RESUMO
BACKGROUND: Biologic therapies approved for treating chronic rhinosinusitis with nasal polyps (CRSwNP) have well-established safety profiles but reports of rheumatic adverse events (AEs) are increasing and not well defined. This review aims to assess the risk and incidence of rheumatic AEs associated with biologic therapy in CRSwNP and summarize current reported management strategies. METHODS: A protocol was registered in PROSPERO [CRD42024525663]. A search was conducted in four electronic databases: Medline (Ovid), Embase, Scopus, and Cochrane CENTRAL from inception until January 4, 2024. Two reviewers independently screened citations and extracted data. Methodological quality was assessed using the Joanna Briggs Institute's critical appraisal tool. Data were pooled using a random effects model to calculate overall incidence and relative risk. RESULTS: Twenty-one studies met the final inclusion criteria, totaling 3434 patients of which 2763 (80%) received either dupilumab (n = 2257; 82%), mepolizumab (n = 372; 13%), or omalizumab (n = 134; 5%) for treatment of CRSwNP. The overall incidence rate for any on-treatment rheumatic AE was 0.05 per person-year (95% CI, 0.03-0.09, I2 = 75%). Biologic therapy increased the risk of developing a rheumatic AE (RR = 2.53; 95% CI, 1.29-4.94) compared with placebo. The most frequently reported rheumatic AE was arthralgia or joint pain (n = 94; 95%), followed by lupus-like syndrome or lupus erythematosus-like reaction (n = 2; 2.5%). Discontinuation of treatment was the most common intervention (n = 21, 39%). CONCLUSION: Biologic therapy increases the risk of rheumatic AEs in CRSwNP patients by over twofold. Healthcare providers should remain vigilant in monitoring rheumatic AEs and apply appropriate management strategies on a case-by-case basis.
Assuntos
Doenças Reumáticas , Rinite , Sinusite , Humanos , Sinusite/tratamento farmacológico , Sinusite/induzido quimicamente , Sinusite/epidemiologia , Rinite/induzido quimicamente , Rinite/tratamento farmacológico , Rinite/epidemiologia , Doença Crônica , Doenças Reumáticas/tratamento farmacológico , Terapia Biológica/efeitos adversos , Pólipos Nasais/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Omalizumab/uso terapêutico , Omalizumab/efeitos adversos , Incidência , RinossinusiteRESUMO
OBJECTIVES: To evaluate epidemiological trends of pediatric esophageal foreign body (EFB) ingestion over two decades. METHODS: A retrospective analysis was performed using data from the National Electronic Injury Surveillance System (NEISS) database for children <18 years who presented to a United States Emergency Department (ED) with EFB between 2003 and 2022. Number of cases and type of EFB were recorded. Rates of EFBs over time were analyzed via linear regression. RESULTS: A total of 52,315 EFB cases were identified over the 20-year period, with a national estimate of 1,589,325 cases. The most frequently ingested objects were coins (37.6%), toys (13.5%), and batteries (6.8%). Overall incidence of EFB ingestion increased from 7.3 to 14.2/10,000 children from 2003 to 2022 (R2 = 0.8, p < 0.0001). Incidence of coin ingestion increased from 3 to 4.5/10,000 children (R2 = 0.06, p = 0.335) but represented a smaller proportion of all EFB over time (66% in 2003 versus 43% in 2022). Incidence of magnet, battery, and toy ingestion have increased from 0.3 to 1.0/10,000 (R2 = 0.9, p < 0.0001), 0.3 to 1/10,000 (R2 = 0.7, p < 0.0001), and 0.6 to 2.3/10,000 (R2 = 0.8, p < 0.0001) children, respectively, between 2003 and 2022. The proportion of magnet, battery, and toy ingestion have increased over time (3.2%, 6.5%, and 11.8%, respectively, in 2003 to 11.4%, 11.7%, and 22.2%, respectively, in 2022). CONCLUSION: Magnet, battery, and toy ingestion have increased significantly in the past two decades, while the proportion of coin ingestion has decreased. This trend may reflect shifts within the consumer market and increased availability of electronics concurrent with the adoption of digital currency. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.
RESUMO
Introduction: Parkinson's disease (PD) is an incurable, progressive, neurodegenerative disorder. As PD advances and symptoms progress, patients become increasingly dependent on family and carers. Traditional cost-effectiveness analyses (CEA) only consider patient and payer-related outcomes, failing to acknowledge impacts on families, carers, and broader society. This novel Social Return on Investment (SROI) analysis aimed to evaluate the broader impact created by improving access to levodopa (LD) device-aided therapies (DATs) for people living with advanced PD (aPD) in Australia. Methods: A forecast SROI analysis over a three-year time horizon was conducted. People living with aPD and their families were recruited for qualitative interviews or a quantitative survey. Secondary research and clinical trial data was used to supplement the primary research. Outcomes were valued and assessed in a SROI value map in Microsoft Excel™. Financial proxies were assigned to each final outcome based on willingness-to-pay, economic valuation, and replacement value. Treatment cost inputs were sourced from Pharmaceutical Benefits Schedule (PBS) and Medicare Benefits Scheme (MBS) published prices. Results: Twenty-four interviews were conducted, and 55 survey responses were received. For every $1 invested in access to LD-based DATs in Australia, an estimated $1.79 of social value is created. Over 3 years, it was estimated $277.16 million will be invested and $406.77 million of social return will be created. This value is shared between people living with aPD (27%), their partners (22%), children (36%), and the Australian Government (15%). Most of the value created is social and emotional in nature, including reduced worry, increased connection to family and friends, and increased hope for the future. Discussion: Investment in LD-based DATs is expected to generate a positive social return. Over 50% of the value is created for the partners and children of people living with aPD. This value would not be captured in traditional CEA. The SROI methodology highlights the importance of investing in aPD treatment, capturing the social value created by improved access to LD-based DATs.
Assuntos
Análise Custo-Benefício , Levodopa , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/economia , Doença de Parkinson/terapia , Austrália , Levodopa/uso terapêutico , Levodopa/economia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Inquéritos e Questionários , Antiparkinsonianos/uso terapêutico , Antiparkinsonianos/economia , Pesquisa Qualitativa , Entrevistas como AssuntoRESUMO
Gastric leiomyomas are benign, submucosal tumors found incidentally on unrelated imaging or during autopsy. The majority of leiomyomas are asymptomatic; however, patients can develop central ulcerations on the lesions leading to upper gastrointestinal (GI) bleeding. A 75-year-old female, with a past medical history of hypertension, hyperlipidemia, and a cerebrovascular accident, presented with complaints of melena, near-syncope events, lightheadedness, weakness, and hematemesis. A computed tomography (CT) of the abdomen with contrast found a heterogeneous low-attenuation mass of 4×4×3 cm3 within the gastric fundus and near the gastroesophageal (GE) junction. After an open gastrostomy and excisional biopsy, the mass was identified as a leiomyoma. This case report reviews the presentation, diagnostic assessments, and treatment of a gastric leiomyoma in a complex location proximal to the gastroesophageal junction. Gastric leiomyomas should be considered as a differential diagnosis for patients presenting with an upper gastrointestinal bleed.
RESUMO
AIM: The primary purpose of this study was to explore relationships between self-efficacy, peer support, coping style, intent to work at the bedside, and resilience in nursing students. BACKGROUND: Resilience correlates with one-year retention at the bedside. Retention of bedside nurses improves patient outcomes. METHOD: A quantitative, correlational design determined relationships between variables. Surveys were completed by 205 participants. Surveys included a program type list, intent to work at the bedside items, the Brief Cope Scale, the General Self-Efficacy Scale, the Peer Group Caring Interaction Scale. RESULTS: Significant relationships were found between resilience and self-efficacy, resilience and coping style, and peer support and approach coping style. Half of the respondents intended to work at the bedside for two years after graduation. Self-efficacy and avoidance coping were resilience predictors. CONCLUSION: To support resilience, educators should facilitate students' development of self-efficacy and approach coping style.
Assuntos
Adaptação Psicológica , Resiliência Psicológica , Autoeficácia , Estudantes de Enfermagem , Humanos , Estudantes de Enfermagem/psicologia , Feminino , Masculino , Adulto , Inquéritos e Questionários , Bacharelado em Enfermagem , Adulto Jovem , Intenção , Grupo AssociadoRESUMO
BACKGROUND: The nursing home population is characterized by multimorbidity and disabilities, which often result in extensive prescription of medication and subsequent polypharmacy. Deprescribing, a planned and supervised process of dose reduction or total cessation of medication, is a solution to combat this. OBJECTIVE: This study aimed to identify barriers and enablers of deprescribing as experienced by nursing home physicians (NHPs) and collaborating pharmacists in the specific nursing home setting. METHODS: This qualitative study utilized a semi-structured interview format with two focus groups consisting of a mix of NHPs and pharmacists. Directed content analysis was performed based on the Theoretical Domains Framework, a validated framework for understanding determinants of behavior change among health care professionals. RESULTS: Sixteen health care professionals participated in two focus groups, including 13 NHPs and three pharmacists. The participating NHPs and pharmacists believed that deprescribing is a valuable process with enablers, such as multidisciplinary collaboration, good communication with patients and family, and involvement of the nursing staff. NHPs and pharmacists view deprescribing as a core task and feel assured in their ability to carry it out successfully. However, they also noted barriers: deprescribing is time-consuming; communication with residents, their relatives or medical specialists is difficult; and electronic patient systems often do not adequately support it. CONCLUSIONS: This study provides insight into the various barriers and enablers faced by NHPs and pharmacists when deprescribing in nursing homes. Specific for this population, deprescribing barriers focus on communication (with residents and their relatives, and also with medical specialists) and resources, while knowledge and expertise are mentioned as enablers.
Assuntos
Desprescrições , Humanos , Grupos Focais , Casas de Saúde , Pessoal de Saúde , PolimedicaçãoRESUMO
BACKGROUND: Intraplaque angiogenesis occurs in response to atherosclerotic plaque hypoxia, which is driven mainly by highly metabolically active macrophages. Improving plaque oxygenation by increasing macrophage hypoxic signaling, thus stimulating intraplaque angiogenesis, could restore cellular function and neovessel maturation, and decrease plaque formation. Prolyl hydroxylases (PHDs) regulate cellular responses to hypoxia. We therefore aimed to elucidate the role of myeloid PHD2, the dominant PHD isoform, on intraplaque angiogenesis in a murine model for venous bypass grafting. METHODS AND RESULTS: Myeloid PHD2 conditional knockout (PHD2cko) and PHD2 wild type mice on an Ldlr-/- background underwent vein graft surgery (n=11-15/group) by interpositioning donor caval veins into the carotid artery of genotype-matched mice. At postoperative day 28, vein grafts were harvested for morphometric and compositional analysis, and blood was collected for flow cytometry. Myeloid PHD2cko induced and improved intraplaque angiogenesis by improving neovessel maturation, which reduced intraplaque hemorrhage. Intima/media ratio was decreased in myeloid PHD2cko vein grafts. In addition, PHD2 deficiency prevented dissection of vein grafts and resulted in an increase in vessel wall collagen content. Moreover, the macrophage proinflammatory phenotype in the vein graft wall was attenuated in myeloid PHD2cko mice. In vitro cultured PHD2cko bone marrow-derived macrophages exhibited an increased proangiogenic phenotype compared with control. CONCLUSIONS: Myeloid PHD2cko reduces vein graft disease and ameliorates vein graft lesion stability by improving intraplaque angiogenesis.
Assuntos
Prolina Dioxigenases do Fator Induzível por Hipóxia , Placa Aterosclerótica , Remodelação Vascular , Animais , Camundongos , Angiogênese , Modelos Animais de Doenças , Hipóxia , Camundongos Knockout , Placa Aterosclerótica/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismoRESUMO
Sleep is essential, but animals may forgo sleep to engage in other critical behaviors, such as feeding and reproduction. Previous studies have shown that female flies exhibit decreased sleep after mating, but our understanding of the process is limited. Here, we report that postmating nighttime sleep loss is modulated by diet and sleep deprivation, demonstrating a complex interaction among sleep, reproduction, and diet. We also find that female-specific pC1 neurons and sleep-promoting dorsal fan-shaped body (dFB) neurons are required for postmating sleep plasticity. Activating pC1 neurons leads to sleep suppression on standard fly culture media but has little sleep effect on sucrose-only food. Published connectome data suggest indirect, inhibitory connections among pC1 subtypes. Using calcium imaging, we show that activating the pC1e subtype inhibits dFB neurons. We propose that pC1 and dFB neurons integrate the mating status, food context, and sleep drive to modulate postmating sleep plasticity.
Assuntos
Proteínas de Drosophila , Distúrbios do Início e da Manutenção do Sono , Animais , Feminino , Drosophila/fisiologia , Proteínas de Drosophila/fisiologia , Sono/fisiologia , Privação do Sono , Drosophila melanogaster/fisiologiaRESUMO
INTRODUCTION: We investigated whether changes in engagement in home-based creative activities were associated with changes in depressive symptoms, anxiety symptoms and life satisfaction during the COVID-19 pandemic, aiming to replicate findings from the UK in a USA sample. METHODS: 3725 adults were included from the COVID-19 Social Study in the USA, a panel study collecting data weekly during the COVID-19 pandemic. We measured engagement in eight types of creative leisure activities on the previous weekday between April and September 2020. Data were analysed using fixed effects regression models. RESULTS: Increased time spent gardening was associated with reductions in depressive and anxiety symptoms and enhanced life satisfaction. Spending more time doing woodwork/DIY and arts/crafts were also associated with enhanced life satisfaction. However, more time watching television, films or other similar media (not for information on COVID-19) was associated with increased depressive symptoms. Other creative activities were not associated with mental health or well-being. CONCLUSION: Some findings differ from evidence obtained in the UK, demonstrating the importance of replicating research across countries. Our findings should also be considered when formulating guidelines for future stay-at-home directives, enabling individuals to stay well despite the closure of public resources.
Assuntos
COVID-19 , Humanos , Adulto , COVID-19/epidemiologia , Saúde Mental , Pandemias , Atividades de Lazer , Recreação , Depressão/epidemiologia , Ansiedade/epidemiologiaRESUMO
Erosive tooth wear is a multifactorial condition of an increasing prevalence. There is a need for discovering individual genetic predisposition for the development of this condition. Considering that the chromosome X locus was previously shown to be associated with dental caries, the aim of the present study was to look for the association between this locus and erosive tooth wear when dietary habits are considered as a co-factor. Saliva samples, erosive wear experience data, and dietary information from 16- to 18-year-old dental patients (n = 705) were used. Genotyping analyses were performed, and thereafter, analyses considering diet and oral hygiene data, using logistic regression, with the assumption that erosive tooth wear is a complex gene-environment model. Genotypic analyses revealed an association between chromosome X marker rs1324156 and erosive tooth wear phenotype. Logistic regression analysis showed that, in the presence of less common allele of rs12687601 and rs1324156, erosive tooth wear more likely develops when associated with numerous dietary variables from the questionnaire. These results indicate that erosive tooth wear may be the result of gene-environment interactions.
Assuntos
Cárie Dentária , Atrito Dentário , Erosão Dentária , Desgaste dos Dentes , Cárie Dentária/epidemiologia , Cárie Dentária/genética , Humanos , Masculino , Adolescente , Desgaste dos Dentes/epidemiologia , Desgaste dos Dentes/genética , Atrito Dentário/epidemiologia , Atrito Dentário/genética , Prevalência , Fenótipo , Erosão Dentária/epidemiologia , Erosão Dentária/genética , Cromossomos Humanos X , Genótipo , Marcadores GenéticosRESUMO
Health of an ecosystem is very much important as we depend on its goods and services for our existence. Because of this, we need to continuously monitor its health for human benefit and for identifying areas for improvement of our natural systems. The present study tries to assess the condition of a coastal ecosystem within the Vembanad Lake, Kerala, India, using key water quality parameters at micro-level. Principal component analysis identified the minimum required water quality dataset for further analysis and was scored using linear scoring functions. The weighted additive method was used to integrate the individual scores to arrive at a final score representing the ecosystem health. Spline interpolation was applied to develop the ecosystem health map of the study area. Using this method, 35.8% area of the aquatic ecosystem studied was characterized as good, 32.2% as moderate, 26.2% as fair and 5.8% as poor. The assessment results can help the policymakers/managers to make appropriate decisions for the better management of the coastal ecosystems studied. Moreover, this methodology can be replicated for the assessment of coastal regions with similar ecosystem characteristics.
Assuntos
Ecossistema , Lagos , Humanos , Conservação dos Recursos Naturais , Monitoramento Ambiental , Qualidade da Água , ÍndiaRESUMO
Arts engagement is a health-related behavior that may be influenced by social inequalities. While the COVID-19 pandemic provided new opportunities for some people to engage in the arts, it might have created barriers for others. We aimed to examine whether there was social patterning in home-based arts engagement during the pandemic in the United States, and whether predictors of engagement differed according to the type of arts activity. We included 4,731 adults who participated in the United States COVID-19 Social Study between April and July 2020. Three types of home-based arts engagement were considered: reading for pleasure, arts or crafts activities, and digital arts activities. Using logistic regression models, we tested cross-sectional associations between a broad range of demographic, socioeconomic, psychosocial, and health-related factors as well as adverse events and worries during lockdown and each type of arts engagement. The factors most strongly associated with all three types of arts engagement were social support, social network size, age, race/ethnicity, keyworker status, and experiencing physical or psychological abuse during the pandemic. However, most socioeconomic and health-related factors were not associated with arts engagement, including household income and mental and physical health problems. Overall, our findings indicate that the social gradient in arts engagement was reduced in the first 4 months of the COVID-19 pandemic in the United States. Given the health benefits of arts engagement, the potential diversification of arts audiences during the pandemic is promising for both population-level health and wellbeing and the future of the arts and cultural sector.
RESUMO
Readiness for practice (RFP) is essential as new nurses will practice in a nursing shortage climate, with high acuity patients and complex technology. Nurse educators are challenged to foster readiness for practice. AIM: The aim of this integrative review was to explore the impact of simulation and senior practicum on graduating senior nursing students' readiness for practice. BACKGROUND: Readiness for practice has been a point of concern for healthcare for quite some time. This has led to a need for better understanding for what RFP means including their perceptions of various stakeholders. Further, it is important to address what teaching and learning strategies can be implemented to assist in ensuring the graduating senior nursing student is ready for practice on graduation and for their first professional practice. Readiness for practice is defined as the ability to safely and competently care for patients by synthesizing theory, skills, attitudes and values in applying clinical reasoning in practice settings. METHOD: An integrative review identified 48 published papers on simulation and senior practicum that met the inclusion criteria. RESULTS: Themes identified from the senior practicum/preceptor literature included clinical reasoning, skills, barriers to the senior practicum and transition. Themes identified regarding simulation as a strategy included preparation, competence development, clinical reasoning and the number of human patient simulators used. CONCLUSION: Although the evidence is not conclusive, simulation and senior practicums have the promise of preparing graduating nursing students for their first professional practice. However, nurse educators must ensure simulations are well-organized with clear objectives and that preceptors are supported in teaching and assessing students.
Assuntos
Bacharelado em Enfermagem , Estudantes de Enfermagem , Competência Clínica , Atenção à Saúde , Docentes de Enfermagem , HumanosRESUMO
BACKGROUND: Patients with end-stage kidney disease who receive haemodialysis experience a protracted treatment regimen that can result in an increased risk of depression and anxiety. Arts-based interventions could address this unique issue; however, no arts-based interventions have been developed for delivery within a haemodialysis unit and evaluation within a randomised controlled trials (RCTs). AIM: To develop a complex arts-based intervention for patients with end-stage kidney disease whilst receiving haemodialysis. METHODS: The development process utilised the Arts in Health framework (Fancourt, 2017). The framework was addressed through the establishment of an interdisciplinary advisory group, collaboration and consultation with stakeholders, a scoping and realist review, shadowing of artists-in-residence, personal arts practice and logic modelling. RESULTS: The intervention involved six 1-h long, one-to-one facilitated sessions focused on creative writing and visual art. Patients could choose between art form and self-select a subject matter. The sessions had a primary focus on skill development and were delivered using principles derived from the psychological theory of flow. CONCLUSION: The Arts in Health framework provided an appropriate and pragmatic approach to intervention development. Complex arts-based interventions can be developed for the purpose of evaluation within a trial framework. This intervention was designed to strike a balance between standardised components, and a person-centred approach necessary to address existential boredom.
RESUMO
BACKGROUND: Haemodialysis can negatively impact quality of life and mental health. Arts-based interventions used successfully in other settings to improve health and well-being, could help address the impact of haemodialysis. This study aimed to evaluate the feasibility and acceptability of conducting a randomised controlled trial (RCT) of an arts-based intervention for patients receiving haemodialysis. METHODS: A parallel convergent mixed-methods design was used, including a pilot cluster RCT and qualitative process evaluation. Phase 1 evaluated recruitment and retention rates through a pilot cluster RCT at a single haemodialysis unit in Northern Ireland. Participants included patients who received haemodialysis for ESKD, were over the age of 18 and had the capacity to consent. These participants were randomised to the intervention or control group according to their haemodialysis shift. The intervention involved six one-hour, one-to-one facilitated arts sessions during haemodialysis. Phase 2 explored intervention and trial acceptability through a qualitative process evaluation using semi-structured interviews based on the RE-AIM framework. Participants included 13 patients who participated in phase 1 of the study, including 9 participants from the experimental group and four participants from the control group, and nine healthcare professionals who were present on the unit during implementation. RESULTS: Out of 122 outpatient haemodialysis patients, 94 were assessed as eligible for participation. Twenty-four participants were randomised, meaning 80% of the target sample size was recruited and the attrition rate at 3 months was 12.5% (n = 3). Participants viewed the arts as more accessible and enjoyable than anticipated following implementation. All participants who started the intervention (n = 11) completed the full six sessions. Qualitative benefits of the intervention suggest improvements in mental well-being. Patient choice and facilitation were important factors for successful implementation. CONCLUSION: An arts-based intervention for patients receiving haemodialysis is acceptable for both patients and healthcare professionals, and a definitive trial is feasible. The intervention may help improve mental-wellbeing in patients receiving haemodialysis, but this requires further investigation in a definitive trial. TRIAL REGISTRATION: The trial was prospectively registered on clinicaltrials.gov on 14/8/2018, registration number NCT03629496 .
Assuntos
Arteterapia , Saúde Mental , Qualidade de Vida , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal/psicologiaRESUMO
The human microbiome encompasses a variety of microorganisms that change dynamically and are in close contact with the body. The microbiome influences health and homeostasis, as well as the immune system, and any significant change in this equilibrium (dysbiosis) triggers both acute and chronic health conditions. Microbiome research has surged, in part, due to advanced sequencing technologies enabling rapid, accurate, and cost-effective identification of the microbiome. A major prerequisite for stool sample collection to study the gut microbiome in longitudinal prospective studies requires standardized protocols that can be easily replicated. However, there are still significant bottlenecks to stool specimen collection that contribute to low patient retention rates in microbiome studies. These barriers are further exacerbated in solid organ transplant recipients where diarrhea is estimated to occur in up to half the patient population. We sought to test two relatively easy sample collection methods (fecal swab and wipes) and compare them to the more cumbersome "gold" standard collection method (scoop) using two different sequencing technologies (16S ribosomal RNA sequencing and shotgun metagenomics). Our comparison of the collection methods shows that both the swabs and the wipes are comparable to the scoop method in terms of bacterial abundance and diversity. The swabs, however, were closer in representation to the scoop and were easier to collect and process compared to the wipes. Potential contamination of the swab and the wipe samples by abundant skin commensals was low in our analysis. Comparison of the two sequencing technologies showed that they were complementary, and that 16S sequencing provided enough coverage to detect and differentiate between bacterial species identified in the collected samples. Our pilot study demonstrates that alternative collection methods for stool sampling are a viable option in clinical applications, such as organ transplant studies. The use of these methods may result in better patient retention recruitment rates in serial microbiome studies.
Assuntos
Metagenômica , Transplante de Órgãos , Estudos de Viabilidade , Fezes , Voluntários Saudáveis , Humanos , Projetos Piloto , Estudos Prospectivos , RNA Ribossômico 16SRESUMO
The native extracellular matrix (ECM) contains a host of matricellular proteins and bioactive factors that regulate cell behavior, and many ECM components have been leveraged to guide cell fate. However, the large size and chemical characteristics of these constituents complicate their incorporation into biomaterials without interfering with material properties, motivating the need for alternative approaches to regulate cellular responses. Mesenchymal stromal cells (MSCs) can promote osseous regeneration in vivo directly or indirectly through multiple means including (1) secretion of proangiogenic and mitogenic factors to initiate formation of a vascular template and recruit host cells into the tissue site or (2) direct differentiation into osteoblasts. As MSC behavior is influenced by the properties of engineered hydrogels, we hypothesized that the biochemical and biophysical properties of alginate could be manipulated to promote the dual contributions of encapsulated MSCs toward bone formation. We functionalized alginate with QK peptide to enhance proangiogenic factor secretion and RGD to promote adhesion, while biomechanical-mediated osteogenic cues were controlled by modulating viscoelastic properties of the alginate substrate. A 1:1 ratio of QK:RGD resulted in the highest levels of both proangiogenic factor secretion and mineralization in vitro. Viscoelastic alginate outperformed purely elastic gels in both categories, and this effect was enhanced by stiffness up to 20 kPa. Furthermore, viscoelastic constructs promoted vessel infiltration and bone regeneration in a rat calvarial defect over 12 weeks. These data suggest that modulating viscoelastic properties of biomaterials, in conjunction with dual peptide functionalization, can simultaneously enhance multiple aspects of MSC regenerative potential and improve neovascularization of engineered tissues.
Assuntos
Hidrogéis , Células-Tronco Mesenquimais , Animais , Diferenciação Celular , Osteogênese , Peptídeos , Ratos , Células EstromaisRESUMO
Traumatic brain injury (TBI) causes cortical dysfunction and can lead to post-traumatic epilepsy. Multiple studies demonstrate that GABAergic inhibitory network function is compromised following TBI, which may contribute to hyperexcitability and motor, behavioral, and cognitive deficits. Preserving the function of GABAergic interneurons, therefore, is a rational therapeutic strategy to preserve cortical function after TBI and prevent long-term clinical complications. Here, we explored an approach based on the ketogenic diet, a neuroprotective and anticonvulsant dietary therapy which results in reduced glycolysis and increased ketosis. Utilizing a pharmacologic inhibitor of glycolysis (2-deoxyglucose, or 2-DG), we found that acute in vitro application of 2-DG decreased the excitability of excitatory neurons, but not inhibitory interneurons, in cortical slices from naïve mice. Employing the controlled cortical impact (CCI) model of TBI in mice, we found that in vitro 2-DG treatment rapidly attenuated epileptiform activity seen in acute cortical slices 3 to 5 weeks after TBI. One week of in vivo 2-DG treatment immediately after TBI prevented the development of epileptiform activity, restored excitatory and inhibitory synaptic activity, and attenuated the loss of parvalbumin-expressing inhibitory interneurons. In summary, 2-DG may have therapeutic potential to restore network function following TBI.
Assuntos
Antimetabólitos/farmacologia , Lesões Encefálicas Traumáticas/metabolismo , Córtex Cerebral/efeitos dos fármacos , Excitabilidade Cortical/efeitos dos fármacos , Desoxiglucose/farmacologia , Epilepsia Pós-Traumática/metabolismo , Neurônios GABAérgicos/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Animais , Contusão Encefálica/metabolismo , Córtex Cerebral/metabolismo , Dieta Cetogênica , Modelos Animais de Doenças , Neurônios GABAérgicos/metabolismo , Técnicas In Vitro , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Camundongos , Inibição Neural/efeitos dos fármacos , Parvalbuminas/metabolismoRESUMO
Healthcare environments have increased in complexity over the last 30 years. However, educational methods to prepare nurses have remained virtually unchanged. To prepare nurses to practice in today's complex practice environment, there are calls for change and transformation in how nursing education is implemented. This transformation requires nurse educators to shift their epistemic beliefs about teaching and learning by considering theories that promote effective learning. An innovative method being used in nursing education is the Flipped Classroom Method (FCM). The FCM is a teaching strategy that encourages critical thinking and application of knowledge obtained outside of the classroom to real-world situations and problems within the classroom. This paper presents a preliminary framework synthesized from multiple theories including andragogy, constructivism, self-efficacy, and diffusion of innovations. The purpose of this preliminary framework is to support the nurse educator's reflections about the learner, their abilities to implement the FCM and to synthesize theoretical constructs to implement the FCM.