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OBJECTIVE: to investigate the contributions of applying the Lean methodology to improve work processes in health and nursing and its impact on associated financial aspects. METHOD: an integrative review, carried out in six databases, whose sample of ten (100.0%) studies was analyzed and summarized descriptively. RESULTS: the outcomes obtained were stratified into: benefits/barriers to Lean Healthcare implementation; economic aspects involving Lean Healthcare implementation; and process improvements through Lean Healthcare implementation. The majority of studies (60.0%) were carried out in university hospitals, contexts that need to continually improve the quality of services provided, generally with scarce and limited resources, which support the viability of maintaining the teaching, research and extension tripod. CONCLUSION: three (30.0%) studies highlighted the financial aspects associated with Lean methodology application. The others only mentioned the possibility of financial gains through improving processes and reducing waste.
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Gestão da Qualidade Total , Humanos , Gestão da Qualidade Total/métodos , Melhoria de Qualidade , Eficiência Organizacional/normas , Enfermagem/métodos , Enfermagem/normasRESUMO
Carriers for RNA delivery must be dynamic, first stabilizing and protecting therapeutic RNA during delivery to the target tissue and across cellular membrane barriers and then releasing the cargo in bioactive form. The chemical space of carriers ranges from small cationic lipids applied in lipoplexes and lipid nanoparticles, over medium-sized sequence-defined xenopeptides, to macromolecular polycations applied in polyplexes and polymer micelles. This perspective highlights the discovery of distinct virus-inspired dynamic processes that capitalize on mutual nanoparticle-host interactions to achieve potent RNA delivery. From the host side, subtle alterations of pH, ion concentration, redox potential, presence of specific proteins, receptors, or enzymes are cues, which must be recognized by the RNA nanocarrier via dynamic chemical designs including cleavable bonds, alterable physicochemical properties, and supramolecular assembly-disassembly processes to respond to changing biological microenvironment during delivery.
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Sinais (Psicologia) , Micelas , Membrana Celular , Polímeros , RNARESUMO
A cationic, dendrimer-like oligo(aminoamide) carrier with four-arm topology based on succinoyl tetraethylene pentamine and histidines, cysteines, and N-terminal azido-lysines was screened for plasmid DNA delivery on various cell lines. The incorporated azides allow modification with various shielding agents of different polyethylene glycol (PEG) lengths and/or different ligands by copper-free click reaction, either before or after polyplex formation. Prefunctionalization was found to be advantageous over postfunctionalization in terms of nanoparticle formation, stability, and efficacy. A length of 24 ethylene oxide repetition units and prefunctionalization of ≥50% of azides per carrier promoted optimal polyplex shielding. PEG shielding resulted in drastically reduced DNA transfer, which could be successfully restored by active lectin targeting via novel GalNAc or mannose ligands, enabling enhanced receptor-mediated endocytosis of the carrier system. The involvement of the asialoglycoprotein receptor (ASGPR) in the uptake of GalNAc-functionalized polyplexes was confirmed in the ASGPR-positive hepatocarcinoma cell lines HepG2 and Huh7. Mannose-modified polyplexes showed superior cellular uptake and transfection efficacy compared to unmodified and shielded polyplexes in mannose-receptor-expressing dendritic cell-like DC2.4 cells.
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Manose , Polietilenoglicóis , Azidas , DNA/metabolismo , TransfecçãoRESUMO
Messenger RNA (mRNA) is a powerful tool for nucleic acid-based therapies and vaccination, but efficient and specific delivery to target tissues remains a significant challenge. In this study, we demonstrate lipoamino xenopeptide carriers as components of highly efficient mRNA LNPs. These lipo-xenopeptides are defined as 2D sequences in different 3D topologies (bundles or different U-shapes). The polar artificial amino acid tetraethylene pentamino succinic acid (Stp) and various lipophilic tertiary lipoamino fatty acids (LAFs) act as ionizable amphiphilic units, connected in different ratios via bisamidated lysines as branching units. A series of more lipophilic LAF4-Stp1 carriers with bundle topology is especially well suited for efficient encapsulation of mRNA into LNPs, facilitated cellular uptake and strongly enhanced endosomal escape. These LNPs display improved, faster transfection kinetics compared to standard LNP formulations, with high potency in a variety of tumor cell lines (including N2a neuroblastoma, HepG2 and Huh7 hepatocellular, and HeLa cervical carcinoma cells), J774A.1 macrophages, and DC2.4 dendritic cells. High transfection levels were obtained even in the presence of serum at very low sub-microgram mRNA doses. Upon intravenous application of only 3 µg mRNA per mouse, in vivo mRNA expression is found with a high selectivity for dendritic cells and macrophages, resulting in a particularly high overall preferred expression in the spleen.
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Nanopartículas , Baço , Camundongos , Animais , Baço/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Nanopartículas/química , Lipídeos/química , Transfecção , Macrófagos/metabolismo , Células Dendríticas/metabolismo , RNA Interferente Pequeno , Lipossomos/metabolismoRESUMO
ABSTRACT Objective: to investigate the contributions of applying the Lean methodology to improve work processes in health and nursing and its impact on associated financial aspects. Method: an integrative review, carried out in six databases, whose sample of ten (100.0%) studies was analyzed and summarized descriptively. Results: the outcomes obtained were stratified into: benefits/barriers to Lean Healthcare implementation; economic aspects involving Lean Healthcare implementation; and process improvements through Lean Healthcare implementation. The majority of studies (60.0%) were carried out in university hospitals, contexts that need to continually improve the quality of services provided, generally with scarce and limited resources, which support the viability of maintaining the teaching, research and extension tripod. Conclusion: three (30.0%) studies highlighted the financial aspects associated with Lean methodology application. The others only mentioned the possibility of financial gains through improving processes and reducing waste.
RESUMEN Objetivo: investigar las contribuciones de la aplicación de la metodología Lean a la mejora de los procesos de trabajo en salud y enfermería y su impacto en los aspectos financieros asociados. Método: revisión integradora, realizada en seis bases de datos, cuya muestra de diez (100,0%) estudios fue analizada y resumida de forma descriptiva. Resultados: los resultados obtenidos se estratificaron en: beneficios/barreras para la implementación de Lean Healthcare; aspectos económicos que implican la implementación de Lean Healthcare; y mejoras de procesos mediante la implementación de Lean Healthcare. La mayoría de los estudios (60,0%) se realizaron en hospitales universitarios, contextos que necesitan mejorar continuamente la calidad de los servicios prestados, generalmente con recursos escasos y limitados, que sustentan la viabilidad de mantener el trípode de docencia, investigación y extensión. Conclusión: tres (30,0%) estudios destacaron los aspectos financieros asociados a la aplicación de la metodología Lean. Los demás solo mencionaron la posibilidad de obtener ganancias financieras mejorando los procesos y reduciendo el desperdicio.
RESUMO Objetivo: investigar as contribuições da aplicação da metodologia Lean para melhoria dos processos de trabalho em saúde e enfermagem e sua repercussão nos aspectos financeiros associados. Método: revisão integrativa, realizada em seis bases de dados, cuja amostra de dez (100,0%) estudos foi analisada e sintetizada descritivamente. Resultados: os desfechos obtidos foram estratificados em: benefícios/barreiras para implantação do Lean Healthcare; aspectos econômicos envolvendo a implantação do Lean Healthcare; e melhorias em processos por meio da implantação do Lean Healthcare. A maioria dos estudos (60,0%) foi realizada em hospitais universitários, contextos que precisam melhorar, continuamente, a qualidade dos serviços prestados, geralmente com recursos escassos e limitados, os quais sustentam a viabilidade da manutenção do tripé ensino, pesquisa e extensão. Conclusão: três (30,0%) estudos evidenciaram os aspectos financeiros associados à aplicação da metodologia Lean. Os demais apenas mencionaram a possibilidade de ganhos financeiros por meio da melhoria de processos e redução de desperdícios.
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Deeper knowledge about the role of the tumor microenvironment (TME) in cancer development and progression has resulted in new strategies such as gene-based cancer immunotherapy. Whereas some approaches focus on the expression of tumoricidal genes within the TME, DNA-based vaccines are intended to be expressed in antigen-presenting cells (e.g., dendritic cells, DCs) in secondary lymphoid organs, which in turn induce anti-tumor T cell responses. Besides effective delivery systems and the requirement of appropriate adjuvants, DNA vaccines themselves need to be optimized regarding efficacy and selectivity. In this work, the concept of DC-focused transcriptional targeting was tested by applying a plasmid encoding for the luciferase reporter gene under the control of a derivative of the human fascin1 gene promoter (pFscnLuc), comprising the proximal core promoter fused to the normally more distantly located DC enhancer region. DC-focused activity of this reporter construct was confirmed in cell culture in comparison to a standard reporter vector encoding for luciferase under the control of the strong ubiquitously active cytomegalovirus promoter and enhancer (pCMVLuc). Both plasmids were also compared upon intravenous administration in mice. The organ- and cell type-specific expression profile of pFscnLuc versus pCMVLuc demonstrated favorable activity especially in the spleen as a central immune organ and within the spleen in DCs.
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Neoplasias , Humanos , Camundongos , Animais , Regiões Promotoras Genéticas , Genes Reporter , Neoplasias/metabolismo , Células Dendríticas , Luciferases/metabolismo , Microambiente TumoralRESUMO
Taking advantage of effective intracellular delivery mechanisms of both cationizable lipids and polymers, highly potent double pH-responsive nucleic acid carriers are generated by combining at least two lipo amino fatty acids (LAFs) as hydrophobic cationizable motifs with hydrophilic cationizable aminoethylene units into novel sequence-defined molecules. The pH-dependent tunable polarity of the LAF is successfully implemented by inserting a central tertiary amine, which disrupts the hydrophobic character once protonated, resulting in pH-dependent structural and physical changes. This "molecular chameleon character" turns out to be advantageous for dynamic nucleic acid delivery via lipopolyplexes. By screening different topologies (blocks, bundles, T-shapes, U-shapes), LAF types, and LAF/aminoethylene ratios, highly potent pDNA, mRNA, and siRNA carriers are identified, which are up to several 100-fold more efficient than previous carrier generations and characterized by very fast transfection kinetics. mRNA lipopolyplexes maintain high transfection activity in cell culture even in the presence of ≥90% serum at an ultra-low mRNA dose of 3 picogram (≈2 nanoparticles/cell), and thus are comparable in potency to viral nanoparticles. Importantly, they show great in vivo performance with high expression levels especially in spleen, tumor, lungs, and liver upon intravenous administration of 1-3 µg luciferase-encoding mRNA in mice.
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Aminas , Polímeros , Camundongos , Animais , Transfecção , Polímeros/química , RNA Mensageiro , RNA Interferente Pequeno/genéticaRESUMO
RESUMO Objetivo: demonstrar a aplicabilidade da ferramenta Healthcare Failure Mode and Effect Analysis para analisar, preventivamente, os riscos relativos ao processo de inserção, manutenção e retirada de cateter intravenoso periférico. Método: estudo teórico, realizado de agosto a novembro de 2022, em São Paulo-SP, Brasil, cujo processo foi mapeado em etapas/atividades, detalhando-se os modos de falha, com o uso da ferramenta. Calculou-se o Risk Priority Number, elaborou-se a matriz de severidade e probabilidade, adaptada à saúde por DeRosier e colaboradores, e propuseram-se as ações para reduzir os modos de falha. Resultados: identificaram-se como maiores riscos: "realizar antissepsia da área a ser puncionada com swab de álcool" e "desinfecção do conector com swab de álcool" sendo recomendados treinamentos e uso de kit de materiais como principais estratégias de mitigação. Conclusão: conhecer os riscos associados ao cateter intravenoso periférico, fundamenta a implementação de estratégias preventivas, minimizando a ocorrência de danos e os custos assistenciais deles decorrentes.
ABSTRACT Objective: to demonstrate the applicability of the Healthcare Failure Mode and Effect Analysis tool to analyze, preventively, the risks related to the process of insertion, maintenance, and removal of peripheral intravenous catheters. Method: theoretical study, conducted from August to November 2022, in São Paulo-SP, Brazil, whose process was mapped in stages/activities, detailing the failure modes, using the tool. The Risk Priority Number was calculated, the severity and probability matrix was elaborated, adapted to health by DeRosier and collaborators, and actions were proposed to reduce failure modes. Results: The major risks identified were: "perform antisepsis of the area to be punctured with an alcohol swab" and "disinfect the connector with an alcohol swab", and were recommended training and use of kit materials as the main mitigation strategies. Conclusion: knowing the risks associated with peripheral intravenous catheters is the basis for the implementation of preventive strategies, minimizing the occurrence of damage and the associated healthcare costs.
RESUMEN Objetivo: demostrar la aplicabilidad de la herramienta Healthcare Failure Mode and Effect Analysis para analizar, de forma preventiva, los riesgos relacionados con el proceso de inserción, mantenimiento y retirada de catéteres intravenosos periféricos. Método: estudio teórico, realizado de agosto a noviembre de 2022, en São Paulo-SP, Brasil, cuyo proceso fue mapeado en etapas/actividades, detallando los modos de falla, utilizando la herramienta. Se calculó el Número de Prioridad de Riesgo, se elaboró la matriz de severidad y probabilidad, adaptada a la salud por DeRosier y colaboradores, y se propusieron acciones para reducir los modos de falla. Resultados: Los principales riesgos identificados fueron: "realizar la antisepsia de la zona a puncionar con un bastoncillo con alcohol" y "desinfectar el conector con un bastoncillo con alcohol", recomendándose como principales estrategias de mitigación la formación y el uso de kits de materiales. Conclusión: Conocer los riesgos asociados al catéter intravenoso periférico sienta las bases para la aplicación de estrategias preventivas, minimizando la aparición de daños y los costes sanitarios derivados de los mismos.
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Gestão de Riscos , Cateterismo , Administração IntravenosaRESUMO
BACKGROUND: Patient and family engagement (PFE) can positively impact the patient experience and care process outcomes. There is no unique type of PFE, and the process is usually defined by the quality management department or professionals responsible for this process in the hospital. The objective of this study is to define PFE in quality management based on the professional's perspective. METHOD: A survey was carried out with 90 professionals from Brazilian hospitals. There were two questions aimed at understanding the concept. The first was a multiple-choice question to identify synonyms. The second was an open-ended question to develop the definition. A content analysis methodology was employed by applying techniques for thematic and inferential analysis. RESULTS: Three words were classified as synonyms by more than 60% of respondents: involvement, participation, and centered care. The participants described patient participation at both the individual (related to the treatment) and organizational levels (related to quality improvement). The PFE in the treatment is related to the development, discussion and decision-making about the therapeutic plan, participation in each step of care, and knowledge of the institution's quality and safety processes. At the organizational level, engagement in quality improvement includes the involvement of the P/F in all processes of the institution, from strategic planning to the design or improvement processes, as well as active participation in institutional committees or commissions. CONCLUSION: The professionals defined engagement in two levels (individual and organizational) and the results suggest that their point of view can influence the practice in the hospitals. Professionals of hospitals that implemented mechanisms of consult defined PFE more in the individual level. On the other hand, professionals of hospitals that implemented mechanisms of involvement considered PFE more focus in the organizational level.
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Pessoal de Saúde , Participação do Paciente , Humanos , Inquéritos e Questionários , Hospitais , Melhoria de QualidadeRESUMO
BACKGROUND: Patient and family engagement (PFE) is considered an essential element of the transformation of the healthcare system. However, it is characterised by its complexity and a small number of institutions that have implemented the mechanisms of engagement. OBJECTIVE: To understand PFE in quality management (QM) in the hospital environment. DESIGN: A qualitative approach was guided by the grounded theory based in Straussian perspective. Data were gathered using semistructured interviews. The coding was performed by excerpts, using an inductive approach and the constant comparison technique. SETTING AND PARTICIPANTS: A total of seven Brazilian hospitals were selected based on the theoretical sampling technique. RESULTS: A total of five categories emerged, namely: patient partner, mechanisms of engagement, internal structure for engagement, maturity of the QM system and openness to change. Externally, three contextual factors can impact the engagement: the local health system, the profile of the community and the change in access to the information. At the centre of the change is the balance in power relations between patients and professionals, the sharing of information from the hospital and a proactive attitude towards improving services. CONCLUSIONS: The PFE involves a cultural and process change. Cultural change is represented by 'openness', that is, openness to learn, to listen and to consider new perspectives. The change in processes is in turn characterised by the phrase 'test and venture' because the model to be adopted may be different between hospitals. The patient's perspective allows actions to be driven towards what really matters to them, ensuring quality of service and safety, obtaining a new perspective to understand and solve problems, and stimulating a sense of urgency, more empathy and compassion in professionals.
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Família , Hospitais , Brasil , Teoria Fundamentada , Humanos , Participação do Paciente , Pesquisa QualitativaRESUMO
Human transferrin protein (Tf) modified polyplexes have already displayed encouraging potential for receptor-mediated nucleic acid delivery into tumors. The use of a blood-derived targeting protein and polydisperse macromolecular cationic subunits however presents a practical challenge for pharmaceutical grade production. Here, Tf receptor (TfR) targeted small interfering RNA (siRNA) polyplexes are designed that are completely composed of synthetic, monodisperse, and sequence-defined subunits generated by solid-phase supported synthesis. An optimized cationizable lipo-oligoaminoamide (lipo-OAA) is used for siRNA core polyplex formation, and a retro-enantio peptide (reTfR) attached via a monodisperse polyethylene glycol (PEG) spacer via click chemistry is applied for targeting. Improved gene silencing is demonstrated in TfR-expressing KB and DU145 cells. Analogous plasmid DNA (pDNA) polyplexes are successfully used for receptor-mediated gene delivery in TfR-rich K562 cells and Neuro2a cells. Six lipo-OAAs differing in their lipidic domain and redox-sensitive attachment of lipid residues are tested in order to evaluate the impact of core polyplex stability on receptor-dependent gene transfer.
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Técnicas de Transferência de Genes , Receptores da Transferrina , Inativação Gênica , Humanos , Polietilenoglicóis/química , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , Receptores da Transferrina/genética , Transferrina/química , Transferrina/genéticaRESUMO
Nanomedicine has a great potential to revolutionize the therapeutic landscape. However, up-to-date results obtained from in vitro experiments predict the in vivo performance of nanoparticles weakly or not at all. There is a need for in vitro experiments that better resemble the in vivo reality. As a result, animal experiments can be reduced, and potent in vivo candidates will not be missed. It is important to gain a deeper knowledge about nanoparticle characteristics in physiological environment. In this context, the protein corona plays a crucial role. Its formation process including driving forces, kinetics, and influencing factors has to be explored in more detail. There exist different methods for the investigation of the protein corona and its impact on physico-chemical and biological properties of nanoparticles, which are compiled and critically reflected in this review article. The obtained information about the protein corona can be exploited to optimize nanoparticles for in vivo application. Still the translation from in vitro to in vivo remains challenging. Functional in vitro screening under physiological conditions such as in full serum, in 3D multicellular spheroids/organoids, or under flow conditions is recommended. Innovative in vivo screening using barcoded nanoparticles can simultaneously test more than hundred samples regarding biodistribution and functional delivery within a single mouse.
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Lipo-oligomers, post-functionalized with ligands to enhance targeting, represent promising new vehicles for the tumor-specific delivery of therapeutic genes such as the sodium iodide symporter (NIS). Due to its iodide trapping activity, NIS is a powerful theranostic tool for diagnostic imaging and the application of therapeutic radionuclides. 124I PET imaging allows non-invasive monitoring of the in vivo biodistribution of functional NIS expression, and application of 131I enables cytoreduction. In our experimental design, we used epidermal growth factor receptor (EGFR)-targeted polyplexes (GE11) initially characterized in vitro using 125I uptake assays. Mice bearing an orthotopic glioblastoma were treated subsequently with mono-dibenzocyclooctyne (DBCO)-PEG24-GE11/NIS or bisDBCO-PEG24-GE11/NIS, and 24-48 h later, 124I uptake was assessed by positron emission tomography (PET) imaging. The best-performing polyplex in the imaging studies was then selected for 131I therapy studies. The in vitro studies showed EGFR-dependent and NIS-specific transfection efficiency of the polyplexes. The injection of monoDBCO-PEG24-GE11/NIS polyplexes 48 h before 124I application was characterized to be the optimal regime in the imaging studies and was therefore used for an 131I therapy study, showing a significant decrease in tumor growth and a significant extension of survival in the therapy group. These studies demonstrate the potential of EGFR-targeted polyplex-mediated NIS gene therapy as a new strategy for the therapy of glioblastoma.
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Currently, messenger RNA (mRNA)-based lipid nanoparticle formulations revolutionize the clinical field. Cationic polymer-based complexes (polyplexes) represent an alternative compound class for mRNA delivery. After establishing branched polyethylenimine with a succinylation degree of 10% (succPEI) as highly effective positive mRNA transfection standard, a diverse library of PEI-like peptides termed sequence-defined oligoaminoamides (OAAs) was screened for mRNA delivery. Notably, sequences, which had previously been identified as potent plasmid DNA (pDNA) or small-interfering RNA (siRNA) carriers, displayed only moderate mRNA transfection activity. A second round of screening combined the cationizable building block succinoyl tetraethylene pentamine and histidines for endosomal buffering, tyrosine tripeptides and various fatty acids for mRNA polyplex stabilization, as well as redox-sensitive units for programmed intracellular release. For the tested OAA carriers, balancing of extracellular stability, endosomal lytic activity, and intracellular release capability was found to be of utmost importance for optimum mRNA transfection efficiency. OAAs with T-shape topology containing two oleic acids as well-stabilizing fatty acids, attached via a dynamic bioreducible building block, displayed superior activity with up to 1000-fold increased transfection efficiency compared to their non-reducible analogs. In the absence of the dynamic linkage, incorporation of shorter less stabilizing fatty acids could only partly compensate for mRNA delivery. Highest GFP expression and the largest fraction of transfected cells (96%) could be detected for the bioreducible OAA with incorporated histidines and a dioleoyl motif, outperforming all other tested carriers as well as the positive control succPEI. The good in vitro performance of the dynamic lead structure was verified in vivo upon intratracheal administration of mRNA complexes in mice.
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Técnicas de Transferência de Genes , Nanopartículas , Animais , Lipossomos , Camundongos , Plasmídeos , Polietilenoimina , RNA Mensageiro , TransfecçãoRESUMO
Recent studies have revealed the importance of long noncoding RNAs (lncRNAs) as tissue-specific regulators of gene expression. There is ample evidence that distinct types of vasculature undergo tight transcriptional control to preserve their structure, identity, and functions. We determine a comprehensive map of lineage-specific lncRNAs in human dermal lymphatic and blood vascular endothelial cells (LECs and BECs), combining RNA-Seq and CAGE-Seq. Subsequent antisense oligonucleotide-knockdown transcriptomic profiling of two LEC- and two BEC-specific lncRNAs identifies LETR1 as a critical gatekeeper of the global LEC transcriptome. Deep RNA-DNA, RNA-protein interaction studies, and phenotype rescue analyses reveal that LETR1 is a nuclear trans-acting lncRNA modulating, via key epigenetic factors, the expression of essential target genes, including KLF4 and SEMA3C, governing the growth and migratory ability of LECs. Together, our study provides several lines of evidence supporting the intriguing concept that every cell type expresses precise lncRNA signatures to control lineage-specific regulatory programs.
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Células Endoteliais/citologia , Fatores de Transcrição Kruppel-Like/metabolismo , Semaforinas/metabolismo , Movimento Celular , Proliferação de Células , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , RNA Longo não Codificante , Semaforinas/genéticaRESUMO
When optimizing nanocarriers, structural motifs that are beneficial for the respective type of cargo need to be identified. Here, succinoyl tetraethylene pentamine (Stp)-based lipo-oligoaminoamides (OAAs) were optimized for the delivery of plasmid DNA (pDNA). Structural variations comprised saturated fatty acids with chain lengths between C2 and C18 and terminal cysteines as units promoting nanoparticle stabilization, histidines for endosomal buffering, and disulfide building blocks for redox-sensitive release. Biophysical and tumor cell culture screening established clear-cut relationships between lipo-OAAs and characteristics of the formed pDNA complexes. Based on the optimized alternating Stp-histidine backbones, lipo-OAAs containing fatty acids with chain lengths around C6 to C10 displayed maximum gene transfer with around 500-fold higher gene expression than that of C18 lipo-OAA analogues. Promising lipo-OAAs, however, showed only moderate in vivo efficiency. In vitro testing in 90% full serum, revealing considerable inhibition of lytic and gene-transfer activity, was found as a new screening model predictive for intravenous applications in vivo.
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Nanopartículas , Endossomos , Técnicas de Transferência de Genes , Histidina , Plasmídeos , TransfecçãoRESUMO
A cationizable sequence-defined lipo-oligoaminoamide (lipo-OAA) conferring stable assembly of siRNA into ~200 nm sized complexes contains an N-terminal azidolysine for covalent coating of formed nanoparticles with dibenzocyclooctyne-amine (DBCO)-modified hyaluronic acid (HA). Depending on the applied equivalents of DBCO-HA, stable nanoparticles with either cationic or anionic surface charge can be formed. The unmodified and two types of covalent HA-modified siRNA nanoparticles differ in their biological characteristics. Both types of HA coated siRNA complexes show an enhanced cellular uptake over uncoated complexes and facilitate efficient gene silencing, but differ in intracellular uptake pathways and distribution. Upon intravenous administration in mice, beyond our expectation and in contrast to the in vitro findings, only the cationic HA nanoparticles but neither the non-coated cationic nor the anionic HA complexes were able to target subcutaneous Huh 7 tumors and exert potent (78%) gene silencing. The favorable and very fast accumulation of cationic HA nanoparticles was confirmed in another subcutaneous tumor model. As evidenced by 3D nanoparticle distribution within Huh 7 tumors evaluated at early time points of 5 min and 45 min, only the cationic HA-based nanoparticles rapidly attach to the tumor endothelium and subsequently penetrate into tumor, in contrast to the analogous anionic HA coated or the cationic non-coated formulation.
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Nanopartículas , Animais , Linhagem Celular Tumoral , Endotélio , Inativação Gênica , Ácido Hialurônico , Camundongos , RNA Interferente PequenoRESUMO
OBJECTIVES: Although different forms of patient feedback are available, their use in hospital management is still limited. The objective of this study is to explore how patient feedback is currently used in hospitals to improve quality. DESIGN: This is a qualitative exploratory multiple case study. Data collection included nine interviews, of an average duration of 50 min, conducted between March and June 2019. Additionally, a document and secondary data analysis were performed. SETTING: This study was conducted in three Brazilian hospitals selected for their solid patient feedback practises. PARTICIPANTS: Managers from the customer service, quality, nursing, operations, projects and patient experience departments of the three hospitals. RESULTS: Despite literature suggesting that organisational objectives regarding patient feedback are not clear, data show that there is managerial concern regarding the promotion of an environment capable of changing according to patient feedback. In these instances, organisational processes were structured to focus on patients' feedback and its receipt by the staff, including a non-punitive culture. Several patient feedback forms are available: voluntary events, patient surveys and informal feedback. Instruments to measure patient feedback focused on specific aspects of healthcare, to identify and clarify the problems for addressal by the management. The net promoter score was the main strategic indicator of patient feedback, used to assess the impact of improvement action. CONCLUSIONS: The hospitals had established objectives that valued the patient's perspective. Involvement of the health team, availability of different channels for feedback and the use of quality tools are considered a good basis for using patient feedback to drive quality improvement.
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Hospitais , Melhoria de Qualidade , Brasil , Retroalimentação , Humanos , Pesquisa QualitativaRESUMO
This theoretical and reflexive study analyzed the risks related to the maintenance of patency of the Peripherally Inserted Central Catheter with the use of saline solution in comparison with saline-filled syringes, through the application of the Healthcare Failure Mode and Effect Analysis - HFMEA. The process was mapped, detailing the failure modes of each step. For the calculation of the Risk Priority Number, the severity and probability of the failure modes were analyzed. This analysis gave rise to the severity and probability matrix. Finally, actions to reduce the failure modes in the maintenance of patency were proposed, considering the use of saline-filled syringes in comparison to the use of saline ampoules. It was verified that the use of saline ampoules is associated with a greater risk, since it requires four stages more than saline-filled syringe does not, increasing the risk of contamination and the level of three different risks, which would result in additional hospital costs. The use of the saline-filled syringe would avoid risks that could negatively affect the patient's health, the nursing professional and the health institution.