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Fabrication and operation on increasingly smaller dimensions have been highly integrated with the development of smart and functional materials, which are key to many technological innovations to meet economic and societal needs. Along with researchers worldwide, the Waterloo Institute for Nanotechnology (WIN) has long realized the synergetic interplays between nanotechnology and functional materials and designated 'Smart & Functional Materials' as one of its four major research themes. Thus far, WIN researchers have utilized the properties of smart polymers, nanoparticles, and nanocomposites to develop active materials, membranes, films, adhesives, coatings, and devices with novel and improved properties and capabilities. In this review article, we aim to highlight some of the recent developments on the subject, including our own research and key research literature, in the context of the UN Sustainability development goals.
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Background: Intervertebral disk (IVD) degeneration affects both humans and canines and is a major cause of low back pain (LBP). Mast cell (MC) and macrophage (MØ) infiltration has been identified in the pathogenesis of IVD degeneration (IVDD) in the human and rodent model but remains understudied in the canine. MC degranulation in the IVD leads to a pro-inflammatory cascade and activates protease activated receptor 2 (PAR2) on IVD cells. The objectives of the present study are to: (1) highlight the pathophysiological changes observed in the degenerate canine IVD, (2) further characterize the inflammatory effect of MCs co-cultured with canine nucleus pulposus (NP) cells, (3) evaluate the effect of construct stiffness on NP and MCs, and (4) identify potential therapeutics to mitigate pathologic changes in the IVD microenvironment. Methods: Canine IVD tissue was isolated from healthy autopsy research dogs (beagle) and pet dogs undergoing laminectomy for IVD herniation. Morphology, protein content, and inflammatory markers were assessed. NP cells isolated from healthy autopsy (Mongrel hounds) tissue were co-cultured with canine MCs within agarose constructs and treated with cromolyn sodium (CS) and PAR2 antagonist (PAR2A). Gene expression, sulfated glycosaminoglycan content, and stiffness of constructs were assessed. Results: CD 31+ blood vessels, mast cell tryptase, and macrophage CD 163+ were increased in the degenerate surgical canine tissue compared to healthy autopsy. Pro-inflammatory genes were upregulated when canine NP cells were co-cultured with MCs and the stiffer microenvironment enhanced these effects. Treatment with CS and PAR2 inhibitors mediated key pro-inflammatory markers in canine NP cells. Conclusion: There is increased MC, MØs, and vascular ingrowth in the degenerate canine IVD tissue, similar to observations in the clinical population with IVDD and LBP. MCs co-cultured with canine NP cells drive inflammation, and CS and PAR2A are potential therapeutics that may mitigate the pathophysiology of IVDD in vitro.
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BACKGROUND: Low back pain is a leading cause of disability worldwide and is frequently attributed to intervertebral disc (IVD) degeneration. Though the contributions of the adjacent cartilage endplates (CEP) to IVD degeneration are well documented, the phenotype and functions of the resident CEP cells are critically understudied. To better characterize CEP cell phenotype and possible mechanisms of CEP degeneration, bulk and single-cell RNA sequencing of non-degenerated and degenerated CEP cells were performed. METHODS: Human lumbar CEP cells from degenerated (Thompson grade ≥ 4) and non-degenerated (Thompson grade ≤ 2) discs were expanded for bulk (N=4 non-degenerated, N=4 degenerated) and single-cell (N=1 non-degenerated, N=1 degenerated) RNA sequencing. Genes identified from bulk RNA sequencing were categorized by function and their expression in non-degenerated and degenerated CEP cells were compared. A PubMed literature review was also performed to determine which genes were previously identified and studied in the CEP, IVD, and other cartilaginous tissues. For single-cell RNA sequencing, different cell clusters were resolved using unsupervised clustering and functional annotation. Differential gene expression analysis and Gene Ontology, respectively, were used to compare gene expression and functional enrichment between cell clusters, as well as between non-degenerated and degenerated CEP samples. RESULTS: Bulk RNA sequencing revealed 38 genes were significantly upregulated and 15 genes were significantly downregulated in degenerated CEP cells relative to non-degenerated cells (|fold change| ≥ 1.5). Of these, only 2 genes were previously studied in CEP cells, and 31 were previously studied in the IVD and other cartilaginous tissues. Single-cell RNA sequencing revealed 11 unique cell clusters, including multiple chondrocyte and progenitor subpopulations with distinct gene expression and functional profiles. Analysis of genes in the bulk RNA sequencing dataset showed that progenitor cell clusters from both samples were enriched in "non-degenerated" genes but not "degenerated" genes. For both bulk- and single-cell analyses, gene expression and pathway enrichment analyses highlighted several pathways that may regulate CEP degeneration, including transcriptional regulation, translational regulation, intracellular transport, and mitochondrial dysfunction. CONCLUSIONS: This thorough analysis using RNA sequencing methods highlighted numerous differences between non-degenerated and degenerated CEP cells, the phenotypic heterogeneity of CEP cells, and several pathways of interest that may be relevant in CEP degeneration.
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Degeneração do Disco Intervertebral , Disco Intervertebral , Humanos , Disco Intervertebral/metabolismo , Cartilagem/metabolismo , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/metabolismo , Condrócitos/metabolismo , Células-Tronco/metabolismoRESUMO
Painful musculoskeletal disorders such as intervertebral disc (IVD) degeneration associated with chronic low back pain (termed "Discogenic back pain", DBP), are a significant socio-economic burden worldwide and contribute to the growing opioid crisis. Yet there are very few if any successful interventions that can restore the tissue's structure and function while also addressing the symptomatic pain. Here we have developed a novel non-viral gene therapy, using engineered extracellular vesicles (eEVs) to deliver the developmental transcription factor FOXF1 to the degenerated IVD in an in vivo model. Injured IVDs treated with eEVs loaded with FOXF1 demonstrated robust sex-specific reductions in pain behaviors compared to control groups. Furthermore, significant restoration of IVD structure and function in animals treated with FOXF1 eEVs were observed, with significant increases in disc height, tissue hydration, proteoglycan content, and mechanical properties. This is the first study to successfully restore tissue function while modulating pain behaviors in an animal model of DBP using eEV-based non-viral delivery of transcription factor genes. Such a strategy can be readily translated to other painful musculoskeletal disorders.
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Vesículas Extracelulares , Terapia Genética , Degeneração do Disco Intervertebral , Animais , Vesículas Extracelulares/metabolismo , Terapia Genética/métodos , Feminino , Masculino , Degeneração do Disco Intervertebral/terapia , Degeneração do Disco Intervertebral/genética , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Disco Intervertebral/patologia , Ratos Sprague-Dawley , Dor nas Costas/terapia , Dor nas Costas/genética , Dor Lombar/terapiaRESUMO
Healthy diet is an important tool to lower the risk and severity of COVID-19 infection. Low diet quality is usually caused by perceived barriers that stop people to do certain behavior. Perceived barriers can be overcome by implementing proper method such as conducting nutrition education. This study aimed to analyze the impact of nutrition education on perceived barrier to healthy diet among adults with and without covid-19 history in Padang, Indonesia. This study was a pre-experimental study using pre and post-design. This study was conducted on 70 adults with or without COVID-19 infection history, residing in Padang, Indonesia. The intervention was given in the form of nutrition education. Difference test was conducted to assess the impact of nutrition education on respondents' nutrition knowledge and perceived barriers. The majority of the respondents both with and without COVID-19 history (71.4 and 80%) had medium level of nutritional knowledge before the intervention. After the intervention, there was a significant (P<0.05) improvement on respondents' nutritional knowledge for both groups (100%). The result also showed 40% of the respondents with COVID-19 history had medium level of perceived barriers, while 28.6% respondents without COVID-19 history (65.7%) had medium level of perceived barriers before the intervention. A significant improvement (P<0.05) also showed on respondents' perceived barriers after the intervention. On both groups more 90% of the respondents only had low level of perceived barriers. The result shows that nutrition education has significant impact both on respondents' nutritional knowledge and perceived barriers.
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INTRODUCCIÓN: Las infecciones intrahospitalarias constituyen un indicador de calidad de atención de los Establecimientos de Salud, aspecto que permite determinar la capacidad técnica del personal de salud y su equipamiento. OBJETIVO: Determinar el perfil epidemiológico de los pacientes con infecciones intrahospitalarias durante el año 2011. MATERIAL Y MÉTODOS: Se realizó un estudio prospectivo, observacional de corte longitudinal a pacientes hospitalizados en la Clínica durante el año 2011. RESULTADOS: Se evaluó 2379 pacientes hospitalizados, con 4,19±0,28 días de hospitalización. Encontrándose a 41 pacientes con Infecciones intrahospitalarias, representando una prevalencia del 1,72%. En el perfil epidemiológico predominó en el sexo femenino, con edades de 68,9±22.72 años, estancia hospitalaria de 14,98±9,6 días, siendo 3,57 veces más alta al promedio de hospitalización en la clínica. La Infección más prevalente fue la Neumonía Intrahospitalaria (60.98%), siendo la tasa asociada a ventilador mecánico de 13,56 por 1000 días de exposición. Las infecciones asociadas a catéter urinario y catéter venoso central son 6.34 y 3.24 por cada 1000 días de exposición respectivamente. La tasa de mortalidad correspondió a 34.15%. CONCLUSIONES: Los pacientes que sufrieron Infección intrahospitalaria; son de características longevas, con antecedentes de enfermedades crónicas, que condicionan una estancia prolongada y teniendo como principales Infecciones intrahospitalarias a la neumonías e infecciones urinarias.
OBJETIVE: To determine the epidemiological profile of patients with hospital-acquired infections in 2011.MATERIAL AND METHODS: We performed a prospective, observational, longitudinal study to inpatients at the Clinic in 2011. RESULTS: We evaluated 2379 patients hospitalized with 4.19 ± 0.28 days in hospital. Found 41 patients with nosocomial infections, representing a prevalence of 1.72%. The epidemiological profile: most were females, aged 68.9 ± 22.72 years, with a hospital stay of 14.98 ± 9.6 days, being 3.57 times higher than average hospital stay. Nosocomial pneumonia was the most prevalent Infection (60.98%), while the rate associated with mechanical ventilator is 13.56 per 1000 days of exposure. The infections related to urinary catheter- and central venous catheter are 6.34 and 3.24 per 1000 days of exposure, respectively. The mortality rate was to 34.15%.CONCLUSIONS: Patients who had nosocomial infections, are elderly patients, with a history of chronic diseases, which condition an extended stay and have as principal nosocomial infections pneumonia and urinary tract infections.