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1.
Br J Nurs ; 32(20): 964-971, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37938996

RESUMO

The incidence of chronic kidney disease is increasing internationally with many risk factors for chronic kidney disease also being risk factors for type 2 diabetes. Nurses should use primary, secondary and tertiary prevention to minimise the incidence of chronic kidney disease when caring for individuals with type 2 diabetes. This article is the second in a two-part series on the interrelationship between these long-term conditions. Part 1 addressed the significance of using primary prevention to promote kidney health in adults living with type 2 diabetes; part 2 will discuss the use of secondary and tertiary prevention relevant to these long-term conditions.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Adulto , Humanos , Diabetes Mellitus Tipo 2/complicações , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco , Rim
2.
Br J Nurs ; 32(18): 874-880, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37830853

RESUMO

The incidence of chronic kidney disease is increasing internationally with risk factors for the condition being the same as those for type 2 diabetes. It is important therefore for nurses to use primary, secondary and tertiary prevention to minimise the incidence of chronic kidney disease when caring for individuals with type 2 diabetes. This article is the first of a two-part series on the interrelationship between these long-term conditions. This article, part 1, addresses the significance of primary prevention in promoting kidney health in adults living with type 2 diabetes, while part 2 will discuss the use of secondary and tertiary prevention relevant to these long-term conditions.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Adulto , Humanos , Diabetes Mellitus Tipo 2/complicações , Fatores de Risco , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Incidência , Rim
3.
Sci Rep ; 13(1): 15889, 2023 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-37741880

RESUMO

Atherosclerosis is a serious cardiovascular disease that is characterised by the development of atheroma, which are lipid-laden plaques that build up within arterial walls due to chronic inflammatory processes. These lesions are fundamentally attributed to a complex cellular crosstalk between vascular smooth muscle cells (VSMCs), vascular endothelial cells (VECs) and central immune cells, such as macrophages (Mɸs), which promote vascular inflammation. The presence of VSMCs exerts both positive and negative effects during atheroma development, which can be attributed to their phenotypic plasticity. Understanding the interactions between these key cell types during the development of vascular inflammation and atheroma will enhance the scope for new therapeutic interventions. This study aims to determine the importance of VSMCs for shaping the extracellular cytokine/chemokine profile and transcriptional responses of VECs (human coronary artery endothelial cells; HCAECs) to activated lipopolysaccharide (LPS)-stimulated THP1 Mɸs, in a 3-cell model of human vascular inflammation. It is evident that within the presence of VSMCs, enhanced cytokine production was associated with up-regulation of genes associated with vascular inflammation t. Results demonstrate that the presence of VSMCs in co-culture experiments enhanced cytokine production (including CXCL1/GROα, IL-6, IL-8 and CCL2/MCP1) and inflammatory gene expression (including genes involved in JAK/STAT, Jun and NFκB signalling) in HCAECs co-cultured with LPS-stimulated THP1 Mɸs. Our results highlight the importance of VSMCs in immune/endothelial cell interplay and indicate that 3-cell, rather than 2-cell co-culture, may be more appropriate for the study of cellular crosstalk between immune and vascular compartments in response to inflammatory and atherogenic stimuli.


Assuntos
Aterosclerose , Placa Aterosclerótica , Humanos , Músculo Liso Vascular/metabolismo , Placa Aterosclerótica/patologia , Células Cultivadas , Células Endoteliais/metabolismo , Lipopolissacarídeos/metabolismo , Citocinas/metabolismo , Aterosclerose/patologia , Inflamação/metabolismo , Miócitos de Músculo Liso/metabolismo
4.
Pediatr Surg Int ; 39(1): 252, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37624471

RESUMO

PURPOSE: To develop guidance for the selection of balloon catheter size when performing an oesophageal dilatation for a stricture post oesophageal atresia repair. METHODS: This was a single centre retrospective study at a paediatric tertiary centre. Dilatations were performed between 2015 and 2020. All dilatations were performed under general anaesthesia using balloon catheters under fluoroscopic guidance. Outliers were excluded using ROUT method and descriptive analysis was calculated to 1SD or IQR depending on the normality of data distribution. RESULTS: 97 patients underwent 341 dilatations. Median age was 19 months (37 weeks corrected gestation-17 years), median weight was 10.7 kg (2.6-72 kg). Balloon catheter sizes ranged from 6-8 mm to 18-20 mm. There was strong correlation between weight and balloon size (r = 0.8, p < 0.0001). There were 2 perforations (0.6%), both diagnosed intra-operatively and treated conservatively. From the results, weight recommendations were created for each balloon size. CONCLUSION: Fluoroscopic balloon dilatation is a safe and effective method to treat anastomotic stricture following oesophageal atresia repair. Previous studies have shown correlation between patient weight and oesophageal diameter. We propose guidance for using an appropriate balloon size based on patient's weight with the aim to reduce complication.


Assuntos
Atresia Esofágica , Criança , Humanos , Lactente , Atresia Esofágica/cirurgia , Dilatação , Constrição Patológica , Estudos Retrospectivos , Fluoroscopia
5.
Int J Palliat Nurs ; 29(6): 274-280, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37339855

RESUMO

BACKGROUND: During the COVID-19 pandemic, redeployed staff whose services were temporarily suspended were offered a range of opportunities for work to support efforts to manage the impact of the pandemic. A new team, known as the Cygnets was established within an existing team SWAN, to provide non-specialist end of life and bereavement care during the COVID-19 pandemic. It is important to evaluate new services and one important component of this is understanding the perceptions of those staff who took on the new role. AIM: To evaluate the service from the perspectives of staff. METHOD: A purposive sample of 14 NHS staff who had worked as Cygnets during the COVID-19 pandemic took part in three focus groups. RESULTS: The themes identified broadly followed the focus group schedule. Participants considered that overall, they had benefited greatly from the challenge of taking on the Cygnet role, and that this had been a learning experience. CONCLUSIONS: This was a rapid response to a need for increased provision of compassionate end-of-life care and was a beneficial experience for staff. More research is required into the broader value of the role within the hospital infrastructure.


Assuntos
COVID-19 , Cuidados Paliativos na Terminalidade da Vida , Assistência Terminal , Humanos , Grupos Focais , Pandemias
6.
ALTEX ; 40(1): 125-140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35796348

RESUMO

Manufacturing and functionalizing materials at the nanoscale has led to the generation of a whole array of nanoforms (NFs) of substances varying in size, morphology, and surface characteristics. Due to financial, time, and ethical considerations, testing every unique NF for adverse effects is virtually impossible. Use of hypothesis-driven grouping and read-across approaches, as supported by the GRACIOUS Framework, represents a promising alternative to case-by-case testing that will make the risk assessment process more efficient. Through application of appropriate grouping hypotheses, the Framework facilitates the assessment of similarity between NFs, thereby supporting grouping and read-across of information, minimizing the need for new testing, and aligning with the 3R principles of replacement, reduction, and refinement of animals in toxicology studies. For each grouping hypothesis an integrated approach to testing and assessment (IATA) guides the user in data gathering and acquisition to test the hypothesis, following a structured format to facilitate efficient decision-making. Here we present the template used to generate the GRACIOUS grouping hypotheses encompassing information relevant to "Lifecycle, environmental release, and human exposure", "What they are: physicochemical characteristics", "Where they go: environmental fate, uptake, and toxicokinetics", and "What they do: human and environmental toxicity". A summary of the template-derived hypotheses focusing on human health is provided, along with an overview of the IATAs generated by the GRACIOUS project. We discuss the application and flexibility of the template, providing the opportunity to expand the application of grouping and read-across in a logical, evidence-based manner to a wider range of NFs and substances.


Assuntos
Substâncias Perigosas , Animais , Humanos , Medição de Risco , Substâncias Perigosas/toxicidade , Substâncias Perigosas/química , Toxicocinética
7.
Part Fibre Toxicol ; 19(1): 68, 2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36461106

RESUMO

BACKGROUND: Nanomaterials can exist in different nanoforms (NFs). Their grouping may be supported by the formulation of hypotheses which can be interrogated via integrated approaches to testing and assessment (IATA). IATAs are decision trees that guide the user through tiered testing strategies (TTS) to collect the required evidence needed to accept or reject a grouping hypothesis. In the present paper, we investigated the applicability of IATAs for ingested NFs using a case study that includes different silicon dioxide, SiO2 NFs. Two oral grouping hypotheses addressing local and systemic toxicity were identified relevant for the grouping of these NFs and verified through the application of oral IATAs. Following different Tier 1 and/or Tier 2 in vitro methods of the TTS (i.e., in vitro dissolution, barrier integrity and inflammation assays), we generated the NF datasets. Furthermore, similarity algorithms (e.g., Bayesian method and Cluster analysis) were utilized to identify similarities among the NFs and establish a provisional group(s). The grouping based on Tier 1 and/or Tier 2 testing was analyzed in relation to available Tier 3 in vivo data in order to verify if the read-across was possible and therefore support a grouping decision. RESULTS: The measurement of the dissolution rate of the silica NFs in the oro-gastrointestinal tract and in the lysosome identified them as gradually dissolving and biopersistent NFs. For the local toxicity to intestinal epithelium (e.g. cytotoxicity, membrane integrity and inflammation), the biological results of the gastrointestinal tract models indicate that all of the silica NFs were similar with respect to the lack of local toxicity and, therefore, belong to the same group; in vivo data (although limited) confirmed the lack of local toxicity of NFs. For systemic toxicity, Tier 1 data did not identify similarity across the NFs, with results across different decision nodes being inconsistent in providing homogeneous group(s). Moreover, the available Tier 3 in vivo data were also insufficient to support decisions based upon the obtained in vitro results and relating to the toxicity of the tested NFs. CONCLUSIONS: The information generated by the tested oral IATAs can be effectively used for similarity assessment to support a grouping decision upon the application of a hypothesis related to toxicity in the gastrointestinal tract. The IATAs facilitated a structured data analysis and, by means of the expert's interpretation, supported read-across with the available in vivo data. The IATAs also supported the users in decision making, for example, reducing the testing when the grouping was well supported by the evidence and/or moving forward to advanced testing (e.g., the use of more suitable cellular models or chronic exposure) to improve the confidence level of the data and obtain more focused information.


Assuntos
Nanoestruturas , Dióxido de Silício , Humanos , Dióxido de Silício/toxicidade , Teorema de Bayes , Nanoestruturas/toxicidade , Medição de Risco , Inflamação
8.
Elife ; 112022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36459486

RESUMO

Different organelles traveling through neurons exhibit distinct properties in vitro, but this has not been investigated in the intact mammalian brain. We established simultaneous dual color two-photon microscopy to visualize the trafficking of Neuropeptide Y (NPY)-, LAMP1-, and RAB7-tagged organelles in thalamocortical axons imaged in mouse cortex in vivo. This revealed that LAMP1- and RAB7-tagged organelles move significantly faster than NPY-tagged organelles in both anterograde and retrograde direction. NPY traveled more selectively in anterograde direction than LAMP1 and RAB7. By using a synapse marker and a calcium sensor, we further investigated the transport dynamics of NPY-tagged organelles. We found that these organelles slow down and pause at synapses. In contrast to previous in vitro studies, a significant increase of transport speed was observed after spontaneous activity and elevated calcium levels in vivo as well as electrically stimulated activity in acute brain slices. Together, we show a remarkable diversity in speeds and properties of three axonal organelle marker in vivo that differ from properties previously observed in vitro.


Assuntos
Cálcio , Neuropeptídeo Y , Animais , Camundongos , Axônios , Neurônios , Organelas , Mamíferos
9.
Aust J Rural Health ; 30(6): 884-890, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35975966

RESUMO

AIMS: This commentary aims to describe a case of how meaningful co-design between rural health service leaders and a health service-embedded research unit can identify emerging research priorities and optimise translation. CONTEXT: The challenges facing rural health services are unique, and the important role of health service leaders in the research response is increasingly recognised. Poorly-designed research can contribute to research waste through reduced applicability of results to rural communities, and an opportunity exists to increase research co-designed with rural health services through the involvement of research users during study planning. APPROACH: In early 2020, leaders at a rural Victorian health service approached the embedded health service research unit to request research be conducted on an emerging issue: rural staff well-being in the face of the COVID-19 pandemic. This was based on their concern regarding the lack of available COVID-19-specific evidence to inform organisational policy. In collaboration with the rural health service executive, a translation-focused study of staff well-being with nine rural Victorian health services was developed. Key co-design activities of the project included involving research end-users as study investigators and conducting formal stakeholder engagement regarding study design and outcomes. CONCLUSION: Meaningful co-design of research with health services is a multifaceted process that can assist researchers and end-users alike in identifying and responding to emerging health issues. In the rural setting where there is a vital need for impactful health research, we recommend that researchers should consider employing co-design processes in order to minimise research waste and optimise the translatability of research findings.


Assuntos
COVID-19 , Serviços de Saúde Rural , Humanos , Pandemias , População Rural
10.
Biophys Chem ; 289: 106863, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35969921

RESUMO

Nucleic acids possess unique biochemical features that make them ideal candidates to inhibit "difficult to target" proteins. The limited stability of nucleic acids in vivo presents a major obstacle to their development as drugs. Here, immobile four-way junctions (4WJs) are used to target the DNA-binding cytokine, High Mobility Group B1. Hybrid 4WJs composed of DNA and peptide nucleic acids (PNA) are investigated. PNA possess enhanced nuclease stability vs. DNA. 4WJs are incubated with Exonuclease III and DNase I. The nuclease assays show that 4WJs containing multiple PNAs possess significantly higher stability. Circular dichroism assays are used to probe the groove topology of 4WJs with the minor groove binder, DAPI. The CD data indicates that multi-PNA 4WJs possess altered minor groove dimensions that reduces DAPI binding affinity. Logic suggests that the minor groove of multi-PNA hybrids possess significant perturbations to the topology and local electrostatic environment that prevents proper binding/recognition by nucleases and thus enhances stability.


Assuntos
Ácidos Nucleicos Peptídicos , Dicroísmo Circular , DNA/química , Modelos Moleculares , Ácidos Nucleicos Peptídicos/química , Ácidos Nucleicos Peptídicos/metabolismo , Eletricidade Estática
11.
Part Fibre Toxicol ; 19(1): 50, 2022 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-35854357

RESUMO

BACKGROUND: The EU-project GRACIOUS developed an Integrated Approach to Testing and Assessment (IATA) to support grouping high aspect ratio nanomaterials (HARNs) presenting a similar inhalation hazard. Application of grouping reduces the need to assess toxicity on a case-by-case basis and supports read-across of hazard data from substances that have the data required for risk assessment (source) to those that lack such data (target). The HARN IATA, based on the fibre paradigm for pathogenic fibres, facilitates structured data gathering to propose groups of similar HARN and to support read-across by prompting users to address relevant questions regarding HARN morphology, biopersistence and inflammatory potential. The IATA is structured in tiers, allowing grouping decisions to be made using simple in vitro or in silico methods in Tier1 progressing to in vivo approaches at the highest Tier3. Here we present a case-study testing the applicability of GRACIOUS IATA to form an evidence-based group of multiwalled carbon nanotubes (MWCNT) posing a similar predicted fibre-hazard, to support read-across and reduce the burden of toxicity testing. RESULTS: The case-study uses data on 15 different MWCNT, obtained from the published literature. By following the IATA, a group of 2 MWCNT was identified (NRCWE006 and NM-401) based on a high degree of similarity. A pairwise similarity assessment was subsequently conducted between the grouped MWCNT to evaluate the potential to conduct read-across and fill data gaps required for regulatory hazard assessment. The similarity assessment, based on expert judgement of Tier 1 assay results, predicts both MWCNT are likely to cause a similar acute in vivo hazard. This result supports the possibility for read-across of sub-chronic and chronic hazard endpoint data for lung fibrosis and carcinogenicity between the 2 grouped MWCNT. The implications of accepting the similarity assessment based on expert judgement of the MWCNT group are considered to stimulate future discussion on the level of similarity between group members considered sufficient to allow regulatory acceptance of a read-across argument. CONCLUSION: This proof-of-concept case-study demonstrates how a grouping hypothesis and IATA may be used to support a nuanced and evidence-based grouping of 'similar' MWCNT and the subsequent interpolation of data between group members to streamline the hazard assessment process.


Assuntos
Nanotubos de Carbono , Fibrose Pulmonar , Administração por Inalação , Humanos , Pulmão , Nanotubos de Carbono/toxicidade , Testes de Toxicidade/métodos
13.
Nanotoxicology ; 16(3): 310-332, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35704509

RESUMO

Exposure to different nanoforms (NFs) via the dermal route is expected in occupational and consumer settings and thus it is important to assess their dermal toxicity and the contribution of dermal exposure to systemic bioavailability. We have formulated four grouping hypotheses for dermal toxicity endpoints which allow NFs to be grouped to streamline and facilitate risk assessment. The grouping hypotheses are developed based on insight into how physicochemical properties of NFs (i.e. composition, dissolution kinetics, size, and flexibility) influence their fate and hazard following dermal exposure. Each hypothesis is accompanied by a tailored Integrated Approach to Testing and Assessment (IATA) that is structured as a decision tree and tiered testing strategies (TTS) for each relevant question (at decision nodes) that indicate what information is needed to guide the user to accept or reject the grouping hypothesis. To develop these hypotheses and IATAs, we gathered and analyzed existing information on skin irritation, skin sensitization, and dermal penetration of NFs from the published literature and performed experimental work to generate data on NF dissolution in sweat simulant fluids. We investigated the dissolution of zinc oxide and silicon dioxide NFs in different artificial sweat fluids, demonstrating the importance of using physiologically relevant conditions for dermal exposure. All existing and generated data informed the formulation of the grouping hypotheses, the IATAs, and the design of the TTS. It is expected that the presented IATAs will accelerate the NF risk assessment for dermal toxicity via the application of read-across.


Assuntos
Nanoestruturas , Medição de Risco , Exposição Ambiental , Nanoestruturas/química , Nanoestruturas/toxicidade , Medição de Risco/métodos , Pele , Sudorese
14.
NanoImpact ; 25: 100389, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35559895

RESUMO

Nanoforms can be manufactured in plenty of variants by differing their physicochemical properties and toxicokinetic behaviour which can affect their hazard potential. To avoid testing of each single nanomaterial and nanoform variation and subsequently save resources, grouping and read-across strategies are used to estimate groups of substances, based on carefully selected evidence, that could potentially have similar human health and environmental hazard impact. A novel computational similarity method is presented aiming to compare dose-response curves and identify sets of similar nanoforms. The suggested method estimates the statistical model that best fits the data by leveraging pairwise Bayes Factor analysis to compare pairs of curves and evaluate whether each of the nanoforms is sufficiently similar to all other nanoforms. Pairwise comparisons to benchmark materials are used to define threshold similarity values and set the criteria for identifying groups of nanoforms with comparatively similar toxicity. Applications to use case data are shown to demonstrate that the method can support grouping hypotheses linked to a certain hazard endpoint and route of exposure.


Assuntos
Nanoestruturas , Teorema de Bayes , Meio Ambiente , Humanos , Nanoestruturas/efeitos adversos , Medição de Risco/métodos
15.
NanoImpact ; 26: 100390, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35560290

RESUMO

Grouping of substances is a method used to streamline hazard and risk assessment. Assessment of similarity provides the scientific evidence needed for formation of groups. This work reports on justification of grouping of nanoforms (NFs) via similarity of their surface reactivity. Four reactivity assays were used for concentration dependent detection of reactive oxygen species (ROS) generated by NFs: abiotic assays FRAS, EPR and DCFH2-DA, as well as the in vitro assay of NRF2/ARE responsive luciferase reporter activation in the HEK293 cell line. Representative materials (CuO, Mn2O3, BaSO4, CeO2 and ZnO) and three case studies of each several NFs of iron oxides, Diketopyrrolopyrroles (DPP)-based organic pigments and silicas were assessed. A novel similarity assessment algorithm was applied to quantify similarities between pairs of NFs, in a four-step workflow on concentration-response curves, individual concentration and response ranges, and finally the representative materials. We found this algorithm to be applicable to all abiotic and in vitro assays that were tested. Justification of grouping must include the increased potency of smaller particles via the scaling of effects with specific surface, and hence quantitative similarity analysis was performed on concentration-response in mass-metrics. CuO and BaSO4 were the most and least reactive representative materials respectively, and all assays found BaSO4/CuO not similar, as confirmed by their different NOAECs of in vivo studies. However, similarity outcomes from different reactivity assays were not always in agreement, highlighting the need to generate data by one assay for the representative materials and the candidate group of NFs. Despite low similarity scores in vitro some pairs of case study NFs can be accepted as sufficiently similar because the in vivo NOAECs are similar, highlighting the conservative assessment by the abiotic assays.


Assuntos
Nanoestruturas , Células HEK293 , Humanos , Espécies Reativas de Oxigênio , Medição de Risco/métodos , Dióxido de Silício
16.
Nat Immunol ; 23(6): 927-939, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35624205

RESUMO

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.


Assuntos
Lesão Pulmonar , Síndrome do Desconforto Respiratório , Animais , Humanos , Hipóxia/etiologia , Inflamação/complicações , Pulmão , Lesão Pulmonar/complicações , Camundongos
17.
Part Fibre Toxicol ; 19(1): 32, 2022 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-35525968

RESUMO

The incorporation of nanomaterials (NMs) in consumer products has proven to be highly valuable in many sectors. Unfortunately, however, the same nano specific physicochemical properties, which make these material attractive, might also contribute to hazards for people exposed to these materials. The physicochemical properties of NMs will impact their interaction with biological surroundings and influence their fate and their potential adverse effects such as genotoxicity. Due to the large and expanding number of NMs produced, their availability in different nanoforms (NFs) and their utilization in various formats, it is impossible for risk assessment to be conducted on an individual NF basis. Alternative methods, such as grouping are needed for streamlining hazard assessment. The GRACIOUS Framework provides a logical and science evidenced approach to group similar NFs, allowing read-across of hazard information from source NFs (or non-NFs) with adequate hazard data to target NFs that lack such data. Here, we propose a simple three-tiered testing strategy to gather evidence to determine whether different NFs are sufficiently similar with respect to their potential to induce genotoxicity, in order to be grouped. The tiered testing strategy includes simple in vitro models as well as a number of alternative more complex multi-cellular in vitro models to allow for a better understanding of secondary NM-induced DNA damage, something that has been more appropriate in vivo until recently.


Assuntos
Nanoestruturas , Dano ao DNA , Humanos , Nanoestruturas/química , Nanoestruturas/toxicidade , Medição de Risco/métodos
18.
Toxicol Mech Methods ; 32(6): 439-452, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35086424

RESUMO

Improved strategies are required for testing nanomaterials (NMs) to make hazard and risk assessment more efficient and sustainable. Including reduced reliance on animal models, without decreasing the level of human health protection. Acellular detection of reactive oxygen species (ROS) may be useful as a screening assay to prioritize NMs of high concern. To improve reliability and reproducibility, and minimize uncertainty, a standard operating procedure (SOP) has been developed for the detection of ROS using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH2-DA) assay. The SOP has undergone an inter- and intra-laboratory comparison, to evaluate robustness, reliability, and reproducibility, using representative materials (ZnO, CuO, Mn2O3, and BaSO4 NMs), and a number of calibration tools to normalize data. The SOP includes an NM positive control (nanoparticle carbon black (NPCB)), a chemical positive control (SIN-1), and a standard curve of fluorescein fluorescence. The interlaboratory comparison demonstrated that arbitrary fluorescence units show high levels of partner variability; however, data normalization improved variability. With statistical analysis, it was shown that the SIN-1 positive control provided an extremely high level of reliability and reproducibility as a positive control and as a normalization tool. The NPCB positive control can be used with a relatively high level of reproducibility, and in terms of the representative materials, the reproducibility CuO induced-effects was better than for Mn2O3. Using this DCFH2-DA acellular assay SOP resulted in a robust intra-laboratory reproduction of ROS measurements from all NMs tested, while effective reproduction across different laboratories was also demonstrated; the effectiveness of attaining reproducibility within the interlaboratory assessment was particle-type-specific.


Assuntos
Nanopartículas , Nanoestruturas , Animais , Bioensaio , Nanoestruturas/toxicidade , Espécies Reativas de Oxigênio , Reprodutibilidade dos Testes
19.
BMJ Open ; 12(12): e066832, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36600439

RESUMO

OBJECTIVES: To evaluate the End-of-Life and Bereavement Care model (SWAN) from conception to current use. DESIGN: A realist evaluation was conducted to understand what works for whom and in what circumstances. The programme theory, derived from a scoping review, comprised: person and family centred care, institutional approaches and infrastructure. Data were collected across three stages (May 2021 to December 2021): semi-structured, online interviews and analysis of routinely collected local and national data. SETTING: Stage 1: Greater Manchester area of England where the SWAN model was developed and implemented. Stage 2: Midlands. Stage 3: National data. PARTICIPANTS: Twenty-three participants were interviewed: Trust SWAN leads, end-of-life care nurses, board members, bereavement services, faith leadership, quality improvement, medicine, nursing, patient transport, mortuary, police and coroners. RESULTS: Results from all three stages were integrated within themes, linked to the mechanisms, context and outcomes for the SWAN model. The mechanisms are: SWAN is a values-based model, promoting person/family-centred care and emphasising personhood after death. Key features are: memory-making, normalisation of death and 'one chance' to get things right. SWAN is an enablement and empowerment model for all involved. The branding is recognisable and raises the profile of end-of-life and bereavement care. The contextual factors for successful implementation and sustainability include leadership, organisational support, teamwork and integrated working, education and engagement and investment in resources and facilities. The outcomes are perceived to be: a consistent approach to end-of-life and bereavement care; a person/family-centred approach to care; empowered and creative staff; an organisational culture that prioritises end-of-life and bereavement care. CONCLUSION: The SWAN model is agile and has transferred to different settings and circumstances. This realist evaluation revealed the mechanisms of the SWAN model, the contextual factors supporting implementation and perceived outcomes for patients, families, staff and the organisation.


Assuntos
Luto , Cuidados Paliativos na Terminalidade da Vida , Assistência Terminal , Humanos , Assistência Terminal/métodos , Inglaterra , Morte
20.
J Foot Ankle Surg ; 61(1): 79-83, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34429264

RESUMO

Arthrodesis of the first metatarsal phalangeal joint (MTPJ) is a widely utilized surgical procedure for a wide array of metatarsal pathologies. This study aims to explore the functional limitations following first MTPJ arthrodesis, overall satisfaction and patient's abilities to achieve activities of daily living (ADL). This prospective cohort study assessed functional limitations as well as footwear and lifestyle restrictions using several questionnaires. One hundred and three participants who had a first MTPJ arthrodesis under the care of a single surgeon were recruited. Pre- and postoperative patient-reported outcome measures were recorded. The American Orthopaedic Foot and Ankle Score (AOFAS) and the Manchester-Oxford Foot Questionnaire were also used to further examine functional status. Hallux valgus angle (HVA) and intermetatarsal angle (IMA) were compared using preoperative and postoperative weightbearing radiographs and successful fusion was recorded. Complications were documented and are discussed in detail. The duration of follow-up was more than 12 months. There was one nonunion in the cohort while 2 patients experienced delay to fusion. Approximately 97% of patients were very satisfied with the procedure and their ability to achieve ADLs post operatively. A further 82.5% of patients were able to return to wearing nonadaptive footwear. The mean reduction in HVA and IMA was 21.78° and 6.84°, respectively. This study demonstrates the safe and successful use of a compression screw/locking plate construct for arthrodesis of the first MTPJ. Furthermore, the study provides clear evidence of high levels of functionality after the procedure with statistically significant differences (p value <.05) in all 4 facets of the AOFAS questionnaire as well as several notable differences in activity levels and footwear restrictions pre and postoperatively.


Assuntos
Hallux Valgus , Ossos do Metatarso , Articulação Metatarsofalângica , Atividades Cotidianas , Artrodese , Parafusos Ósseos , Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Humanos , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Articulação Metatarsofalângica/diagnóstico por imagem , Articulação Metatarsofalângica/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
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