PeerJ Preprints: Rheumatologyhttps://peerj.com/preprints/index.atom?journal=peerj&subject=6800Rheumatology articles published in PeerJ PreprintsDetection of linear features including bone and skin areas in ultrasound images of jointshttps://peerj.com/preprints/35192018-01-102018-01-10Artur BąkJakub SegenKamil WereszczyńskiPawel MielnikMarcin FojcikMarek Kulbacki
Identifying the separate parts in ultrasound images such as bone and skin plays the crucial role in synovitis detection task. This paper presents a detector of bone and skin regions in the form of a classifier which is trained on a set of annotated images. Selected regions have labels: skin or bone or none. Feature vectors used by the classifier are assigned to image pixels as a result of passing the image through the bank of linear and nonlinear filters. The filters include Gaussian blurring filter, its first and second order derivatives, Laplacian as well as positive and negative threshold operations applied to the filtered images. We compared multiple supervised learning classifiers including Naive Bayes, k-Nearest Neighbour, Decision Trees, Random Forest, AdaBoost and Support Vector Machines (SVM) with various kernels, using four classification performance scores and computation time. The Random Forest classifier was selected for the final use, as it gives the best overall evaluation results.
Identifying the separate parts in ultrasound images such as bone and skin plays the crucial role in synovitis detection task. This paper presents a detector of bone and skin regions in the form of a classifier which is trained on a set of annotated images. Selected regions have labels: skin or bone or none. Feature vectors used by the classifier are assigned to image pixels as a result of passing the image through the bank of linear and nonlinear filters. The filters include Gaussian blurring filter, its first and second order derivatives, Laplacian as well as positive and negative threshold operations applied to the filtered images. We compared multiple supervised learning classifiers including Naive Bayes, k-Nearest Neighbour, Decision Trees, Random Forest, AdaBoost and Support Vector Machines (SVM) with various kernels, using four classification performance scores and computation time. The Random Forest classifier was selected for the final use, as it gives the best overall evaluation results.Osmotic pressure characterization of glycosaminoglycans using full-atomistic molecular modelshttps://peerj.com/preprints/30632017-07-012017-07-01Alejandro PandoFederica RigoldiSimone Vesentini
The osmotic pressure of chondroitin sulfate glycosaminoglycans (CS-GAGs) in a simulated physiological environment of articular cartilage is thoroughly examined in silico using full atomistic models. The effects of chemical and physical properties were investigated to elucidate the molecular origins of cartilage biomechanical behavior providing single-atomistic resolution analyses which would not be attainable with in vivo or in in vitro techniques. CS-GAG chains exhibit plastic deformation behavior under compressive load in the extracellular matrix (ECM) and osmotic pressure is the main contributor in balancing external pressures. This study focuses on quantitatively expressing this contribution. Molecular dynamics was used to imitate the physiological environment experienced by GAGs inside articular cartilage by simulating a semipermeable membrane acting on the full atomistic chains during compression. To this end, a variety of validation techniques, pre-simulation tasks, and comparisons were conducted to validate the test methodology. CS-GAGs with varying lengths and sulfation positions underwent simulation under varying molar concentrations. Sulfation positioning is found to have negligible influence on GAG osmotic pressure behavior; attributed to the small distance between the position of 4- and 6- sulfation relative to the intermolecular spacing between the CS chains. However, differences between sulfated and unsulfated chains did have a significant influence on osmotic pressure. Length of disaccharides was also found to have a significant contribution to osmotic pressure. Measurements are comparable to previous coarse grained studies and experimental data.
The osmotic pressure of chondroitin sulfate glycosaminoglycans (CS-GAGs) in a simulated physiological environment of articular cartilage is thoroughly examined in silico using full atomistic models. The effects of chemical and physical properties were investigated to elucidate the molecular origins of cartilage biomechanical behavior providing single-atomistic resolution analyses which would not be attainable with in vivo or in in vitro techniques. CS-GAG chains exhibit plastic deformation behavior under compressive load in the extracellular matrix (ECM) and osmotic pressure is the main contributor in balancing external pressures. This study focuses on quantitatively expressing this contribution. Molecular dynamics was used to imitate the physiological environment experienced by GAGs inside articular cartilage by simulating a semipermeable membrane acting on the full atomistic chains during compression. To this end, a variety of validation techniques, pre-simulation tasks, and comparisons were conducted to validate the test methodology. CS-GAGs with varying lengths and sulfation positions underwent simulation under varying molar concentrations. Sulfation positioning is found to have negligible influence on GAG osmotic pressure behavior; attributed to the small distance between the position of 4- and 6- sulfation relative to the intermolecular spacing between the CS chains. However, differences between sulfated and unsulfated chains did have a significant influence on osmotic pressure. Length of disaccharides was also found to have a significant contribution to osmotic pressure. Measurements are comparable to previous coarse grained studies and experimental data.Functional and spinal neuropeptidomic alterations in a new rat surgical model of osteoarthritic pain: A pilot studyhttps://peerj.com/preprints/27042017-01-062017-01-06Julie-Anne GervaisColombe OtisBertrand LussierMartin GuillotFrancis BeaudryEric Troncy
Background. Osteoarthritis is the leading cause of chronic joint pain, causing important productivity and economic losses. It is believed that peripheral and centralized sensitization play a role in the creation and maintenance of a chronic painful state. Different animal models have been employed for the investigation of pain mechanisms and evaluation of potential treatments, but none of them are ideal in terms of reproducibly, reliability and translational value. Methods. In the search for better animal model, this pilot study was performed with the goal of evaluating pain functional outcomes and spinal biomarkers between three surgical rat models of osteoarthritic pain, i.e. destabilization of the medial meniscus, cranial cruciate ligament transection and the combination of both, and comparing those results to the intra-articular injection of monosodium iodoacetate. Six rats were assigned to each model group and a Sham group. Static weight bearing, punctate tactile paw withdrawal threshold, and spinal neuropeptides (substance P, calcitonin gene-related peptide, bradykinin, and somatostatin) were evaluated for each group. Results. Both the monosodium iodoacetate and combination models induced functional alterations in static weight bearing and punctate tactile paw withdrawal threshold, the changes being more persistent in the combination group. Both also produced an increased release of pro-nociceptive and anti-nociceptive neuropeptides at different time-points. When surgical models were compared, the cranial cruciate ligament transection and destabilization of the medial meniscus models were less interesting, with temporary functional alterations, and no significant change in neuropeptides. Discussion. The surgical induction of osteoarthritis was accompanied by quantifiable neurophysiologic changes relating to non-physiologic pain. Comparison with the monosodium iodoacetate model showed that the interest of a surgical model, especially the combination of destabilization of the medial meniscus and cranial cruciate ligament transection, might reside in more persistent and progressive changes, a model that may represent better the human post-traumatic osteoarthritis.
Background. Osteoarthritis is the leading cause of chronic joint pain, causing important productivity and economic losses. It is believed that peripheral and centralized sensitization play a role in the creation and maintenance of a chronic painful state. Different animal models have been employed for the investigation of pain mechanisms and evaluation of potential treatments, but none of them are ideal in terms of reproducibly, reliability and translational value. Methods. In the search for better animal model, this pilot study was performed with the goal of evaluating pain functional outcomes and spinal biomarkers between three surgical rat models of osteoarthritic pain, i.e. destabilization of the medial meniscus, cranial cruciate ligament transection and the combination of both, and comparing those results to the intra-articular injection of monosodium iodoacetate. Six rats were assigned to each model group and a Sham group. Static weight bearing, punctate tactile paw withdrawal threshold, and spinal neuropeptides (substance P, calcitonin gene-related peptide, bradykinin, and somatostatin) were evaluated for each group. Results. Both the monosodium iodoacetate and combination models induced functional alterations in static weight bearing and punctate tactile paw withdrawal threshold, the changes being more persistent in the combination group. Both also produced an increased release of pro-nociceptive and anti-nociceptive neuropeptides at different time-points. When surgical models were compared, the cranial cruciate ligament transection and destabilization of the medial meniscus models were less interesting, with temporary functional alterations, and no significant change in neuropeptides. Discussion. The surgical induction of osteoarthritis was accompanied by quantifiable neurophysiologic changes relating to non-physiologic pain. Comparison with the monosodium iodoacetate model showed that the interest of a surgical model, especially the combination of destabilization of the medial meniscus and cranial cruciate ligament transection, might reside in more persistent and progressive changes, a model that may represent better the human post-traumatic osteoarthritis.Mechano-adaptation of bone: Are all strains equal?https://peerj.com/preprints/18472016-03-092016-03-09Jörn Rittweger
Bone research has been re-directed in the 1990s by three revolutions: firstly the recognition that bones respond to changes in their mechanical environment in a dose-dependent way; secondly by the idea that these changes in bone size can be understood as self-adaptation to variant forces by a servo-control mechanism (mechanostat theory); and thirdly by the proposition that muscles ‘enslave’ bone’s mechan-adaptation. It has been an inherent assumption in most of these bone studies that bone deformations mostly result from bending and compression, and little to no attention was paid to torsional loading. Notably, axial strains dominate in axial loading, whilst torsional loading is associated with relatively large shear strains. To better understand the mechanical interplay between regional muscle contractions and bone deformations, my team performed the MUST-study: bone pins were inserted into the human tibia, and non-collinear retro-reflective marker clusters were affixed to these pins in order to assess translational and rotational tibia deformations. Results from that study revealed that torsion is a prevailing deformation type within the human tibia, and that tibia torsion is causally linked to calf muscle contractions. Simultaneously, a series of in-silico experiments in our lab with a mechanostat model were undertaken. They revealed that torsion (i) is the most effective mode of bone deformation, and (ii) that it can explain the so-called flexure neutralization of miss-aligned fractures, which is inexplicable on grounds of compression and bending alone. Moreover, recent data also suggest that torsion, rather than impact may the bone-effective agent in the side-differences encountered in tennis players and baseball pitchers. Thus, I am currently following the idea of torsion as an effective deformation mode to elicit bone-anabolic responses. This is in contradiction to the main stream in bone research, which still regards impact loading as the most efficient way. Understanding and settling this question will be important in order to provide optimized exercise prescriptions that will maximize the benefits for bone, and minimize adverse events, such as joint sprains, cartilage damage, and tendon problems.
Bone research has been re-directed in the 1990s by three revolutions: firstly the recognition that bones respond to changes in their mechanical environment in a dose-dependent way; secondly by the idea that these changes in bone size can be understood as self-adaptation to variant forces by a servo-control mechanism (mechanostat theory); and thirdly by the proposition that muscles ‘enslave’ bone’s mechan-adaptation. It has been an inherent assumption in most of these bone studies that bone deformations mostly result from bending and compression, and little to no attention was paid to torsional loading. Notably, axial strains dominate in axial loading, whilst torsional loading is associated with relatively large shear strains. To better understand the mechanical interplay between regional muscle contractions and bone deformations, my team performed the MUST-study: bone pins were inserted into the human tibia, and non-collinear retro-reflective marker clusters were affixed to these pins in order to assess translational and rotational tibia deformations. Results from that study revealed that torsion is a prevailing deformation type within the human tibia, and that tibia torsion is causally linked to calf muscle contractions. Simultaneously, a series of in-silico experiments in our lab with a mechanostat model were undertaken. They revealed that torsion (i) is the most effective mode of bone deformation, and (ii) that it can explain the so-called flexure neutralization of miss-aligned fractures, which is inexplicable on grounds of compression and bending alone. Moreover, recent data also suggest that torsion, rather than impact may the bone-effective agent in the side-differences encountered in tennis players and baseball pitchers. Thus, I am currently following the idea of torsion as an effective deformation mode to elicit bone-anabolic responses. This is in contradiction to the main stream in bone research, which still regards impact loading as the most efficient way. Understanding and settling this question will be important in order to provide optimized exercise prescriptions that will maximize the benefits for bone, and minimize adverse events, such as joint sprains, cartilage damage, and tendon problems.Staphylococcus Aureus carriage and long-term Rituximab treatment for Granulomatosis with polyangiitishttps://peerj.com/preprints/9722015-04-102015-04-10Emilio BesadaWenche KoldingsnesJohannes C Nossent
Objective: Chronic nasal carriage of Staphylococcus aureus (SA) increases the risk of relapse while Rituximab (RTX) is an effective agent for inducing and maintaining remission in patients with Granulomatosis with polyangiitis (GPA). We investigated whether B cell depletion and hypogammaglobulinemia that occur during RTX treatment increase the risk of chronic SA nasal carriage and subsequent disease flares, in GPA patients on long-term RTX maintenance therapy. Methods: Retrospective cohort study from a disease registry involving 29 GPA patients receiving RTX maintenance (median RTX dose of 9 g) during a median period of 49 months. Nasal swabs were collected prior and during RTX for a median of 3 and 9 swabs respectively. Persistent SA nasal carriage was defined with the presence of SA in more than 75 % of nasal swabs. Results: SA nasal carriage did not change during RTX (p=0.297). Persistent SA nasal carriage did not increase the risk of relapses (p=0.844) and of severe infections (p=0.144), but reduced the risk of chronic infections (p=0.044). Non-SA carriers were more prone to discontinue RTX due to hypogammaglobulinemia (p=0.122), since they had more profound decline of serum total Ig both after the first 2 g of RTX (p=0.079) and during RTX maintenance (p=0.063). Conclusion: Long-term RTX maintenance therapy in GPA patients did not significantly influence SA nasal carriage status. Persistent SA carriage during long-term RTX treatment did not increase the risk of relapses and was associated with a lower risk of hypogammaglobulinemia associated chronic infections.
Objective: Chronic nasal carriage of Staphylococcus aureus (SA) increases the risk of relapse while Rituximab (RTX) is an effective agent for inducing and maintaining remission in patients with Granulomatosis with polyangiitis (GPA). We investigated whether B cell depletion and hypogammaglobulinemia that occur during RTX treatment increase the risk of chronic SA nasal carriage and subsequent disease flares, in GPA patients on long-term RTX maintenance therapy. Methods: Retrospective cohort study from a disease registry involving 29 GPA patients receiving RTX maintenance (median RTX dose of 9 g) during a median period of 49 months. Nasal swabs were collected prior and during RTX for a median of 3 and 9 swabs respectively. Persistent SA nasal carriage was defined with the presence of SA in more than 75 % of nasal swabs. Results: SA nasal carriage did not change during RTX (p=0.297). Persistent SA nasal carriage did not increase the risk of relapses (p=0.844) and of severe infections (p=0.144), but reduced the risk of chronic infections (p=0.044). Non-SA carriers were more prone to discontinue RTX due to hypogammaglobulinemia (p=0.122), since they had more profound decline of serum total Ig both after the first 2 g of RTX (p=0.079) and during RTX maintenance (p=0.063). Conclusion: Long-term RTX maintenance therapy in GPA patients did not significantly influence SA nasal carriage status. Persistent SA carriage during long-term RTX treatment did not increase the risk of relapses and was associated with a lower risk of hypogammaglobulinemia associated chronic infections.Pneumocystis jiroveci pneumonia prophylaxis is a challenge in granulomatosis with polyangiitis patients treated with rituximab.https://peerj.com/preprints/149v12013-12-112013-12-11Emilio Besada
All strategies to prevent Pneumocystis jiroveci pneumonia (PCP) during rituximab treatment have their rationale in patients with granulomatosis with polyangiitis (GPA) and to some extent in patients with other autoimmune diseases (AID). Risk factors of PCP and severe infections are very similar in GPA patients. The decision of PCP prophylaxis should not be limited at RTX initiation and during RTX treatment, but should be reassessed continuously in all GPA patients. Since PCP increases the mortality risk in GPA (and AID) patients, the treating physician should always consider PCP as a possible diagnosis in patients treated with RTX - receiving or not PCP prophylaxis.
All strategies to prevent Pneumocystis jiroveci pneumonia (PCP) during rituximab treatment have their rationale in patients with granulomatosis with polyangiitis (GPA) and to some extent in patients with other autoimmune diseases (AID). Risk factors of PCP and severe infections are very similar in GPA patients. The decision of PCP prophylaxis should not be limited at RTX initiation and during RTX treatment, but should be reassessed continuously in all GPA patients. Since PCP increases the mortality risk in GPA (and AID) patients, the treating physician should always consider PCP as a possible diagnosis in patients treated with RTX - receiving or not PCP prophylaxis.