001), yet length of surgery was unaffected. Hidden blood loss was lower in D+ subjects compared to D- subjects (1161±554mL vs. 1667±554mL respectively, p<0.001), bu...
Proceedings of Meetings on Acoustics, 2015
Journal of Biomaterials Science, Polymer Edition, 2016
Inflammation research : official journal of the European Histamine Research Society ... [et al.], Jan 7, 2016
Resolvin D1 (RvD1), an omega-3 fatty acid derivative, has shown remarkable properties in resolvin... more 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. Human OA chondrocytes were treated with either 1 ng/ml interleukin-1β (IL-1β) 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 kinas...
Journal of Cellular Biochemistry, Jul 1, 2012
Nitric oxide (NO) and the lipid peroxidation (LPO) product 4-hydroxynonenal (HNE) are considered ... more Nitric oxide (NO) and the lipid peroxidation (LPO) product 4-hydroxynonenal (HNE) are considered to be key mediators of cartilage destruction in osteoarthritis (OA). NO is also known to be an important intermediary in LPO initiation through peroxynitrite formation. The aim of the present study was to assess the ability of the inducible NO synthase (iNOS) inhibitor N-iminoethyl-L-lysine (L-NIL) to prevent HNE generation via NO suppression in human OA chondrocytes and cartilage explants. Human OA chondrocytes and cartilage explants were treated with L-NIL and thereafter with or without interleukin-1beta (IL-1β) or HNE at cytotoxic or non-cytotoxic concentrations. Parameters related to oxidative stress, apoptosis, inflammation, and catabolism were investigated. L-NIL stifled IL-1β-induced NO release, iNOS activity, nitrated proteins, and HNE generation in a dose-dependent manner. It also blocked IL-1β-induced inactivation of the HNE-metabolizing glutathione-s-transferase (GST). L-NIL r...
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Papers by Julio Fernandes