Exploring SARS-CoV-2 infection and vaccine-induced immunity in chronic myeloid leukemia patients: insights from real-world data in Brazil and the United States.

This study investigates COVID-19 outcomes and immune response in chronic myeloid leukemia (CML) patients post-SARS-CoV-2 vaccination, comparing effectiveness of various vaccine options. Data from 118 CML patients (85 in Brazil, 33 in the US) showed similar infection rates prior (14% Brazil, 9.1% US) and post-vaccination (24.7% vs. 27.3%, respectively). In Brazil, AstraZeneca and CoronaVac were the most commonly used vaccine brands, while in the US, Moderna and Pfizer-BioNTech vaccines dominated. Despite lower seroconversion in the Brazilian cohort, all five vaccine brands analyzed prevented severe COVID-19. Patients who received mRNA and recombinant viral vector vaccines (HR: 2.20; 95%CI 1.07-4.51; p < .031) and those that had achieved at least major molecular response (HR: 1.51; 95% CI 1.01-3.31; p < .0001) showed higher seroconversion rates. Our findings suggest that CML patients can generate antibody responses regardless of the vaccine brand, thereby mitigating severe COVID-19. This effect is more pronounced in patients with well-controlled disease.

An update on stem cell and stem cell-derived extracellular vesicle-based therapy in the management of Alzheimer's disease.

Globally, neurological diseases pose a major burden to healthcare professionals in terms of the management and prevention of the disorder. Among neurological diseases, Alzheimer's disease (AD) accounts for 50%-70% of dementia and is the fifth leading cause of mortality worldwide. AD is a progressive, degenerative neurological disease, with the loss of neurons and synapses in the cerebral cortex and subcortical regions. The management of AD remains a debate among physicians as no standard and specific "disease-modifying" modality is available. The concept of 'Regenerative Medicine' is aimed at regenerating the degenerated neural tissues to reverse the pathology in AD. Genetically modified engineered stem cells modify the course of AD after transplantation into the brain. Extracellular vesicles (EVs) are an emerging new approach in cell communication that involves the transfer of cellular materials from parental cells to recipient cells, resulting in changes at the molecular and signaling levels in the recipient cells. EVs are a type of vesicle that can be transported between cells. Many have proposed that EVs produced from mesenchymal stem cells (MSCs) may have therapeutic promise in the treatment of AD. The biology of AD, as well as the potential applications of stem cells and their derived EVs-based therapy, were explored in this paper.

Correlations between within-subject variability of pain intensity reports and rubber hand illusion proprioceptive drift.

INTRODUCTION: Consistent with the Bayesian brain hypothesis, the within-subject variability of pain intensity reports as captured with the Focused Analgesia Selection Test (FAST) might be a surrogate measure of the certainty in ascending noxious signals. The outcomes of a non-pain-related task, the rubber hand illusion, were hypothesized to reflect the same construct. This study aimed to explore whether within-subject differences in variability of pain intensity reports and the outcomes of the rubber hand illusion might be related. METHODS: Nonclinical participants underwent the classic rubber hand illusion under synchronous (experimental) and asynchronous (control) conditions. Two outcomes were assessed: proprioceptive drift and feeling of ownership. Thereafter, participants underwent the FAST to assess the within-subject variability of pain reports in response to heat stimuli. Intraclass correlation (ICC) and the correlation coefficient (R2) were the main outcomes. Spearman's correlations were used to assess associations between the outcomes of the 2 tasks. RESULTS: Thirty-six volunteers completed the study. Both FAST outcomes-ICC (Spearman's r = 0.355, p = 0.033) and R2 (Spearman's r = 0.349, p = 0.037)-were positively correlated with proprioceptive drift in the synchronous but not asynchronous conditions (p > 0.05). The subjective feeling of ownership and FAST outcomes did not correlate (p > 0.05). CONCLUSIONS: The associations between the 2 tasks' outcomes imply that both tasks at least partly assess similar constructs. Current knowledge suggests that this construct represents the person's certainty in perceiving ascending sensory signals, or, in Bayesian terminology, the certainty of the likelihood.

Intra-Articular Hyaluronic Acid in Osteoarthritis and Tendinopathies: Molecular and Clinical Approaches.

Musculoskeletal diseases continue to rise on a global scale, causing significant socioeconomic impact and decreased quality of life. The most common disorders affecting musculoskeletal structures are osteoarthritis and tendinopathies, complicated orthopedic conditions responsible for major pain and debilitation. Intra-articular hyaluronic acid (HA) has been a safe, effective, and minimally invasive therapeutic tool for treating these diseases. Several studies from bedside to clinical practice reveal the multiple benefits of HA such as lubrication, anti-inflammation, and stimulation of cellular activity associated with proliferation, differentiation, migration, and secretion of additional molecules. Collectively, these effects have demonstrated positive outcomes that assist in the regeneration of chondral and tendinous tissues which are otherwise destroyed by the predominant catabolic and inflammatory conditions seen in tissue injury. The literature describes the physicochemical, mechanical, and biological properties of HA, their commercial product types, and clinical applications individually, while their interfaces are seldom reported. Our review addresses the frontiers of basic sciences, products, and clinical approaches. It provides physicians with a better understanding of the boundaries between the processes that lead to diseases, the molecular mechanisms that contribute to tissue repair, and the benefits of the HA types for a conscientious choice. In addition, it points out the current needs for the treatments.

Bone Marrow Aspirate Concentrate Improves Outcomes in Adults With Osteochondral Dissecans of the Talus and Achilles Rupture.

PURPOSE: The objective of this systematic literature review was to investigate the effects of the clinical application of bone marrow aspirate (BMA) and/or bone marrow aspirate concentrate (BMAC) in tendon and cartilage injuries in the foot and ankle. METHODS: A search of the Embase, MEDLINE/PubMed, CINAHL, and Cochrane databases was performed in January 2021. The risk of bias of the studies was assessed using the tool "A Cochrane Risk of Bias Assessment Tool for Non-Randomized Studies." The outcomes analyzed included pain reduction and functional improvement with the use of BMA/BMAC in patients with tendon and cartilage injuries in the foot and ankle. RESULTS: Eleven studies met the inclusion criteria for analysis, involving a total of 527 subjects with osteochondral lesions (OCLs) of the talus, cartilage lesions of the talus, and acute Achilles tendon rupture. BMAC was applied alone in 4 studies, and in 7 studies, it was compared with other techniques such as matrix-induced autologous chondrocyte implantation, particulate juvenile articular cartilage, or microfracture. Interventions demonstrated improved function and reduced foot and ankle pain and showed no serious adverse effects. CONCLUSIONS: Evidence indicates that BMAC provides good clinical results, with improved function and reduced pain in adults with OCL and cartilage lesions of the talus and acute Achilles tendon rupture. LEVEL OF EVIDENCE: Level IV, systematic review of level II to IV studies.

Platelet-Rich Plasma Gel Matrix (PRP-GM): Description of a New Technique.

Several musculoskeletal conditions are triggered by inflammatory processes that occur along with imbalances between anabolic and catabolic events. Platelet-rich plasma (PRP) is an autologous product derived from peripheral blood with inherent immunomodulatory and anabolic properties. The clinical efficacy of PRP has been evaluated in several musculoskeletal conditions, including osteoarthritis, tendinopathy, and osteonecrosis. When used in combination with hyaluronic acid (HA), a common treatment alternative, the regenerative properties of PRP are significantly enhanced and may provide additional benefits in terms of clinical outcomes. Recently, a new PRP-derived product has been reported in the literature and is being referred to as "plasma gel". Plasma gels are obtained by polymerizing plasmatic proteins, which form solid thermal aggregates cross-linked with fibrin networks. Plasma gels are considered to be a rich source of growth factors and provide chemotactic, migratory, and proliferative properties. Additionally, clot formation and the associated fibrinolytic reactions play an additional role in tissue repair. There are only a few scientific articles focusing on plasma gels. Historically, they have been utilized in the fields of aesthetics and dentistry. Given that the combination of three products (PRP, HA, and plasma gel) could enhance tissue repair and wound healing, in this technical note, we propose a novel regenerative approach, named "PRP-HA cellular gel matrix" (PRP-GM), in which leukocyte-rich PRP (LR-PRP) is mixed with a plasma gel (obtained by heating the plasma up) and HA in one syringe using a three-way stopcock. The final product contains a fibrin-albumin network entangled with HA's polymers, in which the cells and biomolecules derived from PRP are attached and released gradually as fibrinolytic reactions and hyaluronic acid degradation occur. The presence of leukocytes, especially monocytes and macrophages, promotes tissue regeneration, as type 2 macrophages (M2) possess an anti-inflammatory feature. In addition, HA promotes the viscosuplementation of the joint and induces an anti-inflammatory response, resulting in pain relief. This unique combination of biological molecules may contribute to the optimization of regenerative protocols suitable for the treatment of degenerative musculoskeletal diseases.

Full Recovery from O'Donoghue's Triad with Autologous Bone Marrow Aspirate Matrix: A Case Report.

O'Donoghue's triad is an extremely debilitating condition. Although there are many conventional treatments available, there is still no consensus regarding the most effective rehabilitation protocol for a full recovery. Surgical interventions have become an ordinary consideration, but problems may still persist even after the surgical procedure. Orthobiologics, however, have gained considerable popularity in regenerative medicine. Notable autologous alternatives, such as bone marrow aspirate (BMA), are often utilized in clinical settings. To our knowledge, the administration of BMA products for the management of O'Donoghue's triad has not been thoroughly investigated in the literature. In this case report we describe a full recovery from O'Donoghue's triad with BMA matrix in a patient who was recalcitrant to surgical intervention due to fear of complications. Our patient received three BMA matrix injections with four-week intervals, exhibiting significant recovery according to pain scores, functional assessment outcomes, and magnetic resonance imaging (MRI) results. The patient returned to normal activities with no complaints and MRI evidence at follow-up showed significant signs of structural restoration of the musculoskeletal tissues. Here, we demonstrate that autologous BMA products are a feasible alternative for the accelerated recovery of musculoskeletal tissue injury with safety and efficacy.

Performance of indirect immunofluorescence test and immunoblot tests in the evaluation of antinuclear and antimitochondrial antibodies.

BACKGROUND: Antinuclear antibodies (ANA) and antimitochondrial antibodies (AMA) have essential markers for the diagnosis of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). These autoantibodies are detecting different laboratory methods. In this study, we studied the diagnostic performance of used methods in detecting ANA and AMA. METHODS: The autoantibody profiles of patients with AIH and PBC groups were analyzed with the indirect immunofluorescence test (IIF) and liver-specific antigens containing immunoblot test (IB). RESULTS: There were 45 (87%) women in the study group and 8 (53%) women in the control group. The mean age of the patients was 50.5 ± 14.21 years old. The serum ALT and AST levels were higher in AIH, and ALP, GGT, and Ig M were higher in PBC. IIF test results among AIH/PBC groups; there was no difference in overall ANA positivity (p: 0.078). AMA was negative in all patients with AIH but positive in 83.3% of patients with PBC. IB test results among AIH/PBC groups; antibodies against PDGH, LKM-1, and Scl-70 were not observed in any patient with AIH/PBC. Except for M2 (p: 0.001) and M23E (p: 0.007) antibodies, there was no significant difference in antibodies between groups. Out of five PBC patients with negative AMA by IIF method, one was positive for AMA-M2, two were positive anti-gp210, and three were positive anti-M2-3E, but anti-sp100 was negative in all of them by the IB. DISCUSSION: AIH/PBC has complex associations with different autoantibodies, and some of these antibodies are not readily detected by the IIF test. IB assays with a wide variety of liver-specific antigens may be helpful in the diagnosis (especially in patients with AMA negative PBC) and follow-up in AIH/PBC patients.

The Mechanism of Action between Pulsed Radiofrequency and Orthobiologics: Is There a Synergistic Effect?

Radiofrequency energy is a common treatment modality for chronic pain. While there are different forms of radiofrequency-based therapeutics, the common concept is the generation of an electromagnetic field in the applied area, that can result in neuromodulation (pulsed radiofrequency-PRF) or ablation. Our specific focus relates to PRF due to the possibility of modulation that is in accordance with the mechanisms of action of orthobiologics. The proposed mechanism of action of PRF pertaining to pain relief relies on a decrease in pro-inflammatory cytokines, an increase in cytosolic calcium concentration, a general effect on the immune system, and a reduction in the formation of free radical molecules. The primary known properties of orthobiologics constitute the release of growth factors, a stimulus for endogenous repair, analgesia, and improvement of the function of the injured area. In this review, we described the mechanism of action of both treatments and pertinent scientific references to the use of the combination of PRF and orthobiologics. Our hypothesis is a synergic effect with the combination of both techniques which could benefit patients and improve the life quality.

Stromal Vascular Fraction for Knee Osteoarthritis - An Update.

Orthobiologics never cease to cause popularity within the medical science field, distinctly in regenerative medicine. Recently, adipose tissue has been an object of interest for many researchers and medical experts due to the fact that it represents a novel and potential cell source for tissue engineering and regenerative medicine purposes. Stromal vascular fraction (SVF), for instance, which is an adipose tissue-derivative, has generated optimistic results in many scenarios. Its biological potential can be harnessed and administered into injured tissues, particularly areas in which standard healing is disrupted. This is a typical feature of osteoarthritis (OA), a common degenerative joint disease which is outlined by persistent inflammation and destruction of surrounding tissues. SVF is known to carry a large amount of stem and progenitor cells, which are able to perform self-renewal, differentiation, and proliferation. Furthermore, they also secrete several cytokines and several growth factors, effectively sustaining immune modulatory effects and halting the escalated pro-inflammatory status of OA. Although SVF has shown interesting results throughout the medical community, additional research is still highly desirable in order to further elucidate its potential regarding musculoskeletal disorders, especially OA.

Application of Sygen® in Diabetic Peripheral Neuropathies-A Review of Biological Interactions.

This study investigates the role of Sygen® in diabetic peripheral neuropathy, a severe disease that affects the peripheral nervous system in diabetic individuals. This disorder often impacts the lower limbs, causing significant discomfort and, if left untreated, progresses into more serious conditions involving chronic ulcers and even amputation in many cases. Although there are management strategies available, peripheral neuropathies are difficult to treat as they often present multiple causes, especially due to metabolic dysfunction in diabetic individuals. Gangliosides, however, have long been studied and appreciated for their role in neurological diseases. The monosialotetrahexosylganglioside (GM1) ganglioside, popularly known as Sygen, provides beneficial effects such as enhanced neuritic sprouting, neurotrophism, neuroprotection, anti-apoptosis, and anti-excitotoxic activity, being particularly useful in the treatment of neurological complications that arise from diabetes. This product mimics the roles displayed by neurotrophins, improving neuronal function and immunomodulation by attenuating exacerbated inflammation in neurons. Furthermore, Sygen assists in axonal stabilization and keeps nodal and paranodal regions of myelin fibers organized. This maintains an adequate propagation of action potentials and restores standard peripheral nerve function. Given the multifactorial nature of this complicated disorder, medical practitioners must carefully screen the patient to avoid confusion and misdiagnosis. There are several studies analyzing the role of Sygen in neurological disorders. However, the medical literature still needs more robust investigations such as randomized clinical trials regarding the administration of this compound for diabetic peripheral neuropathies, specifically.

First report of root knot nematodes Meloidogyne incognita and M. javanica parasitizing sweet potato, Ipomoea batatas L., in Portugal.

Sweet potato, Ipomoea batatas L., is a tuberous root vegetable rich in low glycemic sugars, vitamins and fibers (Galvão et al., 2021). Although it is widely cropped and consumed in tropical regions, in Europe consumer demand is growing exponentially (CBI, 2021). In Portugal, the production area of sweet potato increased from 588 ha in 2011 to 954 ha in 2017, and exports increased from 2404 tons in 2011 to 13412 tons in 2019 (FAOSTAT, 2021). During a survey carried out in August 2019, sweet potato plants were collected in Almada (38°39'40"N 9°10'54"W) and Belmonte (38°39'40"N 9°10'54"W), South and Centre regions of Portugal, respectively. No symptoms were observed on leaves, however, roots presented numerous galls and/or small spots (females and respective egg masses) were observed in the tuberous root flesh, suggestive of root knot nematodes (RKN, Meloidogyne spp.) infection. At least 8 individual females and respective egg masses were handpicked from roots of each sample and characterized biochemically by electrophoretic analysis of esterases (Pais & Abrantes, 1989). Phenotypes I2 and J3, attributed to M. incognita and M. javanica, respectively, were present in samples from Almada, whereas only phenotype I2 was found from Belmonte sample (Santos et al., 2019). Pure RKN cultures were established on tomato cv. Coração-de-Boi to obtain inoculum for molecular characterization and host suitability assays. Molecular characterization was performed by DNA amplification with M. incognita (Mi-F/Mi-R) and M. javanica (Fjav/Rjav) species-specific primers (Zijlstra et al., 2000; Meng et al., 2004). DNA amplification resulted in unique bands of ≈900 bp and ≈650 bp, respectively, confirming the RKN species identification. The host suitability of sweet potato cvs. Lira (local variety, purple skin, yellow flesh) and Murasaki (purple skin, white/pale to yellow flesh) to M. javanica (Almada) and M. incognita (Belmonte) isolates was assessed. Sweet potato slips with ≈10 cm roots were transplanted to 500 cm3 pots (one slip/pot) and after 2 weeks, each plant was inoculated with 5000 eggs + second-stage juveniles (Pi, initial population density) and maintained in a growth chamber (25±2°C; 12:12 h photoperiod). Tomato cv. Coração-de-Boi was included as a positive control. Each RKN species-plant germplasm combination was repeated 6 times. At 60 days after inoculation, host suitability was evaluated on the basis of root gall index (GI) and reproduction factor (Rf=final population density/Pi) (Sasser et al., 1984). Sweet potato cv. Lira was susceptible (GI=5; Rf=111.8) to M. incognita and resistant (GI=2; Rf=0.11) to M. javanica; while cv. Murasaki was hypersusceptible (GI=5; Rf=0.9) to M. incognita and susceptible (GI=5; Rf=5.5) to M. javanica. Although cultivars varied in their response to M. incognita and M. javanica isolates and variation in the final population density was high, both RKN isolates reproduced in these sweet potato cultivars. In previous studies, cv. Murasaki was considered resistant to M. enterolobii and to M. incognita (La Bonte et al. 2008; Schwarz et al., 2021). Depending on the RKN species, cultivation of cvs. Murasaki and Lira may thus benefit succeeding crops, but they should be combined with other management strategies to further reduce RKN populations in the field. In Portugal, M. incognita and M. javanica have been found associated with economically important horticultural crops, such as tomato and potato, trees and weeds (Santos et al., 2019; Maleita et al., 2021). To our knowledge, these species are reported for the first time parasitizing sweet potato in Portugal and this is the first report on the occurrence of M. incognita and M. javanica infecting sweet potato in Europe. Although findings were not totally unexpected due to the wide distribution and host range of these RKN species, they are of crucial importance since the sweet potato production in Europe has almost doubled from 50 (2011) to 97 thousand tons (2017), with Spain, Portugal, Italy and Greece being the largest producers (FAO, 2021). Our findings also reveal that sweet potato cropped in Portugal have different susceptibility levels to these common RKN species, reinforcing the importance of cultivar selection in RKN management.

Conversion of peach endocarp and polyethylene residue by the co-pyrolysis process.

The south of Brazil has a high production of peaches which generates the stone as residue. The recycling of biomass and plastic waste is a challenge that must be overcome. Therefore, co-pyrolysis emerges as a possibility for joint conversion of peach stone and plastic bags into value-added products. Thus, the objective is to obtain new products, emphasizing the organic fraction of the bio-oil obtained under the best experimental conditions, and to characterize it by GC-MS. The experiments provided a three-phase bio-oil: two organic phases with different densities and an aqueous phase. It was observed that the central point experiment (temperature at 500 °C and blend composition, % peach stone/polyethylene, 80/20) generated the highest yield of bio-oil. However, the experiment at the lowest temperature and with greater addition of plastic waste produced a higher organic fraction. Using gas chromatography, 161 chemical compounds were identified in the denser organic phase, emphasizing the phenols. In the lighter organic fraction, hydrocarbons were the majority among the 70 compounds identified. The results suggest that the interaction between biomass and polyethylene influences the characteristics of the products obtained, since polyethylene acts as dispersant and as hydrogen donor. Co-pyrolysis, in this research, proves to be efficient and viable, allowing the joint destination of those environmental liabilities.

Silicon supplied via foliar application and root to attenuate potassium deficiency in common bean plants.

Potassium (K) deficiency affects physiological performance and decreases vegetative growth in common bean plants. Although silicon (Si) supplied via nutrient solution or foliar application may alleviate nutritional stress, research on the bean crop is incipient. Thus, two experiments were carried out: initially, a test was performed to determine the best source and foliar concentration of silicon. Subsequently, the chosen Si source was supplied in nutrient solution via roots or foliar application to verify whether Si supply forms are efficient in alleviating the effects of K deficiency. For these purposes, a completely randomized 2 × 3 factorial design was used, with two levels of K: deficient (0.2 mmol L-1 of K) and sufficient (6 mmol L-1 of K); and Si: in nutrient solution via roots (2 mmol L-1 of Si) or foliar application (5.4 mmol L-1 of Si) and control (0 mmol L-1 of Si). Our findings revealed that Si supplied via foliar spraying using the source of sodium silicate and stabilized potassium at a concentration of 5.4 mmol L-1 was agronomically viable for the cultivation of bean plant. K deficiency, when not supplied with silicon, compromised plant growth. Moreover, root-and-foliar-applied Si attenuated the effects of K deficiency as it increased chlorophylls and carotenoids content, photosynthetic activity, water use efficiency and vegetative growth. For the first time, the role of Si to mitigate K deficiency in the bean crop was evidenced, with a view to further research on plants that do not accumulate this beneficial element.

Characterization of autologous platelet rich plasma (PRP) and its biological effects in patients with Behçet's Disease.

INTRODUCTION: Behçet's disease (BD) is an immune-mediated chronic systemic vasculitis, characterized by clinical manifestations that include: mucocutaneous ulcers, ocular involvement, immunological alterations, vascular and neurological implications. The available treatments present limitations such as high cost and side effects, and the search for a low-cost biological treatment with immunomodulatory potential becomes of great value. Platelet rich plasma (PRP) has some characteristics that indicate a possible use as an immunomodulator due to the wide range of secreted cytokines, especially through the participation of TGF-ß1 in the differentiation of T regulatory cells (Treg). This study aimed to characterize the PRP poor in leukocytes (P-PRP) of patients with BD and active ulcers and to evaluate its effects as an immunomodulator through a subcutaneous application. METHODS: We selected patients with a diagnosis of BD, with a low dose of prednisone and with no central nervous system or ocular involvement. Platelet and leukocyte count and quantification of 17 cytokines were evaluated in P-PRP. The effects of P-PRP were evaluated by cell frequency of TCD4 +, TCD8 +, Treg, natural killer (NK), and activated NK, as well as by the cytokine profile in patient's plasma, and the clinical manifestations through score and questionnaire. Also, it was evaluated the number and timing of oral ulcer closure. PRP was used as an adjuvant, with 9 applications of 3 mL, over 6 months, with a follow-up of one year. RESULTS: The results using PRP showed adequate values and no significant inter-and intra-individual variations. The systemic evaluations during the use of PRP showed significant alterations, characterized by the increase in Treg cell frequency (p = 0.0416) and a decrease in activated NK cells (p = 0.0010). However, no clinical correlation was observed through score analysis. The most relevant clinical data was the decrease in the closing time of ulcers throughout the application period. CONCLUSION: In a pilot study with BD patients, P-PRP promoted an anti-inflammatory profile characterized by increased Treg cells and decreased activated NK cells and alterations in cytokines. A clinical improvement was observed with a decrease in the number and time of closure of oral ulcers.

Low SARS-CoV-2 seroprevalence in a cohort of Brazilian sickle cell disease patients: Possible effects of emphasis on social isolation for a population initially considered to be at very high risk.

Despite being initially considered at higher risk for severe COVID-19, sickle cell disease (SCD) patients have mostly presented clinical severity similar to the general population. As their vulnerability to become infected remains uncertain, we assessed the seroreactivity for SARS-CoV-2 to estimate the prevalence of infection and possible phenotypic and socioeconomic determinants for their contagion. Serologic evaluation was performed on 135 patients with an overall prevalence of 11%; positivity was associated with older age and use of public transportation. We speculate that social distancing instructions recommended by our clinic may have contributed to lower levels of infection, but potential protection factors need further investigation.

Orthobiologics in the treatment of hip disorders.

Orthobiologics are biological materials that are intended for the regeneration or healing of bone, cartilage and soft tissues. In this review we discuss the use of orthobiologics for hip disorders providing an update. The orthobiologics included in this article are hyaluronic acid, platelet rich plasma, bone marrow, adipose tissue and expanded mesenchymal stem cells. We explain the concepts and definitions of each orthobiological product, and the literature regarding its use in the hip joint. The paucity of guidelines for the production and characterization of the biological products leads to uneven results across the literature. Each biologic therapy has indications and benefits; however, noteworthy are the characterization of the orthobiologics, the application method and outcome analysis for further improvement of each technique.

The protective role of glutathione in osteoarthritis.

It is currently understood that osteoarthritis (OA) is a major chronic inflammatory musculoskeletal disease. While this disease has long been attributed to biomechanical trauma, recent evidence establishes a significant correlation between osteoarthritic progression and unbridled oxidative stress, responsible for prolonged inflammation. Research describes this as a disturbance in the balanced production of reactive oxygen species (ROS) and antioxidant defenses, generating macromolecular damage and disrupted redox signaling and control. Since ROS pathways are being considered new targets for OA treatment, the development of antioxidant therapy to counteract exacerbated oxidative stress is being continuously researched and enhanced in order to fortify the cellular defenses. Experiments with glutathione and its precursor molecule, N-acetylcysteine (NAC), have shown interesting results in the literature for the management of OA, where they have demonstrated efficacy in reducing cartilage degradation and inflammation markers as well as significant improvements in pain and functional outcomes. Glutathione remains a safe, effective and overall cheap treatment alternative in comparison to other current therapeutic solutions and, for these reasons, it may prove to be comparably superior under particular circumstances. METHODS: Literature was reviewed using PubMed and Google Scholar in order to bring up significant evidence and illustrate the defensive mechanisms of antioxidant compounds against oxidative damage in the onset of musculoskeletal diseases. The investigation included a combination of keywords such as: oxidative stress, oxidative damage, inflammation, osteoarthritis, antioxidant, glutathione, n-acetylcysteine, redox, and cell signaling. CONCLUSION: Based on the numerous studies included in this literature review, glutathione and its precursor N-acetylcysteine have demonstrated significant protective effects in events of prolonged, exacerbated oxidative stress as seen in chronic inflammatory musculoskeletal disorders such as osteoarthritis.

Platelet-rich plasma vs bone marrow aspirate concentrate: An overview of mechanisms of action and orthobiologic synergistic effects.

The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disorders has increased considerably over the past decade. Currently, there are multiple alternatives available as suitable treatments; however, the use of autologous blood-derived products such as platelet-rich plasma (PRP), bone marrow aspirate (BMA) and BMA concentrate (BMAC), specifically, is expanding. Although many investigations attempted to demonstrate the effectiveness of these therapies, even with positive results, the literature lacks standardized protocols and overall accuracy in study designs, which leads to variance and difficulty in reproducibility of protocols. The efficacy of PRP for the treatment of cartilage, bone and muscle tissues is well known. Although BMAC has generated optimistic results for the same purposes, its applicability in clinical trials is still relatively recent when compared to PRP. Both products demonstrate the potential to set forth reparative processes, each in their own distinct mechanism. The combination of these biological products has been previously proposed, yet little is known about their synergism. Evidence indicates that growth factor, cytokine, and chemokine profiles seen in both PRP and BMAC vary but are likely to work synergistically to enhance musculoskeletal healing. BMAC products seem to work well without PRP; however, the addition of PRP to BMAC has been shown to act as a rich and natural source of culture medium for stem cells located either peripherally or in the bone marrow itself. Nevertheless, additional variables associated with the use of BMAC and PRP in orthopedics must be further evaluated in order to consolidate the efficacy of this therapeutic strategy.

Esophageal Dilatation as a Predictor of Systemic Sclerosis in Patients with Interstitial Lung Disease.

OBJECTIVE: To determine the predictive value of esophageal dilatation as observed in high-resolution computed tomography (HRCT) for the diagnosis of systemic sclerosis (SSc) in patients with interstitial lung disease (ILD). METHODS: Our sample consisted of patients diagnosed with SSc and proven interstitial lung involvement with available HRCT exams (n = 20). Individuals with other forms of rheumatic ILD were included as a control group (n = 20). Two blinded radiologists independently reviewed the images for the presence of esophageal dilatation, measured at 3 different levels. Interobserver agreement was tested with Lin's concordance correlation coefficient (CCC). Independent t-test was used to compare maximum esophageal diameters between groups. Friedman's test was used to evaluate differences between the 3-level measurements. Receiver operating characteristic analysis was performed. RESULTS: There was a substantial correlation between both readers (CCC = 0.9802-0.9919). Esophageal dilatation was significantly associated with SSc (P = .0012). The optimal calculated cut-off value to differentiate SSc from other ILDs was 18.5 mm (sensitivity and specificity of 70 and 90%, respectively; area under the curve 0.819), measured 1 cm above the diaphragmatic hiatus. CONCLUSION: HRCT may have a discriminative role in the presence of both ILD and esophageal dilatation for the diagnosis of SSc. Our results suggest that a cut-off value for the esophageal diameter of 18.5 mm might propose the diagnosis of SSc with reasonable confidence.