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2.
bioRxiv ; 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38712214

RESUMO

The underlying interactions that occur to maintain skin microbiome composition, function, and overall skin health are largely unknown. Often, these types of interactions are mediated by microbial metabolites. Cobamides, the vitamin B12 family of cofactors, are essential for metabolism in many bacteria, but are only synthesized by a small fraction of prokaryotes, including certain skin-associated species. Therefore, we hypothesize that cobamide sharing mediates skin community dynamics. Preliminary work predicts that several skin-associated Corynebacterium species encode de novo cobamide biosynthesis and that their abundance is associated with skin microbiome diversity. Here, we show that commensal Corynebacterium amycolatum produces cobamides and that this synthesis can be tuned by cobalt limitation. To demonstrate cobamide sharing by C. amycolatum, we employed a co-culture assay using an E. coli cobamide auxotroph and show that C. amycolatum produces sufficient cobamides to support E. coli growth, both in liquid co-culture and when separated spatially on solid medium. We also generated a C. amycolatum non-cobamide-producing strain (cob-) using UV mutagenesis that contains mutated cobamide biosynthesis genes cobK and cobO and confirm that disruption of cobamide biosynthesis abolishes support of E. coli growth through cobamide sharing. Our study provides a unique model to study metabolite sharing by microorganisms, which will be critical for understanding the fundamental interactions that occur within complex microbiomes and for developing approaches to target the human microbiota for health advances.

3.
J Assist Reprod Genet ; 41(5): 1221-1231, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38470550

RESUMO

PURPOSE: We explored and compared perspectives of reproductive endocrinology and infertility specialists (REIs) and in vitro fertilization (IVF) patients regarding polygenic embryo screening (PES), a new type of preimplantation screening that estimates the genetic chances of developing polygenic conditions and traits in the future. METHODS: Qualitative thematic analysis of semi-structured interviews with US-based REIs and IVF patients. RESULTS: Clinicians and patients often held favorable views of screening embryos for physical or psychiatric conditions, though clinicians tended to temper their positive attitudes with specific caveats. Clinicians also expressed negative views about screening embryos for traits more frequently than patients, who generally held more positive views. Most clinicians were either unwilling to discuss or offer PES to patients or were willing to do so only under certain circumstances, while many patients expressed interest in PES. Both stakeholder groups envisioned multiple potential benefits or uses of PES and raised multiple potential, interrelated concerns about PES. CONCLUSION: A gap exists between clinician and patient attitudes toward PES; clinicians generally maintained reservations about such screening and patients indicated interest in it. Clinicians and patients sometimes imagined using PES to prepare for the birth of a predisposed or "affected" individual-a rationale that is often associated with prenatal testing. Many clinicians and patients held different attitudes depending on what is specifically screened, despite the sometimes blurry distinction between conditions and traits. Considerations raised by clinicians and patients may help guide professional societies in developing guidelines to navigate the uncertain terrain of PES.


Assuntos
Fertilização in vitro , Diagnóstico Pré-Implantação , Humanos , Feminino , Adulto , Testes Genéticos , Masculino , Herança Multifatorial/genética , Gravidez , Infertilidade/genética , Infertilidade/psicologia , Infertilidade/diagnóstico , Pesquisa Qualitativa , Atitude do Pessoal de Saúde
5.
Semin Arthritis Rheum ; 66: 152414, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38447468

RESUMO

OBJECTIVES: The Outcome Measures in Rheumatology Clinical Trials (OMERACT) Emerging Leaders Program (ELP) aims to cultivate a cohort of skilled leaders within the OMERACT community empowering them with expertise and knowledge to help shape and steer the organization into the future. This publication highlights the significance of the ELP in driving leadership excellence, its impact on OMERACT's evolution, and the outcomes and learnings from the OMERACT 2023 ELP. METHODS: Insights from the 2018 ELP report informed 2023 program improvements. Engagement was measured by attendance and WhatsApp interactions. Positive program aspects, areas for improvement and ideas for enhancing future ELPs were captured via anonymous survey and participant focus groups. RESULTS: Engagement with the ELP was high with 9 participants, 96 % attendance at all workshops, 154 WhatsApp interactions. All program components were highly rated, with the highest being the 'Psychological Safety' and 'Methodology/Process/Politics' workshops. Future enhancements included creating further networking, connection and support activities, practical leadership and methodological skill development opportunities, and a new stream focussing on organisational advancement. CONCLUSIONS: The 2023 OMERACT ELP was well received and successfully addressed areas previously identified as requiring improvement. New educational enhancements were valued, and the importance of fostering psychological safety at all levels was highlighted. The ELP fortifies OMERACT by nurturing a diverse array of skilled leaders who embody OMERACTs core values. Continuing to refine and evolve the ELP over time will help OMERACT sustain its global influence in patient-centered outcome research.


Assuntos
Liderança , Reumatologia , Humanos , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos como Assunto
6.
Front Bioeng Biotechnol ; 12: 1283752, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38333081

RESUMO

Focal cartilage defects are common in youth and older adults, cause significant morbidity and constitute a major risk factor for developing osteoarthritis (OA). OA is the most common musculoskeletal (MSK) disease worldwide, resulting in pain, stiffness, loss of function, and is currently irreversible. Research into the optimal regenerative approach and methods in the setting of either focal cartilage defects and/or OA holds to the ideal of resolving both diseases. The two fundamentals required for cartilage regenerative treatment are 1) the biological element contributing to the regeneration (e.g., direct application of stem cells, or of an exogenous secretome), and 2) the vehicle by which the biological element is suspended and delivered. The vehicle provides support to the regenerative process by providing a protective environment, a structure that allows cell adherence and migration, and a source of growth and regenerative factors that can activate and sustain regeneration. Models of cartilage diseases include osteochondral defect (OCD) (which usually involve one focal lesion), or OA (which involves a more diffuse articular cartilage loss). Given the differing nature of these models, the optimal regenerative strategy to treat different cartilage diseases may not be universal. This could potentially impact the translatability of a successful approach in one condition to that of the other. An analogy would be the repair of a pothole (OCD) versus repaving the entire road (OA). In this narrative review, we explore the existing literature evaluating cartilage regeneration approaches for OCD and OA in animal then in human studies and the vehicles used for each of these two conditions. We then highlight strengths and challenges faced by the different approaches presented and discuss what might constitute the optimal cartilage regenerative delivery vehicle for clinical cartilage regeneration.

7.
J Clin Immunol ; 44(2): 50, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38231281

RESUMO

Several genetic and immunological risk factors for severe COVID-19 have been identified, with monogenic conditions relating to 13 genes of type I interferon (IFN) immunity proposed to explain 4.8% of critical cases. However, previous cohorts have been clinically heterogeneous and were not subjected to thorough genetic and immunological analyses. We therefore aimed to systematically investigate the prevalence of rare genetic variants causing inborn errors of immunity (IEI) and functionally interrogate the type I IFN pathway in young adults that suffered from critical COVID-19 yet lacked comorbidities. We selected and clinically characterized a cohort of 38 previously healthy individuals under 50 years of age who were treated in intensive care units due to critical COVID-19. Blood samples were collected after convalescence. Two patients had IFN-α autoantibodies. Genome sequencing revealed very rare variants in the type I IFN pathway in 31.6% of the patients, which was similar to controls. Analyses of cryopreserved leukocytes did not indicate any defect in plasmacytoid dendritic cell sensing of TLR7 and TLR9 agonists in patients carrying variants in these pathways. However, lymphocyte STAT phosphorylation and protein upregulation upon IFN-α stimulation revealed three possible cases of impaired type I IFN signaling in carriers of rare variants. Together, our results suggest a strategy of functional screening followed by genome analyses and biochemical validation to uncover undiagnosed causes of critical COVID-19.


Assuntos
COVID-19 , Interferon Tipo I , Humanos , Adulto Jovem , COVID-19/genética , Interferon-alfa , Transdução de Sinais , Autoanticorpos
8.
Clin Exp Rheumatol ; 42(3): 713-717, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37976118

RESUMO

OBJECTIVES: Nerve growth factor ß (ß-NGF) is a protein which is important to the development of neurons particularly those involved in the transmission of pain and is central to the experience of pain in osteoarthritis (OA). Direct NGF antagonism has been shown to reduce OA pain but is associated with rapidly progressive OA. The aim of the study is to investigate the ability of soluble neurotrophin receptors in the NGF pathway to modulate pain in OA. METHODS: Synovial fluid (SF) was obtained from the knee joints of 43 subjects who underwent total knee arthroplasty. Visual analogue scale (VAS) pain scores were obtained prior to surgery. Customised-automated-ELISAs and commercial-ELISAs and LEGENDplex™ were used to measure soluble low-affinity nerve growth factor (LNGFR), soluble tropomyosin receptor kinase (TrkA), proNGF, ß-NGF, other neurotrophins (NT) and cytokines including inflammatory marker TNF-α. RESULTS: The VAS score positively correlated with ß-NGF (r=0.34) and there was positive association trend with neurotrophin-3 (NT-3), BDNF and negative association trend with ProNGF. sLNGFR positively correlated with VAS (r=0.33). The ß-NGF/soluble TrkA ratio showed a strong positive correlation with VAS (r=0.80). In contrast, there was no correlation between pain and the ß-NGF/sLNGFR ratio (r=-0.08). TNF-α positively correlated with ß-NGF (r=0.83), NT-3 (r=0.66), and brain-derived neurotrophic factor (BDNF) (r=0.50) and negatively with ProNGF (r= -0.74) and positively correlated with both soluble TrkA (r=0.62), sLNGFR (r=0.26). CONCLUSIONS: This study suggests that endogenous or cleaved sLNGFR, but not soluble TrkA may participate in OA pain modulation thus supporting further research into soluble LNGFR as a therapeutic target in OA.


Assuntos
Fator de Crescimento Neural , Osteoartrite do Joelho , Humanos , Fator de Crescimento Neural/metabolismo , Fator Neurotrófico Derivado do Encéfalo , Receptor de Fator de Crescimento Neural , Fator de Necrose Tumoral alfa , Receptores de Fator de Crescimento Neural/metabolismo , Dor
9.
J Cereb Blood Flow Metab ; 44(4): 542-555, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37933736

RESUMO

Mild traumatic brain injury (mTBI) involves damage to the cerebrovascular system. Vascular endothelial growth factor-A (VEGF-A) is an important modulator of vascular health and VEGF-A promotes the brain's ability to recover after more severe forms of brain injury; however, the role of VEGF-A in mTBI remains poorly understood. Bevacizumab (BEV) is a monoclonal antibody that binds to VEGF-A and neutralises its actions. To better understand the role of VEGF-A in mTBI recovery, this study examined how BEV treatment affected outcomes in rats given a mTBI. Adult Sprague-Dawley rats were assigned to sham-injury + vehicle treatment (VEH), sham-injury + BEV treatment, mTBI + VEH treatment, mTBI + BEV treatment groups. Treatment was administered intracerebroventricularly via a cannula beginning at the time of injury and continuing until the end of the study. Rats underwent behavioral testing after injury and were euthanized on day 11. In both females and males, BEV had a negative impact on cognitive function. mTBI and BEV treatment increased the expression of inflammatory markers in females. In males, BEV treatment altered markers related to hypoxia and vascular health. These novel findings of sex-specific responses to BEV and mTBI provide important insights into the role of VEGF-A in mTBI.


Assuntos
Concussão Encefálica , Masculino , Feminino , Ratos , Animais , Bevacizumab , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ratos Sprague-Dawley , Modelos Animais de Doenças
10.
J Rheumatol ; 51(3): 285-290, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101919

RESUMO

OBJECTIVE: To evaluate whether a knee flexion contracture (FC) was associated with localized tibial articular cartilage loss over a 1-year period using Osteoarthritis Initiative quantitative data. METHODS: Five hundred seventy-eight participants from a previously established nested case-control study of people with radiographic knee OA with or without progression, based on radiographs and symptoms, had their knee range of extension measured at baseline and received magnetic resonance imaging (MRI) at baseline and 1 year. The tibial articular cartilage of the medial and lateral condyles was segmented into anterior, center, and posterior regions. We tested for associations between knee FC (defined as lack of extension to 0°), and localized changes in tibial articular cartilage thickness or percent of denuded bone (0 mm thickness) after 1 year relative to baseline using ANOVA, controlling for baseline MRI outcomes and clinical factors. RESULTS: Knee FC was associated with denuded bone in the medial condyle center (ß 0.44, 95% CI 0.02-0.86) and preserved cartilage thickness in the medial condyle posterior (ß 0.01, 95% CI 0.002-0.03) regions. CONCLUSION: Knee FC unloading the tibial center region and loading the posterior region was associated with localized articular cartilage loss centrally and preserved articular cartilage posteriorly. These findings are consistent with knee FC negatively affecting unloaded tibial articular cartilage.


Assuntos
Cartilagem Articular , Contratura , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Estudos de Casos e Controles , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia
11.
Arch Phys Med Rehabil ; 104(12): 2067-2074, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37209935

RESUMO

OBJECTIVE: To evaluate whether knee flexion contracture (FC) was associated with leg length inequality (LLI) and/or morbidity in knee osteoarthritis (OA). DESIGN: We accessed 2 databases: (1) the Osteoarthritis Initiative (OAI) cohort, including participants with, or at-risk of OA, and (2) the Ottawa Knee Osteoarthritis cross-sectional database (OKOA), including participants with primary advanced knee OA. Both included demographics, radiographic data, knee range of motion, leg length, pain, and function scales. SETTING: Tertiary care academic rheumatology and orthopedic clinics. PARTICIPANTS: Patients with or at-risk of primary OA. We included 881 OAI and 72 OKOA participants (N=953). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: The primary outcome tested the association between the difference in knee extensions of the OA and contralateral knees (the knee extension difference, or KExD) and LLI. This was evaluated using bivariate regression, followed by a multivariable linear regression model. RESULTS: OAI participants had less severe knee OA [Kellgren and Lawrence (KL) score 1.9±1.3] vs OKOA (KL score 3.4±0.6). The KExD correlated with LLI for both databases (OAI: R=0.167; P≤.001; OKOA: R=0.339; P=.004). Multivariable regression showed an effect of KExD on LLI in both databases (OAI: ß=0.37[0.18,0.57]; P<.001, OKOA: ß=0.73[0.20,1.26]; P=.007). When broken down by subgroup, the OAI moderate-severe OA group showed a significant effect of KExD on LLI (ß=0.60 [0.34,0.85]; P<.001). CONCLUSIONS: OA-related loss of knee extension was associated with LLI for those with moderate-severe OA. Because LLI correlates with worse knee OA symptoms, discovering an FC should cue clinicians to evaluate for LLI, an easily-treatable finding that may help reduce OA-associated morbidity for those approaching the need for arthroplasty.


Assuntos
Contratura , Osteoartrite do Joelho , Humanos , Perna (Membro) , Desigualdade de Membros Inferiores/complicações , Articulação do Joelho , Progressão da Doença
12.
Sports Health ; 15(6): 867-877, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36691685

RESUMO

CONTEXT: Many patients with osteoarthritis (OA) develop range of motion (ROM) restrictions in their affected joints (contractures), associated with worse outcomes and rising healthcare costs. Effective treatment guidance for lost ROM in OA-affected joints is lacking. OBJECTIVE: A systematic review and meta-analysis evaluating the effectiveness of stretching and/or bracing protocols on native (nonoperated) joint ROM in the setting of radiographically diagnosed OA. DATA SOURCES: Seven databases, English-language. STUDY SELECTION: Studies including participants with radiographically diagnosed OA in any native joint evaluating the effect of stretching or bracing on ROM. STUDY DESIGN: Systematic review and meta-analysis. LEVEL OF EVIDENCE: Level 2. DATA EXTRACTION: Two reviewers independently screened articles for inclusion and assessed risk of bias in included trials. Primary outcomes were ROM, pain, and adverse events (AEs). RESULTS: We identified 6284 articles. A total of 9 randomized controlled trials, all evaluating the knee, met eligibility criteria. For stretching, 3 pooled studies reported total ROM, which improved by mean difference (MD) of 9.3° (95% CI 5.0°,13.5°) versus controls. Two pooled studies showed improved knee flexion ROM (MD 10.8° [7.3°,14.2°]) versus controls. Five studies were pooled for knee extension with mean improvement 9.1° [3.4°,14.8°] versus controls. Seven pooled studies showed reduced pain (standardized MD 1.9 [1.2,2.6]). One study reported improved knee extension of 3.7° [2.9°,4.5°] with use of a device. No studies used orthoses. One study reported on AEs, with none noted. Performance bias was present in all included studies, and only 3 studies clearly reported blinding of outcome assessors. Strength of evidence for primary outcomes was considered moderate. CONCLUSION: There was moderate-quality evidence that stretching is an effective strategy for improving knee total, flexion and extension ROM, and pain. Our findings suggest that stretching to regain joint ROM in OA is not futile and that stretching appears to be an appropriate conservative intervention to improve patient outcomes as part of a comprehensive knee OA treatment plan before arthroplasty.


Assuntos
Contratura , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/etiologia , Braquetes , Terapia por Exercício/efeitos adversos , Contratura/etiologia , Dor/etiologia
13.
Rheumatology (Oxford) ; 62(5): 1950-1954, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36179080

RESUMO

OBJECTIVES: Animal studies suggest regional unloading of the knee due to flexion contracture (FC) results in cartilage loss in the anterior tibia. We looked for an association between the range of knee extension and articular cartilage thickness in the tibia of patients with knee OA, using quantitative MRI data from the OA Initiative. METHODS: Baseline knee extension was measured using a goniometer. Cartilage thickness was measured using 3-Tesla coronal MRI images of the knee. The tibia articular cartilage was segmented into medial and lateral regions, then further divided into anterior, central and posterior subregions. We evaluated differences between participants with and without a knee FC and associations between knee extension and cartilage thickness, including percentage denudation of bones (0 mm thickness), using linear models. RESULTS: A total of 596 participants were included. Participants with a knee FC had a larger percentage of denuded bone in the anterolateral tibia vs participants without FC (2.2 ± 0.7% vs 0.4 ± 0.1%; P = 0.006), and knee extension was associated with anterolateral tibia denuded bone (r = 0.16, P < 0.001). After correcting for demographics, knee alignment, and OA severity, presence of FC and lost knee extension were associated with the percentage of denuded bone in the anterolateral tibia [ß = 1.702 (0.634-2.770) and ß = 0.261 (95% CI 0.134, 0.388), respectively]. CONCLUSION: While causation cannot be determined in this study, limitation in knee extension was statistically associated with the percentage of denuded bone in the anterolateral tibia. These novel data support that maintaining range of motion over the entire joint surface may help preserve articular cartilage health.


Assuntos
Cartilagem Articular , Osteoartrite do Joelho , Humanos , Tíbia , Osteoartrite do Joelho/complicações , Fêmur , Articulação do Joelho , Imageamento por Ressonância Magnética/métodos
14.
Front Mol Neurosci ; 15: 937350, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36385769

RESUMO

Mild traumatic brain injury (mTBI) is a common and unmet clinical issue, with limited treatments available to improve recovery. The cerebrovascular system is vital to provide oxygen and nutrition to the brain, and a growing body of research indicates that cerebrovascular injury contributes to mTBI symptomatology. Vascular endothelial growth factor-A (VEGF-A) is a potent promoter of angiogenesis and an important modulator of vascular health. While indirect evidence suggests that increased bioavailability of VEGF-A may be beneficial after mTBI, the direct therapeutic effects of VEGF-A in this context remains unknown. This study therefore aimed to determine whether intracerebroventricular administration of recombinant VEGF-A could improve recovery from mTBI in a rat model. Male and female Sprague-Dawley rats were assigned to four groups: sham + vehicle (VEH), sham + VEGF-A, mTBI + VEH, mTBI + VEGF-A. The mTBI was induced using the lateral impact model, and treatment began at the time of the injury and continued until the end of the study. Rats underwent behavioral testing between days 1 and 10 post-injury, and were euthanized on day 11 for post-mortem analysis. In males, the mTBI + VEGF-A group had significantly worse cognitive recovery in the water maze than all other groups. In females, the VEGF treatment worsened cognitive performance in the water maze regardless of mTBI or sham injury. Analysis of hippocampal tissue found that these cognitive deficits occurred in the presence of gene expression changes related to neuroinflammation and hypoxia in both male and female rats. These findings indicate that the VEGF-A treatment paradigm tested in this study failed to improve mTBI outcomes in either male or female rats.

15.
Front Bioeng Biotechnol ; 10: 866148, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711627

RESUMO

Cartilage injury and degeneration are hallmarks of osteoarthritis (OA), the most common joint disease. OA is a major contributor to pain, loss of function, and reduced quality of life. Over the last decade, considerable research efforts have focused on cell-based therapies, including several stem cell-derived approaches to reverse the cartilage alterations associated with OA. Although several tissue sources for deriving cell-based therapies have been identified, none of the resident stem cell populations have adequately fulfilled the promise of curing OA. Indeed, many cell products do not contain true stem cells. As well, issues with aggressive marketing efforts, combined with a lack of evidence regarding efficacy, lead the several national regulatory bodies to discontinue the use of stem cell therapy for OA until more robust evidence becomes available. A review of the evidence is timely to address the status of cell-based cartilage regeneration. The promise of stem cell therapy is not new and has been used successfully to treat non-arthritic diseases, such as hematopoietic and muscle disorders. These fields of regenerative therapy have the advantage of a considerable foundation of knowledge in the area of stem cell repair mechanisms, the role of the stem cell niche, and niche-supporting cells. This foundation is lacking in the field of cartilage repair. So, where should we look for the ideal stem cell to regenerate cartilage? It has recently been discovered that cartilage itself may contain a population of SC-like progenitors. Other potential tissues include stem cell-rich dental pulp and the adolescent growth plate, the latter of which contains chondrocyte progenitors essential for producing the cartilage scaffold needed for bone growth. In this article, we review the progress on stem cell therapies for arthritic disorders, focusing on the various stem cell populations previously used for cartilage regeneration, successful cases of stem cell therapies in muscle and hemopoietic disorders, some of the reasons why these other fields have been successful (i.e., "lessons learned" to be applied to OA stem cell therapy), and finally, novel potential sources of stem cells for regenerating damaged cartilage in vivo.

16.
Stem Cell Rev Rep ; 18(3): 1054-1066, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34313927

RESUMO

BACKGROUND AND OBJECTIVE: Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are a promising treatment for bone injuries, although studies remain preclinical. A systematic review and meta-analysis can assess the efficacy of MSC-EVs and identify treatment aspects associated with enhanced bone repair. METHODS: English language, preclinical, controlled, in vivo studies identified in our systematic search (up to May 8, 2020) examining the use of MSC-EVs in bone healing were included. Risk of bias (ROB) was assessed using the SYRCLE tool. Aggregate Data Meta-Analysis was performed to determine the effect of MSC-EVs on Bone Volume/Total Volume (BV/TV) and New Bone Formation (NBF). RESULTS: Thirteen studies were included. Twelve reported either BV/TV or NBF and were included in meta-analysis. ROB was unclear in all studies. Overall, MSC-EVs displayed benefit in terms of bone healing for both BV/TV (22.2% mean difference (MD); 95% CI: 15.8-28.5%, p < 0.001) and NBF (26.1% MD; 10.3-41.8%, p = 0.001) versus controls. Substantial heterogeneity, however, was observed between studies. MSC-EVs were reported to activate multiple signaling pathways including mTOR/AKT, AMPK and BMP2. Subgroup analysis indicated no significant difference in the improvement of BV/TV when using modified EVs isolated after gene transfection, preconditioning (p = 0.61), or using EVs in combination with a tissue scaffold and/or hydrogel versus other delivery methods (p = 0.20). CONCLUSION: Use of MSC-EVs to promote healing of bone injury appears promising, however, heterogeneity between studies and the potential for reporting bias limits confidence in the extent of benefit. Reducing bias between studies and addressing aspects of potential reporting bias should augment confidence in future meta-analyses and propel the field towards clinical studies. Forest Plot analysis assessing the percentage change in bone volume (BV) / total volume (TV) in the presence (experimental) or absence (control) of MSC-EVs.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Animais , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Modelos Animais
17.
Clin Exp Rheumatol ; 40(5): 993-998, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34796841

RESUMO

OBJECTIVES: Knee osteoarthritis (OA) is often accompanied by a flexion contracture (FC), resulting in worse clinical outcomes. Our objective was to determine associations between knee FC and specific regional and/or structural alterations on magnetic resonance imaging (MRI) using the Osteoarthritis Initiative (OAI). METHODS: 600 knees from the Foundation for the National Institutes of Health sub-study of the OAI were included. Knee extension was measured with a goniometer and FC was defined as inability to extend the knee to 0°. Structural alterations within the MRI Osteoarthritis Knee Score (MOAKS)-assessed regions that could potentially obstruct knee extension were primarily analysed. Multivariable linear regression models evaluated the effect size of MRI outcomes on knee extension. RESULTS: One-third (33.4%) of all participants had knee FC: 155 mild (1-5°, 26.0%), 44 moderate-severe (≥6°, 7.4%). Mean knee alignment was 0.3±3.7° valgus. Cartilage morphology and bone marrow lesion (BML) scores on the femoral side of the lateral patellofemoral joint were associated with lost knee extension (ß=0.709, p<0.001, and ß=0.666, p<0.001, respectively) as were higher osteophyte scores in multiple regions, worse meniscal score in the medial meniscal body (ß=0.164, p<0.040) and posterior horn (ß=0.400, p<0.001), and a worse effusion score (ß=0.711, p<0.001). CONCLUSIONS: Knee flexion contractures were associated with non-specific, widespread MRI degenerative changes including cartilage loss and BMLs in the lateral patellofemoral joint, osteophytes, meniscal alterations and whole-joint effusion. Loss of knee extension in OA is likely a structurally-multifactorial outcome.


Assuntos
Cartilagem Articular , Contratura , Luxações Articulares , Osteoartrite do Joelho , Cartilagem Articular/patologia , Contratura/diagnóstico por imagem , Contratura/etiologia , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia
18.
Am J Lifestyle Med ; 15(5): 495-497, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646096
19.
Stroke ; 52(10): e618-e621, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34372669

RESUMO

Background and Purpose: Early, frequent rehabilitation is an important factor for optimizing stroke recovery outcomes. Medical comorbidities, such as osteoarthritis, that affect the ability to participate in rehabilitation could therefore have a detrimental impact on such outcomes. Both stroke and osteoarthritis are becoming more common in developed nations as the population ages. First-line osteoarthritis treatments, such as oral nonsteroidal anti-inflammatory drugs, are often avoided poststroke due to interaction with secondary prevention stroke risk-factor management. Our objective was to summarize the current literature concerning co-occurring osteoarthritis and stroke prevalence, its functional impact, and treatment options. Methods: Narrative review using a comprehensive literature search of PubMed, osteoarthritis, and stroke guidelines. Outcomes related to co-occurrence prevalence, osteoarthritis as a stroke risk-factor, osteoarthritis-related imaging and treatment were extracted and summarized descriptively. Overall quality of the evidence was summarized using Grading of Recommendations Assessment, Development and Evaluation. Results: We identified 23 studies and guidelines related to our objective. Overall quality of the evidence was very low. Conclusions: Few trials have investigated the relationship between osteoarthritis and stroke, nor osteoarthritis-specific pain and function management for stroke survivors. High-quality research evaluating the impact of osteoarthritis on stroke rehabilitation is needed.


Assuntos
Osteoartrite/terapia , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/terapia , Humanos , Osteoartrite/complicações , Osteoartrite/epidemiologia , Osteoartrite/reabilitação , Prevalência , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia
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