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1.
Healthcare (Basel) ; 12(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38786441

RESUMO

Nursing students' integration of theoretical knowledge and practical abilities is facilitated by their practice of nursing skills in a clinical environment. A key role of preceptors is to assess the learning goals that nursing students must meet while participating in clinical practice. Consequently, the purpose of this study was to explore the current evidence in relation to competency assessment and assessment approaches, and the willingness of preceptors for assessing nursing students' competency in a clinical setting. The scoping review used the five-stage methodological framework that was developed by Arksey and O'Malley, as well as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. Relevant studies were searched by applying a comprehensive literature search strategy up to April 2024 across the following databases: CINAHL, OVID MEDLINE, EMBASE, and PUBMED. A total of 11,297 studies published between 2000 and April 2024 were revealed, and 38 were eligible for inclusion, which the research team categorised into three main themes: definitions of competence, tools for assessing competence and preceptors' and mentors' viewpoints in relation to the assessment of nursing students' competence. This review established that there are a multitude of quantitative instruments available to assess clinical competence; however, a lack of consistency among assessment instruments and approaches between countries and higher education institutions is prevalent. Existing research evidence suggests that the preceptors carried out the assessment process clinically and they found difficulties in documenting assessment. The assessing of nursing students' competency and the complexity of assessment is a concern for educators and mentors worldwide. The main concern centers around issues such as the interpretation of competence and complex measurement tools.

2.
PLoS One ; 19(4): e0298479, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38625906

RESUMO

OBJECTIVES: (i) To identify peer reviewed publications reporting the mental and/or physical health outcomes of Deaf adults who are sign language users and to synthesise evidence; (ii) If data available, to analyse how the health of the adult Deaf population compares to that of the general population; (iii) to evaluate the quality of evidence in the identified publications; (iv) to identify limitations of the current evidence base and suggest directions for future research. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, PsychINFO, and Web of Science. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: The inclusion criteria were Deaf adult populations who used a signed language, all study types, including methods-focused papers which also contain results in relation to health outcomes of Deaf signing populations. Full-text articles, published in peer-review journals were searched up to 13th June 2023, published in English or a signed language such as ASL (American Sign Language). DATA EXTRACTION: Supported by the Rayyan systematic review software, two authors independently reviewed identified publications at each screening stage (primary and secondary). A third reviewer was consulted to settle any disagreements. Comprehensive data extraction included research design, study sample, methodology, findings, and a quality assessment. RESULTS: Of the 35 included studies, the majority (25 out of 35) concerned mental health outcomes. The findings from this review highlighted the inequalities in health and mental health outcomes for Deaf signing populations in comparison with the general population, gaps in the range of conditions studied in relation to Deaf people, and the poor quality of available data. CONCLUSIONS: Population sample definition and consistency of standards of reporting of health outcomes for Deaf people who use sign language should be improved. Further research on health outcomes not previously reported is needed to gain better understanding of Deaf people's state of health.

3.
Elife ; 132024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38323609

RESUMO

BMP signaling has a conserved function in patterning the dorsal-ventral body axis in Bilateria and the directive axis in anthozoan cnidarians. So far, cnidarian studies have focused on the role of different BMP signaling network components in regulating pSMAD1/5 gradient formation. Much less is known about the target genes downstream of BMP signaling. To address this, we generated a genome-wide list of direct pSMAD1/5 target genes in the anthozoan Nematostella vectensis, several of which were conserved in Drosophila and Xenopus. Our ChIP-seq analysis revealed that many of the regulatory molecules with documented bilaterally symmetric expression in Nematostella are directly controlled by BMP signaling. We identified several so far uncharacterized BMP-dependent transcription factors and signaling molecules, whose bilaterally symmetric expression may be indicative of their involvement in secondary axis patterning. One of these molecules is zswim4-6, which encodes a novel nuclear protein that can modulate the pSMAD1/5 gradient and potentially promote BMP-dependent gene repression.


Assuntos
Anêmonas-do-Mar , Animais , Anêmonas-do-Mar/genética , Regulação da Expressão Gênica no Desenvolvimento , Transdução de Sinais , Genoma , Expressão Gênica , Padronização Corporal/genética
4.
BMC Public Health ; 24(1): 570, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388909

RESUMO

BACKGROUND: Pancreatic cancer, ranking seventh in global cancer-related deaths, poses a significant public health challenge with increasing incidence and mortality. Most cases are diagnosed at an advanced stage, resulting in low survival rates. Early diagnosis significantly impacts prognosis, making symptom awareness crucial. Symptoms are often subtle, leading to delayed help-seeking behaviour. Patients and their carers prioritise increased public awareness, indicating a need for innovative approaches to promote awareness of the disease. METHODS: This study employed a quasi-experimental pre-test/post-test design to assess the relationship between a serious game and pancreatic cancer awareness. Members of the public (N = 727) were recruited internationally, via social media and with signposting by relevant organisations. Participants completed measures of symptom awareness and help-seeking intentions before and after playing the game. The serious game, co-designed with experts by lived experience, patient advocates and healthcare professionals, presented participants with a human anatomy diagram, with each section linked to a question about pancreatic cancer. RESULTS: The serious game demonstrated a statistically significant improvement on pancreatic cancer awareness based on matched paired t-tests. Due to missing data, paired comparisons were only possible for 489 cases. Symptom awareness scores exhibited a statistically significant increase from pre-test to post-test, with a large effect size (p < 0.001, d = 1.43). Help-seeking intentions also markedly improved, showing a significant increase from pre-test to post-test, with a large effect size (p < 0.001, d = 1.10). Independent-samples t-tests were also conducted to determine if there were any group differences on pre- to post-test changes based on age, gender, and previous knowledge and/or experience of pancreatic cancer. Participants overwhelmingly endorsed the game's usability and educational value, suggesting its potential as an effective tool for enhancing public awareness and proactive health-seeking behaviour. DISCUSSION: This study is the first to explore a serious game's utility in pancreatic cancer awareness. Results suggest that such interventions can effectively increase public awareness and influence help-seeking intentions. The co-design process ensured content relevance, and participant satisfaction was high. Findings highlight the game's potential as an accessible and convenient tool for diverse populations.


Assuntos
Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico , Pessoal de Saúde , Comportamentos Relacionados com a Saúde
5.
BMC Health Serv Res ; 23(1): 1440, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114981

RESUMO

BACKGROUND: This study identified and explored how National Health Service (NHS) hearing aid clinics address cultural competence concerning Deaf British Sign Language (BSL) users. This was approached by (i) investigating how organisational processes meet the needs of Deaf signers from a hospital and hearing aid clinic perspective, (ii) analysing policies and guidelines to investigate if they equip practitioners to meet the needs of Deaf signers and (iii) exploring with practitioners who work in hearing aid clinics about their experiences of working with Deaf signers. METHODS: This study utilised a mixed-methods multiple case study design, incorporating documentary analysis and semi-structured interviews. Interview analysis was conducted using Reflexive Thematic Analysis (RTA). The research encompassed two hearing aid clinics in separate hospitals, producing 19 documents and eight interviews (four at each site) with audiologists ensuring a representative mix of professional experience levels. RESULTS: Four themes emerged from the integrated analysis: (1) Understanding Deaf signers; (2) Communicating with Deaf signers; (3) Barriers and Facilitators and (4) Service improvement. A noticeable gap in understanding BSL as both a language and a cultural system was apparent across various policies, strategies, training programmes and staff expertise. Over-reliance on interpreters provided a false sense of accessibility and most participants felt tentative to engage directly with Deaf signers. Positive practices observed at Sites A and B encompassed accurate identification of patients as Deaf signers, improved interpreter availability, communication methods, enhanced training and the encouragement of professional self-awareness. CONCLUSION: This is the first study that explores cultural competence of hearing aid clinics and its staff concerning Deaf signers in the UK. The results show both clinics require development to become an effective provider for culturally Deaf signers. Examples of how to design culturally competent practices have been provided to assist hearing aid clinics. The findings may be applicable to other underrepresented groups who are not typical users of conventional, acoustic hearing aids provided by the NHS.


Assuntos
Surdez , Auxiliares de Audição , Humanos , Língua de Sinais , Competência Cultural , Medicina Estatal , Reino Unido
6.
J Vis Exp ; (200)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37955383

RESUMO

Signaling pathways orchestrate fundamental biological processes, including development, regeneration, homeostasis, and disease. Methods to experimentally manipulate signaling are required to understand how signaling is interpreted in these wide-ranging contexts. Molecular optogenetic tools can provide reversible, tunable manipulations of signaling pathway activity with a high degree of spatiotemporal control and have been applied in vitro, ex vivo, and in vivo. These tools couple light-responsive protein domains, such as the blue light homodimerizing light-oxygen-voltage sensing (LOV) domain, with signaling effectors to confer light-dependent experimental control over signaling. This protocol provides practical guidelines for using the LOV-based bone morphogenetic protein (BMP) and Nodal signaling activators bOpto-BMP and bOpto-Nodal in the optically accessible early zebrafish embryo. It describes two control experiments: A quick phenotype assay to determine appropriate experimental conditions, and an immunofluorescence assay to directly assess signaling. Together, these control experiments can help establish a pipeline for using optogenetic tools in early zebrafish embryos. These strategies provide a powerful platform to investigate the roles of signaling in development, health, and physiology.


Assuntos
Optogenética , Peixe-Zebra , Animais , Peixe-Zebra/genética , Optogenética/métodos , Transdução de Sinais , Luz , Domínios Proteicos , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
7.
Bioconjug Chem ; 34(12): 2205-2214, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38032892

RESUMO

In mammalian cells, growth factor-induced intracellular signaling and protein synthesis play a critical role in cellular physiology and homeostasis. In the brain's glymphatic system (GS), the water-conducting activity of aquaporin-4 (AQPN-4) membrane channels (expressed in polarized fashion on astrocyte end-feet) mediates the clearance of wastes through the convective transport of fluid and solutes through the perivascular space. The glycoprotein erythropoietin (EPO) has been shown to induce the astrocyte expression of AQPN-4 via signaling through the EPO receptor and the JAK/STAT signaling pathway. Here, we self-assemble EPO in a multivalent fashion onto the surface of semiconductor quantum dots (QDs) (driven by polyhistidine-based self-assembly) to drive the interaction of the bioconjugates with EPOR on human astrocytes (HA). This results in a 2-fold augmentation of JAK/STAT signaling activity and a 1.8-fold enhancement in the expression of AQPN-4 in cultured primary HA compared to free EPO. This translates into a 2-fold increase in the water transport rate in HA cells as measured by the calcein AM water transport assay. Importantly, EPO-QD-induced augmented AQPN-4 expression does not elicit any deleterious effect on the astrocyte viability. We discuss our results in the context of the implications of EPO-nanoparticle (NP) bioconjugates for use as research tools to understand the GS and their potential as therapeutics for the modulation of GS function. More generally, our results illustrate the utility of NP bioconjugates for the controlled modulation of growth factor-induced intracellular signaling.


Assuntos
Aquaporinas , Eritropoetina , Pontos Quânticos , Animais , Humanos , Astrócitos/metabolismo , Receptores da Eritropoetina/metabolismo , Eritropoetina/metabolismo , Eritropoetina/farmacologia , Água/metabolismo , Aquaporinas/metabolismo , Aquaporinas/farmacologia , Mamíferos/metabolismo
8.
BMC Health Serv Res ; 23(1): 678, 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37349811

RESUMO

BACKGROUND: Deaf signing populations face inequality in both access to health services and health outcomes. Telemedicine intervention might offer a potential solution to address these inequalities in mental health and health related services, therefore a systematic review was carried out. The review question was: "What is the efficacy and effectiveness of telemedicine intervention for Deaf signing populations in comparison to face-to-face interventions?". METHODS: The PICO framework was applied to identify the components of the review question for this study. The inclusion criteria were: Deaf signing populations; any intervention that includes the delivery of telemedicine therapy and/or the delivery of assessment (e.g. psychological assessments) using telemedicine; and any evidence for the benefits, efficacy and effectiveness of telemedicine intervention with Deaf people whether in health and/or mental health services. The databases PsycINFO, PubMed, Web of Science, CINAHL, and Medline were searched up to August 2021. RESULTS: Following the search strategy, and after the duplicates were removed, 247 records were identified. Following screening, 232 were removed as they did not meet the inclusion criteria. The remaining 15 full-text articles were assessed for eligibility. Only two met the criteria to be included in the review (both concerned telemedicine and mental health interventions). However, they did not fully answer the review's research question. Therefore, the evidence gap remains regarding the effectiveness of telemedicine intervention for Deaf people. CONCLUSIONS: The review has identified a gap in the knowledge on the efficacy and effectiveness of telemedicine intervention for Deaf people when compared with face-to-face interventions.


Assuntos
Saúde Mental , Telemedicina , Humanos
9.
J Deaf Stud Deaf Educ ; 28(3): 267-279, 2023 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-36906841

RESUMO

READY is a self-report prospective longitudinal study of deaf and hard of hearing (DHH) young people aged 16 to 19 years on entry. Its overarching aim is to explore the risk and protective factors for successful transition to adulthood. This article introduces the cohort of 163 DHH young people, background characteristics and study design. Focusing on self-determination and subjective well-being only, those who completed the assessments in written English (n = 133) score significantly lower than general population comparators. Sociodemographic variables explain very little of the variance in well-being scores; higher levels of self-determination are a predictor of higher levels of well-being, outweighing the influence of any background characteristics. Although women and those who are LGBTQ+ have statistically significantly lower well-being scores, these aspects of their identity are not predictive risk factors. These results add to the case for self-determination interventions to support better well-being amongst DHH young people.


Assuntos
Surdez , Perda Auditiva , Pessoas com Deficiência Auditiva , Humanos , Feminino , Adolescente , Estudos Prospectivos , Estudos Longitudinais , Fatores de Risco
10.
Bioconjug Chem ; 34(2): 405-413, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36731145

RESUMO

In mammalian cells, plasma membrane potential plays vital roles in both physiology and pathology and it is controlled by a network of membrane-resident ion channels. There is considerable interest in the use of nanoparticles (NPs) to control biological functions, including the modulation of membrane potential. The photoexcitation of gold NPs (AuNPs) tethered close to the plasma membrane has been shown to induce membrane depolarization via localized heating of the AuNP surface coupled with the opening of voltage-gated sodium channels. Previous work has employed spherical AuNPs (AuNS) with absorption in the 500-600 nm range for this purpose. However, AuNP materials with absorption at longer wavelengths [e.g., near-infrared (NIR)] would enable greater tissue penetration depth in vivo. We show here the use of new anisotropic-shaped AuNPs [gold nanoflowers (AuNFs)] with broad absorption spanning into the NIR part of the spectrum (∼650-1000 nm). The AuNFs are directly synthesized with bidentate thiolate ligands, which preserves the AuNF's shape and colloidal stability, while facilitating conjugation to biomolecules. We describe the characterization of the AuNF particles and demonstrate that they adhere to the plasma membrane when bioconjugated to PEGylated cholesterol (PEG-Chol) moieties. The AuNF-PEG-Chol mediated the depolarization of rat adrenal medulla pheochromocytoma (PC-12) neuron-like cells more effectively than AuNS-PEG-Chol and unconjugated AuNS and AuNF when photoexcited at ∼561 or ∼640 nm. Importantly, AuNF induction of depolarization had no impact on cellular viability. This work demonstrates anisotropic AuNFs as an enabling nanomaterial for use in cellular depolarization and the spatiotemporal control of cellular activity.


Assuntos
Nanopartículas Metálicas , Ratos , Animais , Ouro , Potenciais da Membrana , Polietilenoglicóis , Mamíferos
11.
Int J Audiol ; : 1-10, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36382888

RESUMO

OBJECTIVES: This study concerns culturally Deaf signers in the UK who use hearing aids and (i) explores motivations for hearing aid use (ii) identifies barriers and facilitators to accessing NHS hearing aid services, (iii) examines cultural competency of hearing aid clinics and (iv) identifies factors influencing effective adult hearing aid service provision. DESIGN: Online survey in British Sign Language and English that was informed by Deaf service users. STUDY SAMPLE: 75 Deaf adult BSL users who wear hearing aids and use NHS hearing aid clinics. RESULTS: No specific reason emerged as outstandingly important for hearing aid use; however, assisting with lipreading (57%) and listening to music (52%) were rated as very/extremely important. Access issues reported were contacting clinics, poor communication with staff and lack of Deaf awareness. To be an effective and culturally competent hearing aid clinic for Deaf signers, a good understanding of Deaf culture and language was most rated as important (87%). CONCLUSION: The study is the first that explores hearing aid use and experiences of accessing hearing aid clinics from Deaf signers' perspectives. Enhancements to clinical practice are required to consider culturally Deaf people's motivations for hearing aid use and make services more BSL-friendly.

12.
Elife ; 112022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-36149406

RESUMO

During vertebrate embryogenesis, the germ layers are patterned by secreted Nodal signals. In the classical model, Nodals elicit signaling by binding to a complex comprising Type I/II Activin receptors (Acvr) and the co-receptor Tdgf1. However, it is currently unclear whether receptor binding can also affect the distribution of Nodals themselves through the embryo, and it is unknown which of the putative Acvr paralogs mediate Nodal signaling in zebrafish. Here, we characterize three Type I (Acvr1) and four Type II (Acvr2) homologs and show that - except for Acvr1c - all receptor-encoding transcripts are maternally deposited and present during zebrafish embryogenesis. We generated mutants and used them together with combinatorial morpholino knockdown and CRISPR F0 knockout (KO) approaches to assess compound loss-of-function phenotypes. We discovered that the Acvr2 homologs function partly redundantly and partially independently of Nodal to pattern the early zebrafish embryo, whereas the Type I receptors Acvr1b-a and Acvr1b-b redundantly act as major mediators of Nodal signaling. By combining quantitative analyses with expression manipulations, we found that feedback-regulated Type I receptors and co-receptors can directly influence the diffusion and distribution of Nodals, providing a mechanism for the spatial restriction of Nodal signaling during germ layer patterning.


Building a body is complicated. Cells must organise themselves head-to-tail, belly-to-back, and inside-to-outside. They do this by laying down a chemical map, which is made up of gradients of molecular signals, high in some places and lower in others. The amount of signal each cell receives helps to decide which part of the body it will become. One of the essential signals in developing vertebrates is Nodal. It helps cells to tell inside from outside and left from right. Cells detect Nodal using an activin receptor and co-receptor complex, which catch hold of passing Nodal proteins and transmit developmental signals into cells. An important model to study Nodal signals is the zebrafish embryo, but the identity of the activin receptors and their exact role in this organism has been unclear. To find out more, Preiß, Kögler, Mörsdorf et al. studied the activin receptors Acvr1 and Acvr2 in zebrafish embryos. The experiments revealed that two putative Acvr1 and four Acvr2 receptors were present during early development. To better understand their roles, Preiß et al. eliminated them one at a time, and in combination. Losing single activin receptors had no effect. But losing both Acvr1 receptors together stopped Nodal signalling and changed the distribution of the Nodal gradient. Loss of all Acvr2 receptors also caused developmental problems, but they were partly independent of Nodal. This suggests that Acvr1s seem to be able to transmit signals and to shape the Nodal gradient, and that Acvr2s might have another, so far unknown, role. Nodal signals guide the development of all vertebrates. Understanding how they work in a model species like zebrafish could shed light on their role in other species, including humans. A clearer picture could help to uncover what happens at a molecular level when development goes wrong.


Assuntos
Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Retroalimentação , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta/metabolismo , Receptores de Ativinas Tipo I/genética , Receptores de Ativinas Tipo I/metabolismo , Proteína Nodal/genética , Proteína Nodal/metabolismo , Padronização Corporal/genética , Regulação da Expressão Gênica no Desenvolvimento
13.
Nat Commun ; 13(1): 2948, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35618709

RESUMO

Protein therapeutics frequently face major challenges, including complicated production, instability, poor solubility, and aggregation. De novo protein design can readily address these challenges. Here, we demonstrate the utility of a topological refactoring strategy to design novel granulopoietic proteins starting from the granulocyte-colony stimulating factor (G-CSF) structure. We change a protein fold by rearranging the sequence and optimising it towards the new fold. Testing four designs, we obtain two that possess nanomolar activity, the most active of which is highly thermostable and protease-resistant, and matches its designed structure to atomic accuracy. While the designs possess starkly different sequence and structure from the native G-CSF, they show specific activity in differentiating primary human haematopoietic stem cells into mature neutrophils. The designs also show significant and specific activity in vivo. Our topological refactoring approach is largely independent of sequence or structural context, and is therefore applicable to a wide range of protein targets.


Assuntos
Fator Estimulador de Colônias de Granulócitos , Hematopoese , Fator Estimulador de Colônias de Granulócitos/genética , Células-Tronco Hematopoéticas , Humanos , Neutrófilos
14.
Nano Lett ; 22(12): 5037-5045, 2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35580267

RESUMO

DNA nanostructures have proven potential in biomedicine. However, their intracellular interactions─especially cytosolic stability─remain mostly unknown and attempts to discern this are confounded by the complexities of endocytic uptake and entrapment. Here, we bypass the endocytic uptake and evaluate the DNA structural stability directly in live cells. Commonly used DNA structures─crosshairs and a tetrahedron─were labeled with a multistep Förster resonance energy transfer dye cascade and microinjected into the cytosol of transformed and primary cells. Energy transfer loss, as monitored by fluorescence microscopy, reported the structure's direct time-resolved breakdown in cellula. The results showed rapid degradation of the DNA crosshair within 20 min, while the tetrahedron remained consistently intact for at least 1 h postinjection. Nuclease assays in conjunction with a current understanding of the tetrahedron's torsional rigidity confirmed its higher stability. Such studies can inform design parameters for future DNA nanostructures where programmable degradation rates may be required.


Assuntos
Nanoestruturas , Citosol , DNA/química , Transferência Ressonante de Energia de Fluorescência/métodos , Microscopia de Fluorescência , Nanoestruturas/química
16.
J Prof Nurs ; 37(5): 995-1003, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34742533

RESUMO

Academic-practice partnerships foster innovation and transition to nursing practice in healthcare systems. The purpose of this paper is to describe the impact of a public-private academic-practice partnership for Doctor of Nursing Practice (DNP) education designed to transform a large healthcare system's nursing workforce and model of care. The conceptual framework is organized around Rogers's (2003) principles of diffusion of innovation in organizations. A logic model illuminates how inputs, activities, outputs and outcomes resulted in sustained impact for graduates, the college and the healthcare organization. Partnership outcomes include education of baccalaureate and master's-prepared employed nurses (n = 95) in a DNP program for advanced practice nursing (APN) roles in the healthcare system; dissemination of scholarship; and revision of the healthcare system's research approval process. Sustained impact includes advancement of DNP-prepared graduates to complex leadership and practice roles; development of new programs and advanced practice roles based on scholarly project findings; expansion of population-specific patient programs; and extension of continuum- and access-to-care models in the healthcare organization. Recommendations include continuing development of academic-practice partnerships for transition to practice and advancement of roles and levels of champions to achieve sustained impact of academic-practice partnerships in healthcare organizations.


Assuntos
Prática Avançada de Enfermagem , Educação de Pós-Graduação em Enfermagem , Escolaridade , Bolsas de Estudo , Humanos , Universidades
17.
ACS Sens ; 6(5): 1695-1703, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-33871990

RESUMO

Nitric oxide (NO) is a critical cell signaling molecule with important roles in both normal cellular physiology and pathology. Over the past 20 years, multiple sensing modalities have been developed for the intracellular synthesis (endogenous) and release (exogenous) of NO. In this review, we survey the historical progression of NO sensing platforms, highlight the current state of the art, and offer a forward-looking view of how we expect the field of NO sensing to develop in the context of recent advances in bio-nanotechnology and nanoscale cellular biosensors.


Assuntos
Técnicas Biossensoriais , Óxido Nítrico , Nanotecnologia
18.
PLoS Biol ; 18(12): e3000919, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33351791

RESUMO

Computational protein design is rapidly becoming more powerful, and improving the accuracy of computational methods would greatly streamline protein engineering by eliminating the need for empirical optimization in the laboratory. In this work, we set out to design novel granulopoietic agents using a rescaffolding strategy with the goal of achieving simpler and more stable proteins. All of the 4 experimentally tested designs were folded, monomeric, and stable, while the 2 determined structures agreed with the design models within less than 2.5 Å. Despite the lack of significant topological or sequence similarity to their natural granulopoietic counterpart, 2 designs bound to the granulocyte colony-stimulating factor (G-CSF) receptor and exhibited potent, but delayed, in vitro proliferative activity in a G-CSF-dependent cell line. Interestingly, the designs also induced proliferation and differentiation of primary human hematopoietic stem cells into mature granulocytes, highlighting the utility of our approach to develop highly active therapeutic leads purely based on computational design.


Assuntos
Granulócitos/citologia , Engenharia de Proteínas/métodos , Diferenciação Celular , Células Cultivadas , Biologia Computacional/métodos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Granulócitos/efeitos dos fármacos , Hematopoese/efeitos dos fármacos , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/citologia , Humanos , Neutrófilos , Relação Estrutura-Atividade
19.
Molecules ; 25(23)2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33271886

RESUMO

In nanoparticle (NP)-mediated drug delivery, liposomes are the most widely used drug carrier, and the only NP system currently approved by the FDA for clinical use, owing to their advantageous physicochemical properties and excellent biocompatibility. Recent advances in liposome technology have been focused on bioconjugation strategies to improve drug loading, targeting, and overall efficacy. In this review, we highlight recent literature reports (covering the last five years) focused on bioconjugation strategies for the enhancement of liposome-mediated drug delivery. These advances encompass the improvement of drug loading/incorporation and the specific targeting of liposomes to the site of interest/drug action. We conclude with a section highlighting the role of bioconjugation strategies in liposome systems currently being evaluated for clinical use and a forward-looking discussion of the field of liposomal drug delivery.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Lipossomos/administração & dosagem , Lipossomos/química , Preparações Farmacêuticas/administração & dosagem , Animais , Humanos , Preparações Farmacêuticas/química
20.
Elife ; 92020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33174840

RESUMO

Signaling molecules activate distinct patterns of gene expression to coordinate embryogenesis, but how spatiotemporal expression diversity is generated is an open question. In zebrafish, a BMP signaling gradient patterns the dorsal-ventral axis. We systematically identified target genes responding to BMP and found that they have diverse spatiotemporal expression patterns. Transcriptional responses to optogenetically delivered high- and low-amplitude BMP signaling pulses indicate that spatiotemporal expression is not fully defined by different BMP signaling activation thresholds. Additionally, we observed negligible correlations between spatiotemporal expression and transcription kinetics for the majority of analyzed genes in response to BMP signaling pulses. In contrast, spatial differences between BMP target genes largely collapsed when FGF and Nodal signaling were inhibited. Our results suggest that, similar to other patterning systems, combinatorial signaling is likely to be a major driver of spatial diversity in BMP-dependent gene expression in zebrafish.


Assuntos
Proteínas Morfogenéticas Ósseas/genética , Regulação da Expressão Gênica no Desenvolvimento , Optogenética , Proteínas de Peixe-Zebra/metabolismo , Animais , Padronização Corporal , Proteínas Morfogenéticas Ósseas/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Cinética , Proteína Nodal/genética , Proteína Nodal/metabolismo , Transdução de Sinais , Transcrição Gênica , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética
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