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1.
Proc Natl Acad Sci U S A ; 120(45): e2309156120, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37903261

RESUMO

Cobalt-containing alloys are useful for orthopedic applications due to their low volumetric wear rates, corrosion resistance, high mechanical strength, hardness, and fatigue resistance. Unfortunately, these prosthetics release significant levels of cobalt ions, which was only discovered after their widespread implantation into patients requiring hip replacements. These cobalt ions can result in local toxic effects-including peri-implant toxicity, aseptic loosening, and pseudotumor-as well as systemic toxic effects-including neurological, cardiovascular, and endocrine disorders. Failing metal-on-metal (MoM) implants usually necessitate painful, risky, and costly revision surgeries. To treat metallosis arising from failing MoM implants, a synovial fluid-mimicking chelator was designed to remove these metal ions. Hyaluronic acid (HA), the major chemical component of synovial fluid, was functionalized with British anti-Lewisite (BAL) to create a chelator (BAL-HA). BAL-HA effectively binds cobalt and rescues in vitro cell vitality (up to 370% of cells exposed to IC50 levels of cobalt) and enhances the rate of clearance of cobalt in vivo (t1/2 from 48 h to 6 h). A metallosis model was also created to investigate our therapy. Results demonstrate that BAL-HA chelator system is biocompatible and capable of capturing significant amounts of cobalt ions from the hip joint within 30 min, with no risk of kidney failure. This chelation therapy has the potential to mitigate cobalt toxicity from failing MoM implants through noninvasive injections into the joint.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Prótese de Quadril/efeitos adversos , Ácido Hialurônico , Dimercaprol , Terapia por Quelação , Falha de Prótese , Artroplastia de Quadril/efeitos adversos , Metais , Cobalto , Quelantes/uso terapêutico , Íons
2.
Cleft Palate Craniofac J ; : 10556656241241128, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38545670

RESUMO

BACKGROUND: The effectiveness of virtual-reality (VR) simulation-based training in cleft surgery has not been tested. The purpose of this study was to evaluate learners' acceptance of VR simulation in airway management of a pediatric patient post-cleft palate repair. METHODS: This VR simulation was developed through collaboration between BioDigital and Smile Train. 26 medical students from a single institution completed 10 min of standardized VR training and 5 min of standardized discussion about airway management post-cleft palate repair. They spent 4-8 min in the VR simulation with guidance from a cleft surgery expert. Participants completed pre- and post-surveys evaluating confidence in using VR as an educational tool, understanding of airway management, and opinions on VR in surgical education. Satisfaction was evaluated using a modified Student Evaluation of Educational Quality questionnaire and scored on a 5-point Likert scale. Wilcoxon signed-rank tests were performed to evaluate responses. RESULTS: There was a significant increase in respondents' confidence using VR as an educational tool and understanding of airway management post-cleft palate repair after the simulation (P < .001). Respondents' opinions on incorporating VR in surgical education started high and did not change significantly post-simulation. Participants were satisfied with VR-based simulation and reported it was stimulating (4.31 ± 0.88), increased interest (3.77 ± 1.21), enhanced learning (4.12 ± 1.05), was clear (4.15 ± 0.97), was effective in teaching (4.08 ± 0.81), and would recommend the simulation (4.2 ± 1.04). CONCLUSION: VR-based simulation can significantly increase learners' confidence and skills in airway management post-cleft palate repair. Learners find VR to be effective and recommend its incorporation in surgical education.

3.
Cleft Palate Craniofac J ; : 10556656241230882, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38354301

RESUMO

OBJECTIVE: To evaluate the features, anatomic accuracy, and educational value of a high-fidelity bilateral cleft lip simulator. DESIGN: Evaluation of the simulator by expert cleft surgeons after performing a simulated bilateral cleft lip repair. SETTING: The simulator was evaluated by the surgeons during the Latin American Craniofacial Association meeting. PARTICIPANTS: Eleven experienced cleft surgeons evaluated the simulator. The cleft surgeons were selected based on their availability during the meeting. INTERVENTIONS: The participants performed a simulated bilateral cleft lip repair. They were each provided with a questionnaire assessing the simulator's features, realism and value as a training tool. MAIN OUTCOME MEASURE (S): The main outcome measure are the scores obtained from a Likert-type questionnaire assessing the simulators features, realism and value. RESULTS: Overall, the surgeons agreed with the simulator's realism and anatomic accuracy (average score of 3.7 out of 5). Overall, the surgeons strongly agreed with the value of the simulator as a training tool (average score of 4.6 out of 5). CONCLUSIONS: A high-fidelity bilateral cleft lip simulator was developed that is realistic and valuable as a training tool. The simulator provides a comprehensive training platform to gain hands-on experience in bilateral cleft lip repair before operating on real patients.

4.
Mol Ecol ; 31(7): 2044-2060, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35080063

RESUMO

Because of their steep gradients in abiotic and biotic factors, mountains offer an ideal setting to illuminate the mechanisms that underlie patterns of species distributions and community assembly. We compared the composition of taxonomically and functionally diverse fungal communities in soils along five elevational gradients in mountains of the Neo- and Palaeotropics (northern Argentina, southern Brazil, Panama, Malaysian Borneo and Papua New Guinea). Both the richness and composition of soil fungal communities reflect environmental factors, particularly temperature and soil pH, with some shared patterns among neotropical and palaeotropical regions. Community dynamics are characterized by replacement of species along elevation gradients, implying a relatively narrow elevation range for most fungi, which appears to be driven by contrasting environmental preferences among both functional and taxonomic groups. For functional groups dependent on symbioses with plants (especially ectomycorrhizal fungi), the distribution of host plants drives richness and community composition, resulting in important differences in elevational patterns between neotropical and palaeotropical montane communities. The pronounced compositional and functional turnover along elevation gradients implies that tropical montane forest fungi will be sensitive to climate change, resulting in shifts in composition and functionality over time.


Assuntos
Micobioma , Micorrizas , Biodiversidade , Florestas , Fungos , Micorrizas/genética , Plantas , Solo/química , Microbiologia do Solo
5.
Proc Natl Acad Sci U S A ; 116(11): 4855-4860, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30796184

RESUMO

Synthetic, resorbable scaffolds for bone regeneration have potential to transform the clinical standard of care. Here, we demonstrate that functional graphenic materials (FGMs) could serve as an osteoinductive scaffold: recruiting native cells to the site of injury and promoting differentiation into bone cells. By invoking a Lewis acid-catalyzed Arbuzov reaction, we are able to functionalize graphene oxide (GO) to produce phosphate graphenes (PGs) with unprecedented control of functional group density, mechanical properties, and counterion identity. In aqueous environments, PGs release inducerons, including Ca2+ and PO43- Calcium phosphate graphene (CaPG) intrinsically induces osteogenesis in vitro and in the presence of bone marrow stromal cells (BMSCs), can induce ectopic bone formation in vivo. Additionally, an FGM can be made by noncovalently loading GO with the growth factor recombinant human bone morphogenetic protein 2 (rhBMP-2), producing a scaffold that induces ectopic bone formation with or without BMSCs. The FGMs reported here are intrinsically inductive scaffolds with significant potential to revolutionize the regeneration of bone.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Grafite/farmacologia , Células-Tronco Mesenquimais/citologia , Osseointegração/efeitos dos fármacos , Fosfatos/farmacologia , Alicerces Teciduais/química , Animais , Proteína Morfogenética Óssea 2/farmacologia , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Grafite/síntese química , Grafite/química , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Células NIH 3T3 , Osteogênese/efeitos dos fármacos , Fosfatos/síntese química , Fosfatos/química , Células RAW 264.7 , Proteínas Recombinantes/farmacologia , Fator de Crescimento Transformador beta/farmacologia
6.
J Minim Invasive Gynecol ; 28(3): 490-495, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33310145

RESUMO

OBJECTIVE: To review the current status of robotic training and the impact of various training platforms on the performance of robotic surgical trainees. DATA SOURCES: Literature review of Google Scholar and PubMed. The search terms included a combination of the following: "robotic training," "simulation," "robotic curriculum," "obgyn residency robotic training," "virtual reality robotic training," "DaVinci training," "surgical simulation," "gyn surgical training." The sources considered for inclusion included peer-reviewed articles, literature reviews, textbook chapters, and statements from various institutions involved in resident training. METHODS OF STUDY SELECTION: A literature search of Google Scholar and PubMed using terms related to robotic surgery and robotics training, as mentioned in the "Data Sources" section. RESULTS: Multiple novel platforms that use machine learning and real-time video feedback to teach and evaluate robotic surgical skills have been developed over recent years. Various training curricula, virtual reality simulators, and other robotic training tools have been shown to enhance robotic surgical education and improve surgical skills. The integration of didactic learning, simulation, and intraoperative teaching into more comprehensive training curricula shows positive effects on robotic skills proficiency. Few robotic surgery training curricula have been validated through peer-reviewed study, and there is more work to be completed in this area. In addition, there is a lack of information about how the skills obtained through robotics curricula and simulation translate into operating room performance and patient outcomes. CONCLUSION: Data collected to date show promising advances in the training of robotic surgeons. A diverse array of curricula for training robotic surgeons continue to emerge, and existing teaching modalities are evolving to keep up with the rapidly growing demand for proficient robotic surgeons. Futures areas of growth include establishing competency benchmarks for existing training tools, validating existing curricula, and determining how to translate the acquired skills in simulation into performance in the operating room and patient outcomes. Many surgical training platforms are beginning to expand beyond discrete robotic skills training to procedure-specific and team training. There is still a wealth of research to be done to understand how to create an effective training experience for gynecologic surgical trainees and robotics teams.


Assuntos
Competência Clínica , Invenções , Procedimentos Cirúrgicos Robóticos/métodos , Treinamento por Simulação/métodos , Cirurgiões/educação , Simulação por Computador , Currículo , Humanos , Internato e Residência/métodos , Internato e Residência/tendências , Invenções/tendências , Procedimentos Cirúrgicos Robóticos/tendências , Treinamento por Simulação/tendências , Realidade Virtual
7.
Plant Cell ; 26(6): 2310-2350, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24894045

RESUMO

We investigated the systems response of metabolism and growth after an increase in irradiance in the nonsaturating range in the algal model Chlamydomonas reinhardtii. In a three-step process, photosynthesis and the levels of metabolites increased immediately, growth increased after 10 to 15 min, and transcript and protein abundance responded by 40 and 120 to 240 min, respectively. In the first phase, starch and metabolites provided a transient buffer for carbon until growth increased. This uncouples photosynthesis from growth in a fluctuating light environment. In the first and second phases, rising metabolite levels and increased polysome loading drove an increase in fluxes. Most Calvin-Benson cycle (CBC) enzymes were substrate-limited in vivo, and strikingly, many were present at higher concentrations than their substrates, explaining how rising metabolite levels stimulate CBC flux. Rubisco, fructose-1,6-biosphosphatase, and seduheptulose-1,7-bisphosphatase were close to substrate saturation in vivo, and flux was increased by posttranslational activation. In the third phase, changes in abundance of particular proteins, including increases in plastidial ATP synthase and some CBC enzymes, relieved potential bottlenecks and readjusted protein allocation between different processes. Despite reasonable overall agreement between changes in transcript and protein abundance (R2 = 0.24), many proteins, including those in photosynthesis, changed independently of transcript abundance.

8.
Muscle Nerve ; 53(4): 598-607, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26202157

RESUMO

INTRODUCTION: Magnetic stimulation (MS) has the ability to induce muscle twitch and has long been proposed as a therapeutic modality for skeletal muscle diseases. However, the molecular mechanisms underlying its means of action have not been defined. METHODS: Muscle regeneration after trauma was studied in a standard muscle injury mouse model. The influence of MS on the formation of motor units, posttrauma muscle/nerve regeneration, and vascularization was investigated. RESULTS: We found that MS does not cause systemic or muscle damage but improves muscle regeneration by significantly minimizing the presence of inflammatory infiltrate and formation of scars after trauma. It avoids posttrauma muscle atrophy, induces muscle hypertrophy, and increases the metabolism and turnover of muscle. It triples the expression of muscle markers and significantly improves muscle functional recovery after trauma. CONCLUSIONS: Our results indicate that MS supports muscle and nerve regeneration by activating muscle-nerve cross-talk and inducing the maturation of neuromuscular junctions.


Assuntos
Magnetoterapia/métodos , Músculo Esquelético/lesões , Músculo Esquelético/fisiologia , Atrofia Muscular/fisiopatologia , Atrofia Muscular/terapia , Regeneração Nervosa/fisiologia , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Contração Muscular/fisiologia , Junção Neuromuscular/fisiologia , Técnicas de Cultura de Órgãos
9.
Plant Physiol ; 165(3): 1380-1391, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24808102

RESUMO

Large-scale modeling of plant metabolism provides the possibility to compare and contrast different cellular and environmental scenarios with the ultimate aim of identifying the components underlying the respective plant behavior. The existing models of Arabidopsis (Arabidopsis thaliana) are top-down assembled, whereby the starting point is the annotated genome, in particular, the metabolic genes. Hence, dead-end metabolites and blocked reactions can arise that are subsequently addressed by using gap-filling algorithms in combination with species-unspecific genes. Here, we present a bottom-up-assembled, large-scale model that relies solely on Arabidopsis-specific annotations and results in the inclusion of only manually curated reactions. While the existing models are largely condition unspecific by employing a single biomass reaction, we provide three biomass compositions that pertain to realistic and frequently examined scenarios: carbon-limiting, nitrogen-limiting, and optimal growth conditions. The comparative analysis indicates that the proposed Arabidopsis core model exhibits comparable efficiency in carbon utilization and flexibility to the existing network alternatives. Moreover, the model is utilized to quantify the energy demand of amino acid and enzyme de novo synthesis in photoautotrophic growth conditions. Illustrated by the case of the most abundant protein in the world, Rubisco, we determine its synthesis cost in terms of ATP requirements. This, in turn, allows us to explore the tradeoff between protein synthesis and growth in Arabidopsis. Altogether, the model provides a solid basis for completely species-specific integration of high-throughput data, such as gene expression levels, and for condition-specific investigations of in silico metabolic engineering strategies.

10.
Am J Primatol ; 75(9): 947-58, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23649750

RESUMO

Human and nonhuman animals show personality: temporal and contextual consistency in behavior patterns that vary among individuals. In contrast to most other species, personality of chimpanzees, Pan troglodytes, has mainly been studied with non-behavioral methods. We examined boldness, exploration tendency, persistence and tool-orientation in 29 captive chimpanzees using repeated experiments conducted in an ecologically valid social setting. High temporal repeatability and contextual consistency in all these traits indicated they reflected personality. In addition, Principal Component Analysis revealed two independent syndromes, labeled exploration-persistence and boldness. We found no sex or rank differences in the trait scores, but the scores declined with age. Nonetheless, there was considerable inter-individual variation within age-classes, suggesting that behavior was not merely determined by age but also by dispositional effects. In conclusion, our study complements earlier rating studies and adds new traits to the chimpanzee personality, thereby supporting the existence of multiple personality traits among chimpanzees. We stress the importance of ecologically valid behavioral research to assess multiple personality traits and their association, as it allows inclusion of ape studies in the comparison of personality structures across species studied behaviorally, and furthers our attempts to unravel the causes and consequences of animal personality.


Assuntos
Comportamento Animal , Pan troglodytes/fisiologia , Personalidade/fisiologia , Comportamento Social , Comportamento de Utilização de Ferramentas/fisiologia , Animais , Feminino , Masculino , Análise de Componente Principal
11.
Plast Reconstr Surg Glob Open ; 11(9): e5300, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37790141

RESUMO

Background: In October 2012, an open-access, multimedia digital cleft simulator was released. Its purpose was to address global disparities in cleft surgery education, providing an easily accessible surgical atlas for trainees globally. The simulator platform includes a three-dimensional surgical simulation of cleft care procedures, intraoperative videos, and voiceover. This report aims to assess the simulator's demographics and usage in its tenth year since inception. Finally, we also aim to understand the traction of virtual reality in cleft surgical education. Methods: Usage data of the simulator over 10 years were retrospectively collected and analyzed. Data parameters included the number of users, sessions, countries reached, and content access. An electronic survey was emailed to registered users to assess the benefits of the simulator. Results: The total number of new and active simulator users reached 7687 and 12,042. The simulator was accessed an average of 172.9.0 ± 197.5 times per month. Low- to middle-income regions accounted for 43% of these sessions. The mean session duration was 11.4 ± 6.3 minutes, yielding a total screen time of 3022 hours. A total of 331 individuals responded to the survey, of whom 80.8% found the simulator to be very useful or extremely useful. Of those involved in education, 45.0% implemented the simulator as a teaching tool. Conclusions: Global utilization of the simulator has been sustained after 10 years from inception with an increased presence in low- to middle-income nations. Future similar surgical simulators may provide sustainable training platforms to surgeons in low- and high-resource areas.

12.
Sci Rep ; 12(1): 6960, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35484292

RESUMO

Bone regenerative engineering could replace autografts; however, no synthetic material fulfills all design criteria. Nanocarbons incorporated into three-dimensional printed (3DP) matrices can improve properties, but incorporation is constrained to low wt%. Further, unmodified nanocarbons have limited osteogenic potential. Functionalization to calcium phosphate graphene (CaPG) imparts osteoinductivity and osteoconductivity, but loading into matrices remained limited. This work presents ultra-high content (90%), 3DP-CaPG matrices. 3DP-CaPG matrices are highly porous (95%), moderately stiff (3 MPa), and mechanically robust. In vitro, they are cytocompatible and induce osteogenic differentiation of human mesenchymal stem cells (hMSCs), indicated by alkaline phosphatase, mineralization, and COL1α1 expression. In vivo, bone regeneration was studied using a transgenic fluorescent-reporter mouse non-union calvarial defect model. 3DP-CaPG stimulates cellular ingrowth, retains donor cells, and induces osteogenic differentiation. Histology shows TRAP staining around struts, suggesting potential osteoclast activity. Apparent resorption of 3DP-CaPG was observed and presented no toxicity. 3DP-CaPG represents an advancement towards a synthetic bone regeneration matrix.


Assuntos
Grafite , Células-Tronco Mesenquimais , Animais , Camundongos , Fosfatos de Cálcio , Grafite/farmacologia , Osteogênese , Impressão Tridimensional , Alicerces Teciduais
13.
J Clin Med ; 11(4)2022 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-35207391

RESUMO

BACKGROUND: Biotin, a water-soluble B vitamin, has demonstrable anti-inflammatory properties. A biotin-deficient diet induced a colitis-like phenotype in mice, alleviable by biotin substitution. Mice with dextran sulfate sodium (DSS)-induced colitis showed biotin deficiency and diminished levels of sodium-dependent multivitamin transporter, a protein involved in biotin absorption. Biotin substitution induced remission by reducing activation of NF-κB, a transcription factor involved in intestinal permeability and inflammatory bowel disease (IBD). We investigated for the first time a possible clinical role of biotin status in IBD. METHODS: In a comparative, retrospective, cross-sectional study, serum samples of 138 patients with IBD (67 female; 72 Crohn's disease (CD), 66 ulcerative colitis (UC)) aged 18-65 years and with a mean age (±SD) of 42.5 ± 14.3 years as well as 80 healthy blood donors (40 female; 40.0 ± 10.0 years; range 20-60 years) were analyzed. Inflammation was defined as hsCRP ≥5 mg/L, and to determine biotin status, serum 3-hydroxyisovaleryl carnitine (3HIVc) levels were measured by LC-MS/MS. RESULTS: A total of 138 patients with IBD (67f; 72CD/66 UC; 42.5 ± 14.3 years) were enrolled: 83/138 had inflammation. Mean serum 3HIVc levels were significantly higher in IBD patients but unaffected by inflammation. Biotin deficiency (95th percentile of controls: >30 nmol/L 3HIVc) was significantly more common in IBD patients versus controls. CONCLUSION: High serum 3HIVc levels and biotin deficiency were associated with IBD but not inflammatory activity or disease type. Our findings suggest biotin may play a role as cause or effect in IBD pathogenesis. Routine assessment and supplementation of biotin may ameliorate IBD and support intestinal integrity.

14.
Health Secur ; 20(5): 408-423, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36286588

RESUMO

Nanotechnology, the multidisciplinary field based on the exploitation of the unique physicochemical properties of nanoparticles (NPs) and nanoscale materials, has opened a new realm of possibilities for biological research and biomedical applications. The development and deployment of mRNA-NP vaccines for COVID-19, for example, may revolutionize vaccines and therapeutics. However, regulatory and ethical frameworks that protect the health and safety of the global community and environment are lagging, particularly for nanotechnology geared toward biological applications (ie, bionanotechnology). In this article, while not comprehensive, we attempt to illustrate the breadth and promise of bionanotechnology developments, and how they may present future safety and security challenges. Specifically, we address current advancements to streamline the development of engineered NPs for in vivo applications and provide discussion on nano-bio interactions, NP in vivo delivery, nanoenhancement of human performance, nanomedicine, and the impacts of NPs on human health and the environment.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , Nanomedicina , Nanotecnologia , RNA Mensageiro
15.
Rapid Commun Mass Spectrom ; 25(19): 2844-50, 2011 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-21913263

RESUMO

A simple, sensitive and fast method for the determination of melamine and its derivatives in milk powder using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was developed. Neither time-consuming sample preparation, nor special target plates, or other extra equipment are necessary. The common matrix sinapinic acid (SA) was used with a dried-droplet preparation. Detection limits (signal-to-noise (S/N) ratio = 3) for standard solutions of melamine, ammeline and cyanuric acid were 10, 25 and 10 µg/L, respectively. The limit of quantification (LOQ) for melamine was 25 µg/L and excellent linearity (R(2): 0.9990) was maintained over the range of 10-2000 µg/L. Ammeline and cyanuric acid were analyzed with an LOQ of 50 µg/L and also excellent linearity (R(2): 0.9997 and R(2): 0.9998). Good accuracy and precision were obtained for all concentrations within the range of the standard curve. The developed method was successfully used for the determination of melamine, ammeline and cyanuric acid in milk powder samples with a simple sample preparation. The LOQ of melamine was 0.5 µg/g. Ammeline and cyanuric acid were detectable at 0.5 and 5 µg/g. This method showed excellent accuracy, precision and linearity and significantly reduces the needed analysis time, as only approximately 10 s/sample measuring time is required. To the authors' knowledge, this is the first published method to quantify melamine and derivatives by MALDI-TOF-MS.


Assuntos
Leite/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Triazinas/análise , Animais , Ácidos Cumáricos/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
Gerontology ; 57(1): 37-43, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20134150

RESUMO

Aging is associated with far-reaching changes in physiological functions resulting in morbidity and ultimately death. Age-related frailty, insecurity and reduced physical activity contribute to a progressive loss of muscle mass and function, commonly referred to as sarcopenia. Due to the increase in life expectancy in many countries, loss of muscle mass and its consequences gain in relevance for public health. At the same time, the molecular mechanisms that underlie sarcopenia are poorly understood and therefore, therapeutic approaches are limited. Interestingly though, endurance, strength and stretching exercise is significantly superior to all known pharmacological, nutritional and hormonal interventions for stabilizing, alleviating and reversing sarcopenia. Thus, increased knowledge about the plastic changes of skeletal muscle after physical activity and the signaling factors that mediate the beneficial effects of exercise on other organs might yield a better understanding of the disease and open new avenues for treatment. Here, we discuss how current discoveries about the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a key exercise factor in muscle, and myokines, factors produced and secreted by active muscle fibers, expand our view of the pathological changes and the therapeutic options for sarcopenia.


Assuntos
Envelhecimento/fisiologia , Proteínas de Choque Térmico/fisiologia , Proteínas Musculares/fisiologia , Músculo Esquelético/fisiologia , Fatores de Transcrição/fisiologia , Idoso , Terapia por Exercício , Humanos , Modelos Biológicos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Sarcopenia/etiologia , Sarcopenia/fisiopatologia , Sarcopenia/terapia
17.
Adv Healthc Mater ; 10(7): e2001761, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33645004

RESUMO

Extensive cytocompatibility testing of 2D nanocarbon materials including graphene oxide (GO) has been performed, but results remain contradictory. Literature has yet to account for settling-although sedimentation is visible to the eye and physics suggests that even individual graphenic flakes will settle. To investigate settling, a series of functional graphenic materials (FGMs) with differing oxidation levels, functionalities, and physical dimensions are synthesized. Though zeta potential indicates colloidal stability, significant gravitational settling of the FGMs is theoretically and experimentally demonstrated. By creating a setup to culture cells in traditional and inverted orientations in the same well, a "blanket effect" is demonstrated in which FGMs settle out of solution and cover cells at the bottom of the well, ultimately reducing viability. Inverted cells protected from the blanket effect are unaffected. Therefore, these results demonstrate that settling is a crucial factor that must be considered for FGM cytocompatibility experiments.


Assuntos
Grafite , Oxirredução
18.
Biomater Sci ; 9(7): 2467-2479, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33404025

RESUMO

The balance of bacterial populations in the human body is critical for human health. Researchers have aimed to control bacterial populations using antibiotic substrates. However, antibiotic materials that non-selectively kill bacteria can compromise health by eliminating beneficial bacteria, which leaves the body vulnerable to colonization by harmful pathogens. Due to their chemical tunablity and unique surface properties, graphene oxide (GO)-based materials - termed "functional graphenic materials" (FGMs) - have been previously designed to be antibacterial but have the capacity to actively adhere and instruct probiotics to maintain human health. Numerous studies have demonstrated that negatively and positively charged surfaces influence bacterial adhesion through electrostatic interactions with the negatively charged bacterial surface. We found that tuning the surface charge of FGMs provides an avenue to control bacterial attachment without compromising vitality. Using E. coli as a model organism for Gram-negative bacteria, we demonstrate that negatively charged Claisen graphene (CG), a reduced and carboxylated FGM, is bacterio-repellent through electrostatic repulsion with the bacterial surface. Though positively charged poly-l-lysine (PLL) is antibacterial when free in solution by inserting into the bacterial cell wall, here, we found that covalent conjugation of PLL to CG (giving PLLn-G) masks the antimicrobial activity of PLL by restricting polypeptide mobility. This allows the immobilized positive charge of the PLLn-Gs to be leveraged for E. coli adhesion through electrostatic attraction. We identified the magnitude of positive charge of the PLLn-G conjugates, which is modulated by the length of the PLL peptide, as an important parameter to tune the balance between the opposing forces of bacterial adhesion and proliferation. We also tested adhesion of Gram-positive B. subtilis to these FGMs and found that the effect of FGM charge is less pronounced. B. subtilis adheres nondiscriminatory to all FGMs, regardless of charge, but adhesion is scarce and localized. Overall, this work demonstrates that FGMs can be tuned to selectively control bacterial response, paving the way for future development of FGM-based biomaterials as bacterio-instructive scaffolds through careful design of FGM surface chemistry.


Assuntos
Aderência Bacteriana , Escherichia coli , Materiais Biocompatíveis/farmacologia , Bactérias Gram-Negativas , Humanos , Propriedades de Superfície
19.
ACS Omega ; 6(29): 18694-18701, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34337208

RESUMO

Emergent technologies are driving forces in the development of innovative art media that progress the field of modern art. Recently, artists have capitalized on the versatility of a new technology to create, restore, and modify art: additive manufacturing or three-dimensional (3D) printing. Additively manufactured art relies heavily on plastic-based materials, which typically require high heat to induce melting for workability. The necessity for heat limits plastic media to dedicated 3D printers. In contrast, biologically derived polymers such as polysaccharides used to create "bioinks" often do not require heating the material for workability, broadening the types of techniques available for printing. Here, we detail the formulation of a bioink consisting of mica pigments suspended in alginate as a new, vibrant art medium for 2D and 3D compositions. The properties that make alginate an ideal colorant binder are detailed: low cost with wide availability, nontoxicity and biocompatibility, minimal color, and an array of attractive physicochemical properties that offer workability and processing into 2D and 3D structures. Further, the chemical composition, morphology, and dispersibility of an array of mica pigment additives are characterized in detail as they pertain to the quality of an art medium. Alginate-based media with eight mica colors were formulated, where mica addition resulted in vibrantly colored inks with moderate hiding power and coverage of substrates necessary for 2D printing with thin horizontal and vertical lines. The utility of the media is demonstrated via the generation of 2D and 3D vibrant structures.

20.
RSC Adv ; 10(14): 8548-8557, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35497868

RESUMO

Traditional metal implants such as titanium, cobalt, and chromium have found wide utility in medicine; however, these come with a risk of toxicity. To overcome metal-related toxicity and enable degradability, polyesters including polycaprolactone (PCL), polylactic acid (PLA), and polyglycolic acid (PGA) show promise for the replacement of various biomedical applications of metals due to their accepted biocompatibility and FDA approval. However, polyesters are less stiff than their metallic counterparts, limiting their application to non-load bearing injury sites, such as fixation hardware for fingers. To improve mechanical properties, graphene oxide (GO)-polyester composites are a promising class of biodegradable scaffolds. Initial reports of these composites are encouraging, but mechanical properties still fall short. Traditional composites rely on non-covalent association between GO and the polyesters, which often leads to failure at the interface and weakens the overall strength of the material. Herein, we present a strategy for attachment of these FDA-approved polyesters onto a derivative of GO using a robust covalent bond. By covalently functionalizing the graphenic backbone with polyesters and without metal catalysts, we create functional graphenic materials (FGMs) to not only simultaneously retain biodegradability and compatibility, but also mechanically strengthen PCL, PLA, and PGA; we observed an average increase in the Young's modulus of over 140% compared to the graphenic backbone. These polyester-functionalized FGMs are a promising platform technology for tissue implants.

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